Idiopathic Cough PowerPoint Presentation

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CHRONIC COUGH MÜNEVVER ERDİNÇ Department of Chest Diseases Ege University Faculty of Medicine Differential Diagnosis And Treatment In Adults

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CHRONIC COUGH MÜNEVVER ERDİNÇ Department of Chest Diseases Ege University Faculty of Medicine Differential Diagnosis And Treatment In Adults Acute Cough lasting less than 3 weeks Subacute Cough lasting 3 to 8 weeks Chronic Cough Lasting more than 8 weeks Morice AH.Eur Respir J 2004 :24:481-492 Fontana GA.Thorax 2003;58:1092-1095 Irwin RS.NEJM 343(23): 1715-1721,2000 Irwin RS. Chest 1998; 114(suppl1) :133S-181S

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CHRONIC COUGH MÜNEVVER ERDİNÇ Department of Chest Diseases Ege University Faculty of Medicine Differential Diagnosis And Treatment In Adults Acute Cough lasting less than 3 weeks Subacute Cough lasting 3 to 8 weeks Chronic Cough Lasting more than 8 weeks Morice AH.Eur Respir J 2004 :24:481-492 Fontana GA.Thorax 2003;58:1092-1095 Irwin RS.NEJM 343(23): 1715-1721,2000 Irwin RS. Chest 1998; 114(suppl1) :133S-181S Differantial Diagnosis of Chronic Cough in Adults PNDS Allergic rhinitis Chronic sinusitis GERD Cough variant asthma ACEI induced cough Pertusis Neurogenic Traumatic Postinfectious cough Phychogenic cough Chronic aspiration Zenker diverticulosis Foreign body Chronic bronchitis Bronchiectasis Lung cancer Subglottic stenosis Tracheomalasie Tracheoesophageal fistul Tuerculosis Sarcoidosis Congestive heart failure Simpson CB. Otolaryngology–Head Neck Surg 2006; 134: 693-700

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CHRONIC COUGH MÜNEVVER ERDİNÇ Department of Chest Diseases Ege University Faculty of Medicine Differential Diagnosis And Treatment In Adults Acute Cough lasting less than 3 weeks Subacute Cough lasting 3 to 8 weeks Chronic Cough Lasting more than 8 weeks Morice AH.Eur Respir J 2004 :24:481-492 Fontana GA.Thorax 2003;58:1092-1095 Irwin RS.NEJM 343(23): 1715-1721,2000 Irwin RS. Chest 1998; 114(suppl1) :133S-181S Differantial Diagnosis of Chronic Cough in Adults PNDS Allergic rhinitis Chronic sinusitis GERD Cough variant asthma ACEI induced cough Pertusis Neurogenic Traumatic Postinfectious cough Phychogenic cough Chronic aspiration Zenker diverticulosis Foreign body Chronic bronchitis Bronchiectasis Lung cancer Subglottic stenosis Tracheomalasie Tracheoesophageal fistul Tuerculosis Sarcoidosis Congestive heart failure Simpson CB. Otolaryngology–Head Neck Surg 2006; 134: 693-700 In prospective studies in adults, chronic cough is most commonly due to 6 disorders : Upper Airway Cough Syndrome (UACS) Asthma GERD Chronic Bronchitis Bronchiectasis Non-asthmatic Eosinophilic Bronchitis Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S

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CHRONIC COUGH MÜNEVVER ERDİNÇ Department of Chest Diseases Ege University Faculty of Medicine Differential Diagnosis And Treatment In Adults Acute Cough lasting less than 3 weeks Subacute Cough lasting 3 to 8 weeks Chronic Cough Lasting more than 8 weeks Morice AH.Eur Respir J 2004 :24:481-492 Fontana GA.Thorax 2003;58:1092-1095 Irwin RS.NEJM 343(23): 1715-1721,2000 Irwin RS. Chest 1998; 114(suppl1) :133S-181S Differantial Diagnosis of Chronic Cough in Adults PNDS Allergic rhinitis Chronic sinusitis GERD Cough variant asthma ACEI induced cough Pertusis Neurogenic Traumatic Postinfectious cough Phychogenic cough Chronic aspiration Zenker diverticulosis Foreign body Chronic bronchitis Bronchiectasis Lung cancer Subglottic stenosis Tracheomalasie Tracheoesophageal fistul Tuerculosis Sarcoidosis Congestive heart failure Simpson CB. Otolaryngology–Head Neck Surg 2006; 134: 693-700 In prospective studies in adults, chronic cough is most commonly due to 6 disorders : Upper Airway Cough Syndrome (UACS) Asthma GERD Chronic Bronchitis Bronchiectasis Non-asthmatic Eosinophilic Bronchitis Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S New Considerations Eosinophilic bronchitis Atopic cough Non acid(volume)/ weakly acid reflux Idiopathic (unexplained) öksürük

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CHRONIC COUGH MÜNEVVER ERDİNÇ Department of Chest Diseases Ege University Faculty of Medicine Differential Diagnosis And Treatment In Adults Acute Cough lasting less than 3 weeks Subacute Cough lasting 3 to 8 weeks Chronic Cough Lasting more than 8 weeks Morice AH.Eur Respir J 2004 :24:481-492 Fontana GA.Thorax 2003;58:1092-1095 Irwin RS.NEJM 343(23): 1715-1721,2000 Irwin RS. Chest 1998; 114(suppl1) :133S-181S Differantial Diagnosis of Chronic Cough in Adults PNDS Allergic rhinitis Chronic sinusitis GERD Cough variant asthma ACEI induced cough Pertusis Neurogenic Traumatic Postinfectious cough Phychogenic cough Chronic aspiration Zenker diverticulosis Foreign body Chronic bronchitis Bronchiectasis Lung cancer Subglottic stenosis Tracheomalasie Tracheoesophageal fistul Tuerculosis Sarcoidosis Congestive heart failure Simpson CB. Otolaryngology–Head Neck Surg 2006; 134: 693-700 In prospective studies in adults, chronic cough is most commonly due to 6 disorders : Upper Airway Cough Syndrome (UACS) Asthma GERD Chronic Bronchitis Bronchiectasis Non-asthmatic Eosinophilic Bronchitis Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S New Considerations Eosinophilic bronchitis Atopic cough Non acid(volume)/ weakly acid reflux Idiopathic (unexplained) öksürük Diagnosis and Management of Cough ACCP Evidence-Based CPG 2006 Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S Plevkova, et al. Respir Physiol Neurobiol 2004; 142: 225-235 Postnasal drip syndrome (PNDS) renamed upper airway cough syndrome (UACS) Upper airway afferents may reflexly enhance coughing Nonasthmatic eosinophilic bronchitis recognized as a common cause of chronic cough Idiopathic cough renamed unexplained cough The term acid reflux disease, unless it can be definitively shown to apply, replaced by reflux disease Update of current diagnostic and therapeutic approaches Common diseases, Uncommon diseases New algorithms for the management of cough in adults and children An empiric integrative approach is recommended

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CHRONIC COUGH MÜNEVVER ERDİNÇ Department of Chest Diseases Ege University Faculty of Medicine Differential Diagnosis And Treatment In Adults Acute Cough lasting less than 3 weeks Subacute Cough lasting 3 to 8 weeks Chronic Cough Lasting more than 8 weeks Morice AH.Eur Respir J 2004 :24:481-492 Fontana GA.Thorax 2003;58:1092-1095 Irwin RS.NEJM 343(23): 1715-1721,2000 Irwin RS. Chest 1998; 114(suppl1) :133S-181S Differantial Diagnosis of Chronic Cough in Adults PNDS Allergic rhinitis Chronic sinusitis GERD Cough variant asthma ACEI induced cough Pertusis Neurogenic Traumatic Postinfectious cough Phychogenic cough Chronic aspiration Zenker diverticulosis Foreign body Chronic bronchitis Bronchiectasis Lung cancer Subglottic stenosis Tracheomalasie Tracheoesophageal fistul Tuerculosis Sarcoidosis Congestive heart failure Simpson CB. Otolaryngology–Head Neck Surg 2006; 134: 693-700 In prospective studies in adults, chronic cough is most commonly due to 6 disorders : Upper Airway Cough Syndrome (UACS) Asthma GERD Chronic Bronchitis Bronchiectasis Non-asthmatic Eosinophilic Bronchitis Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S New Considerations Eosinophilic bronchitis Atopic cough Non acid(volume)/ weakly acid reflux Idiopathic (unexplained) öksürük Diagnosis and Management of Cough ACCP Evidence-Based CPG 2006 Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S Plevkova, et al. Respir Physiol Neurobiol 2004; 142: 225-235 Postnasal drip syndrome (PNDS) renamed upper airway cough syndrome (UACS) Upper airway afferents may reflexly enhance coughing Nonasthmatic eosinophilic bronchitis recognized as a common cause of chronic cough Idiopathic cough renamed unexplained cough The term acid reflux disease, unless it can be definitively shown to apply, replaced by reflux disease Update of current diagnostic and therapeutic approaches Common diseases, Uncommon diseases New algorithms for the management of cough in adults and children An empiric integrative approach is recommended 10 12 13 12 16 6 4 ASTHMA PNDS GERD Chest 1999;116:279-284 1. Gastroesophageal reflux disease (21-41%) 2. Cough variant asthma (24-59%) 3. Postnasal drip syndrome (41-58%)

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CHRONIC COUGH MÜNEVVER ERDİNÇ Department of Chest Diseases Ege University Faculty of Medicine Differential Diagnosis And Treatment In Adults Acute Cough lasting less than 3 weeks Subacute Cough lasting 3 to 8 weeks Chronic Cough Lasting more than 8 weeks Morice AH.Eur Respir J 2004 :24:481-492 Fontana GA.Thorax 2003;58:1092-1095 Irwin RS.NEJM 343(23): 1715-1721,2000 Irwin RS. Chest 1998; 114(suppl1) :133S-181S Differantial Diagnosis of Chronic Cough in Adults PNDS Allergic rhinitis Chronic sinusitis GERD Cough variant asthma ACEI induced cough Pertusis Neurogenic Traumatic Postinfectious cough Phychogenic cough Chronic aspiration Zenker diverticulosis Foreign body Chronic bronchitis Bronchiectasis Lung cancer Subglottic stenosis Tracheomalasie Tracheoesophageal fistul Tuerculosis Sarcoidosis Congestive heart failure Simpson CB. Otolaryngology–Head Neck Surg 2006; 134: 693-700 In prospective studies in adults, chronic cough is most commonly due to 6 disorders : Upper Airway Cough Syndrome (UACS) Asthma GERD Chronic Bronchitis Bronchiectasis Non-asthmatic Eosinophilic Bronchitis Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S New Considerations Eosinophilic bronchitis Atopic cough Non acid(volume)/ weakly acid reflux Idiopathic (unexplained) öksürük Diagnosis and Management of Cough ACCP Evidence-Based CPG 2006 Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S Plevkova, et al. Respir Physiol Neurobiol 2004; 142: 225-235 Postnasal drip syndrome (PNDS) renamed upper airway cough syndrome (UACS) Upper airway afferents may reflexly enhance coughing Nonasthmatic eosinophilic bronchitis recognized as a common cause of chronic cough Idiopathic cough renamed unexplained cough The term acid reflux disease, unless it can be definitively shown to apply, replaced by reflux disease Update of current diagnostic and therapeutic approaches Common diseases, Uncommon diseases New algorithms for the management of cough in adults and children An empiric integrative approach is recommended 10 12 13 12 16 6 4 ASTHMA PNDS GERD Chest 1999;116:279-284 1. Gastroesophageal reflux disease (21-41%) 2. Cough variant asthma (24-59%) 3. Postnasal drip syndrome (41-58%) Chest 1999;116:279-281 Percentage of Cases Presenting 1,2,3, and 4 Causative Factors

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CHRONIC COUGH MÜNEVVER ERDİNÇ Department of Chest Diseases Ege University Faculty of Medicine Differential Diagnosis And Treatment In Adults Acute Cough lasting less than 3 weeks Subacute Cough lasting 3 to 8 weeks Chronic Cough Lasting more than 8 weeks Morice AH.Eur Respir J 2004 :24:481-492 Fontana GA.Thorax 2003;58:1092-1095 Irwin RS.NEJM 343(23): 1715-1721,2000 Irwin RS. Chest 1998; 114(suppl1) :133S-181S Differantial Diagnosis of Chronic Cough in Adults PNDS Allergic rhinitis Chronic sinusitis GERD Cough variant asthma ACEI induced cough Pertusis Neurogenic Traumatic Postinfectious cough Phychogenic cough Chronic aspiration Zenker diverticulosis Foreign body Chronic bronchitis Bronchiectasis Lung cancer Subglottic stenosis Tracheomalasie Tracheoesophageal fistul Tuerculosis Sarcoidosis Congestive heart failure Simpson CB. Otolaryngology–Head Neck Surg 2006; 134: 693-700 In prospective studies in adults, chronic cough is most commonly due to 6 disorders : Upper Airway Cough Syndrome (UACS) Asthma GERD Chronic Bronchitis Bronchiectasis Non-asthmatic Eosinophilic Bronchitis Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S New Considerations Eosinophilic bronchitis Atopic cough Non acid(volume)/ weakly acid reflux Idiopathic (unexplained) öksürük Diagnosis and Management of Cough ACCP Evidence-Based CPG 2006 Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S Plevkova, et al. Respir Physiol Neurobiol 2004; 142: 225-235 Postnasal drip syndrome (PNDS) renamed upper airway cough syndrome (UACS) Upper airway afferents may reflexly enhance coughing Nonasthmatic eosinophilic bronchitis recognized as a common cause of chronic cough Idiopathic cough renamed unexplained cough The term acid reflux disease, unless it can be definitively shown to apply, replaced by reflux disease Update of current diagnostic and therapeutic approaches Common diseases, Uncommon diseases New algorithms for the management of cough in adults and children An empiric integrative approach is recommended 10 12 13 12 16 6 4 ASTHMA PNDS GERD Chest 1999;116:279-284 1. Gastroesophageal reflux disease (21-41%) 2. Cough variant asthma (24-59%) 3. Postnasal drip syndrome (41-58%) Chest 1999;116:279-281 Percentage of Cases Presenting 1,2,3, and 4 Causative Factors İmmunocompetent patients Not exposed to enviromental irritants Chest radiograph is normal Not taking an ACE inhibitor Not a current smoker Asthma and/or GERD, PNDS responsible for 93.6% of the cases of chronic cough Harding SM .Chest 2003;123:659-660

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CHRONIC COUGH MÜNEVVER ERDİNÇ Department of Chest Diseases Ege University Faculty of Medicine Differential Diagnosis And Treatment In Adults Acute Cough lasting less than 3 weeks Subacute Cough lasting 3 to 8 weeks Chronic Cough Lasting more than 8 weeks Morice AH.Eur Respir J 2004 :24:481-492 Fontana GA.Thorax 2003;58:1092-1095 Irwin RS.NEJM 343(23): 1715-1721,2000 Irwin RS. Chest 1998; 114(suppl1) :133S-181S Differantial Diagnosis of Chronic Cough in Adults PNDS Allergic rhinitis Chronic sinusitis GERD Cough variant asthma ACEI induced cough Pertusis Neurogenic Traumatic Postinfectious cough Phychogenic cough Chronic aspiration Zenker diverticulosis Foreign body Chronic bronchitis Bronchiectasis Lung cancer Subglottic stenosis Tracheomalasie Tracheoesophageal fistul Tuerculosis Sarcoidosis Congestive heart failure Simpson CB. Otolaryngology–Head Neck Surg 2006; 134: 693-700 In prospective studies in adults, chronic cough is most commonly due to 6 disorders : Upper Airway Cough Syndrome (UACS) Asthma GERD Chronic Bronchitis Bronchiectasis Non-asthmatic Eosinophilic Bronchitis Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S New Considerations Eosinophilic bronchitis Atopic cough Non acid(volume)/ weakly acid reflux Idiopathic (unexplained) öksürük Diagnosis and Management of Cough ACCP Evidence-Based CPG 2006 Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S Plevkova, et al. Respir Physiol Neurobiol 2004; 142: 225-235 Postnasal drip syndrome (PNDS) renamed upper airway cough syndrome (UACS) Upper airway afferents may reflexly enhance coughing Nonasthmatic eosinophilic bronchitis recognized as a common cause of chronic cough Idiopathic cough renamed unexplained cough The term acid reflux disease, unless it can be definitively shown to apply, replaced by reflux disease Update of current diagnostic and therapeutic approaches Common diseases, Uncommon diseases New algorithms for the management of cough in adults and children An empiric integrative approach is recommended 10 12 13 12 16 6 4 ASTHMA PNDS GERD Chest 1999;116:279-284 1. Gastroesophageal reflux disease (21-41%) 2. Cough variant asthma (24-59%) 3. Postnasal drip syndrome (41-58%) Chest 1999;116:279-281 Percentage of Cases Presenting 1,2,3, and 4 Causative Factors İmmunocompetent patients Not exposed to enviromental irritants Chest radiograph is normal Not taking an ACE inhibitor Not a current smoker Asthma and/or GERD, PNDS responsible for 93.6% of the cases of chronic cough Harding SM .Chest 2003;123:659-660 Changing Trends in Diagnosis Percentage of Diagnosis (%) GERD ASTHMA RHINITIS

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CHRONIC COUGH MÜNEVVER ERDİNÇ Department of Chest Diseases Ege University Faculty of Medicine Differential Diagnosis And Treatment In Adults Acute Cough lasting less than 3 weeks Subacute Cough lasting 3 to 8 weeks Chronic Cough Lasting more than 8 weeks Morice AH.Eur Respir J 2004 :24:481-492 Fontana GA.Thorax 2003;58:1092-1095 Irwin RS.NEJM 343(23): 1715-1721,2000 Irwin RS. Chest 1998; 114(suppl1) :133S-181S Differantial Diagnosis of Chronic Cough in Adults PNDS Allergic rhinitis Chronic sinusitis GERD Cough variant asthma ACEI induced cough Pertusis Neurogenic Traumatic Postinfectious cough Phychogenic cough Chronic aspiration Zenker diverticulosis Foreign body Chronic bronchitis Bronchiectasis Lung cancer Subglottic stenosis Tracheomalasie Tracheoesophageal fistul Tuerculosis Sarcoidosis Congestive heart failure Simpson CB. Otolaryngology–Head Neck Surg 2006; 134: 693-700 In prospective studies in adults, chronic cough is most commonly due to 6 disorders : Upper Airway Cough Syndrome (UACS) Asthma GERD Chronic Bronchitis Bronchiectasis Non-asthmatic Eosinophilic Bronchitis Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S New Considerations Eosinophilic bronchitis Atopic cough Non acid(volume)/ weakly acid reflux Idiopathic (unexplained) öksürük Diagnosis and Management of Cough ACCP Evidence-Based CPG 2006 Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S Plevkova, et al. Respir Physiol Neurobiol 2004; 142: 225-235 Postnasal drip syndrome (PNDS) renamed upper airway cough syndrome (UACS) Upper airway afferents may reflexly enhance coughing Nonasthmatic eosinophilic bronchitis recognized as a common cause of chronic cough Idiopathic cough renamed unexplained cough The term acid reflux disease, unless it can be definitively shown to apply, replaced by reflux disease Update of current diagnostic and therapeutic approaches Common diseases, Uncommon diseases New algorithms for the management of cough in adults and children An empiric integrative approach is recommended 10 12 13 12 16 6 4 ASTHMA PNDS GERD Chest 1999;116:279-284 1. Gastroesophageal reflux disease (21-41%) 2. Cough variant asthma (24-59%) 3. Postnasal drip syndrome (41-58%) Chest 1999;116:279-281 Percentage of Cases Presenting 1,2,3, and 4 Causative Factors İmmunocompetent patients Not exposed to enviromental irritants Chest radiograph is normal Not taking an ACE inhibitor Not a current smoker Asthma and/or GERD, PNDS responsible for 93.6% of the cases of chronic cough Harding SM .Chest 2003;123:659-660 Changing Trends in Diagnosis Percentage of Diagnosis (%) GERD ASTHMA RHINITIS Impaired esophageal clearance Functional defect in LES syphincter Hiatal hernia Delayed gastric emptying İncreased intra-abdominal pressure GERD ? Decreased saliva Heartburn (pyrosis) and regurgitation At least weekly symptoms extraesophageal reflux symptoms and/or esophageal mucosal damage / Katzka & DiMarino 1995

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CHRONIC COUGH MÜNEVVER ERDİNÇ Department of Chest Diseases Ege University Faculty of Medicine Differential Diagnosis And Treatment In Adults Acute Cough lasting less than 3 weeks Subacute Cough lasting 3 to 8 weeks Chronic Cough Lasting more than 8 weeks Morice AH.Eur Respir J 2004 :24:481-492 Fontana GA.Thorax 2003;58:1092-1095 Irwin RS.NEJM 343(23): 1715-1721,2000 Irwin RS. Chest 1998; 114(suppl1) :133S-181S Differantial Diagnosis of Chronic Cough in Adults PNDS Allergic rhinitis Chronic sinusitis GERD Cough variant asthma ACEI induced cough Pertusis Neurogenic Traumatic Postinfectious cough Phychogenic cough Chronic aspiration Zenker diverticulosis Foreign body Chronic bronchitis Bronchiectasis Lung cancer Subglottic stenosis Tracheomalasie Tracheoesophageal fistul Tuerculosis Sarcoidosis Congestive heart failure Simpson CB. Otolaryngology–Head Neck Surg 2006; 134: 693-700 In prospective studies in adults, chronic cough is most commonly due to 6 disorders : Upper Airway Cough Syndrome (UACS) Asthma GERD Chronic Bronchitis Bronchiectasis Non-asthmatic Eosinophilic Bronchitis Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S New Considerations Eosinophilic bronchitis Atopic cough Non acid(volume)/ weakly acid reflux Idiopathic (unexplained) öksürük Diagnosis and Management of Cough ACCP Evidence-Based CPG 2006 Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S Plevkova, et al. Respir Physiol Neurobiol 2004; 142: 225-235 Postnasal drip syndrome (PNDS) renamed upper airway cough syndrome (UACS) Upper airway afferents may reflexly enhance coughing Nonasthmatic eosinophilic bronchitis recognized as a common cause of chronic cough Idiopathic cough renamed unexplained cough The term acid reflux disease, unless it can be definitively shown to apply, replaced by reflux disease Update of current diagnostic and therapeutic approaches Common diseases, Uncommon diseases New algorithms for the management of cough in adults and children An empiric integrative approach is recommended 10 12 13 12 16 6 4 ASTHMA PNDS GERD Chest 1999;116:279-284 1. Gastroesophageal reflux disease (21-41%) 2. Cough variant asthma (24-59%) 3. Postnasal drip syndrome (41-58%) Chest 1999;116:279-281 Percentage of Cases Presenting 1,2,3, and 4 Causative Factors İmmunocompetent patients Not exposed to enviromental irritants Chest radiograph is normal Not taking an ACE inhibitor Not a current smoker Asthma and/or GERD, PNDS responsible for 93.6% of the cases of chronic cough Harding SM .Chest 2003;123:659-660 Changing Trends in Diagnosis Percentage of Diagnosis (%) GERD ASTHMA RHINITIS Impaired esophageal clearance Functional defect in LES syphincter Hiatal hernia Delayed gastric emptying İncreased intra-abdominal pressure GERD ? Decreased saliva Heartburn (pyrosis) and regurgitation At least weekly symptoms extraesophageal reflux symptoms and/or esophageal mucosal damage / Katzka & DiMarino 1995 FLR Signs Edema and hyperemia of larynx Vocal cord erythema, polyps, granulomas, ulcers Hyperemia and lymphoid hyperplasia of posterior pharynx Interarytenoid changes Subglottic stenosis

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CHRONIC COUGH MÜNEVVER ERDİNÇ Department of Chest Diseases Ege University Faculty of Medicine Differential Diagnosis And Treatment In Adults Acute Cough lasting less than 3 weeks Subacute Cough lasting 3 to 8 weeks Chronic Cough Lasting more than 8 weeks Morice AH.Eur Respir J 2004 :24:481-492 Fontana GA.Thorax 2003;58:1092-1095 Irwin RS.NEJM 343(23): 1715-1721,2000 Irwin RS. Chest 1998; 114(suppl1) :133S-181S Differantial Diagnosis of Chronic Cough in Adults PNDS Allergic rhinitis Chronic sinusitis GERD Cough variant asthma ACEI induced cough Pertusis Neurogenic Traumatic Postinfectious cough Phychogenic cough Chronic aspiration Zenker diverticulosis Foreign body Chronic bronchitis Bronchiectasis Lung cancer Subglottic stenosis Tracheomalasie Tracheoesophageal fistul Tuerculosis Sarcoidosis Congestive heart failure Simpson CB. Otolaryngology–Head Neck Surg 2006; 134: 693-700 In prospective studies in adults, chronic cough is most commonly due to 6 disorders : Upper Airway Cough Syndrome (UACS) Asthma GERD Chronic Bronchitis Bronchiectasis Non-asthmatic Eosinophilic Bronchitis Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S New Considerations Eosinophilic bronchitis Atopic cough Non acid(volume)/ weakly acid reflux Idiopathic (unexplained) öksürük Diagnosis and Management of Cough ACCP Evidence-Based CPG 2006 Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S Plevkova, et al. Respir Physiol Neurobiol 2004; 142: 225-235 Postnasal drip syndrome (PNDS) renamed upper airway cough syndrome (UACS) Upper airway afferents may reflexly enhance coughing Nonasthmatic eosinophilic bronchitis recognized as a common cause of chronic cough Idiopathic cough renamed unexplained cough The term acid reflux disease, unless it can be definitively shown to apply, replaced by reflux disease Update of current diagnostic and therapeutic approaches Common diseases, Uncommon diseases New algorithms for the management of cough in adults and children An empiric integrative approach is recommended 10 12 13 12 16 6 4 ASTHMA PNDS GERD Chest 1999;116:279-284 1. Gastroesophageal reflux disease (21-41%) 2. Cough variant asthma (24-59%) 3. Postnasal drip syndrome (41-58%) Chest 1999;116:279-281 Percentage of Cases Presenting 1,2,3, and 4 Causative Factors İmmunocompetent patients Not exposed to enviromental irritants Chest radiograph is normal Not taking an ACE inhibitor Not a current smoker Asthma and/or GERD, PNDS responsible for 93.6% of the cases of chronic cough Harding SM .Chest 2003;123:659-660 Changing Trends in Diagnosis Percentage of Diagnosis (%) GERD ASTHMA RHINITIS Impaired esophageal clearance Functional defect in LES syphincter Hiatal hernia Delayed gastric emptying İncreased intra-abdominal pressure GERD ? Decreased saliva Heartburn (pyrosis) and regurgitation At least weekly symptoms extraesophageal reflux symptoms and/or esophageal mucosal damage / Katzka & DiMarino 1995 FLR Signs Edema and hyperemia of larynx Vocal cord erythema, polyps, granulomas, ulcers Hyperemia and lymphoid hyperplasia of posterior pharynx Interarytenoid changes Subglottic stenosis GERD-related cough incidence 5 - 55% May be the sole presenting symptom(1/3) Thorax 2003:58;1092-1095) (Chest 1997; 111: 1389-1402) Irwin RS. Chest 2006;129:80S-94S Association between cough and reflux is important Esophageal-tracheal-bronchial reflex Microaspiration Pathogenesis ARRD 1981;123:413-417 Arch Intern Med 1996;156:997 Chest 1993;104:1511-1517 El Hennawi, 2004 OHNS Nonacidic factors? Esophageal dismotility?

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CHRONIC COUGH MÜNEVVER ERDİNÇ Department of Chest Diseases Ege University Faculty of Medicine Differential Diagnosis And Treatment In Adults Acute Cough lasting less than 3 weeks Subacute Cough lasting 3 to 8 weeks Chronic Cough Lasting more than 8 weeks Morice AH.Eur Respir J 2004 :24:481-492 Fontana GA.Thorax 2003;58:1092-1095 Irwin RS.NEJM 343(23): 1715-1721,2000 Irwin RS. Chest 1998; 114(suppl1) :133S-181S Differantial Diagnosis of Chronic Cough in Adults PNDS Allergic rhinitis Chronic sinusitis GERD Cough variant asthma ACEI induced cough Pertusis Neurogenic Traumatic Postinfectious cough Phychogenic cough Chronic aspiration Zenker diverticulosis Foreign body Chronic bronchitis Bronchiectasis Lung cancer Subglottic stenosis Tracheomalasie Tracheoesophageal fistul Tuerculosis Sarcoidosis Congestive heart failure Simpson CB. Otolaryngology–Head Neck Surg 2006; 134: 693-700 In prospective studies in adults, chronic cough is most commonly due to 6 disorders : Upper Airway Cough Syndrome (UACS) Asthma GERD Chronic Bronchitis Bronchiectasis Non-asthmatic Eosinophilic Bronchitis Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S New Considerations Eosinophilic bronchitis Atopic cough Non acid(volume)/ weakly acid reflux Idiopathic (unexplained) öksürük Diagnosis and Management of Cough ACCP Evidence-Based CPG 2006 Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S Plevkova, et al. Respir Physiol Neurobiol 2004; 142: 225-235 Postnasal drip syndrome (PNDS) renamed upper airway cough syndrome (UACS) Upper airway afferents may reflexly enhance coughing Nonasthmatic eosinophilic bronchitis recognized as a common cause of chronic cough Idiopathic cough renamed unexplained cough The term acid reflux disease, unless it can be definitively shown to apply, replaced by reflux disease Update of current diagnostic and therapeutic approaches Common diseases, Uncommon diseases New algorithms for the management of cough in adults and children An empiric integrative approach is recommended 10 12 13 12 16 6 4 ASTHMA PNDS GERD Chest 1999;116:279-284 1. Gastroesophageal reflux disease (21-41%) 2. Cough variant asthma (24-59%) 3. Postnasal drip syndrome (41-58%) Chest 1999;116:279-281 Percentage of Cases Presenting 1,2,3, and 4 Causative Factors İmmunocompetent patients Not exposed to enviromental irritants Chest radiograph is normal Not taking an ACE inhibitor Not a current smoker Asthma and/or GERD, PNDS responsible for 93.6% of the cases of chronic cough Harding SM .Chest 2003;123:659-660 Changing Trends in Diagnosis Percentage of Diagnosis (%) GERD ASTHMA RHINITIS Impaired esophageal clearance Functional defect in LES syphincter Hiatal hernia Delayed gastric emptying İncreased intra-abdominal pressure GERD ? Decreased saliva Heartburn (pyrosis) and regurgitation At least weekly symptoms extraesophageal reflux symptoms and/or esophageal mucosal damage / Katzka & DiMarino 1995 FLR Signs Edema and hyperemia of larynx Vocal cord erythema, polyps, granulomas, ulcers Hyperemia and lymphoid hyperplasia of posterior pharynx Interarytenoid changes Subglottic stenosis GERD-related cough incidence 5 - 55% May be the sole presenting symptom(1/3) Thorax 2003:58;1092-1095) (Chest 1997; 111: 1389-1402) Irwin RS. Chest 2006;129:80S-94S Association between cough and reflux is important Esophageal-tracheal-bronchial reflex Microaspiration Pathogenesis ARRD 1981;123:413-417 Arch Intern Med 1996;156:997 Chest 1993;104:1511-1517 El Hennawi, 2004 OHNS Nonacidic factors? Esophageal dismotility? . Mediator Release . Inflammation . Edema . Mucus . Smooth Muscle Microaspiration REFLUX Esophageal Vagal Afferents Bronchial Hyperreactivity Airway Vagal Afferents CNS Stein MR.Am J Med 2003 Chest 1997;111: 1389-1402 Airway Airway Vagal Efferents Esophagus Tracheobronchial Tree

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CHRONIC COUGH MÜNEVVER ERDİNÇ Department of Chest Diseases Ege University Faculty of Medicine Differential Diagnosis And Treatment In Adults Acute Cough lasting less than 3 weeks Subacute Cough lasting 3 to 8 weeks Chronic Cough Lasting more than 8 weeks Morice AH.Eur Respir J 2004 :24:481-492 Fontana GA.Thorax 2003;58:1092-1095 Irwin RS.NEJM 343(23): 1715-1721,2000 Irwin RS. Chest 1998; 114(suppl1) :133S-181S Differantial Diagnosis of Chronic Cough in Adults PNDS Allergic rhinitis Chronic sinusitis GERD Cough variant asthma ACEI induced cough Pertusis Neurogenic Traumatic Postinfectious cough Phychogenic cough Chronic aspiration Zenker diverticulosis Foreign body Chronic bronchitis Bronchiectasis Lung cancer Subglottic stenosis Tracheomalasie Tracheoesophageal fistul Tuerculosis Sarcoidosis Congestive heart failure Simpson CB. Otolaryngology–Head Neck Surg 2006; 134: 693-700 In prospective studies in adults, chronic cough is most commonly due to 6 disorders : Upper Airway Cough Syndrome (UACS) Asthma GERD Chronic Bronchitis Bronchiectasis Non-asthmatic Eosinophilic Bronchitis Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S New Considerations Eosinophilic bronchitis Atopic cough Non acid(volume)/ weakly acid reflux Idiopathic (unexplained) öksürük Diagnosis and Management of Cough ACCP Evidence-Based CPG 2006 Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S Plevkova, et al. Respir Physiol Neurobiol 2004; 142: 225-235 Postnasal drip syndrome (PNDS) renamed upper airway cough syndrome (UACS) Upper airway afferents may reflexly enhance coughing Nonasthmatic eosinophilic bronchitis recognized as a common cause of chronic cough Idiopathic cough renamed unexplained cough The term acid reflux disease, unless it can be definitively shown to apply, replaced by reflux disease Update of current diagnostic and therapeutic approaches Common diseases, Uncommon diseases New algorithms for the management of cough in adults and children An empiric integrative approach is recommended 10 12 13 12 16 6 4 ASTHMA PNDS GERD Chest 1999;116:279-284 1. Gastroesophageal reflux disease (21-41%) 2. Cough variant asthma (24-59%) 3. Postnasal drip syndrome (41-58%) Chest 1999;116:279-281 Percentage of Cases Presenting 1,2,3, and 4 Causative Factors İmmunocompetent patients Not exposed to enviromental irritants Chest radiograph is normal Not taking an ACE inhibitor Not a current smoker Asthma and/or GERD, PNDS responsible for 93.6% of the cases of chronic cough Harding SM .Chest 2003;123:659-660 Changing Trends in Diagnosis Percentage of Diagnosis (%) GERD ASTHMA RHINITIS Impaired esophageal clearance Functional defect in LES syphincter Hiatal hernia Delayed gastric emptying İncreased intra-abdominal pressure GERD ? Decreased saliva Heartburn (pyrosis) and regurgitation At least weekly symptoms extraesophageal reflux symptoms and/or esophageal mucosal damage / Katzka & DiMarino 1995 FLR Signs Edema and hyperemia of larynx Vocal cord erythema, polyps, granulomas, ulcers Hyperemia and lymphoid hyperplasia of posterior pharynx Interarytenoid changes Subglottic stenosis GERD-related cough incidence 5 - 55% May be the sole presenting symptom(1/3) Thorax 2003:58;1092-1095) (Chest 1997; 111: 1389-1402) Irwin RS. Chest 2006;129:80S-94S Association between cough and reflux is important Esophageal-tracheal-bronchial reflex Microaspiration Pathogenesis ARRD 1981;123:413-417 Arch Intern Med 1996;156:997 Chest 1993;104:1511-1517 El Hennawi, 2004 OHNS Nonacidic factors? Esophageal dismotility? . Mediator Release . Inflammation . Edema . Mucus . Smooth Muscle Microaspiration REFLUX Esophageal Vagal Afferents Bronchial Hyperreactivity Airway Vagal Afferents CNS Stein MR.Am J Med 2003 Chest 1997;111: 1389-1402 Airway Airway Vagal Efferents Esophagus Tracheobronchial Tree Stomach Oesophagus

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CHRONIC COUGH MÜNEVVER ERDİNÇ Department of Chest Diseases Ege University Faculty of Medicine Differential Diagnosis And Treatment In Adults Acute Cough lasting less than 3 weeks Subacute Cough lasting 3 to 8 weeks Chronic Cough Lasting more than 8 weeks Morice AH.Eur Respir J 2004 :24:481-492 Fontana GA.Thorax 2003;58:1092-1095 Irwin RS.NEJM 343(23): 1715-1721,2000 Irwin RS. Chest 1998; 114(suppl1) :133S-181S Differantial Diagnosis of Chronic Cough in Adults PNDS Allergic rhinitis Chronic sinusitis GERD Cough variant asthma ACEI induced cough Pertusis Neurogenic Traumatic Postinfectious cough Phychogenic cough Chronic aspiration Zenker diverticulosis Foreign body Chronic bronchitis Bronchiectasis Lung cancer Subglottic stenosis Tracheomalasie Tracheoesophageal fistul Tuerculosis Sarcoidosis Congestive heart failure Simpson CB. Otolaryngology–Head Neck Surg 2006; 134: 693-700 In prospective studies in adults, chronic cough is most commonly due to 6 disorders : Upper Airway Cough Syndrome (UACS) Asthma GERD Chronic Bronchitis Bronchiectasis Non-asthmatic Eosinophilic Bronchitis Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S New Considerations Eosinophilic bronchitis Atopic cough Non acid(volume)/ weakly acid reflux Idiopathic (unexplained) öksürük Diagnosis and Management of Cough ACCP Evidence-Based CPG 2006 Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S Plevkova, et al. Respir Physiol Neurobiol 2004; 142: 225-235 Postnasal drip syndrome (PNDS) renamed upper airway cough syndrome (UACS) Upper airway afferents may reflexly enhance coughing Nonasthmatic eosinophilic bronchitis recognized as a common cause of chronic cough Idiopathic cough renamed unexplained cough The term acid reflux disease, unless it can be definitively shown to apply, replaced by reflux disease Update of current diagnostic and therapeutic approaches Common diseases, Uncommon diseases New algorithms for the management of cough in adults and children An empiric integrative approach is recommended 10 12 13 12 16 6 4 ASTHMA PNDS GERD Chest 1999;116:279-284 1. Gastroesophageal reflux disease (21-41%) 2. Cough variant asthma (24-59%) 3. Postnasal drip syndrome (41-58%) Chest 1999;116:279-281 Percentage of Cases Presenting 1,2,3, and 4 Causative Factors İmmunocompetent patients Not exposed to enviromental irritants Chest radiograph is normal Not taking an ACE inhibitor Not a current smoker Asthma and/or GERD, PNDS responsible for 93.6% of the cases of chronic cough Harding SM .Chest 2003;123:659-660 Changing Trends in Diagnosis Percentage of Diagnosis (%) GERD ASTHMA RHINITIS Impaired esophageal clearance Functional defect in LES syphincter Hiatal hernia Delayed gastric emptying İncreased intra-abdominal pressure GERD ? Decreased saliva Heartburn (pyrosis) and regurgitation At least weekly symptoms extraesophageal reflux symptoms and/or esophageal mucosal damage / Katzka & DiMarino 1995 FLR Signs Edema and hyperemia of larynx Vocal cord erythema, polyps, granulomas, ulcers Hyperemia and lymphoid hyperplasia of posterior pharynx Interarytenoid changes Subglottic stenosis GERD-related cough incidence 5 - 55% May be the sole presenting symptom(1/3) Thorax 2003:58;1092-1095) (Chest 1997; 111: 1389-1402) Irwin RS. Chest 2006;129:80S-94S Association between cough and reflux is important Esophageal-tracheal-bronchial reflex Microaspiration Pathogenesis ARRD 1981;123:413-417 Arch Intern Med 1996;156:997 Chest 1993;104:1511-1517 El Hennawi, 2004 OHNS Nonacidic factors? Esophageal dismotility? . Mediator Release . Inflammation . Edema . Mucus . Smooth Muscle Microaspiration REFLUX Esophageal Vagal Afferents Bronchial Hyperreactivity Airway Vagal Afferents CNS Stein MR.Am J Med 2003 Chest 1997;111: 1389-1402 Airway Airway Vagal Efferents Esophagus Tracheobronchial Tree Stomach Oesophagus Pharyngeal pHmetry + - Not GERD Clinical GERD symptoms ? Nonacid, weakly acid reflux? Increase dose PPI + alginate İmproved Not improved Continue pHmetry under treatment Consider  Simultaneously dual probes 24 hours pHmonitoring and intraesophageal impedance Irwin RS.AJRCCM 165:1469-74,2002 McGarvey LPA.Thorax 59:342-346,2004

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CHRONIC COUGH MÜNEVVER ERDİNÇ Department of Chest Diseases Ege University Faculty of Medicine Differential Diagnosis And Treatment In Adults Acute Cough lasting less than 3 weeks Subacute Cough lasting 3 to 8 weeks Chronic Cough Lasting more than 8 weeks Morice AH.Eur Respir J 2004 :24:481-492 Fontana GA.Thorax 2003;58:1092-1095 Irwin RS.NEJM 343(23): 1715-1721,2000 Irwin RS. Chest 1998; 114(suppl1) :133S-181S Differantial Diagnosis of Chronic Cough in Adults PNDS Allergic rhinitis Chronic sinusitis GERD Cough variant asthma ACEI induced cough Pertusis Neurogenic Traumatic Postinfectious cough Phychogenic cough Chronic aspiration Zenker diverticulosis Foreign body Chronic bronchitis Bronchiectasis Lung cancer Subglottic stenosis Tracheomalasie Tracheoesophageal fistul Tuerculosis Sarcoidosis Congestive heart failure Simpson CB. Otolaryngology–Head Neck Surg 2006; 134: 693-700 In prospective studies in adults, chronic cough is most commonly due to 6 disorders : Upper Airway Cough Syndrome (UACS) Asthma GERD Chronic Bronchitis Bronchiectasis Non-asthmatic Eosinophilic Bronchitis Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S New Considerations Eosinophilic bronchitis Atopic cough Non acid(volume)/ weakly acid reflux Idiopathic (unexplained) öksürük Diagnosis and Management of Cough ACCP Evidence-Based CPG 2006 Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S Plevkova, et al. Respir Physiol Neurobiol 2004; 142: 225-235 Postnasal drip syndrome (PNDS) renamed upper airway cough syndrome (UACS) Upper airway afferents may reflexly enhance coughing Nonasthmatic eosinophilic bronchitis recognized as a common cause of chronic cough Idiopathic cough renamed unexplained cough The term acid reflux disease, unless it can be definitively shown to apply, replaced by reflux disease Update of current diagnostic and therapeutic approaches Common diseases, Uncommon diseases New algorithms for the management of cough in adults and children An empiric integrative approach is recommended 10 12 13 12 16 6 4 ASTHMA PNDS GERD Chest 1999;116:279-284 1. Gastroesophageal reflux disease (21-41%) 2. Cough variant asthma (24-59%) 3. Postnasal drip syndrome (41-58%) Chest 1999;116:279-281 Percentage of Cases Presenting 1,2,3, and 4 Causative Factors İmmunocompetent patients Not exposed to enviromental irritants Chest radiograph is normal Not taking an ACE inhibitor Not a current smoker Asthma and/or GERD, PNDS responsible for 93.6% of the cases of chronic cough Harding SM .Chest 2003;123:659-660 Changing Trends in Diagnosis Percentage of Diagnosis (%) GERD ASTHMA RHINITIS Impaired esophageal clearance Functional defect in LES syphincter Hiatal hernia Delayed gastric emptying İncreased intra-abdominal pressure GERD ? Decreased saliva Heartburn (pyrosis) and regurgitation At least weekly symptoms extraesophageal reflux symptoms and/or esophageal mucosal damage / Katzka & DiMarino 1995 FLR Signs Edema and hyperemia of larynx Vocal cord erythema, polyps, granulomas, ulcers Hyperemia and lymphoid hyperplasia of posterior pharynx Interarytenoid changes Subglottic stenosis GERD-related cough incidence 5 - 55% May be the sole presenting symptom(1/3) Thorax 2003:58;1092-1095) (Chest 1997; 111: 1389-1402) Irwin RS. Chest 2006;129:80S-94S Association between cough and reflux is important Esophageal-tracheal-bronchial reflex Microaspiration Pathogenesis ARRD 1981;123:413-417 Arch Intern Med 1996;156:997 Chest 1993;104:1511-1517 El Hennawi, 2004 OHNS Nonacidic factors? Esophageal dismotility? . Mediator Release . Inflammation . Edema . Mucus . Smooth Muscle Microaspiration REFLUX Esophageal Vagal Afferents Bronchial Hyperreactivity Airway Vagal Afferents CNS Stein MR.Am J Med 2003 Chest 1997;111: 1389-1402 Airway Airway Vagal Efferents Esophagus Tracheobronchial Tree Stomach Oesophagus Pharyngeal pHmetry + - Not GERD Clinical GERD symptoms ? Nonacid, weakly acid reflux? Increase dose PPI + alginate İmproved Not improved Continue pHmetry under treatment Consider  Simultaneously dual probes 24 hours pHmonitoring and intraesophageal impedance Irwin RS.AJRCCM 165:1469-74,2002 McGarvey LPA.Thorax 59:342-346,2004 15 cm 17 cm 6 impedance channels 1 pH electrode + Adult Standard Model ZAN-S61C01E Multichannel intraluminal impedance-pH catheter

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CHRONIC COUGH MÜNEVVER ERDİNÇ Department of Chest Diseases Ege University Faculty of Medicine Differential Diagnosis And Treatment In Adults Acute Cough lasting less than 3 weeks Subacute Cough lasting 3 to 8 weeks Chronic Cough Lasting more than 8 weeks Morice AH.Eur Respir J 2004 :24:481-492 Fontana GA.Thorax 2003;58:1092-1095 Irwin RS.NEJM 343(23): 1715-1721,2000 Irwin RS. Chest 1998; 114(suppl1) :133S-181S Differantial Diagnosis of Chronic Cough in Adults PNDS Allergic rhinitis Chronic sinusitis GERD Cough variant asthma ACEI induced cough Pertusis Neurogenic Traumatic Postinfectious cough Phychogenic cough Chronic aspiration Zenker diverticulosis Foreign body Chronic bronchitis Bronchiectasis Lung cancer Subglottic stenosis Tracheomalasie Tracheoesophageal fistul Tuerculosis Sarcoidosis Congestive heart failure Simpson CB. Otolaryngology–Head Neck Surg 2006; 134: 693-700 In prospective studies in adults, chronic cough is most commonly due to 6 disorders : Upper Airway Cough Syndrome (UACS) Asthma GERD Chronic Bronchitis Bronchiectasis Non-asthmatic Eosinophilic Bronchitis Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S New Considerations Eosinophilic bronchitis Atopic cough Non acid(volume)/ weakly acid reflux Idiopathic (unexplained) öksürük Diagnosis and Management of Cough ACCP Evidence-Based CPG 2006 Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S Plevkova, et al. Respir Physiol Neurobiol 2004; 142: 225-235 Postnasal drip syndrome (PNDS) renamed upper airway cough syndrome (UACS) Upper airway afferents may reflexly enhance coughing Nonasthmatic eosinophilic bronchitis recognized as a common cause of chronic cough Idiopathic cough renamed unexplained cough The term acid reflux disease, unless it can be definitively shown to apply, replaced by reflux disease Update of current diagnostic and therapeutic approaches Common diseases, Uncommon diseases New algorithms for the management of cough in adults and children An empiric integrative approach is recommended 10 12 13 12 16 6 4 ASTHMA PNDS GERD Chest 1999;116:279-284 1. Gastroesophageal reflux disease (21-41%) 2. Cough variant asthma (24-59%) 3. Postnasal drip syndrome (41-58%) Chest 1999;116:279-281 Percentage of Cases Presenting 1,2,3, and 4 Causative Factors İmmunocompetent patients Not exposed to enviromental irritants Chest radiograph is normal Not taking an ACE inhibitor Not a current smoker Asthma and/or GERD, PNDS responsible for 93.6% of the cases of chronic cough Harding SM .Chest 2003;123:659-660 Changing Trends in Diagnosis Percentage of Diagnosis (%) GERD ASTHMA RHINITIS Impaired esophageal clearance Functional defect in LES syphincter Hiatal hernia Delayed gastric emptying İncreased intra-abdominal pressure GERD ? Decreased saliva Heartburn (pyrosis) and regurgitation At least weekly symptoms extraesophageal reflux symptoms and/or esophageal mucosal damage / Katzka & DiMarino 1995 FLR Signs Edema and hyperemia of larynx Vocal cord erythema, polyps, granulomas, ulcers Hyperemia and lymphoid hyperplasia of posterior pharynx Interarytenoid changes Subglottic stenosis GERD-related cough incidence 5 - 55% May be the sole presenting symptom(1/3) Thorax 2003:58;1092-1095) (Chest 1997; 111: 1389-1402) Irwin RS. Chest 2006;129:80S-94S Association between cough and reflux is important Esophageal-tracheal-bronchial reflex Microaspiration Pathogenesis ARRD 1981;123:413-417 Arch Intern Med 1996;156:997 Chest 1993;104:1511-1517 El Hennawi, 2004 OHNS Nonacidic factors? Esophageal dismotility? . Mediator Release . Inflammation . Edema . Mucus . Smooth Muscle Microaspiration REFLUX Esophageal Vagal Afferents Bronchial Hyperreactivity Airway Vagal Afferents CNS Stein MR.Am J Med 2003 Chest 1997;111: 1389-1402 Airway Airway Vagal Efferents Esophagus Tracheobronchial Tree Stomach Oesophagus Pharyngeal pHmetry + - Not GERD Clinical GERD symptoms ? Nonacid, weakly acid reflux? Increase dose PPI + alginate İmproved Not improved Continue pHmetry under treatment Consider  Simultaneously dual probes 24 hours pHmonitoring and intraesophageal impedance Irwin RS.AJRCCM 165:1469-74,2002 McGarvey LPA.Thorax 59:342-346,2004 15 cm 17 cm 6 impedance channels 1 pH electrode + Adult Standard Model ZAN-S61C01E Multichannel intraluminal impedance-pH catheter Non acid reflux On going reflux of ‘non-acid’ material may be responsible for continuing symptoms while on acid-suppressing medications

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CHRONIC COUGH MÜNEVVER ERDİNÇ Department of Chest Diseases Ege University Faculty of Medicine Differential Diagnosis And Treatment In Adults Acute Cough lasting less than 3 weeks Subacute Cough lasting 3 to 8 weeks Chronic Cough Lasting more than 8 weeks Morice AH.Eur Respir J 2004 :24:481-492 Fontana GA.Thorax 2003;58:1092-1095 Irwin RS.NEJM 343(23): 1715-1721,2000 Irwin RS. Chest 1998; 114(suppl1) :133S-181S Differantial Diagnosis of Chronic Cough in Adults PNDS Allergic rhinitis Chronic sinusitis GERD Cough variant asthma ACEI induced cough Pertusis Neurogenic Traumatic Postinfectious cough Phychogenic cough Chronic aspiration Zenker diverticulosis Foreign body Chronic bronchitis Bronchiectasis Lung cancer Subglottic stenosis Tracheomalasie Tracheoesophageal fistul Tuerculosis Sarcoidosis Congestive heart failure Simpson CB. Otolaryngology–Head Neck Surg 2006; 134: 693-700 In prospective studies in adults, chronic cough is most commonly due to 6 disorders : Upper Airway Cough Syndrome (UACS) Asthma GERD Chronic Bronchitis Bronchiectasis Non-asthmatic Eosinophilic Bronchitis Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S New Considerations Eosinophilic bronchitis Atopic cough Non acid(volume)/ weakly acid reflux Idiopathic (unexplained) öksürük Diagnosis and Management of Cough ACCP Evidence-Based CPG 2006 Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S Plevkova, et al. Respir Physiol Neurobiol 2004; 142: 225-235 Postnasal drip syndrome (PNDS) renamed upper airway cough syndrome (UACS) Upper airway afferents may reflexly enhance coughing Nonasthmatic eosinophilic bronchitis recognized as a common cause of chronic cough Idiopathic cough renamed unexplained cough The term acid reflux disease, unless it can be definitively shown to apply, replaced by reflux disease Update of current diagnostic and therapeutic approaches Common diseases, Uncommon diseases New algorithms for the management of cough in adults and children An empiric integrative approach is recommended 10 12 13 12 16 6 4 ASTHMA PNDS GERD Chest 1999;116:279-284 1. Gastroesophageal reflux disease (21-41%) 2. Cough variant asthma (24-59%) 3. Postnasal drip syndrome (41-58%) Chest 1999;116:279-281 Percentage of Cases Presenting 1,2,3, and 4 Causative Factors İmmunocompetent patients Not exposed to enviromental irritants Chest radiograph is normal Not taking an ACE inhibitor Not a current smoker Asthma and/or GERD, PNDS responsible for 93.6% of the cases of chronic cough Harding SM .Chest 2003;123:659-660 Changing Trends in Diagnosis Percentage of Diagnosis (%) GERD ASTHMA RHINITIS Impaired esophageal clearance Functional defect in LES syphincter Hiatal hernia Delayed gastric emptying İncreased intra-abdominal pressure GERD ? Decreased saliva Heartburn (pyrosis) and regurgitation At least weekly symptoms extraesophageal reflux symptoms and/or esophageal mucosal damage / Katzka & DiMarino 1995 FLR Signs Edema and hyperemia of larynx Vocal cord erythema, polyps, granulomas, ulcers Hyperemia and lymphoid hyperplasia of posterior pharynx Interarytenoid changes Subglottic stenosis GERD-related cough incidence 5 - 55% May be the sole presenting symptom(1/3) Thorax 2003:58;1092-1095) (Chest 1997; 111: 1389-1402) Irwin RS. Chest 2006;129:80S-94S Association between cough and reflux is important Esophageal-tracheal-bronchial reflex Microaspiration Pathogenesis ARRD 1981;123:413-417 Arch Intern Med 1996;156:997 Chest 1993;104:1511-1517 El Hennawi, 2004 OHNS Nonacidic factors? Esophageal dismotility? . Mediator Release . Inflammation . Edema . Mucus . Smooth Muscle Microaspiration REFLUX Esophageal Vagal Afferents Bronchial Hyperreactivity Airway Vagal Afferents CNS Stein MR.Am J Med 2003 Chest 1997;111: 1389-1402 Airway Airway Vagal Efferents Esophagus Tracheobronchial Tree Stomach Oesophagus Pharyngeal pHmetry + - Not GERD Clinical GERD symptoms ? Nonacid, weakly acid reflux? Increase dose PPI + alginate İmproved Not improved Continue pHmetry under treatment Consider  Simultaneously dual probes 24 hours pHmonitoring and intraesophageal impedance Irwin RS.AJRCCM 165:1469-74,2002 McGarvey LPA.Thorax 59:342-346,2004 15 cm 17 cm 6 impedance channels 1 pH electrode + Adult Standard Model ZAN-S61C01E Multichannel intraluminal impedance-pH catheter Non acid reflux On going reflux of ‘non-acid’ material may be responsible for continuing symptoms while on acid-suppressing medications Therapy in Esophageal-pulmonary reflux Conservative and lifestyle measures Ampirical therapy: Acid suppression Proton pump inhibitors  PPI x 2 / 3 months Therapy failure  24 hour intraesophageal pHmetry ( pharyngeal pHmetry )  GERD (+) High dose PPI + H2 blocker agent Surgery(Fundoplication) Pulmonary and Crit Care Update 1994; Vol 9 Morice AH. ERJ 2004;24:481-492

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CHRONIC COUGH MÜNEVVER ERDİNÇ Department of Chest Diseases Ege University Faculty of Medicine Differential Diagnosis And Treatment In Adults Acute Cough lasting less than 3 weeks Subacute Cough lasting 3 to 8 weeks Chronic Cough Lasting more than 8 weeks Morice AH.Eur Respir J 2004 :24:481-492 Fontana GA.Thorax 2003;58:1092-1095 Irwin RS.NEJM 343(23): 1715-1721,2000 Irwin RS. Chest 1998; 114(suppl1) :133S-181S Differantial Diagnosis of Chronic Cough in Adults PNDS Allergic rhinitis Chronic sinusitis GERD Cough variant asthma ACEI induced cough Pertusis Neurogenic Traumatic Postinfectious cough Phychogenic cough Chronic aspiration Zenker diverticulosis Foreign body Chronic bronchitis Bronchiectasis Lung cancer Subglottic stenosis Tracheomalasie Tracheoesophageal fistul Tuerculosis Sarcoidosis Congestive heart failure Simpson CB. Otolaryngology–Head Neck Surg 2006; 134: 693-700 In prospective studies in adults, chronic cough is most commonly due to 6 disorders : Upper Airway Cough Syndrome (UACS) Asthma GERD Chronic Bronchitis Bronchiectasis Non-asthmatic Eosinophilic Bronchitis Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S New Considerations Eosinophilic bronchitis Atopic cough Non acid(volume)/ weakly acid reflux Idiopathic (unexplained) öksürük Diagnosis and Management of Cough ACCP Evidence-Based CPG 2006 Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S Plevkova, et al. Respir Physiol Neurobiol 2004; 142: 225-235 Postnasal drip syndrome (PNDS) renamed upper airway cough syndrome (UACS) Upper airway afferents may reflexly enhance coughing Nonasthmatic eosinophilic bronchitis recognized as a common cause of chronic cough Idiopathic cough renamed unexplained cough The term acid reflux disease, unless it can be definitively shown to apply, replaced by reflux disease Update of current diagnostic and therapeutic approaches Common diseases, Uncommon diseases New algorithms for the management of cough in adults and children An empiric integrative approach is recommended 10 12 13 12 16 6 4 ASTHMA PNDS GERD Chest 1999;116:279-284 1. Gastroesophageal reflux disease (21-41%) 2. Cough variant asthma (24-59%) 3. Postnasal drip syndrome (41-58%) Chest 1999;116:279-281 Percentage of Cases Presenting 1,2,3, and 4 Causative Factors İmmunocompetent patients Not exposed to enviromental irritants Chest radiograph is normal Not taking an ACE inhibitor Not a current smoker Asthma and/or GERD, PNDS responsible for 93.6% of the cases of chronic cough Harding SM .Chest 2003;123:659-660 Changing Trends in Diagnosis Percentage of Diagnosis (%) GERD ASTHMA RHINITIS Impaired esophageal clearance Functional defect in LES syphincter Hiatal hernia Delayed gastric emptying İncreased intra-abdominal pressure GERD ? Decreased saliva Heartburn (pyrosis) and regurgitation At least weekly symptoms extraesophageal reflux symptoms and/or esophageal mucosal damage / Katzka & DiMarino 1995 FLR Signs Edema and hyperemia of larynx Vocal cord erythema, polyps, granulomas, ulcers Hyperemia and lymphoid hyperplasia of posterior pharynx Interarytenoid changes Subglottic stenosis GERD-related cough incidence 5 - 55% May be the sole presenting symptom(1/3) Thorax 2003:58;1092-1095) (Chest 1997; 111: 1389-1402) Irwin RS. Chest 2006;129:80S-94S Association between cough and reflux is important Esophageal-tracheal-bronchial reflex Microaspiration Pathogenesis ARRD 1981;123:413-417 Arch Intern Med 1996;156:997 Chest 1993;104:1511-1517 El Hennawi, 2004 OHNS Nonacidic factors? Esophageal dismotility? . Mediator Release . Inflammation . Edema . Mucus . Smooth Muscle Microaspiration REFLUX Esophageal Vagal Afferents Bronchial Hyperreactivity Airway Vagal Afferents CNS Stein MR.Am J Med 2003 Chest 1997;111: 1389-1402 Airway Airway Vagal Efferents Esophagus Tracheobronchial Tree Stomach Oesophagus Pharyngeal pHmetry + - Not GERD Clinical GERD symptoms ? Nonacid, weakly acid reflux? Increase dose PPI + alginate İmproved Not improved Continue pHmetry under treatment Consider  Simultaneously dual probes 24 hours pHmonitoring and intraesophageal impedance Irwin RS.AJRCCM 165:1469-74,2002 McGarvey LPA.Thorax 59:342-346,2004 15 cm 17 cm 6 impedance channels 1 pH electrode + Adult Standard Model ZAN-S61C01E Multichannel intraluminal impedance-pH catheter Non acid reflux On going reflux of ‘non-acid’ material may be responsible for continuing symptoms while on acid-suppressing medications Therapy in Esophageal-pulmonary reflux Conservative and lifestyle measures Ampirical therapy: Acid suppression Proton pump inhibitors  PPI x 2 / 3 months Therapy failure  24 hour intraesophageal pHmetry ( pharyngeal pHmetry )  GERD (+) High dose PPI + H2 blocker agent Surgery(Fundoplication) Pulmonary and Crit Care Update 1994; Vol 9 Morice AH. ERJ 2004;24:481-492 Weeks of antireflux therapy Patients responded No No (%) 2 16 (41) 4 38 (86) 6 42 (95) 8 43 (99) 12 weeks 44 (100) Poe RH.Chest 2003;123:679-684 Cumulative Response to GERD Therapy

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CHRONIC COUGH MÜNEVVER ERDİNÇ Department of Chest Diseases Ege University Faculty of Medicine Differential Diagnosis And Treatment In Adults Acute Cough lasting less than 3 weeks Subacute Cough lasting 3 to 8 weeks Chronic Cough Lasting more than 8 weeks Morice AH.Eur Respir J 2004 :24:481-492 Fontana GA.Thorax 2003;58:1092-1095 Irwin RS.NEJM 343(23): 1715-1721,2000 Irwin RS. Chest 1998; 114(suppl1) :133S-181S Differantial Diagnosis of Chronic Cough in Adults PNDS Allergic rhinitis Chronic sinusitis GERD Cough variant asthma ACEI induced cough Pertusis Neurogenic Traumatic Postinfectious cough Phychogenic cough Chronic aspiration Zenker diverticulosis Foreign body Chronic bronchitis Bronchiectasis Lung cancer Subglottic stenosis Tracheomalasie Tracheoesophageal fistul Tuerculosis Sarcoidosis Congestive heart failure Simpson CB. Otolaryngology–Head Neck Surg 2006; 134: 693-700 In prospective studies in adults, chronic cough is most commonly due to 6 disorders : Upper Airway Cough Syndrome (UACS) Asthma GERD Chronic Bronchitis Bronchiectasis Non-asthmatic Eosinophilic Bronchitis Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S New Considerations Eosinophilic bronchitis Atopic cough Non acid(volume)/ weakly acid reflux Idiopathic (unexplained) öksürük Diagnosis and Management of Cough ACCP Evidence-Based CPG 2006 Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S Plevkova, et al. Respir Physiol Neurobiol 2004; 142: 225-235 Postnasal drip syndrome (PNDS) renamed upper airway cough syndrome (UACS) Upper airway afferents may reflexly enhance coughing Nonasthmatic eosinophilic bronchitis recognized as a common cause of chronic cough Idiopathic cough renamed unexplained cough The term acid reflux disease, unless it can be definitively shown to apply, replaced by reflux disease Update of current diagnostic and therapeutic approaches Common diseases, Uncommon diseases New algorithms for the management of cough in adults and children An empiric integrative approach is recommended 10 12 13 12 16 6 4 ASTHMA PNDS GERD Chest 1999;116:279-284 1. Gastroesophageal reflux disease (21-41%) 2. Cough variant asthma (24-59%) 3. Postnasal drip syndrome (41-58%) Chest 1999;116:279-281 Percentage of Cases Presenting 1,2,3, and 4 Causative Factors İmmunocompetent patients Not exposed to enviromental irritants Chest radiograph is normal Not taking an ACE inhibitor Not a current smoker Asthma and/or GERD, PNDS responsible for 93.6% of the cases of chronic cough Harding SM .Chest 2003;123:659-660 Changing Trends in Diagnosis Percentage of Diagnosis (%) GERD ASTHMA RHINITIS Impaired esophageal clearance Functional defect in LES syphincter Hiatal hernia Delayed gastric emptying İncreased intra-abdominal pressure GERD ? Decreased saliva Heartburn (pyrosis) and regurgitation At least weekly symptoms extraesophageal reflux symptoms and/or esophageal mucosal damage / Katzka & DiMarino 1995 FLR Signs Edema and hyperemia of larynx Vocal cord erythema, polyps, granulomas, ulcers Hyperemia and lymphoid hyperplasia of posterior pharynx Interarytenoid changes Subglottic stenosis GERD-related cough incidence 5 - 55% May be the sole presenting symptom(1/3) Thorax 2003:58;1092-1095) (Chest 1997; 111: 1389-1402) Irwin RS. Chest 2006;129:80S-94S Association between cough and reflux is important Esophageal-tracheal-bronchial reflex Microaspiration Pathogenesis ARRD 1981;123:413-417 Arch Intern Med 1996;156:997 Chest 1993;104:1511-1517 El Hennawi, 2004 OHNS Nonacidic factors? Esophageal dismotility? . Mediator Release . Inflammation . Edema . Mucus . Smooth Muscle Microaspiration REFLUX Esophageal Vagal Afferents Bronchial Hyperreactivity Airway Vagal Afferents CNS Stein MR.Am J Med 2003 Chest 1997;111: 1389-1402 Airway Airway Vagal Efferents Esophagus Tracheobronchial Tree Stomach Oesophagus Pharyngeal pHmetry + - Not GERD Clinical GERD symptoms ? Nonacid, weakly acid reflux? Increase dose PPI + alginate İmproved Not improved Continue pHmetry under treatment Consider  Simultaneously dual probes 24 hours pHmonitoring and intraesophageal impedance Irwin RS.AJRCCM 165:1469-74,2002 McGarvey LPA.Thorax 59:342-346,2004 15 cm 17 cm 6 impedance channels 1 pH electrode + Adult Standard Model ZAN-S61C01E Multichannel intraluminal impedance-pH catheter Non acid reflux On going reflux of ‘non-acid’ material may be responsible for continuing symptoms while on acid-suppressing medications Therapy in Esophageal-pulmonary reflux Conservative and lifestyle measures Ampirical therapy: Acid suppression Proton pump inhibitors  PPI x 2 / 3 months Therapy failure  24 hour intraesophageal pHmetry ( pharyngeal pHmetry )  GERD (+) High dose PPI + H2 blocker agent Surgery(Fundoplication) Pulmonary and Crit Care Update 1994; Vol 9 Morice AH. ERJ 2004;24:481-492 Weeks of antireflux therapy Patients responded No No (%) 2 16 (41) 4 38 (86) 6 42 (95) 8 43 (99) 12 weeks 44 (100) Poe RH.Chest 2003;123:679-684 Cumulative Response to GERD Therapy Preop pH <4: %23.6 De Meester: 85 Postop pH <4: %2.4 De Meester: 9.9

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CHRONIC COUGH MÜNEVVER ERDİNÇ Department of Chest Diseases Ege University Faculty of Medicine Differential Diagnosis And Treatment In Adults Acute Cough lasting less than 3 weeks Subacute Cough lasting 3 to 8 weeks Chronic Cough Lasting more than 8 weeks Morice AH.Eur Respir J 2004 :24:481-492 Fontana GA.Thorax 2003;58:1092-1095 Irwin RS.NEJM 343(23): 1715-1721,2000 Irwin RS. Chest 1998; 114(suppl1) :133S-181S Differantial Diagnosis of Chronic Cough in Adults PNDS Allergic rhinitis Chronic sinusitis GERD Cough variant asthma ACEI induced cough Pertusis Neurogenic Traumatic Postinfectious cough Phychogenic cough Chronic aspiration Zenker diverticulosis Foreign body Chronic bronchitis Bronchiectasis Lung cancer Subglottic stenosis Tracheomalasie Tracheoesophageal fistul Tuerculosis Sarcoidosis Congestive heart failure Simpson CB. Otolaryngology–Head Neck Surg 2006; 134: 693-700 In prospective studies in adults, chronic cough is most commonly due to 6 disorders : Upper Airway Cough Syndrome (UACS) Asthma GERD Chronic Bronchitis Bronchiectasis Non-asthmatic Eosinophilic Bronchitis Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S New Considerations Eosinophilic bronchitis Atopic cough Non acid(volume)/ weakly acid reflux Idiopathic (unexplained) öksürük Diagnosis and Management of Cough ACCP Evidence-Based CPG 2006 Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S Plevkova, et al. Respir Physiol Neurobiol 2004; 142: 225-235 Postnasal drip syndrome (PNDS) renamed upper airway cough syndrome (UACS) Upper airway afferents may reflexly enhance coughing Nonasthmatic eosinophilic bronchitis recognized as a common cause of chronic cough Idiopathic cough renamed unexplained cough The term acid reflux disease, unless it can be definitively shown to apply, replaced by reflux disease Update of current diagnostic and therapeutic approaches Common diseases, Uncommon diseases New algorithms for the management of cough in adults and children An empiric integrative approach is recommended 10 12 13 12 16 6 4 ASTHMA PNDS GERD Chest 1999;116:279-284 1. Gastroesophageal reflux disease (21-41%) 2. Cough variant asthma (24-59%) 3. Postnasal drip syndrome (41-58%) Chest 1999;116:279-281 Percentage of Cases Presenting 1,2,3, and 4 Causative Factors İmmunocompetent patients Not exposed to enviromental irritants Chest radiograph is normal Not taking an ACE inhibitor Not a current smoker Asthma and/or GERD, PNDS responsible for 93.6% of the cases of chronic cough Harding SM .Chest 2003;123:659-660 Changing Trends in Diagnosis Percentage of Diagnosis (%) GERD ASTHMA RHINITIS Impaired esophageal clearance Functional defect in LES syphincter Hiatal hernia Delayed gastric emptying İncreased intra-abdominal pressure GERD ? Decreased saliva Heartburn (pyrosis) and regurgitation At least weekly symptoms extraesophageal reflux symptoms and/or esophageal mucosal damage / Katzka & DiMarino 1995 FLR Signs Edema and hyperemia of larynx Vocal cord erythema, polyps, granulomas, ulcers Hyperemia and lymphoid hyperplasia of posterior pharynx Interarytenoid changes Subglottic stenosis GERD-related cough incidence 5 - 55% May be the sole presenting symptom(1/3) Thorax 2003:58;1092-1095) (Chest 1997; 111: 1389-1402) Irwin RS. Chest 2006;129:80S-94S Association between cough and reflux is important Esophageal-tracheal-bronchial reflex Microaspiration Pathogenesis ARRD 1981;123:413-417 Arch Intern Med 1996;156:997 Chest 1993;104:1511-1517 El Hennawi, 2004 OHNS Nonacidic factors? Esophageal dismotility? . Mediator Release . Inflammation . Edema . Mucus . Smooth Muscle Microaspiration REFLUX Esophageal Vagal Afferents Bronchial Hyperreactivity Airway Vagal Afferents CNS Stein MR.Am J Med 2003 Chest 1997;111: 1389-1402 Airway Airway Vagal Efferents Esophagus Tracheobronchial Tree Stomach Oesophagus Pharyngeal pHmetry + - Not GERD Clinical GERD symptoms ? Nonacid, weakly acid reflux? Increase dose PPI + alginate İmproved Not improved Continue pHmetry under treatment Consider  Simultaneously dual probes 24 hours pHmonitoring and intraesophageal impedance Irwin RS.AJRCCM 165:1469-74,2002 McGarvey LPA.Thorax 59:342-346,2004 15 cm 17 cm 6 impedance channels 1 pH electrode + Adult Standard Model ZAN-S61C01E Multichannel intraluminal impedance-pH catheter Non acid reflux On going reflux of ‘non-acid’ material may be responsible for continuing symptoms while on acid-suppressing medications Therapy in Esophageal-pulmonary reflux Conservative and lifestyle measures Ampirical therapy: Acid suppression Proton pump inhibitors  PPI x 2 / 3 months Therapy failure  24 hour intraesophageal pHmetry ( pharyngeal pHmetry )  GERD (+) High dose PPI + H2 blocker agent Surgery(Fundoplication) Pulmonary and Crit Care Update 1994; Vol 9 Morice AH. ERJ 2004;24:481-492 Weeks of antireflux therapy Patients responded No No (%) 2 16 (41) 4 38 (86) 6 42 (95) 8 43 (99) 12 weeks 44 (100) Poe RH.Chest 2003;123:679-684 Cumulative Response to GERD Therapy Preop pH <4: %23.6 De Meester: 85 Postop pH <4: %2.4 De Meester: 9.9 1. Chronic cough for at least 2 months 2. Immunocompetent patients 3. Chest radiograph is normal 4. Not exposed to enviromental irritants nor a present smoker 5. Not taking an ACE inhibitor 6. Symptomatic asthma has been ruled out 7. Rhinosinus diseases has been ruled out: 8. ‘Silent sinusitis’ has been ruled out 9. Nonasthmatic eosinophilic bronchitis has been ruled out: BPT is negative Cough has not improved with asthma therapy First generation H1 antagonists has been used Eo 3% in induced sputum Cough has not improved with steroids Irwin RS. Chest 2006;129:80S-94S İrwin RS. AJRCCM Vol 165; 1469-1474, 2002 Clinical Profile That Chronic Cough İs Likely Due To ‘Silent GERD’

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CHRONIC COUGH MÜNEVVER ERDİNÇ Department of Chest Diseases Ege University Faculty of Medicine Differential Diagnosis And Treatment In Adults Acute Cough lasting less than 3 weeks Subacute Cough lasting 3 to 8 weeks Chronic Cough Lasting more than 8 weeks Morice AH.Eur Respir J 2004 :24:481-492 Fontana GA.Thorax 2003;58:1092-1095 Irwin RS.NEJM 343(23): 1715-1721,2000 Irwin RS. Chest 1998; 114(suppl1) :133S-181S Differantial Diagnosis of Chronic Cough in Adults PNDS Allergic rhinitis Chronic sinusitis GERD Cough variant asthma ACEI induced cough Pertusis Neurogenic Traumatic Postinfectious cough Phychogenic cough Chronic aspiration Zenker diverticulosis Foreign body Chronic bronchitis Bronchiectasis Lung cancer Subglottic stenosis Tracheomalasie Tracheoesophageal fistul Tuerculosis Sarcoidosis Congestive heart failure Simpson CB. Otolaryngology–Head Neck Surg 2006; 134: 693-700 In prospective studies in adults, chronic cough is most commonly due to 6 disorders : Upper Airway Cough Syndrome (UACS) Asthma GERD Chronic Bronchitis Bronchiectasis Non-asthmatic Eosinophilic Bronchitis Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S New Considerations Eosinophilic bronchitis Atopic cough Non acid(volume)/ weakly acid reflux Idiopathic (unexplained) öksürük Diagnosis and Management of Cough ACCP Evidence-Based CPG 2006 Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S Plevkova, et al. Respir Physiol Neurobiol 2004; 142: 225-235 Postnasal drip syndrome (PNDS) renamed upper airway cough syndrome (UACS) Upper airway afferents may reflexly enhance coughing Nonasthmatic eosinophilic bronchitis recognized as a common cause of chronic cough Idiopathic cough renamed unexplained cough The term acid reflux disease, unless it can be definitively shown to apply, replaced by reflux disease Update of current diagnostic and therapeutic approaches Common diseases, Uncommon diseases New algorithms for the management of cough in adults and children An empiric integrative approach is recommended 10 12 13 12 16 6 4 ASTHMA PNDS GERD Chest 1999;116:279-284 1. Gastroesophageal reflux disease (21-41%) 2. Cough variant asthma (24-59%) 3. Postnasal drip syndrome (41-58%) Chest 1999;116:279-281 Percentage of Cases Presenting 1,2,3, and 4 Causative Factors İmmunocompetent patients Not exposed to enviromental irritants Chest radiograph is normal Not taking an ACE inhibitor Not a current smoker Asthma and/or GERD, PNDS responsible for 93.6% of the cases of chronic cough Harding SM .Chest 2003;123:659-660 Changing Trends in Diagnosis Percentage of Diagnosis (%) GERD ASTHMA RHINITIS Impaired esophageal clearance Functional defect in LES syphincter Hiatal hernia Delayed gastric emptying İncreased intra-abdominal pressure GERD ? Decreased saliva Heartburn (pyrosis) and regurgitation At least weekly symptoms extraesophageal reflux symptoms and/or esophageal mucosal damage / Katzka & DiMarino 1995 FLR Signs Edema and hyperemia of larynx Vocal cord erythema, polyps, granulomas, ulcers Hyperemia and lymphoid hyperplasia of posterior pharynx Interarytenoid changes Subglottic stenosis GERD-related cough incidence 5 - 55% May be the sole presenting symptom(1/3) Thorax 2003:58;1092-1095) (Chest 1997; 111: 1389-1402) Irwin RS. Chest 2006;129:80S-94S Association between cough and reflux is important Esophageal-tracheal-bronchial reflex Microaspiration Pathogenesis ARRD 1981;123:413-417 Arch Intern Med 1996;156:997 Chest 1993;104:1511-1517 El Hennawi, 2004 OHNS Nonacidic factors? Esophageal dismotility? . Mediator Release . Inflammation . Edema . Mucus . Smooth Muscle Microaspiration REFLUX Esophageal Vagal Afferents Bronchial Hyperreactivity Airway Vagal Afferents CNS Stein MR.Am J Med 2003 Chest 1997;111: 1389-1402 Airway Airway Vagal Efferents Esophagus Tracheobronchial Tree Stomach Oesophagus Pharyngeal pHmetry + - Not GERD Clinical GERD symptoms ? Nonacid, weakly acid reflux? Increase dose PPI + alginate İmproved Not improved Continue pHmetry under treatment Consider  Simultaneously dual probes 24 hours pHmonitoring and intraesophageal impedance Irwin RS.AJRCCM 165:1469-74,2002 McGarvey LPA.Thorax 59:342-346,2004 15 cm 17 cm 6 impedance channels 1 pH electrode + Adult Standard Model ZAN-S61C01E Multichannel intraluminal impedance-pH catheter Non acid reflux On going reflux of ‘non-acid’ material may be responsible for continuing symptoms while on acid-suppressing medications Therapy in Esophageal-pulmonary reflux Conservative and lifestyle measures Ampirical therapy: Acid suppression Proton pump inhibitors  PPI x 2 / 3 months Therapy failure  24 hour intraesophageal pHmetry ( pharyngeal pHmetry )  GERD (+) High dose PPI + H2 blocker agent Surgery(Fundoplication) Pulmonary and Crit Care Update 1994; Vol 9 Morice AH. ERJ 2004;24:481-492 Weeks of antireflux therapy Patients responded No No (%) 2 16 (41) 4 38 (86) 6 42 (95) 8 43 (99) 12 weeks 44 (100) Poe RH.Chest 2003;123:679-684 Cumulative Response to GERD Therapy Preop pH <4: %23.6 De Meester: 85 Postop pH <4: %2.4 De Meester: 9.9 1. Chronic cough for at least 2 months 2. Immunocompetent patients 3. Chest radiograph is normal 4. Not exposed to enviromental irritants nor a present smoker 5. Not taking an ACE inhibitor 6. Symptomatic asthma has been ruled out 7. Rhinosinus diseases has been ruled out: 8. ‘Silent sinusitis’ has been ruled out 9. Nonasthmatic eosinophilic bronchitis has been ruled out: BPT is negative Cough has not improved with asthma therapy First generation H1 antagonists has been used Eo 3% in induced sputum Cough has not improved with steroids Irwin RS. Chest 2006;129:80S-94S İrwin RS. AJRCCM Vol 165; 1469-1474, 2002 Clinical Profile That Chronic Cough İs Likely Due To ‘Silent GERD’ Postnasal Drip Syndrome (PNDS) Prevalence : 8 – 87% Pathogenesis : The sensation of drainage of secretions from the nose or paranasal sinuses into the pharynx Clinical Presentation: Dripping sensation Tickle in the throat Nasal congestion Mucus in oropharynx Cobblestone appearence of oropharynx ACCP consensus. CHEST 1998; 114: 133-181 ERS Task Force. ERS Journal ; 24: 553-566 Pathogenic Triad in Chronic Cough. CHEST 1999; 116: 279-284 Evaluation of chronic cough. UPTODATE 2005

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CHRONIC COUGH MÜNEVVER ERDİNÇ Department of Chest Diseases Ege University Faculty of Medicine Differential Diagnosis And Treatment In Adults Acute Cough lasting less than 3 weeks Subacute Cough lasting 3 to 8 weeks Chronic Cough Lasting more than 8 weeks Morice AH.Eur Respir J 2004 :24:481-492 Fontana GA.Thorax 2003;58:1092-1095 Irwin RS.NEJM 343(23): 1715-1721,2000 Irwin RS. Chest 1998; 114(suppl1) :133S-181S Differantial Diagnosis of Chronic Cough in Adults PNDS Allergic rhinitis Chronic sinusitis GERD Cough variant asthma ACEI induced cough Pertusis Neurogenic Traumatic Postinfectious cough Phychogenic cough Chronic aspiration Zenker diverticulosis Foreign body Chronic bronchitis Bronchiectasis Lung cancer Subglottic stenosis Tracheomalasie Tracheoesophageal fistul Tuerculosis Sarcoidosis Congestive heart failure Simpson CB. Otolaryngology–Head Neck Surg 2006; 134: 693-700 In prospective studies in adults, chronic cough is most commonly due to 6 disorders : Upper Airway Cough Syndrome (UACS) Asthma GERD Chronic Bronchitis Bronchiectasis Non-asthmatic Eosinophilic Bronchitis Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S New Considerations Eosinophilic bronchitis Atopic cough Non acid(volume)/ weakly acid reflux Idiopathic (unexplained) öksürük Diagnosis and Management of Cough ACCP Evidence-Based CPG 2006 Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S Plevkova, et al. Respir Physiol Neurobiol 2004; 142: 225-235 Postnasal drip syndrome (PNDS) renamed upper airway cough syndrome (UACS) Upper airway afferents may reflexly enhance coughing Nonasthmatic eosinophilic bronchitis recognized as a common cause of chronic cough Idiopathic cough renamed unexplained cough The term acid reflux disease, unless it can be definitively shown to apply, replaced by reflux disease Update of current diagnostic and therapeutic approaches Common diseases, Uncommon diseases New algorithms for the management of cough in adults and children An empiric integrative approach is recommended 10 12 13 12 16 6 4 ASTHMA PNDS GERD Chest 1999;116:279-284 1. Gastroesophageal reflux disease (21-41%) 2. Cough variant asthma (24-59%) 3. Postnasal drip syndrome (41-58%) Chest 1999;116:279-281 Percentage of Cases Presenting 1,2,3, and 4 Causative Factors İmmunocompetent patients Not exposed to enviromental irritants Chest radiograph is normal Not taking an ACE inhibitor Not a current smoker Asthma and/or GERD, PNDS responsible for 93.6% of the cases of chronic cough Harding SM .Chest 2003;123:659-660 Changing Trends in Diagnosis Percentage of Diagnosis (%) GERD ASTHMA RHINITIS Impaired esophageal clearance Functional defect in LES syphincter Hiatal hernia Delayed gastric emptying İncreased intra-abdominal pressure GERD ? Decreased saliva Heartburn (pyrosis) and regurgitation At least weekly symptoms extraesophageal reflux symptoms and/or esophageal mucosal damage / Katzka & DiMarino 1995 FLR Signs Edema and hyperemia of larynx Vocal cord erythema, polyps, granulomas, ulcers Hyperemia and lymphoid hyperplasia of posterior pharynx Interarytenoid changes Subglottic stenosis GERD-related cough incidence 5 - 55% May be the sole presenting symptom(1/3) Thorax 2003:58;1092-1095) (Chest 1997; 111: 1389-1402) Irwin RS. Chest 2006;129:80S-94S Association between cough and reflux is important Esophageal-tracheal-bronchial reflex Microaspiration Pathogenesis ARRD 1981;123:413-417 Arch Intern Med 1996;156:997 Chest 1993;104:1511-1517 El Hennawi, 2004 OHNS Nonacidic factors? Esophageal dismotility? . Mediator Release . Inflammation . Edema . Mucus . Smooth Muscle Microaspiration REFLUX Esophageal Vagal Afferents Bronchial Hyperreactivity Airway Vagal Afferents CNS Stein MR.Am J Med 2003 Chest 1997;111: 1389-1402 Airway Airway Vagal Efferents Esophagus Tracheobronchial Tree Stomach Oesophagus Pharyngeal pHmetry + - Not GERD Clinical GERD symptoms ? Nonacid, weakly acid reflux? Increase dose PPI + alginate İmproved Not improved Continue pHmetry under treatment Consider  Simultaneously dual probes 24 hours pHmonitoring and intraesophageal impedance Irwin RS.AJRCCM 165:1469-74,2002 McGarvey LPA.Thorax 59:342-346,2004 15 cm 17 cm 6 impedance channels 1 pH electrode + Adult Standard Model ZAN-S61C01E Multichannel intraluminal impedance-pH catheter Non acid reflux On going reflux of ‘non-acid’ material may be responsible for continuing symptoms while on acid-suppressing medications Therapy in Esophageal-pulmonary reflux Conservative and lifestyle measures Ampirical therapy: Acid suppression Proton pump inhibitors  PPI x 2 / 3 months Therapy failure  24 hour intraesophageal pHmetry ( pharyngeal pHmetry )  GERD (+) High dose PPI + H2 blocker agent Surgery(Fundoplication) Pulmonary and Crit Care Update 1994; Vol 9 Morice AH. ERJ 2004;24:481-492 Weeks of antireflux therapy Patients responded No No (%) 2 16 (41) 4 38 (86) 6 42 (95) 8 43 (99) 12 weeks 44 (100) Poe RH.Chest 2003;123:679-684 Cumulative Response to GERD Therapy Preop pH <4: %23.6 De Meester: 85 Postop pH <4: %2.4 De Meester: 9.9 1. Chronic cough for at least 2 months 2. Immunocompetent patients 3. Chest radiograph is normal 4. Not exposed to enviromental irritants nor a present smoker 5. Not taking an ACE inhibitor 6. Symptomatic asthma has been ruled out 7. Rhinosinus diseases has been ruled out: 8. ‘Silent sinusitis’ has been ruled out 9. Nonasthmatic eosinophilic bronchitis has been ruled out: BPT is negative Cough has not improved with asthma therapy First generation H1 antagonists has been used Eo 3% in induced sputum Cough has not improved with steroids Irwin RS. Chest 2006;129:80S-94S İrwin RS. AJRCCM Vol 165; 1469-1474, 2002 Clinical Profile That Chronic Cough İs Likely Due To ‘Silent GERD’ Postnasal Drip Syndrome (PNDS) Prevalence : 8 – 87% Pathogenesis : The sensation of drainage of secretions from the nose or paranasal sinuses into the pharynx Clinical Presentation: Dripping sensation Tickle in the throat Nasal congestion Mucus in oropharynx Cobblestone appearence of oropharynx ACCP consensus. CHEST 1998; 114: 133-181 ERS Task Force. ERS Journal ; 24: 553-566 Pathogenic Triad in Chronic Cough. CHEST 1999; 116: 279-284 Evaluation of chronic cough. UPTODATE 2005 Chest 2006;129:63S-71S In patient with chronic cough that is related to upper airway abnormalities Upper Airway Cough Syndrome

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CHRONIC COUGH MÜNEVVER ERDİNÇ Department of Chest Diseases Ege University Faculty of Medicine Differential Diagnosis And Treatment In Adults Acute Cough lasting less than 3 weeks Subacute Cough lasting 3 to 8 weeks Chronic Cough Lasting more than 8 weeks Morice AH.Eur Respir J 2004 :24:481-492 Fontana GA.Thorax 2003;58:1092-1095 Irwin RS.NEJM 343(23): 1715-1721,2000 Irwin RS. Chest 1998; 114(suppl1) :133S-181S Differantial Diagnosis of Chronic Cough in Adults PNDS Allergic rhinitis Chronic sinusitis GERD Cough variant asthma ACEI induced cough Pertusis Neurogenic Traumatic Postinfectious cough Phychogenic cough Chronic aspiration Zenker diverticulosis Foreign body Chronic bronchitis Bronchiectasis Lung cancer Subglottic stenosis Tracheomalasie Tracheoesophageal fistul Tuerculosis Sarcoidosis Congestive heart failure Simpson CB. Otolaryngology–Head Neck Surg 2006; 134: 693-700 In prospective studies in adults, chronic cough is most commonly due to 6 disorders : Upper Airway Cough Syndrome (UACS) Asthma GERD Chronic Bronchitis Bronchiectasis Non-asthmatic Eosinophilic Bronchitis Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S New Considerations Eosinophilic bronchitis Atopic cough Non acid(volume)/ weakly acid reflux Idiopathic (unexplained) öksürük Diagnosis and Management of Cough ACCP Evidence-Based CPG 2006 Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S Plevkova, et al. Respir Physiol Neurobiol 2004; 142: 225-235 Postnasal drip syndrome (PNDS) renamed upper airway cough syndrome (UACS) Upper airway afferents may reflexly enhance coughing Nonasthmatic eosinophilic bronchitis recognized as a common cause of chronic cough Idiopathic cough renamed unexplained cough The term acid reflux disease, unless it can be definitively shown to apply, replaced by reflux disease Update of current diagnostic and therapeutic approaches Common diseases, Uncommon diseases New algorithms for the management of cough in adults and children An empiric integrative approach is recommended 10 12 13 12 16 6 4 ASTHMA PNDS GERD Chest 1999;116:279-284 1. Gastroesophageal reflux disease (21-41%) 2. Cough variant asthma (24-59%) 3. Postnasal drip syndrome (41-58%) Chest 1999;116:279-281 Percentage of Cases Presenting 1,2,3, and 4 Causative Factors İmmunocompetent patients Not exposed to enviromental irritants Chest radiograph is normal Not taking an ACE inhibitor Not a current smoker Asthma and/or GERD, PNDS responsible for 93.6% of the cases of chronic cough Harding SM .Chest 2003;123:659-660 Changing Trends in Diagnosis Percentage of Diagnosis (%) GERD ASTHMA RHINITIS Impaired esophageal clearance Functional defect in LES syphincter Hiatal hernia Delayed gastric emptying İncreased intra-abdominal pressure GERD ? Decreased saliva Heartburn (pyrosis) and regurgitation At least weekly symptoms extraesophageal reflux symptoms and/or esophageal mucosal damage / Katzka & DiMarino 1995 FLR Signs Edema and hyperemia of larynx Vocal cord erythema, polyps, granulomas, ulcers Hyperemia and lymphoid hyperplasia of posterior pharynx Interarytenoid changes Subglottic stenosis GERD-related cough incidence 5 - 55% May be the sole presenting symptom(1/3) Thorax 2003:58;1092-1095) (Chest 1997; 111: 1389-1402) Irwin RS. Chest 2006;129:80S-94S Association between cough and reflux is important Esophageal-tracheal-bronchial reflex Microaspiration Pathogenesis ARRD 1981;123:413-417 Arch Intern Med 1996;156:997 Chest 1993;104:1511-1517 El Hennawi, 2004 OHNS Nonacidic factors? Esophageal dismotility? . Mediator Release . Inflammation . Edema . Mucus . Smooth Muscle Microaspiration REFLUX Esophageal Vagal Afferents Bronchial Hyperreactivity Airway Vagal Afferents CNS Stein MR.Am J Med 2003 Chest 1997;111: 1389-1402 Airway Airway Vagal Efferents Esophagus Tracheobronchial Tree Stomach Oesophagus Pharyngeal pHmetry + - Not GERD Clinical GERD symptoms ? Nonacid, weakly acid reflux? Increase dose PPI + alginate İmproved Not improved Continue pHmetry under treatment Consider  Simultaneously dual probes 24 hours pHmonitoring and intraesophageal impedance Irwin RS.AJRCCM 165:1469-74,2002 McGarvey LPA.Thorax 59:342-346,2004 15 cm 17 cm 6 impedance channels 1 pH electrode + Adult Standard Model ZAN-S61C01E Multichannel intraluminal impedance-pH catheter Non acid reflux On going reflux of ‘non-acid’ material may be responsible for continuing symptoms while on acid-suppressing medications Therapy in Esophageal-pulmonary reflux Conservative and lifestyle measures Ampirical therapy: Acid suppression Proton pump inhibitors  PPI x 2 / 3 months Therapy failure  24 hour intraesophageal pHmetry ( pharyngeal pHmetry )  GERD (+) High dose PPI + H2 blocker agent Surgery(Fundoplication) Pulmonary and Crit Care Update 1994; Vol 9 Morice AH. ERJ 2004;24:481-492 Weeks of antireflux therapy Patients responded No No (%) 2 16 (41) 4 38 (86) 6 42 (95) 8 43 (99) 12 weeks 44 (100) Poe RH.Chest 2003;123:679-684 Cumulative Response to GERD Therapy Preop pH <4: %23.6 De Meester: 85 Postop pH <4: %2.4 De Meester: 9.9 1. Chronic cough for at least 2 months 2. Immunocompetent patients 3. Chest radiograph is normal 4. Not exposed to enviromental irritants nor a present smoker 5. Not taking an ACE inhibitor 6. Symptomatic asthma has been ruled out 7. Rhinosinus diseases has been ruled out: 8. ‘Silent sinusitis’ has been ruled out 9. Nonasthmatic eosinophilic bronchitis has been ruled out: BPT is negative Cough has not improved with asthma therapy First generation H1 antagonists has been used Eo 3% in induced sputum Cough has not improved with steroids Irwin RS. Chest 2006;129:80S-94S İrwin RS. AJRCCM Vol 165; 1469-1474, 2002 Clinical Profile That Chronic Cough İs Likely Due To ‘Silent GERD’ Postnasal Drip Syndrome (PNDS) Prevalence : 8 – 87% Pathogenesis : The sensation of drainage of secretions from the nose or paranasal sinuses into the pharynx Clinical Presentation: Dripping sensation Tickle in the throat Nasal congestion Mucus in oropharynx Cobblestone appearence of oropharynx ACCP consensus. CHEST 1998; 114: 133-181 ERS Task Force. ERS Journal ; 24: 553-566 Pathogenic Triad in Chronic Cough. CHEST 1999; 116: 279-284 Evaluation of chronic cough. UPTODATE 2005 Chest 2006;129:63S-71S In patient with chronic cough that is related to upper airway abnormalities Upper Airway Cough Syndrome UACS Treatment Antihistamines / decongestant combinations - “Older” sedating antihistamines more effective - Treatment effect should be observed in 1 week Additional / Alternative treatments : Ipratropium nasal spray : 2-7 days Nasal steroids (such as BDP, FP,BUD) : 2-3 days - 2 week 3 months prescribed

Slide 26 -

CHRONIC COUGH MÜNEVVER ERDİNÇ Department of Chest Diseases Ege University Faculty of Medicine Differential Diagnosis And Treatment In Adults Acute Cough lasting less than 3 weeks Subacute Cough lasting 3 to 8 weeks Chronic Cough Lasting more than 8 weeks Morice AH.Eur Respir J 2004 :24:481-492 Fontana GA.Thorax 2003;58:1092-1095 Irwin RS.NEJM 343(23): 1715-1721,2000 Irwin RS. Chest 1998; 114(suppl1) :133S-181S Differantial Diagnosis of Chronic Cough in Adults PNDS Allergic rhinitis Chronic sinusitis GERD Cough variant asthma ACEI induced cough Pertusis Neurogenic Traumatic Postinfectious cough Phychogenic cough Chronic aspiration Zenker diverticulosis Foreign body Chronic bronchitis Bronchiectasis Lung cancer Subglottic stenosis Tracheomalasie Tracheoesophageal fistul Tuerculosis Sarcoidosis Congestive heart failure Simpson CB. Otolaryngology–Head Neck Surg 2006; 134: 693-700 In prospective studies in adults, chronic cough is most commonly due to 6 disorders : Upper Airway Cough Syndrome (UACS) Asthma GERD Chronic Bronchitis Bronchiectasis Non-asthmatic Eosinophilic Bronchitis Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S New Considerations Eosinophilic bronchitis Atopic cough Non acid(volume)/ weakly acid reflux Idiopathic (unexplained) öksürük Diagnosis and Management of Cough ACCP Evidence-Based CPG 2006 Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S Plevkova, et al. Respir Physiol Neurobiol 2004; 142: 225-235 Postnasal drip syndrome (PNDS) renamed upper airway cough syndrome (UACS) Upper airway afferents may reflexly enhance coughing Nonasthmatic eosinophilic bronchitis recognized as a common cause of chronic cough Idiopathic cough renamed unexplained cough The term acid reflux disease, unless it can be definitively shown to apply, replaced by reflux disease Update of current diagnostic and therapeutic approaches Common diseases, Uncommon diseases New algorithms for the management of cough in adults and children An empiric integrative approach is recommended 10 12 13 12 16 6 4 ASTHMA PNDS GERD Chest 1999;116:279-284 1. Gastroesophageal reflux disease (21-41%) 2. Cough variant asthma (24-59%) 3. Postnasal drip syndrome (41-58%) Chest 1999;116:279-281 Percentage of Cases Presenting 1,2,3, and 4 Causative Factors İmmunocompetent patients Not exposed to enviromental irritants Chest radiograph is normal Not taking an ACE inhibitor Not a current smoker Asthma and/or GERD, PNDS responsible for 93.6% of the cases of chronic cough Harding SM .Chest 2003;123:659-660 Changing Trends in Diagnosis Percentage of Diagnosis (%) GERD ASTHMA RHINITIS Impaired esophageal clearance Functional defect in LES syphincter Hiatal hernia Delayed gastric emptying İncreased intra-abdominal pressure GERD ? Decreased saliva Heartburn (pyrosis) and regurgitation At least weekly symptoms extraesophageal reflux symptoms and/or esophageal mucosal damage / Katzka & DiMarino 1995 FLR Signs Edema and hyperemia of larynx Vocal cord erythema, polyps, granulomas, ulcers Hyperemia and lymphoid hyperplasia of posterior pharynx Interarytenoid changes Subglottic stenosis GERD-related cough incidence 5 - 55% May be the sole presenting symptom(1/3) Thorax 2003:58;1092-1095) (Chest 1997; 111: 1389-1402) Irwin RS. Chest 2006;129:80S-94S Association between cough and reflux is important Esophageal-tracheal-bronchial reflex Microaspiration Pathogenesis ARRD 1981;123:413-417 Arch Intern Med 1996;156:997 Chest 1993;104:1511-1517 El Hennawi, 2004 OHNS Nonacidic factors? Esophageal dismotility? . Mediator Release . Inflammation . Edema . Mucus . Smooth Muscle Microaspiration REFLUX Esophageal Vagal Afferents Bronchial Hyperreactivity Airway Vagal Afferents CNS Stein MR.Am J Med 2003 Chest 1997;111: 1389-1402 Airway Airway Vagal Efferents Esophagus Tracheobronchial Tree Stomach Oesophagus Pharyngeal pHmetry + - Not GERD Clinical GERD symptoms ? Nonacid, weakly acid reflux? Increase dose PPI + alginate İmproved Not improved Continue pHmetry under treatment Consider  Simultaneously dual probes 24 hours pHmonitoring and intraesophageal impedance Irwin RS.AJRCCM 165:1469-74,2002 McGarvey LPA.Thorax 59:342-346,2004 15 cm 17 cm 6 impedance channels 1 pH electrode + Adult Standard Model ZAN-S61C01E Multichannel intraluminal impedance-pH catheter Non acid reflux On going reflux of ‘non-acid’ material may be responsible for continuing symptoms while on acid-suppressing medications Therapy in Esophageal-pulmonary reflux Conservative and lifestyle measures Ampirical therapy: Acid suppression Proton pump inhibitors  PPI x 2 / 3 months Therapy failure  24 hour intraesophageal pHmetry ( pharyngeal pHmetry )  GERD (+) High dose PPI + H2 blocker agent Surgery(Fundoplication) Pulmonary and Crit Care Update 1994; Vol 9 Morice AH. ERJ 2004;24:481-492 Weeks of antireflux therapy Patients responded No No (%) 2 16 (41) 4 38 (86) 6 42 (95) 8 43 (99) 12 weeks 44 (100) Poe RH.Chest 2003;123:679-684 Cumulative Response to GERD Therapy Preop pH <4: %23.6 De Meester: 85 Postop pH <4: %2.4 De Meester: 9.9 1. Chronic cough for at least 2 months 2. Immunocompetent patients 3. Chest radiograph is normal 4. Not exposed to enviromental irritants nor a present smoker 5. Not taking an ACE inhibitor 6. Symptomatic asthma has been ruled out 7. Rhinosinus diseases has been ruled out: 8. ‘Silent sinusitis’ has been ruled out 9. Nonasthmatic eosinophilic bronchitis has been ruled out: BPT is negative Cough has not improved with asthma therapy First generation H1 antagonists has been used Eo 3% in induced sputum Cough has not improved with steroids Irwin RS. Chest 2006;129:80S-94S İrwin RS. AJRCCM Vol 165; 1469-1474, 2002 Clinical Profile That Chronic Cough İs Likely Due To ‘Silent GERD’ Postnasal Drip Syndrome (PNDS) Prevalence : 8 – 87% Pathogenesis : The sensation of drainage of secretions from the nose or paranasal sinuses into the pharynx Clinical Presentation: Dripping sensation Tickle in the throat Nasal congestion Mucus in oropharynx Cobblestone appearence of oropharynx ACCP consensus. CHEST 1998; 114: 133-181 ERS Task Force. ERS Journal ; 24: 553-566 Pathogenic Triad in Chronic Cough. CHEST 1999; 116: 279-284 Evaluation of chronic cough. UPTODATE 2005 Chest 2006;129:63S-71S In patient with chronic cough that is related to upper airway abnormalities Upper Airway Cough Syndrome UACS Treatment Antihistamines / decongestant combinations - “Older” sedating antihistamines more effective - Treatment effect should be observed in 1 week Additional / Alternative treatments : Ipratropium nasal spray : 2-7 days Nasal steroids (such as BDP, FP,BUD) : 2-3 days - 2 week 3 months prescribed Eosinophilic Eronchitis Airway obstruction Bronchial hyperreactivity NO YES YES NO Asthmatic Coughs Cough Variant Asthma Asthma

Slide 27 -

CHRONIC COUGH MÜNEVVER ERDİNÇ Department of Chest Diseases Ege University Faculty of Medicine Differential Diagnosis And Treatment In Adults Acute Cough lasting less than 3 weeks Subacute Cough lasting 3 to 8 weeks Chronic Cough Lasting more than 8 weeks Morice AH.Eur Respir J 2004 :24:481-492 Fontana GA.Thorax 2003;58:1092-1095 Irwin RS.NEJM 343(23): 1715-1721,2000 Irwin RS. Chest 1998; 114(suppl1) :133S-181S Differantial Diagnosis of Chronic Cough in Adults PNDS Allergic rhinitis Chronic sinusitis GERD Cough variant asthma ACEI induced cough Pertusis Neurogenic Traumatic Postinfectious cough Phychogenic cough Chronic aspiration Zenker diverticulosis Foreign body Chronic bronchitis Bronchiectasis Lung cancer Subglottic stenosis Tracheomalasie Tracheoesophageal fistul Tuerculosis Sarcoidosis Congestive heart failure Simpson CB. Otolaryngology–Head Neck Surg 2006; 134: 693-700 In prospective studies in adults, chronic cough is most commonly due to 6 disorders : Upper Airway Cough Syndrome (UACS) Asthma GERD Chronic Bronchitis Bronchiectasis Non-asthmatic Eosinophilic Bronchitis Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S New Considerations Eosinophilic bronchitis Atopic cough Non acid(volume)/ weakly acid reflux Idiopathic (unexplained) öksürük Diagnosis and Management of Cough ACCP Evidence-Based CPG 2006 Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S Plevkova, et al. Respir Physiol Neurobiol 2004; 142: 225-235 Postnasal drip syndrome (PNDS) renamed upper airway cough syndrome (UACS) Upper airway afferents may reflexly enhance coughing Nonasthmatic eosinophilic bronchitis recognized as a common cause of chronic cough Idiopathic cough renamed unexplained cough The term acid reflux disease, unless it can be definitively shown to apply, replaced by reflux disease Update of current diagnostic and therapeutic approaches Common diseases, Uncommon diseases New algorithms for the management of cough in adults and children An empiric integrative approach is recommended 10 12 13 12 16 6 4 ASTHMA PNDS GERD Chest 1999;116:279-284 1. Gastroesophageal reflux disease (21-41%) 2. Cough variant asthma (24-59%) 3. Postnasal drip syndrome (41-58%) Chest 1999;116:279-281 Percentage of Cases Presenting 1,2,3, and 4 Causative Factors İmmunocompetent patients Not exposed to enviromental irritants Chest radiograph is normal Not taking an ACE inhibitor Not a current smoker Asthma and/or GERD, PNDS responsible for 93.6% of the cases of chronic cough Harding SM .Chest 2003;123:659-660 Changing Trends in Diagnosis Percentage of Diagnosis (%) GERD ASTHMA RHINITIS Impaired esophageal clearance Functional defect in LES syphincter Hiatal hernia Delayed gastric emptying İncreased intra-abdominal pressure GERD ? Decreased saliva Heartburn (pyrosis) and regurgitation At least weekly symptoms extraesophageal reflux symptoms and/or esophageal mucosal damage / Katzka & DiMarino 1995 FLR Signs Edema and hyperemia of larynx Vocal cord erythema, polyps, granulomas, ulcers Hyperemia and lymphoid hyperplasia of posterior pharynx Interarytenoid changes Subglottic stenosis GERD-related cough incidence 5 - 55% May be the sole presenting symptom(1/3) Thorax 2003:58;1092-1095) (Chest 1997; 111: 1389-1402) Irwin RS. Chest 2006;129:80S-94S Association between cough and reflux is important Esophageal-tracheal-bronchial reflex Microaspiration Pathogenesis ARRD 1981;123:413-417 Arch Intern Med 1996;156:997 Chest 1993;104:1511-1517 El Hennawi, 2004 OHNS Nonacidic factors? Esophageal dismotility? . Mediator Release . Inflammation . Edema . Mucus . Smooth Muscle Microaspiration REFLUX Esophageal Vagal Afferents Bronchial Hyperreactivity Airway Vagal Afferents CNS Stein MR.Am J Med 2003 Chest 1997;111: 1389-1402 Airway Airway Vagal Efferents Esophagus Tracheobronchial Tree Stomach Oesophagus Pharyngeal pHmetry + - Not GERD Clinical GERD symptoms ? Nonacid, weakly acid reflux? Increase dose PPI + alginate İmproved Not improved Continue pHmetry under treatment Consider  Simultaneously dual probes 24 hours pHmonitoring and intraesophageal impedance Irwin RS.AJRCCM 165:1469-74,2002 McGarvey LPA.Thorax 59:342-346,2004 15 cm 17 cm 6 impedance channels 1 pH electrode + Adult Standard Model ZAN-S61C01E Multichannel intraluminal impedance-pH catheter Non acid reflux On going reflux of ‘non-acid’ material may be responsible for continuing symptoms while on acid-suppressing medications Therapy in Esophageal-pulmonary reflux Conservative and lifestyle measures Ampirical therapy: Acid suppression Proton pump inhibitors  PPI x 2 / 3 months Therapy failure  24 hour intraesophageal pHmetry ( pharyngeal pHmetry )  GERD (+) High dose PPI + H2 blocker agent Surgery(Fundoplication) Pulmonary and Crit Care Update 1994; Vol 9 Morice AH. ERJ 2004;24:481-492 Weeks of antireflux therapy Patients responded No No (%) 2 16 (41) 4 38 (86) 6 42 (95) 8 43 (99) 12 weeks 44 (100) Poe RH.Chest 2003;123:679-684 Cumulative Response to GERD Therapy Preop pH <4: %23.6 De Meester: 85 Postop pH <4: %2.4 De Meester: 9.9 1. Chronic cough for at least 2 months 2. Immunocompetent patients 3. Chest radiograph is normal 4. Not exposed to enviromental irritants nor a present smoker 5. Not taking an ACE inhibitor 6. Symptomatic asthma has been ruled out 7. Rhinosinus diseases has been ruled out: 8. ‘Silent sinusitis’ has been ruled out 9. Nonasthmatic eosinophilic bronchitis has been ruled out: BPT is negative Cough has not improved with asthma therapy First generation H1 antagonists has been used Eo 3% in induced sputum Cough has not improved with steroids Irwin RS. Chest 2006;129:80S-94S İrwin RS. AJRCCM Vol 165; 1469-1474, 2002 Clinical Profile That Chronic Cough İs Likely Due To ‘Silent GERD’ Postnasal Drip Syndrome (PNDS) Prevalence : 8 – 87% Pathogenesis : The sensation of drainage of secretions from the nose or paranasal sinuses into the pharynx Clinical Presentation: Dripping sensation Tickle in the throat Nasal congestion Mucus in oropharynx Cobblestone appearence of oropharynx ACCP consensus. CHEST 1998; 114: 133-181 ERS Task Force. ERS Journal ; 24: 553-566 Pathogenic Triad in Chronic Cough. CHEST 1999; 116: 279-284 Evaluation of chronic cough. UPTODATE 2005 Chest 2006;129:63S-71S In patient with chronic cough that is related to upper airway abnormalities Upper Airway Cough Syndrome UACS Treatment Antihistamines / decongestant combinations - “Older” sedating antihistamines more effective - Treatment effect should be observed in 1 week Additional / Alternative treatments : Ipratropium nasal spray : 2-7 days Nasal steroids (such as BDP, FP,BUD) : 2-3 days - 2 week 3 months prescribed Eosinophilic Eronchitis Airway obstruction Bronchial hyperreactivity NO YES YES NO Asthmatic Coughs Cough Variant Asthma Asthma Cough Variant Asthma Prevalence : 24 – 59% Clinical Diagnosis Gold standard  History - Episodic symptoms, Family history Reversibility testing PEF monitoring Bronchoprovocation test Differential Diagnosis: Decreased of cough with classical asthma therapy ACCP consensus. CHEST 1998; 114: 133-181 ERS Task Force. ERS Journal ; 24: 553-566 The Journal of Respiratory Disease; 25; 310-315 THORAX 59; 342-346

Slide 28 -

CHRONIC COUGH MÜNEVVER ERDİNÇ Department of Chest Diseases Ege University Faculty of Medicine Differential Diagnosis And Treatment In Adults Acute Cough lasting less than 3 weeks Subacute Cough lasting 3 to 8 weeks Chronic Cough Lasting more than 8 weeks Morice AH.Eur Respir J 2004 :24:481-492 Fontana GA.Thorax 2003;58:1092-1095 Irwin RS.NEJM 343(23): 1715-1721,2000 Irwin RS. Chest 1998; 114(suppl1) :133S-181S Differantial Diagnosis of Chronic Cough in Adults PNDS Allergic rhinitis Chronic sinusitis GERD Cough variant asthma ACEI induced cough Pertusis Neurogenic Traumatic Postinfectious cough Phychogenic cough Chronic aspiration Zenker diverticulosis Foreign body Chronic bronchitis Bronchiectasis Lung cancer Subglottic stenosis Tracheomalasie Tracheoesophageal fistul Tuerculosis Sarcoidosis Congestive heart failure Simpson CB. Otolaryngology–Head Neck Surg 2006; 134: 693-700 In prospective studies in adults, chronic cough is most commonly due to 6 disorders : Upper Airway Cough Syndrome (UACS) Asthma GERD Chronic Bronchitis Bronchiectasis Non-asthmatic Eosinophilic Bronchitis Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S New Considerations Eosinophilic bronchitis Atopic cough Non acid(volume)/ weakly acid reflux Idiopathic (unexplained) öksürük Diagnosis and Management of Cough ACCP Evidence-Based CPG 2006 Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S Plevkova, et al. Respir Physiol Neurobiol 2004; 142: 225-235 Postnasal drip syndrome (PNDS) renamed upper airway cough syndrome (UACS) Upper airway afferents may reflexly enhance coughing Nonasthmatic eosinophilic bronchitis recognized as a common cause of chronic cough Idiopathic cough renamed unexplained cough The term acid reflux disease, unless it can be definitively shown to apply, replaced by reflux disease Update of current diagnostic and therapeutic approaches Common diseases, Uncommon diseases New algorithms for the management of cough in adults and children An empiric integrative approach is recommended 10 12 13 12 16 6 4 ASTHMA PNDS GERD Chest 1999;116:279-284 1. Gastroesophageal reflux disease (21-41%) 2. Cough variant asthma (24-59%) 3. Postnasal drip syndrome (41-58%) Chest 1999;116:279-281 Percentage of Cases Presenting 1,2,3, and 4 Causative Factors İmmunocompetent patients Not exposed to enviromental irritants Chest radiograph is normal Not taking an ACE inhibitor Not a current smoker Asthma and/or GERD, PNDS responsible for 93.6% of the cases of chronic cough Harding SM .Chest 2003;123:659-660 Changing Trends in Diagnosis Percentage of Diagnosis (%) GERD ASTHMA RHINITIS Impaired esophageal clearance Functional defect in LES syphincter Hiatal hernia Delayed gastric emptying İncreased intra-abdominal pressure GERD ? Decreased saliva Heartburn (pyrosis) and regurgitation At least weekly symptoms extraesophageal reflux symptoms and/or esophageal mucosal damage / Katzka & DiMarino 1995 FLR Signs Edema and hyperemia of larynx Vocal cord erythema, polyps, granulomas, ulcers Hyperemia and lymphoid hyperplasia of posterior pharynx Interarytenoid changes Subglottic stenosis GERD-related cough incidence 5 - 55% May be the sole presenting symptom(1/3) Thorax 2003:58;1092-1095) (Chest 1997; 111: 1389-1402) Irwin RS. Chest 2006;129:80S-94S Association between cough and reflux is important Esophageal-tracheal-bronchial reflex Microaspiration Pathogenesis ARRD 1981;123:413-417 Arch Intern Med 1996;156:997 Chest 1993;104:1511-1517 El Hennawi, 2004 OHNS Nonacidic factors? Esophageal dismotility? . Mediator Release . Inflammation . Edema . Mucus . Smooth Muscle Microaspiration REFLUX Esophageal Vagal Afferents Bronchial Hyperreactivity Airway Vagal Afferents CNS Stein MR.Am J Med 2003 Chest 1997;111: 1389-1402 Airway Airway Vagal Efferents Esophagus Tracheobronchial Tree Stomach Oesophagus Pharyngeal pHmetry + - Not GERD Clinical GERD symptoms ? Nonacid, weakly acid reflux? Increase dose PPI + alginate İmproved Not improved Continue pHmetry under treatment Consider  Simultaneously dual probes 24 hours pHmonitoring and intraesophageal impedance Irwin RS.AJRCCM 165:1469-74,2002 McGarvey LPA.Thorax 59:342-346,2004 15 cm 17 cm 6 impedance channels 1 pH electrode + Adult Standard Model ZAN-S61C01E Multichannel intraluminal impedance-pH catheter Non acid reflux On going reflux of ‘non-acid’ material may be responsible for continuing symptoms while on acid-suppressing medications Therapy in Esophageal-pulmonary reflux Conservative and lifestyle measures Ampirical therapy: Acid suppression Proton pump inhibitors  PPI x 2 / 3 months Therapy failure  24 hour intraesophageal pHmetry ( pharyngeal pHmetry )  GERD (+) High dose PPI + H2 blocker agent Surgery(Fundoplication) Pulmonary and Crit Care Update 1994; Vol 9 Morice AH. ERJ 2004;24:481-492 Weeks of antireflux therapy Patients responded No No (%) 2 16 (41) 4 38 (86) 6 42 (95) 8 43 (99) 12 weeks 44 (100) Poe RH.Chest 2003;123:679-684 Cumulative Response to GERD Therapy Preop pH <4: %23.6 De Meester: 85 Postop pH <4: %2.4 De Meester: 9.9 1. Chronic cough for at least 2 months 2. Immunocompetent patients 3. Chest radiograph is normal 4. Not exposed to enviromental irritants nor a present smoker 5. Not taking an ACE inhibitor 6. Symptomatic asthma has been ruled out 7. Rhinosinus diseases has been ruled out: 8. ‘Silent sinusitis’ has been ruled out 9. Nonasthmatic eosinophilic bronchitis has been ruled out: BPT is negative Cough has not improved with asthma therapy First generation H1 antagonists has been used Eo 3% in induced sputum Cough has not improved with steroids Irwin RS. Chest 2006;129:80S-94S İrwin RS. AJRCCM Vol 165; 1469-1474, 2002 Clinical Profile That Chronic Cough İs Likely Due To ‘Silent GERD’ Postnasal Drip Syndrome (PNDS) Prevalence : 8 – 87% Pathogenesis : The sensation of drainage of secretions from the nose or paranasal sinuses into the pharynx Clinical Presentation: Dripping sensation Tickle in the throat Nasal congestion Mucus in oropharynx Cobblestone appearence of oropharynx ACCP consensus. CHEST 1998; 114: 133-181 ERS Task Force. ERS Journal ; 24: 553-566 Pathogenic Triad in Chronic Cough. CHEST 1999; 116: 279-284 Evaluation of chronic cough. UPTODATE 2005 Chest 2006;129:63S-71S In patient with chronic cough that is related to upper airway abnormalities Upper Airway Cough Syndrome UACS Treatment Antihistamines / decongestant combinations - “Older” sedating antihistamines more effective - Treatment effect should be observed in 1 week Additional / Alternative treatments : Ipratropium nasal spray : 2-7 days Nasal steroids (such as BDP, FP,BUD) : 2-3 days - 2 week 3 months prescribed Eosinophilic Eronchitis Airway obstruction Bronchial hyperreactivity NO YES YES NO Asthmatic Coughs Cough Variant Asthma Asthma Cough Variant Asthma Prevalence : 24 – 59% Clinical Diagnosis Gold standard  History - Episodic symptoms, Family history Reversibility testing PEF monitoring Bronchoprovocation test Differential Diagnosis: Decreased of cough with classical asthma therapy ACCP consensus. CHEST 1998; 114: 133-181 ERS Task Force. ERS Journal ; 24: 553-566 The Journal of Respiratory Disease; 25; 310-315 THORAX 59; 342-346 Middle age patients Smoking is unusual, occupational ? Prevalence of atopy similar population Good respond to inhaled steroids Gibson et al. Lancet 1989 Chest 2006;129:116S-121S Eosinophilic Bronchitis Isolated chronic cough,  productive of sputum Normal lung function without variable airflow limitation Airway hyperresponsiveness absent Eosinophilia in sputum and BAL Cough reflex to capsaicin increased Normal daily variability in peak expiratory flow (<20%)

Slide 29 -

CHRONIC COUGH MÜNEVVER ERDİNÇ Department of Chest Diseases Ege University Faculty of Medicine Differential Diagnosis And Treatment In Adults Acute Cough lasting less than 3 weeks Subacute Cough lasting 3 to 8 weeks Chronic Cough Lasting more than 8 weeks Morice AH.Eur Respir J 2004 :24:481-492 Fontana GA.Thorax 2003;58:1092-1095 Irwin RS.NEJM 343(23): 1715-1721,2000 Irwin RS. Chest 1998; 114(suppl1) :133S-181S Differantial Diagnosis of Chronic Cough in Adults PNDS Allergic rhinitis Chronic sinusitis GERD Cough variant asthma ACEI induced cough Pertusis Neurogenic Traumatic Postinfectious cough Phychogenic cough Chronic aspiration Zenker diverticulosis Foreign body Chronic bronchitis Bronchiectasis Lung cancer Subglottic stenosis Tracheomalasie Tracheoesophageal fistul Tuerculosis Sarcoidosis Congestive heart failure Simpson CB. Otolaryngology–Head Neck Surg 2006; 134: 693-700 In prospective studies in adults, chronic cough is most commonly due to 6 disorders : Upper Airway Cough Syndrome (UACS) Asthma GERD Chronic Bronchitis Bronchiectasis Non-asthmatic Eosinophilic Bronchitis Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S New Considerations Eosinophilic bronchitis Atopic cough Non acid(volume)/ weakly acid reflux Idiopathic (unexplained) öksürük Diagnosis and Management of Cough ACCP Evidence-Based CPG 2006 Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S Plevkova, et al. Respir Physiol Neurobiol 2004; 142: 225-235 Postnasal drip syndrome (PNDS) renamed upper airway cough syndrome (UACS) Upper airway afferents may reflexly enhance coughing Nonasthmatic eosinophilic bronchitis recognized as a common cause of chronic cough Idiopathic cough renamed unexplained cough The term acid reflux disease, unless it can be definitively shown to apply, replaced by reflux disease Update of current diagnostic and therapeutic approaches Common diseases, Uncommon diseases New algorithms for the management of cough in adults and children An empiric integrative approach is recommended 10 12 13 12 16 6 4 ASTHMA PNDS GERD Chest 1999;116:279-284 1. Gastroesophageal reflux disease (21-41%) 2. Cough variant asthma (24-59%) 3. Postnasal drip syndrome (41-58%) Chest 1999;116:279-281 Percentage of Cases Presenting 1,2,3, and 4 Causative Factors İmmunocompetent patients Not exposed to enviromental irritants Chest radiograph is normal Not taking an ACE inhibitor Not a current smoker Asthma and/or GERD, PNDS responsible for 93.6% of the cases of chronic cough Harding SM .Chest 2003;123:659-660 Changing Trends in Diagnosis Percentage of Diagnosis (%) GERD ASTHMA RHINITIS Impaired esophageal clearance Functional defect in LES syphincter Hiatal hernia Delayed gastric emptying İncreased intra-abdominal pressure GERD ? Decreased saliva Heartburn (pyrosis) and regurgitation At least weekly symptoms extraesophageal reflux symptoms and/or esophageal mucosal damage / Katzka & DiMarino 1995 FLR Signs Edema and hyperemia of larynx Vocal cord erythema, polyps, granulomas, ulcers Hyperemia and lymphoid hyperplasia of posterior pharynx Interarytenoid changes Subglottic stenosis GERD-related cough incidence 5 - 55% May be the sole presenting symptom(1/3) Thorax 2003:58;1092-1095) (Chest 1997; 111: 1389-1402) Irwin RS. Chest 2006;129:80S-94S Association between cough and reflux is important Esophageal-tracheal-bronchial reflex Microaspiration Pathogenesis ARRD 1981;123:413-417 Arch Intern Med 1996;156:997 Chest 1993;104:1511-1517 El Hennawi, 2004 OHNS Nonacidic factors? Esophageal dismotility? . Mediator Release . Inflammation . Edema . Mucus . Smooth Muscle Microaspiration REFLUX Esophageal Vagal Afferents Bronchial Hyperreactivity Airway Vagal Afferents CNS Stein MR.Am J Med 2003 Chest 1997;111: 1389-1402 Airway Airway Vagal Efferents Esophagus Tracheobronchial Tree Stomach Oesophagus Pharyngeal pHmetry + - Not GERD Clinical GERD symptoms ? Nonacid, weakly acid reflux? Increase dose PPI + alginate İmproved Not improved Continue pHmetry under treatment Consider  Simultaneously dual probes 24 hours pHmonitoring and intraesophageal impedance Irwin RS.AJRCCM 165:1469-74,2002 McGarvey LPA.Thorax 59:342-346,2004 15 cm 17 cm 6 impedance channels 1 pH electrode + Adult Standard Model ZAN-S61C01E Multichannel intraluminal impedance-pH catheter Non acid reflux On going reflux of ‘non-acid’ material may be responsible for continuing symptoms while on acid-suppressing medications Therapy in Esophageal-pulmonary reflux Conservative and lifestyle measures Ampirical therapy: Acid suppression Proton pump inhibitors  PPI x 2 / 3 months Therapy failure  24 hour intraesophageal pHmetry ( pharyngeal pHmetry )  GERD (+) High dose PPI + H2 blocker agent Surgery(Fundoplication) Pulmonary and Crit Care Update 1994; Vol 9 Morice AH. ERJ 2004;24:481-492 Weeks of antireflux therapy Patients responded No No (%) 2 16 (41) 4 38 (86) 6 42 (95) 8 43 (99) 12 weeks 44 (100) Poe RH.Chest 2003;123:679-684 Cumulative Response to GERD Therapy Preop pH <4: %23.6 De Meester: 85 Postop pH <4: %2.4 De Meester: 9.9 1. Chronic cough for at least 2 months 2. Immunocompetent patients 3. Chest radiograph is normal 4. Not exposed to enviromental irritants nor a present smoker 5. Not taking an ACE inhibitor 6. Symptomatic asthma has been ruled out 7. Rhinosinus diseases has been ruled out: 8. ‘Silent sinusitis’ has been ruled out 9. Nonasthmatic eosinophilic bronchitis has been ruled out: BPT is negative Cough has not improved with asthma therapy First generation H1 antagonists has been used Eo 3% in induced sputum Cough has not improved with steroids Irwin RS. Chest 2006;129:80S-94S İrwin RS. AJRCCM Vol 165; 1469-1474, 2002 Clinical Profile That Chronic Cough İs Likely Due To ‘Silent GERD’ Postnasal Drip Syndrome (PNDS) Prevalence : 8 – 87% Pathogenesis : The sensation of drainage of secretions from the nose or paranasal sinuses into the pharynx Clinical Presentation: Dripping sensation Tickle in the throat Nasal congestion Mucus in oropharynx Cobblestone appearence of oropharynx ACCP consensus. CHEST 1998; 114: 133-181 ERS Task Force. ERS Journal ; 24: 553-566 Pathogenic Triad in Chronic Cough. CHEST 1999; 116: 279-284 Evaluation of chronic cough. UPTODATE 2005 Chest 2006;129:63S-71S In patient with chronic cough that is related to upper airway abnormalities Upper Airway Cough Syndrome UACS Treatment Antihistamines / decongestant combinations - “Older” sedating antihistamines more effective - Treatment effect should be observed in 1 week Additional / Alternative treatments : Ipratropium nasal spray : 2-7 days Nasal steroids (such as BDP, FP,BUD) : 2-3 days - 2 week 3 months prescribed Eosinophilic Eronchitis Airway obstruction Bronchial hyperreactivity NO YES YES NO Asthmatic Coughs Cough Variant Asthma Asthma Cough Variant Asthma Prevalence : 24 – 59% Clinical Diagnosis Gold standard  History - Episodic symptoms, Family history Reversibility testing PEF monitoring Bronchoprovocation test Differential Diagnosis: Decreased of cough with classical asthma therapy ACCP consensus. CHEST 1998; 114: 133-181 ERS Task Force. ERS Journal ; 24: 553-566 The Journal of Respiratory Disease; 25; 310-315 THORAX 59; 342-346 Middle age patients Smoking is unusual, occupational ? Prevalence of atopy similar population Good respond to inhaled steroids Gibson et al. Lancet 1989 Chest 2006;129:116S-121S Eosinophilic Bronchitis Isolated chronic cough,  productive of sputum Normal lung function without variable airflow limitation Airway hyperresponsiveness absent Eosinophilia in sputum and BAL Cough reflex to capsaicin increased Normal daily variability in peak expiratory flow (<20%) 1)Kim et al AJRCCM 2003; 2) Brightling et al AJRCCM 1999;160:406-10, 3) Joo Korean JIM 2002;17:31-7, 4) Carney et al AJRCCM 1997; 156:211-6, 5) Ma et al Zhongua 2003;26:362-5, 6) Ayik, Erdinc et al Respir Med 2003;97:695-701 Eosinophilic Bronchitis A Worldwide Disease

Slide 30 -

CHRONIC COUGH MÜNEVVER ERDİNÇ Department of Chest Diseases Ege University Faculty of Medicine Differential Diagnosis And Treatment In Adults Acute Cough lasting less than 3 weeks Subacute Cough lasting 3 to 8 weeks Chronic Cough Lasting more than 8 weeks Morice AH.Eur Respir J 2004 :24:481-492 Fontana GA.Thorax 2003;58:1092-1095 Irwin RS.NEJM 343(23): 1715-1721,2000 Irwin RS. Chest 1998; 114(suppl1) :133S-181S Differantial Diagnosis of Chronic Cough in Adults PNDS Allergic rhinitis Chronic sinusitis GERD Cough variant asthma ACEI induced cough Pertusis Neurogenic Traumatic Postinfectious cough Phychogenic cough Chronic aspiration Zenker diverticulosis Foreign body Chronic bronchitis Bronchiectasis Lung cancer Subglottic stenosis Tracheomalasie Tracheoesophageal fistul Tuerculosis Sarcoidosis Congestive heart failure Simpson CB. Otolaryngology–Head Neck Surg 2006; 134: 693-700 In prospective studies in adults, chronic cough is most commonly due to 6 disorders : Upper Airway Cough Syndrome (UACS) Asthma GERD Chronic Bronchitis Bronchiectasis Non-asthmatic Eosinophilic Bronchitis Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S New Considerations Eosinophilic bronchitis Atopic cough Non acid(volume)/ weakly acid reflux Idiopathic (unexplained) öksürük Diagnosis and Management of Cough ACCP Evidence-Based CPG 2006 Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S Plevkova, et al. Respir Physiol Neurobiol 2004; 142: 225-235 Postnasal drip syndrome (PNDS) renamed upper airway cough syndrome (UACS) Upper airway afferents may reflexly enhance coughing Nonasthmatic eosinophilic bronchitis recognized as a common cause of chronic cough Idiopathic cough renamed unexplained cough The term acid reflux disease, unless it can be definitively shown to apply, replaced by reflux disease Update of current diagnostic and therapeutic approaches Common diseases, Uncommon diseases New algorithms for the management of cough in adults and children An empiric integrative approach is recommended 10 12 13 12 16 6 4 ASTHMA PNDS GERD Chest 1999;116:279-284 1. Gastroesophageal reflux disease (21-41%) 2. Cough variant asthma (24-59%) 3. Postnasal drip syndrome (41-58%) Chest 1999;116:279-281 Percentage of Cases Presenting 1,2,3, and 4 Causative Factors İmmunocompetent patients Not exposed to enviromental irritants Chest radiograph is normal Not taking an ACE inhibitor Not a current smoker Asthma and/or GERD, PNDS responsible for 93.6% of the cases of chronic cough Harding SM .Chest 2003;123:659-660 Changing Trends in Diagnosis Percentage of Diagnosis (%) GERD ASTHMA RHINITIS Impaired esophageal clearance Functional defect in LES syphincter Hiatal hernia Delayed gastric emptying İncreased intra-abdominal pressure GERD ? Decreased saliva Heartburn (pyrosis) and regurgitation At least weekly symptoms extraesophageal reflux symptoms and/or esophageal mucosal damage / Katzka & DiMarino 1995 FLR Signs Edema and hyperemia of larynx Vocal cord erythema, polyps, granulomas, ulcers Hyperemia and lymphoid hyperplasia of posterior pharynx Interarytenoid changes Subglottic stenosis GERD-related cough incidence 5 - 55% May be the sole presenting symptom(1/3) Thorax 2003:58;1092-1095) (Chest 1997; 111: 1389-1402) Irwin RS. Chest 2006;129:80S-94S Association between cough and reflux is important Esophageal-tracheal-bronchial reflex Microaspiration Pathogenesis ARRD 1981;123:413-417 Arch Intern Med 1996;156:997 Chest 1993;104:1511-1517 El Hennawi, 2004 OHNS Nonacidic factors? Esophageal dismotility? . Mediator Release . Inflammation . Edema . Mucus . Smooth Muscle Microaspiration REFLUX Esophageal Vagal Afferents Bronchial Hyperreactivity Airway Vagal Afferents CNS Stein MR.Am J Med 2003 Chest 1997;111: 1389-1402 Airway Airway Vagal Efferents Esophagus Tracheobronchial Tree Stomach Oesophagus Pharyngeal pHmetry + - Not GERD Clinical GERD symptoms ? Nonacid, weakly acid reflux? Increase dose PPI + alginate İmproved Not improved Continue pHmetry under treatment Consider  Simultaneously dual probes 24 hours pHmonitoring and intraesophageal impedance Irwin RS.AJRCCM 165:1469-74,2002 McGarvey LPA.Thorax 59:342-346,2004 15 cm 17 cm 6 impedance channels 1 pH electrode + Adult Standard Model ZAN-S61C01E Multichannel intraluminal impedance-pH catheter Non acid reflux On going reflux of ‘non-acid’ material may be responsible for continuing symptoms while on acid-suppressing medications Therapy in Esophageal-pulmonary reflux Conservative and lifestyle measures Ampirical therapy: Acid suppression Proton pump inhibitors  PPI x 2 / 3 months Therapy failure  24 hour intraesophageal pHmetry ( pharyngeal pHmetry )  GERD (+) High dose PPI + H2 blocker agent Surgery(Fundoplication) Pulmonary and Crit Care Update 1994; Vol 9 Morice AH. ERJ 2004;24:481-492 Weeks of antireflux therapy Patients responded No No (%) 2 16 (41) 4 38 (86) 6 42 (95) 8 43 (99) 12 weeks 44 (100) Poe RH.Chest 2003;123:679-684 Cumulative Response to GERD Therapy Preop pH <4: %23.6 De Meester: 85 Postop pH <4: %2.4 De Meester: 9.9 1. Chronic cough for at least 2 months 2. Immunocompetent patients 3. Chest radiograph is normal 4. Not exposed to enviromental irritants nor a present smoker 5. Not taking an ACE inhibitor 6. Symptomatic asthma has been ruled out 7. Rhinosinus diseases has been ruled out: 8. ‘Silent sinusitis’ has been ruled out 9. Nonasthmatic eosinophilic bronchitis has been ruled out: BPT is negative Cough has not improved with asthma therapy First generation H1 antagonists has been used Eo 3% in induced sputum Cough has not improved with steroids Irwin RS. Chest 2006;129:80S-94S İrwin RS. AJRCCM Vol 165; 1469-1474, 2002 Clinical Profile That Chronic Cough İs Likely Due To ‘Silent GERD’ Postnasal Drip Syndrome (PNDS) Prevalence : 8 – 87% Pathogenesis : The sensation of drainage of secretions from the nose or paranasal sinuses into the pharynx Clinical Presentation: Dripping sensation Tickle in the throat Nasal congestion Mucus in oropharynx Cobblestone appearence of oropharynx ACCP consensus. CHEST 1998; 114: 133-181 ERS Task Force. ERS Journal ; 24: 553-566 Pathogenic Triad in Chronic Cough. CHEST 1999; 116: 279-284 Evaluation of chronic cough. UPTODATE 2005 Chest 2006;129:63S-71S In patient with chronic cough that is related to upper airway abnormalities Upper Airway Cough Syndrome UACS Treatment Antihistamines / decongestant combinations - “Older” sedating antihistamines more effective - Treatment effect should be observed in 1 week Additional / Alternative treatments : Ipratropium nasal spray : 2-7 days Nasal steroids (such as BDP, FP,BUD) : 2-3 days - 2 week 3 months prescribed Eosinophilic Eronchitis Airway obstruction Bronchial hyperreactivity NO YES YES NO Asthmatic Coughs Cough Variant Asthma Asthma Cough Variant Asthma Prevalence : 24 – 59% Clinical Diagnosis Gold standard  History - Episodic symptoms, Family history Reversibility testing PEF monitoring Bronchoprovocation test Differential Diagnosis: Decreased of cough with classical asthma therapy ACCP consensus. CHEST 1998; 114: 133-181 ERS Task Force. ERS Journal ; 24: 553-566 The Journal of Respiratory Disease; 25; 310-315 THORAX 59; 342-346 Middle age patients Smoking is unusual, occupational ? Prevalence of atopy similar population Good respond to inhaled steroids Gibson et al. Lancet 1989 Chest 2006;129:116S-121S Eosinophilic Bronchitis Isolated chronic cough,  productive of sputum Normal lung function without variable airflow limitation Airway hyperresponsiveness absent Eosinophilia in sputum and BAL Cough reflex to capsaicin increased Normal daily variability in peak expiratory flow (<20%) 1)Kim et al AJRCCM 2003; 2) Brightling et al AJRCCM 1999;160:406-10, 3) Joo Korean JIM 2002;17:31-7, 4) Carney et al AJRCCM 1997; 156:211-6, 5) Ma et al Zhongua 2003;26:362-5, 6) Ayik, Erdinc et al Respir Med 2003;97:695-701 Eosinophilic Bronchitis A Worldwide Disease Causes of chronic cough Ayık SÖ, Başoğlu ÖK, Erdinç M. Respir Med Vol. 97 (2003) 695-701

Slide 31 -

CHRONIC COUGH MÜNEVVER ERDİNÇ Department of Chest Diseases Ege University Faculty of Medicine Differential Diagnosis And Treatment In Adults Acute Cough lasting less than 3 weeks Subacute Cough lasting 3 to 8 weeks Chronic Cough Lasting more than 8 weeks Morice AH.Eur Respir J 2004 :24:481-492 Fontana GA.Thorax 2003;58:1092-1095 Irwin RS.NEJM 343(23): 1715-1721,2000 Irwin RS. Chest 1998; 114(suppl1) :133S-181S Differantial Diagnosis of Chronic Cough in Adults PNDS Allergic rhinitis Chronic sinusitis GERD Cough variant asthma ACEI induced cough Pertusis Neurogenic Traumatic Postinfectious cough Phychogenic cough Chronic aspiration Zenker diverticulosis Foreign body Chronic bronchitis Bronchiectasis Lung cancer Subglottic stenosis Tracheomalasie Tracheoesophageal fistul Tuerculosis Sarcoidosis Congestive heart failure Simpson CB. Otolaryngology–Head Neck Surg 2006; 134: 693-700 In prospective studies in adults, chronic cough is most commonly due to 6 disorders : Upper Airway Cough Syndrome (UACS) Asthma GERD Chronic Bronchitis Bronchiectasis Non-asthmatic Eosinophilic Bronchitis Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S New Considerations Eosinophilic bronchitis Atopic cough Non acid(volume)/ weakly acid reflux Idiopathic (unexplained) öksürük Diagnosis and Management of Cough ACCP Evidence-Based CPG 2006 Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S Plevkova, et al. Respir Physiol Neurobiol 2004; 142: 225-235 Postnasal drip syndrome (PNDS) renamed upper airway cough syndrome (UACS) Upper airway afferents may reflexly enhance coughing Nonasthmatic eosinophilic bronchitis recognized as a common cause of chronic cough Idiopathic cough renamed unexplained cough The term acid reflux disease, unless it can be definitively shown to apply, replaced by reflux disease Update of current diagnostic and therapeutic approaches Common diseases, Uncommon diseases New algorithms for the management of cough in adults and children An empiric integrative approach is recommended 10 12 13 12 16 6 4 ASTHMA PNDS GERD Chest 1999;116:279-284 1. Gastroesophageal reflux disease (21-41%) 2. Cough variant asthma (24-59%) 3. Postnasal drip syndrome (41-58%) Chest 1999;116:279-281 Percentage of Cases Presenting 1,2,3, and 4 Causative Factors İmmunocompetent patients Not exposed to enviromental irritants Chest radiograph is normal Not taking an ACE inhibitor Not a current smoker Asthma and/or GERD, PNDS responsible for 93.6% of the cases of chronic cough Harding SM .Chest 2003;123:659-660 Changing Trends in Diagnosis Percentage of Diagnosis (%) GERD ASTHMA RHINITIS Impaired esophageal clearance Functional defect in LES syphincter Hiatal hernia Delayed gastric emptying İncreased intra-abdominal pressure GERD ? Decreased saliva Heartburn (pyrosis) and regurgitation At least weekly symptoms extraesophageal reflux symptoms and/or esophageal mucosal damage / Katzka & DiMarino 1995 FLR Signs Edema and hyperemia of larynx Vocal cord erythema, polyps, granulomas, ulcers Hyperemia and lymphoid hyperplasia of posterior pharynx Interarytenoid changes Subglottic stenosis GERD-related cough incidence 5 - 55% May be the sole presenting symptom(1/3) Thorax 2003:58;1092-1095) (Chest 1997; 111: 1389-1402) Irwin RS. Chest 2006;129:80S-94S Association between cough and reflux is important Esophageal-tracheal-bronchial reflex Microaspiration Pathogenesis ARRD 1981;123:413-417 Arch Intern Med 1996;156:997 Chest 1993;104:1511-1517 El Hennawi, 2004 OHNS Nonacidic factors? Esophageal dismotility? . Mediator Release . Inflammation . Edema . Mucus . Smooth Muscle Microaspiration REFLUX Esophageal Vagal Afferents Bronchial Hyperreactivity Airway Vagal Afferents CNS Stein MR.Am J Med 2003 Chest 1997;111: 1389-1402 Airway Airway Vagal Efferents Esophagus Tracheobronchial Tree Stomach Oesophagus Pharyngeal pHmetry + - Not GERD Clinical GERD symptoms ? Nonacid, weakly acid reflux? Increase dose PPI + alginate İmproved Not improved Continue pHmetry under treatment Consider  Simultaneously dual probes 24 hours pHmonitoring and intraesophageal impedance Irwin RS.AJRCCM 165:1469-74,2002 McGarvey LPA.Thorax 59:342-346,2004 15 cm 17 cm 6 impedance channels 1 pH electrode + Adult Standard Model ZAN-S61C01E Multichannel intraluminal impedance-pH catheter Non acid reflux On going reflux of ‘non-acid’ material may be responsible for continuing symptoms while on acid-suppressing medications Therapy in Esophageal-pulmonary reflux Conservative and lifestyle measures Ampirical therapy: Acid suppression Proton pump inhibitors  PPI x 2 / 3 months Therapy failure  24 hour intraesophageal pHmetry ( pharyngeal pHmetry )  GERD (+) High dose PPI + H2 blocker agent Surgery(Fundoplication) Pulmonary and Crit Care Update 1994; Vol 9 Morice AH. ERJ 2004;24:481-492 Weeks of antireflux therapy Patients responded No No (%) 2 16 (41) 4 38 (86) 6 42 (95) 8 43 (99) 12 weeks 44 (100) Poe RH.Chest 2003;123:679-684 Cumulative Response to GERD Therapy Preop pH <4: %23.6 De Meester: 85 Postop pH <4: %2.4 De Meester: 9.9 1. Chronic cough for at least 2 months 2. Immunocompetent patients 3. Chest radiograph is normal 4. Not exposed to enviromental irritants nor a present smoker 5. Not taking an ACE inhibitor 6. Symptomatic asthma has been ruled out 7. Rhinosinus diseases has been ruled out: 8. ‘Silent sinusitis’ has been ruled out 9. Nonasthmatic eosinophilic bronchitis has been ruled out: BPT is negative Cough has not improved with asthma therapy First generation H1 antagonists has been used Eo 3% in induced sputum Cough has not improved with steroids Irwin RS. Chest 2006;129:80S-94S İrwin RS. AJRCCM Vol 165; 1469-1474, 2002 Clinical Profile That Chronic Cough İs Likely Due To ‘Silent GERD’ Postnasal Drip Syndrome (PNDS) Prevalence : 8 – 87% Pathogenesis : The sensation of drainage of secretions from the nose or paranasal sinuses into the pharynx Clinical Presentation: Dripping sensation Tickle in the throat Nasal congestion Mucus in oropharynx Cobblestone appearence of oropharynx ACCP consensus. CHEST 1998; 114: 133-181 ERS Task Force. ERS Journal ; 24: 553-566 Pathogenic Triad in Chronic Cough. CHEST 1999; 116: 279-284 Evaluation of chronic cough. UPTODATE 2005 Chest 2006;129:63S-71S In patient with chronic cough that is related to upper airway abnormalities Upper Airway Cough Syndrome UACS Treatment Antihistamines / decongestant combinations - “Older” sedating antihistamines more effective - Treatment effect should be observed in 1 week Additional / Alternative treatments : Ipratropium nasal spray : 2-7 days Nasal steroids (such as BDP, FP,BUD) : 2-3 days - 2 week 3 months prescribed Eosinophilic Eronchitis Airway obstruction Bronchial hyperreactivity NO YES YES NO Asthmatic Coughs Cough Variant Asthma Asthma Cough Variant Asthma Prevalence : 24 – 59% Clinical Diagnosis Gold standard  History - Episodic symptoms, Family history Reversibility testing PEF monitoring Bronchoprovocation test Differential Diagnosis: Decreased of cough with classical asthma therapy ACCP consensus. CHEST 1998; 114: 133-181 ERS Task Force. ERS Journal ; 24: 553-566 The Journal of Respiratory Disease; 25; 310-315 THORAX 59; 342-346 Middle age patients Smoking is unusual, occupational ? Prevalence of atopy similar population Good respond to inhaled steroids Gibson et al. Lancet 1989 Chest 2006;129:116S-121S Eosinophilic Bronchitis Isolated chronic cough,  productive of sputum Normal lung function without variable airflow limitation Airway hyperresponsiveness absent Eosinophilia in sputum and BAL Cough reflex to capsaicin increased Normal daily variability in peak expiratory flow (<20%) 1)Kim et al AJRCCM 2003; 2) Brightling et al AJRCCM 1999;160:406-10, 3) Joo Korean JIM 2002;17:31-7, 4) Carney et al AJRCCM 1997; 156:211-6, 5) Ma et al Zhongua 2003;26:362-5, 6) Ayik, Erdinc et al Respir Med 2003;97:695-701 Eosinophilic Bronchitis A Worldwide Disease Causes of chronic cough Ayık SÖ, Başoğlu ÖK, Erdinç M. Respir Med Vol. 97 (2003) 695-701 Causes of Isolated Chronic Cough Brightling CE et al. AJRCCM 1999

Slide 32 -

CHRONIC COUGH MÜNEVVER ERDİNÇ Department of Chest Diseases Ege University Faculty of Medicine Differential Diagnosis And Treatment In Adults Acute Cough lasting less than 3 weeks Subacute Cough lasting 3 to 8 weeks Chronic Cough Lasting more than 8 weeks Morice AH.Eur Respir J 2004 :24:481-492 Fontana GA.Thorax 2003;58:1092-1095 Irwin RS.NEJM 343(23): 1715-1721,2000 Irwin RS. Chest 1998; 114(suppl1) :133S-181S Differantial Diagnosis of Chronic Cough in Adults PNDS Allergic rhinitis Chronic sinusitis GERD Cough variant asthma ACEI induced cough Pertusis Neurogenic Traumatic Postinfectious cough Phychogenic cough Chronic aspiration Zenker diverticulosis Foreign body Chronic bronchitis Bronchiectasis Lung cancer Subglottic stenosis Tracheomalasie Tracheoesophageal fistul Tuerculosis Sarcoidosis Congestive heart failure Simpson CB. Otolaryngology–Head Neck Surg 2006; 134: 693-700 In prospective studies in adults, chronic cough is most commonly due to 6 disorders : Upper Airway Cough Syndrome (UACS) Asthma GERD Chronic Bronchitis Bronchiectasis Non-asthmatic Eosinophilic Bronchitis Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S New Considerations Eosinophilic bronchitis Atopic cough Non acid(volume)/ weakly acid reflux Idiopathic (unexplained) öksürük Diagnosis and Management of Cough ACCP Evidence-Based CPG 2006 Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S Plevkova, et al. Respir Physiol Neurobiol 2004; 142: 225-235 Postnasal drip syndrome (PNDS) renamed upper airway cough syndrome (UACS) Upper airway afferents may reflexly enhance coughing Nonasthmatic eosinophilic bronchitis recognized as a common cause of chronic cough Idiopathic cough renamed unexplained cough The term acid reflux disease, unless it can be definitively shown to apply, replaced by reflux disease Update of current diagnostic and therapeutic approaches Common diseases, Uncommon diseases New algorithms for the management of cough in adults and children An empiric integrative approach is recommended 10 12 13 12 16 6 4 ASTHMA PNDS GERD Chest 1999;116:279-284 1. Gastroesophageal reflux disease (21-41%) 2. Cough variant asthma (24-59%) 3. Postnasal drip syndrome (41-58%) Chest 1999;116:279-281 Percentage of Cases Presenting 1,2,3, and 4 Causative Factors İmmunocompetent patients Not exposed to enviromental irritants Chest radiograph is normal Not taking an ACE inhibitor Not a current smoker Asthma and/or GERD, PNDS responsible for 93.6% of the cases of chronic cough Harding SM .Chest 2003;123:659-660 Changing Trends in Diagnosis Percentage of Diagnosis (%) GERD ASTHMA RHINITIS Impaired esophageal clearance Functional defect in LES syphincter Hiatal hernia Delayed gastric emptying İncreased intra-abdominal pressure GERD ? Decreased saliva Heartburn (pyrosis) and regurgitation At least weekly symptoms extraesophageal reflux symptoms and/or esophageal mucosal damage / Katzka & DiMarino 1995 FLR Signs Edema and hyperemia of larynx Vocal cord erythema, polyps, granulomas, ulcers Hyperemia and lymphoid hyperplasia of posterior pharynx Interarytenoid changes Subglottic stenosis GERD-related cough incidence 5 - 55% May be the sole presenting symptom(1/3) Thorax 2003:58;1092-1095) (Chest 1997; 111: 1389-1402) Irwin RS. Chest 2006;129:80S-94S Association between cough and reflux is important Esophageal-tracheal-bronchial reflex Microaspiration Pathogenesis ARRD 1981;123:413-417 Arch Intern Med 1996;156:997 Chest 1993;104:1511-1517 El Hennawi, 2004 OHNS Nonacidic factors? Esophageal dismotility? . Mediator Release . Inflammation . Edema . Mucus . Smooth Muscle Microaspiration REFLUX Esophageal Vagal Afferents Bronchial Hyperreactivity Airway Vagal Afferents CNS Stein MR.Am J Med 2003 Chest 1997;111: 1389-1402 Airway Airway Vagal Efferents Esophagus Tracheobronchial Tree Stomach Oesophagus Pharyngeal pHmetry + - Not GERD Clinical GERD symptoms ? Nonacid, weakly acid reflux? Increase dose PPI + alginate İmproved Not improved Continue pHmetry under treatment Consider  Simultaneously dual probes 24 hours pHmonitoring and intraesophageal impedance Irwin RS.AJRCCM 165:1469-74,2002 McGarvey LPA.Thorax 59:342-346,2004 15 cm 17 cm 6 impedance channels 1 pH electrode + Adult Standard Model ZAN-S61C01E Multichannel intraluminal impedance-pH catheter Non acid reflux On going reflux of ‘non-acid’ material may be responsible for continuing symptoms while on acid-suppressing medications Therapy in Esophageal-pulmonary reflux Conservative and lifestyle measures Ampirical therapy: Acid suppression Proton pump inhibitors  PPI x 2 / 3 months Therapy failure  24 hour intraesophageal pHmetry ( pharyngeal pHmetry )  GERD (+) High dose PPI + H2 blocker agent Surgery(Fundoplication) Pulmonary and Crit Care Update 1994; Vol 9 Morice AH. ERJ 2004;24:481-492 Weeks of antireflux therapy Patients responded No No (%) 2 16 (41) 4 38 (86) 6 42 (95) 8 43 (99) 12 weeks 44 (100) Poe RH.Chest 2003;123:679-684 Cumulative Response to GERD Therapy Preop pH <4: %23.6 De Meester: 85 Postop pH <4: %2.4 De Meester: 9.9 1. Chronic cough for at least 2 months 2. Immunocompetent patients 3. Chest radiograph is normal 4. Not exposed to enviromental irritants nor a present smoker 5. Not taking an ACE inhibitor 6. Symptomatic asthma has been ruled out 7. Rhinosinus diseases has been ruled out: 8. ‘Silent sinusitis’ has been ruled out 9. Nonasthmatic eosinophilic bronchitis has been ruled out: BPT is negative Cough has not improved with asthma therapy First generation H1 antagonists has been used Eo 3% in induced sputum Cough has not improved with steroids Irwin RS. Chest 2006;129:80S-94S İrwin RS. AJRCCM Vol 165; 1469-1474, 2002 Clinical Profile That Chronic Cough İs Likely Due To ‘Silent GERD’ Postnasal Drip Syndrome (PNDS) Prevalence : 8 – 87% Pathogenesis : The sensation of drainage of secretions from the nose or paranasal sinuses into the pharynx Clinical Presentation: Dripping sensation Tickle in the throat Nasal congestion Mucus in oropharynx Cobblestone appearence of oropharynx ACCP consensus. CHEST 1998; 114: 133-181 ERS Task Force. ERS Journal ; 24: 553-566 Pathogenic Triad in Chronic Cough. CHEST 1999; 116: 279-284 Evaluation of chronic cough. UPTODATE 2005 Chest 2006;129:63S-71S In patient with chronic cough that is related to upper airway abnormalities Upper Airway Cough Syndrome UACS Treatment Antihistamines / decongestant combinations - “Older” sedating antihistamines more effective - Treatment effect should be observed in 1 week Additional / Alternative treatments : Ipratropium nasal spray : 2-7 days Nasal steroids (such as BDP, FP,BUD) : 2-3 days - 2 week 3 months prescribed Eosinophilic Eronchitis Airway obstruction Bronchial hyperreactivity NO YES YES NO Asthmatic Coughs Cough Variant Asthma Asthma Cough Variant Asthma Prevalence : 24 – 59% Clinical Diagnosis Gold standard  History - Episodic symptoms, Family history Reversibility testing PEF monitoring Bronchoprovocation test Differential Diagnosis: Decreased of cough with classical asthma therapy ACCP consensus. CHEST 1998; 114: 133-181 ERS Task Force. ERS Journal ; 24: 553-566 The Journal of Respiratory Disease; 25; 310-315 THORAX 59; 342-346 Middle age patients Smoking is unusual, occupational ? Prevalence of atopy similar population Good respond to inhaled steroids Gibson et al. Lancet 1989 Chest 2006;129:116S-121S Eosinophilic Bronchitis Isolated chronic cough,  productive of sputum Normal lung function without variable airflow limitation Airway hyperresponsiveness absent Eosinophilia in sputum and BAL Cough reflex to capsaicin increased Normal daily variability in peak expiratory flow (<20%) 1)Kim et al AJRCCM 2003; 2) Brightling et al AJRCCM 1999;160:406-10, 3) Joo Korean JIM 2002;17:31-7, 4) Carney et al AJRCCM 1997; 156:211-6, 5) Ma et al Zhongua 2003;26:362-5, 6) Ayik, Erdinc et al Respir Med 2003;97:695-701 Eosinophilic Bronchitis A Worldwide Disease Causes of chronic cough Ayık SÖ, Başoğlu ÖK, Erdinç M. Respir Med Vol. 97 (2003) 695-701 Causes of Isolated Chronic Cough Brightling CE et al. AJRCCM 1999 Asthmatic Cough Airway obstruction Reversibility PEF değişkenliği Increased NO all of them PEF monitoring

Slide 33 -

CHRONIC COUGH MÜNEVVER ERDİNÇ Department of Chest Diseases Ege University Faculty of Medicine Differential Diagnosis And Treatment In Adults Acute Cough lasting less than 3 weeks Subacute Cough lasting 3 to 8 weeks Chronic Cough Lasting more than 8 weeks Morice AH.Eur Respir J 2004 :24:481-492 Fontana GA.Thorax 2003;58:1092-1095 Irwin RS.NEJM 343(23): 1715-1721,2000 Irwin RS. Chest 1998; 114(suppl1) :133S-181S Differantial Diagnosis of Chronic Cough in Adults PNDS Allergic rhinitis Chronic sinusitis GERD Cough variant asthma ACEI induced cough Pertusis Neurogenic Traumatic Postinfectious cough Phychogenic cough Chronic aspiration Zenker diverticulosis Foreign body Chronic bronchitis Bronchiectasis Lung cancer Subglottic stenosis Tracheomalasie Tracheoesophageal fistul Tuerculosis Sarcoidosis Congestive heart failure Simpson CB. Otolaryngology–Head Neck Surg 2006; 134: 693-700 In prospective studies in adults, chronic cough is most commonly due to 6 disorders : Upper Airway Cough Syndrome (UACS) Asthma GERD Chronic Bronchitis Bronchiectasis Non-asthmatic Eosinophilic Bronchitis Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S New Considerations Eosinophilic bronchitis Atopic cough Non acid(volume)/ weakly acid reflux Idiopathic (unexplained) öksürük Diagnosis and Management of Cough ACCP Evidence-Based CPG 2006 Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S Plevkova, et al. Respir Physiol Neurobiol 2004; 142: 225-235 Postnasal drip syndrome (PNDS) renamed upper airway cough syndrome (UACS) Upper airway afferents may reflexly enhance coughing Nonasthmatic eosinophilic bronchitis recognized as a common cause of chronic cough Idiopathic cough renamed unexplained cough The term acid reflux disease, unless it can be definitively shown to apply, replaced by reflux disease Update of current diagnostic and therapeutic approaches Common diseases, Uncommon diseases New algorithms for the management of cough in adults and children An empiric integrative approach is recommended 10 12 13 12 16 6 4 ASTHMA PNDS GERD Chest 1999;116:279-284 1. Gastroesophageal reflux disease (21-41%) 2. Cough variant asthma (24-59%) 3. Postnasal drip syndrome (41-58%) Chest 1999;116:279-281 Percentage of Cases Presenting 1,2,3, and 4 Causative Factors İmmunocompetent patients Not exposed to enviromental irritants Chest radiograph is normal Not taking an ACE inhibitor Not a current smoker Asthma and/or GERD, PNDS responsible for 93.6% of the cases of chronic cough Harding SM .Chest 2003;123:659-660 Changing Trends in Diagnosis Percentage of Diagnosis (%) GERD ASTHMA RHINITIS Impaired esophageal clearance Functional defect in LES syphincter Hiatal hernia Delayed gastric emptying İncreased intra-abdominal pressure GERD ? Decreased saliva Heartburn (pyrosis) and regurgitation At least weekly symptoms extraesophageal reflux symptoms and/or esophageal mucosal damage / Katzka & DiMarino 1995 FLR Signs Edema and hyperemia of larynx Vocal cord erythema, polyps, granulomas, ulcers Hyperemia and lymphoid hyperplasia of posterior pharynx Interarytenoid changes Subglottic stenosis GERD-related cough incidence 5 - 55% May be the sole presenting symptom(1/3) Thorax 2003:58;1092-1095) (Chest 1997; 111: 1389-1402) Irwin RS. Chest 2006;129:80S-94S Association between cough and reflux is important Esophageal-tracheal-bronchial reflex Microaspiration Pathogenesis ARRD 1981;123:413-417 Arch Intern Med 1996;156:997 Chest 1993;104:1511-1517 El Hennawi, 2004 OHNS Nonacidic factors? Esophageal dismotility? . Mediator Release . Inflammation . Edema . Mucus . Smooth Muscle Microaspiration REFLUX Esophageal Vagal Afferents Bronchial Hyperreactivity Airway Vagal Afferents CNS Stein MR.Am J Med 2003 Chest 1997;111: 1389-1402 Airway Airway Vagal Efferents Esophagus Tracheobronchial Tree Stomach Oesophagus Pharyngeal pHmetry + - Not GERD Clinical GERD symptoms ? Nonacid, weakly acid reflux? Increase dose PPI + alginate İmproved Not improved Continue pHmetry under treatment Consider  Simultaneously dual probes 24 hours pHmonitoring and intraesophageal impedance Irwin RS.AJRCCM 165:1469-74,2002 McGarvey LPA.Thorax 59:342-346,2004 15 cm 17 cm 6 impedance channels 1 pH electrode + Adult Standard Model ZAN-S61C01E Multichannel intraluminal impedance-pH catheter Non acid reflux On going reflux of ‘non-acid’ material may be responsible for continuing symptoms while on acid-suppressing medications Therapy in Esophageal-pulmonary reflux Conservative and lifestyle measures Ampirical therapy: Acid suppression Proton pump inhibitors  PPI x 2 / 3 months Therapy failure  24 hour intraesophageal pHmetry ( pharyngeal pHmetry )  GERD (+) High dose PPI + H2 blocker agent Surgery(Fundoplication) Pulmonary and Crit Care Update 1994; Vol 9 Morice AH. ERJ 2004;24:481-492 Weeks of antireflux therapy Patients responded No No (%) 2 16 (41) 4 38 (86) 6 42 (95) 8 43 (99) 12 weeks 44 (100) Poe RH.Chest 2003;123:679-684 Cumulative Response to GERD Therapy Preop pH <4: %23.6 De Meester: 85 Postop pH <4: %2.4 De Meester: 9.9 1. Chronic cough for at least 2 months 2. Immunocompetent patients 3. Chest radiograph is normal 4. Not exposed to enviromental irritants nor a present smoker 5. Not taking an ACE inhibitor 6. Symptomatic asthma has been ruled out 7. Rhinosinus diseases has been ruled out: 8. ‘Silent sinusitis’ has been ruled out 9. Nonasthmatic eosinophilic bronchitis has been ruled out: BPT is negative Cough has not improved with asthma therapy First generation H1 antagonists has been used Eo 3% in induced sputum Cough has not improved with steroids Irwin RS. Chest 2006;129:80S-94S İrwin RS. AJRCCM Vol 165; 1469-1474, 2002 Clinical Profile That Chronic Cough İs Likely Due To ‘Silent GERD’ Postnasal Drip Syndrome (PNDS) Prevalence : 8 – 87% Pathogenesis : The sensation of drainage of secretions from the nose or paranasal sinuses into the pharynx Clinical Presentation: Dripping sensation Tickle in the throat Nasal congestion Mucus in oropharynx Cobblestone appearence of oropharynx ACCP consensus. CHEST 1998; 114: 133-181 ERS Task Force. ERS Journal ; 24: 553-566 Pathogenic Triad in Chronic Cough. CHEST 1999; 116: 279-284 Evaluation of chronic cough. UPTODATE 2005 Chest 2006;129:63S-71S In patient with chronic cough that is related to upper airway abnormalities Upper Airway Cough Syndrome UACS Treatment Antihistamines / decongestant combinations - “Older” sedating antihistamines more effective - Treatment effect should be observed in 1 week Additional / Alternative treatments : Ipratropium nasal spray : 2-7 days Nasal steroids (such as BDP, FP,BUD) : 2-3 days - 2 week 3 months prescribed Eosinophilic Eronchitis Airway obstruction Bronchial hyperreactivity NO YES YES NO Asthmatic Coughs Cough Variant Asthma Asthma Cough Variant Asthma Prevalence : 24 – 59% Clinical Diagnosis Gold standard  History - Episodic symptoms, Family history Reversibility testing PEF monitoring Bronchoprovocation test Differential Diagnosis: Decreased of cough with classical asthma therapy ACCP consensus. CHEST 1998; 114: 133-181 ERS Task Force. ERS Journal ; 24: 553-566 The Journal of Respiratory Disease; 25; 310-315 THORAX 59; 342-346 Middle age patients Smoking is unusual, occupational ? Prevalence of atopy similar population Good respond to inhaled steroids Gibson et al. Lancet 1989 Chest 2006;129:116S-121S Eosinophilic Bronchitis Isolated chronic cough,  productive of sputum Normal lung function without variable airflow limitation Airway hyperresponsiveness absent Eosinophilia in sputum and BAL Cough reflex to capsaicin increased Normal daily variability in peak expiratory flow (<20%) 1)Kim et al AJRCCM 2003; 2) Brightling et al AJRCCM 1999;160:406-10, 3) Joo Korean JIM 2002;17:31-7, 4) Carney et al AJRCCM 1997; 156:211-6, 5) Ma et al Zhongua 2003;26:362-5, 6) Ayik, Erdinc et al Respir Med 2003;97:695-701 Eosinophilic Bronchitis A Worldwide Disease Causes of chronic cough Ayık SÖ, Başoğlu ÖK, Erdinç M. Respir Med Vol. 97 (2003) 695-701 Causes of Isolated Chronic Cough Brightling CE et al. AJRCCM 1999 Asthmatic Cough Airway obstruction Reversibility PEF değişkenliği Increased NO all of them PEF monitoring

Slide 34 -

CHRONIC COUGH MÜNEVVER ERDİNÇ Department of Chest Diseases Ege University Faculty of Medicine Differential Diagnosis And Treatment In Adults Acute Cough lasting less than 3 weeks Subacute Cough lasting 3 to 8 weeks Chronic Cough Lasting more than 8 weeks Morice AH.Eur Respir J 2004 :24:481-492 Fontana GA.Thorax 2003;58:1092-1095 Irwin RS.NEJM 343(23): 1715-1721,2000 Irwin RS. Chest 1998; 114(suppl1) :133S-181S Differantial Diagnosis of Chronic Cough in Adults PNDS Allergic rhinitis Chronic sinusitis GERD Cough variant asthma ACEI induced cough Pertusis Neurogenic Traumatic Postinfectious cough Phychogenic cough Chronic aspiration Zenker diverticulosis Foreign body Chronic bronchitis Bronchiectasis Lung cancer Subglottic stenosis Tracheomalasie Tracheoesophageal fistul Tuerculosis Sarcoidosis Congestive heart failure Simpson CB. Otolaryngology–Head Neck Surg 2006; 134: 693-700 In prospective studies in adults, chronic cough is most commonly due to 6 disorders : Upper Airway Cough Syndrome (UACS) Asthma GERD Chronic Bronchitis Bronchiectasis Non-asthmatic Eosinophilic Bronchitis Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S New Considerations Eosinophilic bronchitis Atopic cough Non acid(volume)/ weakly acid reflux Idiopathic (unexplained) öksürük Diagnosis and Management of Cough ACCP Evidence-Based CPG 2006 Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S Plevkova, et al. Respir Physiol Neurobiol 2004; 142: 225-235 Postnasal drip syndrome (PNDS) renamed upper airway cough syndrome (UACS) Upper airway afferents may reflexly enhance coughing Nonasthmatic eosinophilic bronchitis recognized as a common cause of chronic cough Idiopathic cough renamed unexplained cough The term acid reflux disease, unless it can be definitively shown to apply, replaced by reflux disease Update of current diagnostic and therapeutic approaches Common diseases, Uncommon diseases New algorithms for the management of cough in adults and children An empiric integrative approach is recommended 10 12 13 12 16 6 4 ASTHMA PNDS GERD Chest 1999;116:279-284 1. Gastroesophageal reflux disease (21-41%) 2. Cough variant asthma (24-59%) 3. Postnasal drip syndrome (41-58%) Chest 1999;116:279-281 Percentage of Cases Presenting 1,2,3, and 4 Causative Factors İmmunocompetent patients Not exposed to enviromental irritants Chest radiograph is normal Not taking an ACE inhibitor Not a current smoker Asthma and/or GERD, PNDS responsible for 93.6% of the cases of chronic cough Harding SM .Chest 2003;123:659-660 Changing Trends in Diagnosis Percentage of Diagnosis (%) GERD ASTHMA RHINITIS Impaired esophageal clearance Functional defect in LES syphincter Hiatal hernia Delayed gastric emptying İncreased intra-abdominal pressure GERD ? Decreased saliva Heartburn (pyrosis) and regurgitation At least weekly symptoms extraesophageal reflux symptoms and/or esophageal mucosal damage / Katzka & DiMarino 1995 FLR Signs Edema and hyperemia of larynx Vocal cord erythema, polyps, granulomas, ulcers Hyperemia and lymphoid hyperplasia of posterior pharynx Interarytenoid changes Subglottic stenosis GERD-related cough incidence 5 - 55% May be the sole presenting symptom(1/3) Thorax 2003:58;1092-1095) (Chest 1997; 111: 1389-1402) Irwin RS. Chest 2006;129:80S-94S Association between cough and reflux is important Esophageal-tracheal-bronchial reflex Microaspiration Pathogenesis ARRD 1981;123:413-417 Arch Intern Med 1996;156:997 Chest 1993;104:1511-1517 El Hennawi, 2004 OHNS Nonacidic factors? Esophageal dismotility? . Mediator Release . Inflammation . Edema . Mucus . Smooth Muscle Microaspiration REFLUX Esophageal Vagal Afferents Bronchial Hyperreactivity Airway Vagal Afferents CNS Stein MR.Am J Med 2003 Chest 1997;111: 1389-1402 Airway Airway Vagal Efferents Esophagus Tracheobronchial Tree Stomach Oesophagus Pharyngeal pHmetry + - Not GERD Clinical GERD symptoms ? Nonacid, weakly acid reflux? Increase dose PPI + alginate İmproved Not improved Continue pHmetry under treatment Consider  Simultaneously dual probes 24 hours pHmonitoring and intraesophageal impedance Irwin RS.AJRCCM 165:1469-74,2002 McGarvey LPA.Thorax 59:342-346,2004 15 cm 17 cm 6 impedance channels 1 pH electrode + Adult Standard Model ZAN-S61C01E Multichannel intraluminal impedance-pH catheter Non acid reflux On going reflux of ‘non-acid’ material may be responsible for continuing symptoms while on acid-suppressing medications Therapy in Esophageal-pulmonary reflux Conservative and lifestyle measures Ampirical therapy: Acid suppression Proton pump inhibitors  PPI x 2 / 3 months Therapy failure  24 hour intraesophageal pHmetry ( pharyngeal pHmetry )  GERD (+) High dose PPI + H2 blocker agent Surgery(Fundoplication) Pulmonary and Crit Care Update 1994; Vol 9 Morice AH. ERJ 2004;24:481-492 Weeks of antireflux therapy Patients responded No No (%) 2 16 (41) 4 38 (86) 6 42 (95) 8 43 (99) 12 weeks 44 (100) Poe RH.Chest 2003;123:679-684 Cumulative Response to GERD Therapy Preop pH <4: %23.6 De Meester: 85 Postop pH <4: %2.4 De Meester: 9.9 1. Chronic cough for at least 2 months 2. Immunocompetent patients 3. Chest radiograph is normal 4. Not exposed to enviromental irritants nor a present smoker 5. Not taking an ACE inhibitor 6. Symptomatic asthma has been ruled out 7. Rhinosinus diseases has been ruled out: 8. ‘Silent sinusitis’ has been ruled out 9. Nonasthmatic eosinophilic bronchitis has been ruled out: BPT is negative Cough has not improved with asthma therapy First generation H1 antagonists has been used Eo 3% in induced sputum Cough has not improved with steroids Irwin RS. Chest 2006;129:80S-94S İrwin RS. AJRCCM Vol 165; 1469-1474, 2002 Clinical Profile That Chronic Cough İs Likely Due To ‘Silent GERD’ Postnasal Drip Syndrome (PNDS) Prevalence : 8 – 87% Pathogenesis : The sensation of drainage of secretions from the nose or paranasal sinuses into the pharynx Clinical Presentation: Dripping sensation Tickle in the throat Nasal congestion Mucus in oropharynx Cobblestone appearence of oropharynx ACCP consensus. CHEST 1998; 114: 133-181 ERS Task Force. ERS Journal ; 24: 553-566 Pathogenic Triad in Chronic Cough. CHEST 1999; 116: 279-284 Evaluation of chronic cough. UPTODATE 2005 Chest 2006;129:63S-71S In patient with chronic cough that is related to upper airway abnormalities Upper Airway Cough Syndrome UACS Treatment Antihistamines / decongestant combinations - “Older” sedating antihistamines more effective - Treatment effect should be observed in 1 week Additional / Alternative treatments : Ipratropium nasal spray : 2-7 days Nasal steroids (such as BDP, FP,BUD) : 2-3 days - 2 week 3 months prescribed Eosinophilic Eronchitis Airway obstruction Bronchial hyperreactivity NO YES YES NO Asthmatic Coughs Cough Variant Asthma Asthma Cough Variant Asthma Prevalence : 24 – 59% Clinical Diagnosis Gold standard  History - Episodic symptoms, Family history Reversibility testing PEF monitoring Bronchoprovocation test Differential Diagnosis: Decreased of cough with classical asthma therapy ACCP consensus. CHEST 1998; 114: 133-181 ERS Task Force. ERS Journal ; 24: 553-566 The Journal of Respiratory Disease; 25; 310-315 THORAX 59; 342-346 Middle age patients Smoking is unusual, occupational ? Prevalence of atopy similar population Good respond to inhaled steroids Gibson et al. Lancet 1989 Chest 2006;129:116S-121S Eosinophilic Bronchitis Isolated chronic cough,  productive of sputum Normal lung function without variable airflow limitation Airway hyperresponsiveness absent Eosinophilia in sputum and BAL Cough reflex to capsaicin increased Normal daily variability in peak expiratory flow (<20%) 1)Kim et al AJRCCM 2003; 2) Brightling et al AJRCCM 1999;160:406-10, 3) Joo Korean JIM 2002;17:31-7, 4) Carney et al AJRCCM 1997; 156:211-6, 5) Ma et al Zhongua 2003;26:362-5, 6) Ayik, Erdinc et al Respir Med 2003;97:695-701 Eosinophilic Bronchitis A Worldwide Disease Causes of chronic cough Ayık SÖ, Başoğlu ÖK, Erdinç M. Respir Med Vol. 97 (2003) 695-701 Causes of Isolated Chronic Cough Brightling CE et al. AJRCCM 1999 Asthmatic Cough Airway obstruction Reversibility PEF değişkenliği Increased NO all of them PEF monitoring Prevalence: 0-50% More agressive diagnosis and treatments UACS, GERD and postinfectious cough leads to lower incidence ‘unexplained’. Airway inflammation Mast cell, histamin, cysteinil LTs, PD2, PE2 Irwin RS,et al. Chest 2006;130:362-370 Chronic Unexplained (Idiopathic) Cough

Slide 35 -

CHRONIC COUGH MÜNEVVER ERDİNÇ Department of Chest Diseases Ege University Faculty of Medicine Differential Diagnosis And Treatment In Adults Acute Cough lasting less than 3 weeks Subacute Cough lasting 3 to 8 weeks Chronic Cough Lasting more than 8 weeks Morice AH.Eur Respir J 2004 :24:481-492 Fontana GA.Thorax 2003;58:1092-1095 Irwin RS.NEJM 343(23): 1715-1721,2000 Irwin RS. Chest 1998; 114(suppl1) :133S-181S Differantial Diagnosis of Chronic Cough in Adults PNDS Allergic rhinitis Chronic sinusitis GERD Cough variant asthma ACEI induced cough Pertusis Neurogenic Traumatic Postinfectious cough Phychogenic cough Chronic aspiration Zenker diverticulosis Foreign body Chronic bronchitis Bronchiectasis Lung cancer Subglottic stenosis Tracheomalasie Tracheoesophageal fistul Tuerculosis Sarcoidosis Congestive heart failure Simpson CB. Otolaryngology–Head Neck Surg 2006; 134: 693-700 In prospective studies in adults, chronic cough is most commonly due to 6 disorders : Upper Airway Cough Syndrome (UACS) Asthma GERD Chronic Bronchitis Bronchiectasis Non-asthmatic Eosinophilic Bronchitis Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S New Considerations Eosinophilic bronchitis Atopic cough Non acid(volume)/ weakly acid reflux Idiopathic (unexplained) öksürük Diagnosis and Management of Cough ACCP Evidence-Based CPG 2006 Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S Plevkova, et al. Respir Physiol Neurobiol 2004; 142: 225-235 Postnasal drip syndrome (PNDS) renamed upper airway cough syndrome (UACS) Upper airway afferents may reflexly enhance coughing Nonasthmatic eosinophilic bronchitis recognized as a common cause of chronic cough Idiopathic cough renamed unexplained cough The term acid reflux disease, unless it can be definitively shown to apply, replaced by reflux disease Update of current diagnostic and therapeutic approaches Common diseases, Uncommon diseases New algorithms for the management of cough in adults and children An empiric integrative approach is recommended 10 12 13 12 16 6 4 ASTHMA PNDS GERD Chest 1999;116:279-284 1. Gastroesophageal reflux disease (21-41%) 2. Cough variant asthma (24-59%) 3. Postnasal drip syndrome (41-58%) Chest 1999;116:279-281 Percentage of Cases Presenting 1,2,3, and 4 Causative Factors İmmunocompetent patients Not exposed to enviromental irritants Chest radiograph is normal Not taking an ACE inhibitor Not a current smoker Asthma and/or GERD, PNDS responsible for 93.6% of the cases of chronic cough Harding SM .Chest 2003;123:659-660 Changing Trends in Diagnosis Percentage of Diagnosis (%) GERD ASTHMA RHINITIS Impaired esophageal clearance Functional defect in LES syphincter Hiatal hernia Delayed gastric emptying İncreased intra-abdominal pressure GERD ? Decreased saliva Heartburn (pyrosis) and regurgitation At least weekly symptoms extraesophageal reflux symptoms and/or esophageal mucosal damage / Katzka & DiMarino 1995 FLR Signs Edema and hyperemia of larynx Vocal cord erythema, polyps, granulomas, ulcers Hyperemia and lymphoid hyperplasia of posterior pharynx Interarytenoid changes Subglottic stenosis GERD-related cough incidence 5 - 55% May be the sole presenting symptom(1/3) Thorax 2003:58;1092-1095) (Chest 1997; 111: 1389-1402) Irwin RS. Chest 2006;129:80S-94S Association between cough and reflux is important Esophageal-tracheal-bronchial reflex Microaspiration Pathogenesis ARRD 1981;123:413-417 Arch Intern Med 1996;156:997 Chest 1993;104:1511-1517 El Hennawi, 2004 OHNS Nonacidic factors? Esophageal dismotility? . Mediator Release . Inflammation . Edema . Mucus . Smooth Muscle Microaspiration REFLUX Esophageal Vagal Afferents Bronchial Hyperreactivity Airway Vagal Afferents CNS Stein MR.Am J Med 2003 Chest 1997;111: 1389-1402 Airway Airway Vagal Efferents Esophagus Tracheobronchial Tree Stomach Oesophagus Pharyngeal pHmetry + - Not GERD Clinical GERD symptoms ? Nonacid, weakly acid reflux? Increase dose PPI + alginate İmproved Not improved Continue pHmetry under treatment Consider  Simultaneously dual probes 24 hours pHmonitoring and intraesophageal impedance Irwin RS.AJRCCM 165:1469-74,2002 McGarvey LPA.Thorax 59:342-346,2004 15 cm 17 cm 6 impedance channels 1 pH electrode + Adult Standard Model ZAN-S61C01E Multichannel intraluminal impedance-pH catheter Non acid reflux On going reflux of ‘non-acid’ material may be responsible for continuing symptoms while on acid-suppressing medications Therapy in Esophageal-pulmonary reflux Conservative and lifestyle measures Ampirical therapy: Acid suppression Proton pump inhibitors  PPI x 2 / 3 months Therapy failure  24 hour intraesophageal pHmetry ( pharyngeal pHmetry )  GERD (+) High dose PPI + H2 blocker agent Surgery(Fundoplication) Pulmonary and Crit Care Update 1994; Vol 9 Morice AH. ERJ 2004;24:481-492 Weeks of antireflux therapy Patients responded No No (%) 2 16 (41) 4 38 (86) 6 42 (95) 8 43 (99) 12 weeks 44 (100) Poe RH.Chest 2003;123:679-684 Cumulative Response to GERD Therapy Preop pH <4: %23.6 De Meester: 85 Postop pH <4: %2.4 De Meester: 9.9 1. Chronic cough for at least 2 months 2. Immunocompetent patients 3. Chest radiograph is normal 4. Not exposed to enviromental irritants nor a present smoker 5. Not taking an ACE inhibitor 6. Symptomatic asthma has been ruled out 7. Rhinosinus diseases has been ruled out: 8. ‘Silent sinusitis’ has been ruled out 9. Nonasthmatic eosinophilic bronchitis has been ruled out: BPT is negative Cough has not improved with asthma therapy First generation H1 antagonists has been used Eo 3% in induced sputum Cough has not improved with steroids Irwin RS. Chest 2006;129:80S-94S İrwin RS. AJRCCM Vol 165; 1469-1474, 2002 Clinical Profile That Chronic Cough İs Likely Due To ‘Silent GERD’ Postnasal Drip Syndrome (PNDS) Prevalence : 8 – 87% Pathogenesis : The sensation of drainage of secretions from the nose or paranasal sinuses into the pharynx Clinical Presentation: Dripping sensation Tickle in the throat Nasal congestion Mucus in oropharynx Cobblestone appearence of oropharynx ACCP consensus. CHEST 1998; 114: 133-181 ERS Task Force. ERS Journal ; 24: 553-566 Pathogenic Triad in Chronic Cough. CHEST 1999; 116: 279-284 Evaluation of chronic cough. UPTODATE 2005 Chest 2006;129:63S-71S In patient with chronic cough that is related to upper airway abnormalities Upper Airway Cough Syndrome UACS Treatment Antihistamines / decongestant combinations - “Older” sedating antihistamines more effective - Treatment effect should be observed in 1 week Additional / Alternative treatments : Ipratropium nasal spray : 2-7 days Nasal steroids (such as BDP, FP,BUD) : 2-3 days - 2 week 3 months prescribed Eosinophilic Eronchitis Airway obstruction Bronchial hyperreactivity NO YES YES NO Asthmatic Coughs Cough Variant Asthma Asthma Cough Variant Asthma Prevalence : 24 – 59% Clinical Diagnosis Gold standard  History - Episodic symptoms, Family history Reversibility testing PEF monitoring Bronchoprovocation test Differential Diagnosis: Decreased of cough with classical asthma therapy ACCP consensus. CHEST 1998; 114: 133-181 ERS Task Force. ERS Journal ; 24: 553-566 The Journal of Respiratory Disease; 25; 310-315 THORAX 59; 342-346 Middle age patients Smoking is unusual, occupational ? Prevalence of atopy similar population Good respond to inhaled steroids Gibson et al. Lancet 1989 Chest 2006;129:116S-121S Eosinophilic Bronchitis Isolated chronic cough,  productive of sputum Normal lung function without variable airflow limitation Airway hyperresponsiveness absent Eosinophilia in sputum and BAL Cough reflex to capsaicin increased Normal daily variability in peak expiratory flow (<20%) 1)Kim et al AJRCCM 2003; 2) Brightling et al AJRCCM 1999;160:406-10, 3) Joo Korean JIM 2002;17:31-7, 4) Carney et al AJRCCM 1997; 156:211-6, 5) Ma et al Zhongua 2003;26:362-5, 6) Ayik, Erdinc et al Respir Med 2003;97:695-701 Eosinophilic Bronchitis A Worldwide Disease Causes of chronic cough Ayık SÖ, Başoğlu ÖK, Erdinç M. Respir Med Vol. 97 (2003) 695-701 Causes of Isolated Chronic Cough Brightling CE et al. AJRCCM 1999 Asthmatic Cough Airway obstruction Reversibility PEF değişkenliği Increased NO all of them PEF monitoring Prevalence: 0-50% More agressive diagnosis and treatments UACS, GERD and postinfectious cough leads to lower incidence ‘unexplained’. Airway inflammation Mast cell, histamin, cysteinil LTs, PD2, PE2 Irwin RS,et al. Chest 2006;130:362-370 Chronic Unexplained (Idiopathic) Cough Important missed history (smoking,ACEI,enviromental,drugs,allergy) Failure to do correct diagnostic tests Failure to use ‘empiric’ treatment Failure to use effective therapy Unknown disease process Potential Reasons Chronic Unexplained (Idiopathic) Cough « Truly idiopathic cough is rare and misdiagnosis very common, especially if cough is provoked by sites outside the airways » Eur Respir J 24: 481-492 2004

Slide 36 -

CHRONIC COUGH MÜNEVVER ERDİNÇ Department of Chest Diseases Ege University Faculty of Medicine Differential Diagnosis And Treatment In Adults Acute Cough lasting less than 3 weeks Subacute Cough lasting 3 to 8 weeks Chronic Cough Lasting more than 8 weeks Morice AH.Eur Respir J 2004 :24:481-492 Fontana GA.Thorax 2003;58:1092-1095 Irwin RS.NEJM 343(23): 1715-1721,2000 Irwin RS. Chest 1998; 114(suppl1) :133S-181S Differantial Diagnosis of Chronic Cough in Adults PNDS Allergic rhinitis Chronic sinusitis GERD Cough variant asthma ACEI induced cough Pertusis Neurogenic Traumatic Postinfectious cough Phychogenic cough Chronic aspiration Zenker diverticulosis Foreign body Chronic bronchitis Bronchiectasis Lung cancer Subglottic stenosis Tracheomalasie Tracheoesophageal fistul Tuerculosis Sarcoidosis Congestive heart failure Simpson CB. Otolaryngology–Head Neck Surg 2006; 134: 693-700 In prospective studies in adults, chronic cough is most commonly due to 6 disorders : Upper Airway Cough Syndrome (UACS) Asthma GERD Chronic Bronchitis Bronchiectasis Non-asthmatic Eosinophilic Bronchitis Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S New Considerations Eosinophilic bronchitis Atopic cough Non acid(volume)/ weakly acid reflux Idiopathic (unexplained) öksürük Diagnosis and Management of Cough ACCP Evidence-Based CPG 2006 Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S Plevkova, et al. Respir Physiol Neurobiol 2004; 142: 225-235 Postnasal drip syndrome (PNDS) renamed upper airway cough syndrome (UACS) Upper airway afferents may reflexly enhance coughing Nonasthmatic eosinophilic bronchitis recognized as a common cause of chronic cough Idiopathic cough renamed unexplained cough The term acid reflux disease, unless it can be definitively shown to apply, replaced by reflux disease Update of current diagnostic and therapeutic approaches Common diseases, Uncommon diseases New algorithms for the management of cough in adults and children An empiric integrative approach is recommended 10 12 13 12 16 6 4 ASTHMA PNDS GERD Chest 1999;116:279-284 1. Gastroesophageal reflux disease (21-41%) 2. Cough variant asthma (24-59%) 3. Postnasal drip syndrome (41-58%) Chest 1999;116:279-281 Percentage of Cases Presenting 1,2,3, and 4 Causative Factors İmmunocompetent patients Not exposed to enviromental irritants Chest radiograph is normal Not taking an ACE inhibitor Not a current smoker Asthma and/or GERD, PNDS responsible for 93.6% of the cases of chronic cough Harding SM .Chest 2003;123:659-660 Changing Trends in Diagnosis Percentage of Diagnosis (%) GERD ASTHMA RHINITIS Impaired esophageal clearance Functional defect in LES syphincter Hiatal hernia Delayed gastric emptying İncreased intra-abdominal pressure GERD ? Decreased saliva Heartburn (pyrosis) and regurgitation At least weekly symptoms extraesophageal reflux symptoms and/or esophageal mucosal damage / Katzka & DiMarino 1995 FLR Signs Edema and hyperemia of larynx Vocal cord erythema, polyps, granulomas, ulcers Hyperemia and lymphoid hyperplasia of posterior pharynx Interarytenoid changes Subglottic stenosis GERD-related cough incidence 5 - 55% May be the sole presenting symptom(1/3) Thorax 2003:58;1092-1095) (Chest 1997; 111: 1389-1402) Irwin RS. Chest 2006;129:80S-94S Association between cough and reflux is important Esophageal-tracheal-bronchial reflex Microaspiration Pathogenesis ARRD 1981;123:413-417 Arch Intern Med 1996;156:997 Chest 1993;104:1511-1517 El Hennawi, 2004 OHNS Nonacidic factors? Esophageal dismotility? . Mediator Release . Inflammation . Edema . Mucus . Smooth Muscle Microaspiration REFLUX Esophageal Vagal Afferents Bronchial Hyperreactivity Airway Vagal Afferents CNS Stein MR.Am J Med 2003 Chest 1997;111: 1389-1402 Airway Airway Vagal Efferents Esophagus Tracheobronchial Tree Stomach Oesophagus Pharyngeal pHmetry + - Not GERD Clinical GERD symptoms ? Nonacid, weakly acid reflux? Increase dose PPI + alginate İmproved Not improved Continue pHmetry under treatment Consider  Simultaneously dual probes 24 hours pHmonitoring and intraesophageal impedance Irwin RS.AJRCCM 165:1469-74,2002 McGarvey LPA.Thorax 59:342-346,2004 15 cm 17 cm 6 impedance channels 1 pH electrode + Adult Standard Model ZAN-S61C01E Multichannel intraluminal impedance-pH catheter Non acid reflux On going reflux of ‘non-acid’ material may be responsible for continuing symptoms while on acid-suppressing medications Therapy in Esophageal-pulmonary reflux Conservative and lifestyle measures Ampirical therapy: Acid suppression Proton pump inhibitors  PPI x 2 / 3 months Therapy failure  24 hour intraesophageal pHmetry ( pharyngeal pHmetry )  GERD (+) High dose PPI + H2 blocker agent Surgery(Fundoplication) Pulmonary and Crit Care Update 1994; Vol 9 Morice AH. ERJ 2004;24:481-492 Weeks of antireflux therapy Patients responded No No (%) 2 16 (41) 4 38 (86) 6 42 (95) 8 43 (99) 12 weeks 44 (100) Poe RH.Chest 2003;123:679-684 Cumulative Response to GERD Therapy Preop pH <4: %23.6 De Meester: 85 Postop pH <4: %2.4 De Meester: 9.9 1. Chronic cough for at least 2 months 2. Immunocompetent patients 3. Chest radiograph is normal 4. Not exposed to enviromental irritants nor a present smoker 5. Not taking an ACE inhibitor 6. Symptomatic asthma has been ruled out 7. Rhinosinus diseases has been ruled out: 8. ‘Silent sinusitis’ has been ruled out 9. Nonasthmatic eosinophilic bronchitis has been ruled out: BPT is negative Cough has not improved with asthma therapy First generation H1 antagonists has been used Eo 3% in induced sputum Cough has not improved with steroids Irwin RS. Chest 2006;129:80S-94S İrwin RS. AJRCCM Vol 165; 1469-1474, 2002 Clinical Profile That Chronic Cough İs Likely Due To ‘Silent GERD’ Postnasal Drip Syndrome (PNDS) Prevalence : 8 – 87% Pathogenesis : The sensation of drainage of secretions from the nose or paranasal sinuses into the pharynx Clinical Presentation: Dripping sensation Tickle in the throat Nasal congestion Mucus in oropharynx Cobblestone appearence of oropharynx ACCP consensus. CHEST 1998; 114: 133-181 ERS Task Force. ERS Journal ; 24: 553-566 Pathogenic Triad in Chronic Cough. CHEST 1999; 116: 279-284 Evaluation of chronic cough. UPTODATE 2005 Chest 2006;129:63S-71S In patient with chronic cough that is related to upper airway abnormalities Upper Airway Cough Syndrome UACS Treatment Antihistamines / decongestant combinations - “Older” sedating antihistamines more effective - Treatment effect should be observed in 1 week Additional / Alternative treatments : Ipratropium nasal spray : 2-7 days Nasal steroids (such as BDP, FP,BUD) : 2-3 days - 2 week 3 months prescribed Eosinophilic Eronchitis Airway obstruction Bronchial hyperreactivity NO YES YES NO Asthmatic Coughs Cough Variant Asthma Asthma Cough Variant Asthma Prevalence : 24 – 59% Clinical Diagnosis Gold standard  History - Episodic symptoms, Family history Reversibility testing PEF monitoring Bronchoprovocation test Differential Diagnosis: Decreased of cough with classical asthma therapy ACCP consensus. CHEST 1998; 114: 133-181 ERS Task Force. ERS Journal ; 24: 553-566 The Journal of Respiratory Disease; 25; 310-315 THORAX 59; 342-346 Middle age patients Smoking is unusual, occupational ? Prevalence of atopy similar population Good respond to inhaled steroids Gibson et al. Lancet 1989 Chest 2006;129:116S-121S Eosinophilic Bronchitis Isolated chronic cough,  productive of sputum Normal lung function without variable airflow limitation Airway hyperresponsiveness absent Eosinophilia in sputum and BAL Cough reflex to capsaicin increased Normal daily variability in peak expiratory flow (<20%) 1)Kim et al AJRCCM 2003; 2) Brightling et al AJRCCM 1999;160:406-10, 3) Joo Korean JIM 2002;17:31-7, 4) Carney et al AJRCCM 1997; 156:211-6, 5) Ma et al Zhongua 2003;26:362-5, 6) Ayik, Erdinc et al Respir Med 2003;97:695-701 Eosinophilic Bronchitis A Worldwide Disease Causes of chronic cough Ayık SÖ, Başoğlu ÖK, Erdinç M. Respir Med Vol. 97 (2003) 695-701 Causes of Isolated Chronic Cough Brightling CE et al. AJRCCM 1999 Asthmatic Cough Airway obstruction Reversibility PEF değişkenliği Increased NO all of them PEF monitoring Prevalence: 0-50% More agressive diagnosis and treatments UACS, GERD and postinfectious cough leads to lower incidence ‘unexplained’. Airway inflammation Mast cell, histamin, cysteinil LTs, PD2, PE2 Irwin RS,et al. Chest 2006;130:362-370 Chronic Unexplained (Idiopathic) Cough Important missed history (smoking,ACEI,enviromental,drugs,allergy) Failure to do correct diagnostic tests Failure to use ‘empiric’ treatment Failure to use effective therapy Unknown disease process Potential Reasons Chronic Unexplained (Idiopathic) Cough « Truly idiopathic cough is rare and misdiagnosis very common, especially if cough is provoked by sites outside the airways » Eur Respir J 24: 481-492 2004 Idiopathic cough % ? Studies in the 1980’s % patients

Slide 37 -

CHRONIC COUGH MÜNEVVER ERDİNÇ Department of Chest Diseases Ege University Faculty of Medicine Differential Diagnosis And Treatment In Adults Acute Cough lasting less than 3 weeks Subacute Cough lasting 3 to 8 weeks Chronic Cough Lasting more than 8 weeks Morice AH.Eur Respir J 2004 :24:481-492 Fontana GA.Thorax 2003;58:1092-1095 Irwin RS.NEJM 343(23): 1715-1721,2000 Irwin RS. Chest 1998; 114(suppl1) :133S-181S Differantial Diagnosis of Chronic Cough in Adults PNDS Allergic rhinitis Chronic sinusitis GERD Cough variant asthma ACEI induced cough Pertusis Neurogenic Traumatic Postinfectious cough Phychogenic cough Chronic aspiration Zenker diverticulosis Foreign body Chronic bronchitis Bronchiectasis Lung cancer Subglottic stenosis Tracheomalasie Tracheoesophageal fistul Tuerculosis Sarcoidosis Congestive heart failure Simpson CB. Otolaryngology–Head Neck Surg 2006; 134: 693-700 In prospective studies in adults, chronic cough is most commonly due to 6 disorders : Upper Airway Cough Syndrome (UACS) Asthma GERD Chronic Bronchitis Bronchiectasis Non-asthmatic Eosinophilic Bronchitis Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S New Considerations Eosinophilic bronchitis Atopic cough Non acid(volume)/ weakly acid reflux Idiopathic (unexplained) öksürük Diagnosis and Management of Cough ACCP Evidence-Based CPG 2006 Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S Plevkova, et al. Respir Physiol Neurobiol 2004; 142: 225-235 Postnasal drip syndrome (PNDS) renamed upper airway cough syndrome (UACS) Upper airway afferents may reflexly enhance coughing Nonasthmatic eosinophilic bronchitis recognized as a common cause of chronic cough Idiopathic cough renamed unexplained cough The term acid reflux disease, unless it can be definitively shown to apply, replaced by reflux disease Update of current diagnostic and therapeutic approaches Common diseases, Uncommon diseases New algorithms for the management of cough in adults and children An empiric integrative approach is recommended 10 12 13 12 16 6 4 ASTHMA PNDS GERD Chest 1999;116:279-284 1. Gastroesophageal reflux disease (21-41%) 2. Cough variant asthma (24-59%) 3. Postnasal drip syndrome (41-58%) Chest 1999;116:279-281 Percentage of Cases Presenting 1,2,3, and 4 Causative Factors İmmunocompetent patients Not exposed to enviromental irritants Chest radiograph is normal Not taking an ACE inhibitor Not a current smoker Asthma and/or GERD, PNDS responsible for 93.6% of the cases of chronic cough Harding SM .Chest 2003;123:659-660 Changing Trends in Diagnosis Percentage of Diagnosis (%) GERD ASTHMA RHINITIS Impaired esophageal clearance Functional defect in LES syphincter Hiatal hernia Delayed gastric emptying İncreased intra-abdominal pressure GERD ? Decreased saliva Heartburn (pyrosis) and regurgitation At least weekly symptoms extraesophageal reflux symptoms and/or esophageal mucosal damage / Katzka & DiMarino 1995 FLR Signs Edema and hyperemia of larynx Vocal cord erythema, polyps, granulomas, ulcers Hyperemia and lymphoid hyperplasia of posterior pharynx Interarytenoid changes Subglottic stenosis GERD-related cough incidence 5 - 55% May be the sole presenting symptom(1/3) Thorax 2003:58;1092-1095) (Chest 1997; 111: 1389-1402) Irwin RS. Chest 2006;129:80S-94S Association between cough and reflux is important Esophageal-tracheal-bronchial reflex Microaspiration Pathogenesis ARRD 1981;123:413-417 Arch Intern Med 1996;156:997 Chest 1993;104:1511-1517 El Hennawi, 2004 OHNS Nonacidic factors? Esophageal dismotility? . Mediator Release . Inflammation . Edema . Mucus . Smooth Muscle Microaspiration REFLUX Esophageal Vagal Afferents Bronchial Hyperreactivity Airway Vagal Afferents CNS Stein MR.Am J Med 2003 Chest 1997;111: 1389-1402 Airway Airway Vagal Efferents Esophagus Tracheobronchial Tree Stomach Oesophagus Pharyngeal pHmetry + - Not GERD Clinical GERD symptoms ? Nonacid, weakly acid reflux? Increase dose PPI + alginate İmproved Not improved Continue pHmetry under treatment Consider  Simultaneously dual probes 24 hours pHmonitoring and intraesophageal impedance Irwin RS.AJRCCM 165:1469-74,2002 McGarvey LPA.Thorax 59:342-346,2004 15 cm 17 cm 6 impedance channels 1 pH electrode + Adult Standard Model ZAN-S61C01E Multichannel intraluminal impedance-pH catheter Non acid reflux On going reflux of ‘non-acid’ material may be responsible for continuing symptoms while on acid-suppressing medications Therapy in Esophageal-pulmonary reflux Conservative and lifestyle measures Ampirical therapy: Acid suppression Proton pump inhibitors  PPI x 2 / 3 months Therapy failure  24 hour intraesophageal pHmetry ( pharyngeal pHmetry )  GERD (+) High dose PPI + H2 blocker agent Surgery(Fundoplication) Pulmonary and Crit Care Update 1994; Vol 9 Morice AH. ERJ 2004;24:481-492 Weeks of antireflux therapy Patients responded No No (%) 2 16 (41) 4 38 (86) 6 42 (95) 8 43 (99) 12 weeks 44 (100) Poe RH.Chest 2003;123:679-684 Cumulative Response to GERD Therapy Preop pH <4: %23.6 De Meester: 85 Postop pH <4: %2.4 De Meester: 9.9 1. Chronic cough for at least 2 months 2. Immunocompetent patients 3. Chest radiograph is normal 4. Not exposed to enviromental irritants nor a present smoker 5. Not taking an ACE inhibitor 6. Symptomatic asthma has been ruled out 7. Rhinosinus diseases has been ruled out: 8. ‘Silent sinusitis’ has been ruled out 9. Nonasthmatic eosinophilic bronchitis has been ruled out: BPT is negative Cough has not improved with asthma therapy First generation H1 antagonists has been used Eo 3% in induced sputum Cough has not improved with steroids Irwin RS. Chest 2006;129:80S-94S İrwin RS. AJRCCM Vol 165; 1469-1474, 2002 Clinical Profile That Chronic Cough İs Likely Due To ‘Silent GERD’ Postnasal Drip Syndrome (PNDS) Prevalence : 8 – 87% Pathogenesis : The sensation of drainage of secretions from the nose or paranasal sinuses into the pharynx Clinical Presentation: Dripping sensation Tickle in the throat Nasal congestion Mucus in oropharynx Cobblestone appearence of oropharynx ACCP consensus. CHEST 1998; 114: 133-181 ERS Task Force. ERS Journal ; 24: 553-566 Pathogenic Triad in Chronic Cough. CHEST 1999; 116: 279-284 Evaluation of chronic cough. UPTODATE 2005 Chest 2006;129:63S-71S In patient with chronic cough that is related to upper airway abnormalities Upper Airway Cough Syndrome UACS Treatment Antihistamines / decongestant combinations - “Older” sedating antihistamines more effective - Treatment effect should be observed in 1 week Additional / Alternative treatments : Ipratropium nasal spray : 2-7 days Nasal steroids (such as BDP, FP,BUD) : 2-3 days - 2 week 3 months prescribed Eosinophilic Eronchitis Airway obstruction Bronchial hyperreactivity NO YES YES NO Asthmatic Coughs Cough Variant Asthma Asthma Cough Variant Asthma Prevalence : 24 – 59% Clinical Diagnosis Gold standard  History - Episodic symptoms, Family history Reversibility testing PEF monitoring Bronchoprovocation test Differential Diagnosis: Decreased of cough with classical asthma therapy ACCP consensus. CHEST 1998; 114: 133-181 ERS Task Force. ERS Journal ; 24: 553-566 The Journal of Respiratory Disease; 25; 310-315 THORAX 59; 342-346 Middle age patients Smoking is unusual, occupational ? Prevalence of atopy similar population Good respond to inhaled steroids Gibson et al. Lancet 1989 Chest 2006;129:116S-121S Eosinophilic Bronchitis Isolated chronic cough,  productive of sputum Normal lung function without variable airflow limitation Airway hyperresponsiveness absent Eosinophilia in sputum and BAL Cough reflex to capsaicin increased Normal daily variability in peak expiratory flow (<20%) 1)Kim et al AJRCCM 2003; 2) Brightling et al AJRCCM 1999;160:406-10, 3) Joo Korean JIM 2002;17:31-7, 4) Carney et al AJRCCM 1997; 156:211-6, 5) Ma et al Zhongua 2003;26:362-5, 6) Ayik, Erdinc et al Respir Med 2003;97:695-701 Eosinophilic Bronchitis A Worldwide Disease Causes of chronic cough Ayık SÖ, Başoğlu ÖK, Erdinç M. Respir Med Vol. 97 (2003) 695-701 Causes of Isolated Chronic Cough Brightling CE et al. AJRCCM 1999 Asthmatic Cough Airway obstruction Reversibility PEF değişkenliği Increased NO all of them PEF monitoring Prevalence: 0-50% More agressive diagnosis and treatments UACS, GERD and postinfectious cough leads to lower incidence ‘unexplained’. Airway inflammation Mast cell, histamin, cysteinil LTs, PD2, PE2 Irwin RS,et al. Chest 2006;130:362-370 Chronic Unexplained (Idiopathic) Cough Important missed history (smoking,ACEI,enviromental,drugs,allergy) Failure to do correct diagnostic tests Failure to use ‘empiric’ treatment Failure to use effective therapy Unknown disease process Potential Reasons Chronic Unexplained (Idiopathic) Cough « Truly idiopathic cough is rare and misdiagnosis very common, especially if cough is provoked by sites outside the airways » Eur Respir J 24: 481-492 2004 Idiopathic cough % ? Studies in the 1980’s % patients 1990-1995 Idiopathic cough % ? % patients

Slide 38 -

CHRONIC COUGH MÜNEVVER ERDİNÇ Department of Chest Diseases Ege University Faculty of Medicine Differential Diagnosis And Treatment In Adults Acute Cough lasting less than 3 weeks Subacute Cough lasting 3 to 8 weeks Chronic Cough Lasting more than 8 weeks Morice AH.Eur Respir J 2004 :24:481-492 Fontana GA.Thorax 2003;58:1092-1095 Irwin RS.NEJM 343(23): 1715-1721,2000 Irwin RS. Chest 1998; 114(suppl1) :133S-181S Differantial Diagnosis of Chronic Cough in Adults PNDS Allergic rhinitis Chronic sinusitis GERD Cough variant asthma ACEI induced cough Pertusis Neurogenic Traumatic Postinfectious cough Phychogenic cough Chronic aspiration Zenker diverticulosis Foreign body Chronic bronchitis Bronchiectasis Lung cancer Subglottic stenosis Tracheomalasie Tracheoesophageal fistul Tuerculosis Sarcoidosis Congestive heart failure Simpson CB. Otolaryngology–Head Neck Surg 2006; 134: 693-700 In prospective studies in adults, chronic cough is most commonly due to 6 disorders : Upper Airway Cough Syndrome (UACS) Asthma GERD Chronic Bronchitis Bronchiectasis Non-asthmatic Eosinophilic Bronchitis Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S New Considerations Eosinophilic bronchitis Atopic cough Non acid(volume)/ weakly acid reflux Idiopathic (unexplained) öksürük Diagnosis and Management of Cough ACCP Evidence-Based CPG 2006 Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S Plevkova, et al. Respir Physiol Neurobiol 2004; 142: 225-235 Postnasal drip syndrome (PNDS) renamed upper airway cough syndrome (UACS) Upper airway afferents may reflexly enhance coughing Nonasthmatic eosinophilic bronchitis recognized as a common cause of chronic cough Idiopathic cough renamed unexplained cough The term acid reflux disease, unless it can be definitively shown to apply, replaced by reflux disease Update of current diagnostic and therapeutic approaches Common diseases, Uncommon diseases New algorithms for the management of cough in adults and children An empiric integrative approach is recommended 10 12 13 12 16 6 4 ASTHMA PNDS GERD Chest 1999;116:279-284 1. Gastroesophageal reflux disease (21-41%) 2. Cough variant asthma (24-59%) 3. Postnasal drip syndrome (41-58%) Chest 1999;116:279-281 Percentage of Cases Presenting 1,2,3, and 4 Causative Factors İmmunocompetent patients Not exposed to enviromental irritants Chest radiograph is normal Not taking an ACE inhibitor Not a current smoker Asthma and/or GERD, PNDS responsible for 93.6% of the cases of chronic cough Harding SM .Chest 2003;123:659-660 Changing Trends in Diagnosis Percentage of Diagnosis (%) GERD ASTHMA RHINITIS Impaired esophageal clearance Functional defect in LES syphincter Hiatal hernia Delayed gastric emptying İncreased intra-abdominal pressure GERD ? Decreased saliva Heartburn (pyrosis) and regurgitation At least weekly symptoms extraesophageal reflux symptoms and/or esophageal mucosal damage / Katzka & DiMarino 1995 FLR Signs Edema and hyperemia of larynx Vocal cord erythema, polyps, granulomas, ulcers Hyperemia and lymphoid hyperplasia of posterior pharynx Interarytenoid changes Subglottic stenosis GERD-related cough incidence 5 - 55% May be the sole presenting symptom(1/3) Thorax 2003:58;1092-1095) (Chest 1997; 111: 1389-1402) Irwin RS. Chest 2006;129:80S-94S Association between cough and reflux is important Esophageal-tracheal-bronchial reflex Microaspiration Pathogenesis ARRD 1981;123:413-417 Arch Intern Med 1996;156:997 Chest 1993;104:1511-1517 El Hennawi, 2004 OHNS Nonacidic factors? Esophageal dismotility? . Mediator Release . Inflammation . Edema . Mucus . Smooth Muscle Microaspiration REFLUX Esophageal Vagal Afferents Bronchial Hyperreactivity Airway Vagal Afferents CNS Stein MR.Am J Med 2003 Chest 1997;111: 1389-1402 Airway Airway Vagal Efferents Esophagus Tracheobronchial Tree Stomach Oesophagus Pharyngeal pHmetry + - Not GERD Clinical GERD symptoms ? Nonacid, weakly acid reflux? Increase dose PPI + alginate İmproved Not improved Continue pHmetry under treatment Consider  Simultaneously dual probes 24 hours pHmonitoring and intraesophageal impedance Irwin RS.AJRCCM 165:1469-74,2002 McGarvey LPA.Thorax 59:342-346,2004 15 cm 17 cm 6 impedance channels 1 pH electrode + Adult Standard Model ZAN-S61C01E Multichannel intraluminal impedance-pH catheter Non acid reflux On going reflux of ‘non-acid’ material may be responsible for continuing symptoms while on acid-suppressing medications Therapy in Esophageal-pulmonary reflux Conservative and lifestyle measures Ampirical therapy: Acid suppression Proton pump inhibitors  PPI x 2 / 3 months Therapy failure  24 hour intraesophageal pHmetry ( pharyngeal pHmetry )  GERD (+) High dose PPI + H2 blocker agent Surgery(Fundoplication) Pulmonary and Crit Care Update 1994; Vol 9 Morice AH. ERJ 2004;24:481-492 Weeks of antireflux therapy Patients responded No No (%) 2 16 (41) 4 38 (86) 6 42 (95) 8 43 (99) 12 weeks 44 (100) Poe RH.Chest 2003;123:679-684 Cumulative Response to GERD Therapy Preop pH <4: %23.6 De Meester: 85 Postop pH <4: %2.4 De Meester: 9.9 1. Chronic cough for at least 2 months 2. Immunocompetent patients 3. Chest radiograph is normal 4. Not exposed to enviromental irritants nor a present smoker 5. Not taking an ACE inhibitor 6. Symptomatic asthma has been ruled out 7. Rhinosinus diseases has been ruled out: 8. ‘Silent sinusitis’ has been ruled out 9. Nonasthmatic eosinophilic bronchitis has been ruled out: BPT is negative Cough has not improved with asthma therapy First generation H1 antagonists has been used Eo 3% in induced sputum Cough has not improved with steroids Irwin RS. Chest 2006;129:80S-94S İrwin RS. AJRCCM Vol 165; 1469-1474, 2002 Clinical Profile That Chronic Cough İs Likely Due To ‘Silent GERD’ Postnasal Drip Syndrome (PNDS) Prevalence : 8 – 87% Pathogenesis : The sensation of drainage of secretions from the nose or paranasal sinuses into the pharynx Clinical Presentation: Dripping sensation Tickle in the throat Nasal congestion Mucus in oropharynx Cobblestone appearence of oropharynx ACCP consensus. CHEST 1998; 114: 133-181 ERS Task Force. ERS Journal ; 24: 553-566 Pathogenic Triad in Chronic Cough. CHEST 1999; 116: 279-284 Evaluation of chronic cough. UPTODATE 2005 Chest 2006;129:63S-71S In patient with chronic cough that is related to upper airway abnormalities Upper Airway Cough Syndrome UACS Treatment Antihistamines / decongestant combinations - “Older” sedating antihistamines more effective - Treatment effect should be observed in 1 week Additional / Alternative treatments : Ipratropium nasal spray : 2-7 days Nasal steroids (such as BDP, FP,BUD) : 2-3 days - 2 week 3 months prescribed Eosinophilic Eronchitis Airway obstruction Bronchial hyperreactivity NO YES YES NO Asthmatic Coughs Cough Variant Asthma Asthma Cough Variant Asthma Prevalence : 24 – 59% Clinical Diagnosis Gold standard  History - Episodic symptoms, Family history Reversibility testing PEF monitoring Bronchoprovocation test Differential Diagnosis: Decreased of cough with classical asthma therapy ACCP consensus. CHEST 1998; 114: 133-181 ERS Task Force. ERS Journal ; 24: 553-566 The Journal of Respiratory Disease; 25; 310-315 THORAX 59; 342-346 Middle age patients Smoking is unusual, occupational ? Prevalence of atopy similar population Good respond to inhaled steroids Gibson et al. Lancet 1989 Chest 2006;129:116S-121S Eosinophilic Bronchitis Isolated chronic cough,  productive of sputum Normal lung function without variable airflow limitation Airway hyperresponsiveness absent Eosinophilia in sputum and BAL Cough reflex to capsaicin increased Normal daily variability in peak expiratory flow (<20%) 1)Kim et al AJRCCM 2003; 2) Brightling et al AJRCCM 1999;160:406-10, 3) Joo Korean JIM 2002;17:31-7, 4) Carney et al AJRCCM 1997; 156:211-6, 5) Ma et al Zhongua 2003;26:362-5, 6) Ayik, Erdinc et al Respir Med 2003;97:695-701 Eosinophilic Bronchitis A Worldwide Disease Causes of chronic cough Ayık SÖ, Başoğlu ÖK, Erdinç M. Respir Med Vol. 97 (2003) 695-701 Causes of Isolated Chronic Cough Brightling CE et al. AJRCCM 1999 Asthmatic Cough Airway obstruction Reversibility PEF değişkenliği Increased NO all of them PEF monitoring Prevalence: 0-50% More agressive diagnosis and treatments UACS, GERD and postinfectious cough leads to lower incidence ‘unexplained’. Airway inflammation Mast cell, histamin, cysteinil LTs, PD2, PE2 Irwin RS,et al. Chest 2006;130:362-370 Chronic Unexplained (Idiopathic) Cough Important missed history (smoking,ACEI,enviromental,drugs,allergy) Failure to do correct diagnostic tests Failure to use ‘empiric’ treatment Failure to use effective therapy Unknown disease process Potential Reasons Chronic Unexplained (Idiopathic) Cough « Truly idiopathic cough is rare and misdiagnosis very common, especially if cough is provoked by sites outside the airways » Eur Respir J 24: 481-492 2004 Idiopathic cough % ? Studies in the 1980’s % patients 1990-1995 Idiopathic cough % ? % patients Idiopathic cough % ? 1996-1999 % patients

Slide 39 -

CHRONIC COUGH MÜNEVVER ERDİNÇ Department of Chest Diseases Ege University Faculty of Medicine Differential Diagnosis And Treatment In Adults Acute Cough lasting less than 3 weeks Subacute Cough lasting 3 to 8 weeks Chronic Cough Lasting more than 8 weeks Morice AH.Eur Respir J 2004 :24:481-492 Fontana GA.Thorax 2003;58:1092-1095 Irwin RS.NEJM 343(23): 1715-1721,2000 Irwin RS. Chest 1998; 114(suppl1) :133S-181S Differantial Diagnosis of Chronic Cough in Adults PNDS Allergic rhinitis Chronic sinusitis GERD Cough variant asthma ACEI induced cough Pertusis Neurogenic Traumatic Postinfectious cough Phychogenic cough Chronic aspiration Zenker diverticulosis Foreign body Chronic bronchitis Bronchiectasis Lung cancer Subglottic stenosis Tracheomalasie Tracheoesophageal fistul Tuerculosis Sarcoidosis Congestive heart failure Simpson CB. Otolaryngology–Head Neck Surg 2006; 134: 693-700 In prospective studies in adults, chronic cough is most commonly due to 6 disorders : Upper Airway Cough Syndrome (UACS) Asthma GERD Chronic Bronchitis Bronchiectasis Non-asthmatic Eosinophilic Bronchitis Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S New Considerations Eosinophilic bronchitis Atopic cough Non acid(volume)/ weakly acid reflux Idiopathic (unexplained) öksürük Diagnosis and Management of Cough ACCP Evidence-Based CPG 2006 Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S Plevkova, et al. Respir Physiol Neurobiol 2004; 142: 225-235 Postnasal drip syndrome (PNDS) renamed upper airway cough syndrome (UACS) Upper airway afferents may reflexly enhance coughing Nonasthmatic eosinophilic bronchitis recognized as a common cause of chronic cough Idiopathic cough renamed unexplained cough The term acid reflux disease, unless it can be definitively shown to apply, replaced by reflux disease Update of current diagnostic and therapeutic approaches Common diseases, Uncommon diseases New algorithms for the management of cough in adults and children An empiric integrative approach is recommended 10 12 13 12 16 6 4 ASTHMA PNDS GERD Chest 1999;116:279-284 1. Gastroesophageal reflux disease (21-41%) 2. Cough variant asthma (24-59%) 3. Postnasal drip syndrome (41-58%) Chest 1999;116:279-281 Percentage of Cases Presenting 1,2,3, and 4 Causative Factors İmmunocompetent patients Not exposed to enviromental irritants Chest radiograph is normal Not taking an ACE inhibitor Not a current smoker Asthma and/or GERD, PNDS responsible for 93.6% of the cases of chronic cough Harding SM .Chest 2003;123:659-660 Changing Trends in Diagnosis Percentage of Diagnosis (%) GERD ASTHMA RHINITIS Impaired esophageal clearance Functional defect in LES syphincter Hiatal hernia Delayed gastric emptying İncreased intra-abdominal pressure GERD ? Decreased saliva Heartburn (pyrosis) and regurgitation At least weekly symptoms extraesophageal reflux symptoms and/or esophageal mucosal damage / Katzka & DiMarino 1995 FLR Signs Edema and hyperemia of larynx Vocal cord erythema, polyps, granulomas, ulcers Hyperemia and lymphoid hyperplasia of posterior pharynx Interarytenoid changes Subglottic stenosis GERD-related cough incidence 5 - 55% May be the sole presenting symptom(1/3) Thorax 2003:58;1092-1095) (Chest 1997; 111: 1389-1402) Irwin RS. Chest 2006;129:80S-94S Association between cough and reflux is important Esophageal-tracheal-bronchial reflex Microaspiration Pathogenesis ARRD 1981;123:413-417 Arch Intern Med 1996;156:997 Chest 1993;104:1511-1517 El Hennawi, 2004 OHNS Nonacidic factors? Esophageal dismotility? . Mediator Release . Inflammation . Edema . Mucus . Smooth Muscle Microaspiration REFLUX Esophageal Vagal Afferents Bronchial Hyperreactivity Airway Vagal Afferents CNS Stein MR.Am J Med 2003 Chest 1997;111: 1389-1402 Airway Airway Vagal Efferents Esophagus Tracheobronchial Tree Stomach Oesophagus Pharyngeal pHmetry + - Not GERD Clinical GERD symptoms ? Nonacid, weakly acid reflux? Increase dose PPI + alginate İmproved Not improved Continue pHmetry under treatment Consider  Simultaneously dual probes 24 hours pHmonitoring and intraesophageal impedance Irwin RS.AJRCCM 165:1469-74,2002 McGarvey LPA.Thorax 59:342-346,2004 15 cm 17 cm 6 impedance channels 1 pH electrode + Adult Standard Model ZAN-S61C01E Multichannel intraluminal impedance-pH catheter Non acid reflux On going reflux of ‘non-acid’ material may be responsible for continuing symptoms while on acid-suppressing medications Therapy in Esophageal-pulmonary reflux Conservative and lifestyle measures Ampirical therapy: Acid suppression Proton pump inhibitors  PPI x 2 / 3 months Therapy failure  24 hour intraesophageal pHmetry ( pharyngeal pHmetry )  GERD (+) High dose PPI + H2 blocker agent Surgery(Fundoplication) Pulmonary and Crit Care Update 1994; Vol 9 Morice AH. ERJ 2004;24:481-492 Weeks of antireflux therapy Patients responded No No (%) 2 16 (41) 4 38 (86) 6 42 (95) 8 43 (99) 12 weeks 44 (100) Poe RH.Chest 2003;123:679-684 Cumulative Response to GERD Therapy Preop pH <4: %23.6 De Meester: 85 Postop pH <4: %2.4 De Meester: 9.9 1. Chronic cough for at least 2 months 2. Immunocompetent patients 3. Chest radiograph is normal 4. Not exposed to enviromental irritants nor a present smoker 5. Not taking an ACE inhibitor 6. Symptomatic asthma has been ruled out 7. Rhinosinus diseases has been ruled out: 8. ‘Silent sinusitis’ has been ruled out 9. Nonasthmatic eosinophilic bronchitis has been ruled out: BPT is negative Cough has not improved with asthma therapy First generation H1 antagonists has been used Eo 3% in induced sputum Cough has not improved with steroids Irwin RS. Chest 2006;129:80S-94S İrwin RS. AJRCCM Vol 165; 1469-1474, 2002 Clinical Profile That Chronic Cough İs Likely Due To ‘Silent GERD’ Postnasal Drip Syndrome (PNDS) Prevalence : 8 – 87% Pathogenesis : The sensation of drainage of secretions from the nose or paranasal sinuses into the pharynx Clinical Presentation: Dripping sensation Tickle in the throat Nasal congestion Mucus in oropharynx Cobblestone appearence of oropharynx ACCP consensus. CHEST 1998; 114: 133-181 ERS Task Force. ERS Journal ; 24: 553-566 Pathogenic Triad in Chronic Cough. CHEST 1999; 116: 279-284 Evaluation of chronic cough. UPTODATE 2005 Chest 2006;129:63S-71S In patient with chronic cough that is related to upper airway abnormalities Upper Airway Cough Syndrome UACS Treatment Antihistamines / decongestant combinations - “Older” sedating antihistamines more effective - Treatment effect should be observed in 1 week Additional / Alternative treatments : Ipratropium nasal spray : 2-7 days Nasal steroids (such as BDP, FP,BUD) : 2-3 days - 2 week 3 months prescribed Eosinophilic Eronchitis Airway obstruction Bronchial hyperreactivity NO YES YES NO Asthmatic Coughs Cough Variant Asthma Asthma Cough Variant Asthma Prevalence : 24 – 59% Clinical Diagnosis Gold standard  History - Episodic symptoms, Family history Reversibility testing PEF monitoring Bronchoprovocation test Differential Diagnosis: Decreased of cough with classical asthma therapy ACCP consensus. CHEST 1998; 114: 133-181 ERS Task Force. ERS Journal ; 24: 553-566 The Journal of Respiratory Disease; 25; 310-315 THORAX 59; 342-346 Middle age patients Smoking is unusual, occupational ? Prevalence of atopy similar population Good respond to inhaled steroids Gibson et al. Lancet 1989 Chest 2006;129:116S-121S Eosinophilic Bronchitis Isolated chronic cough,  productive of sputum Normal lung function without variable airflow limitation Airway hyperresponsiveness absent Eosinophilia in sputum and BAL Cough reflex to capsaicin increased Normal daily variability in peak expiratory flow (<20%) 1)Kim et al AJRCCM 2003; 2) Brightling et al AJRCCM 1999;160:406-10, 3) Joo Korean JIM 2002;17:31-7, 4) Carney et al AJRCCM 1997; 156:211-6, 5) Ma et al Zhongua 2003;26:362-5, 6) Ayik, Erdinc et al Respir Med 2003;97:695-701 Eosinophilic Bronchitis A Worldwide Disease Causes of chronic cough Ayık SÖ, Başoğlu ÖK, Erdinç M. Respir Med Vol. 97 (2003) 695-701 Causes of Isolated Chronic Cough Brightling CE et al. AJRCCM 1999 Asthmatic Cough Airway obstruction Reversibility PEF değişkenliği Increased NO all of them PEF monitoring Prevalence: 0-50% More agressive diagnosis and treatments UACS, GERD and postinfectious cough leads to lower incidence ‘unexplained’. Airway inflammation Mast cell, histamin, cysteinil LTs, PD2, PE2 Irwin RS,et al. Chest 2006;130:362-370 Chronic Unexplained (Idiopathic) Cough Important missed history (smoking,ACEI,enviromental,drugs,allergy) Failure to do correct diagnostic tests Failure to use ‘empiric’ treatment Failure to use effective therapy Unknown disease process Potential Reasons Chronic Unexplained (Idiopathic) Cough « Truly idiopathic cough is rare and misdiagnosis very common, especially if cough is provoked by sites outside the airways » Eur Respir J 24: 481-492 2004 Idiopathic cough % ? Studies in the 1980’s % patients 1990-1995 Idiopathic cough % ? % patients Idiopathic cough % ? 1996-1999 % patients Idiopathic cough % ? 2000  % patients

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CHRONIC COUGH MÜNEVVER ERDİNÇ Department of Chest Diseases Ege University Faculty of Medicine Differential Diagnosis And Treatment In Adults Acute Cough lasting less than 3 weeks Subacute Cough lasting 3 to 8 weeks Chronic Cough Lasting more than 8 weeks Morice AH.Eur Respir J 2004 :24:481-492 Fontana GA.Thorax 2003;58:1092-1095 Irwin RS.NEJM 343(23): 1715-1721,2000 Irwin RS. Chest 1998; 114(suppl1) :133S-181S Differantial Diagnosis of Chronic Cough in Adults PNDS Allergic rhinitis Chronic sinusitis GERD Cough variant asthma ACEI induced cough Pertusis Neurogenic Traumatic Postinfectious cough Phychogenic cough Chronic aspiration Zenker diverticulosis Foreign body Chronic bronchitis Bronchiectasis Lung cancer Subglottic stenosis Tracheomalasie Tracheoesophageal fistul Tuerculosis Sarcoidosis Congestive heart failure Simpson CB. Otolaryngology–Head Neck Surg 2006; 134: 693-700 In prospective studies in adults, chronic cough is most commonly due to 6 disorders : Upper Airway Cough Syndrome (UACS) Asthma GERD Chronic Bronchitis Bronchiectasis Non-asthmatic Eosinophilic Bronchitis Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S New Considerations Eosinophilic bronchitis Atopic cough Non acid(volume)/ weakly acid reflux Idiopathic (unexplained) öksürük Diagnosis and Management of Cough ACCP Evidence-Based CPG 2006 Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S Plevkova, et al. Respir Physiol Neurobiol 2004; 142: 225-235 Postnasal drip syndrome (PNDS) renamed upper airway cough syndrome (UACS) Upper airway afferents may reflexly enhance coughing Nonasthmatic eosinophilic bronchitis recognized as a common cause of chronic cough Idiopathic cough renamed unexplained cough The term acid reflux disease, unless it can be definitively shown to apply, replaced by reflux disease Update of current diagnostic and therapeutic approaches Common diseases, Uncommon diseases New algorithms for the management of cough in adults and children An empiric integrative approach is recommended 10 12 13 12 16 6 4 ASTHMA PNDS GERD Chest 1999;116:279-284 1. Gastroesophageal reflux disease (21-41%) 2. Cough variant asthma (24-59%) 3. Postnasal drip syndrome (41-58%) Chest 1999;116:279-281 Percentage of Cases Presenting 1,2,3, and 4 Causative Factors İmmunocompetent patients Not exposed to enviromental irritants Chest radiograph is normal Not taking an ACE inhibitor Not a current smoker Asthma and/or GERD, PNDS responsible for 93.6% of the cases of chronic cough Harding SM .Chest 2003;123:659-660 Changing Trends in Diagnosis Percentage of Diagnosis (%) GERD ASTHMA RHINITIS Impaired esophageal clearance Functional defect in LES syphincter Hiatal hernia Delayed gastric emptying İncreased intra-abdominal pressure GERD ? Decreased saliva Heartburn (pyrosis) and regurgitation At least weekly symptoms extraesophageal reflux symptoms and/or esophageal mucosal damage / Katzka & DiMarino 1995 FLR Signs Edema and hyperemia of larynx Vocal cord erythema, polyps, granulomas, ulcers Hyperemia and lymphoid hyperplasia of posterior pharynx Interarytenoid changes Subglottic stenosis GERD-related cough incidence 5 - 55% May be the sole presenting symptom(1/3) Thorax 2003:58;1092-1095) (Chest 1997; 111: 1389-1402) Irwin RS. Chest 2006;129:80S-94S Association between cough and reflux is important Esophageal-tracheal-bronchial reflex Microaspiration Pathogenesis ARRD 1981;123:413-417 Arch Intern Med 1996;156:997 Chest 1993;104:1511-1517 El Hennawi, 2004 OHNS Nonacidic factors? Esophageal dismotility? . Mediator Release . Inflammation . Edema . Mucus . Smooth Muscle Microaspiration REFLUX Esophageal Vagal Afferents Bronchial Hyperreactivity Airway Vagal Afferents CNS Stein MR.Am J Med 2003 Chest 1997;111: 1389-1402 Airway Airway Vagal Efferents Esophagus Tracheobronchial Tree Stomach Oesophagus Pharyngeal pHmetry + - Not GERD Clinical GERD symptoms ? Nonacid, weakly acid reflux? Increase dose PPI + alginate İmproved Not improved Continue pHmetry under treatment Consider  Simultaneously dual probes 24 hours pHmonitoring and intraesophageal impedance Irwin RS.AJRCCM 165:1469-74,2002 McGarvey LPA.Thorax 59:342-346,2004 15 cm 17 cm 6 impedance channels 1 pH electrode + Adult Standard Model ZAN-S61C01E Multichannel intraluminal impedance-pH catheter Non acid reflux On going reflux of ‘non-acid’ material may be responsible for continuing symptoms while on acid-suppressing medications Therapy in Esophageal-pulmonary reflux Conservative and lifestyle measures Ampirical therapy: Acid suppression Proton pump inhibitors  PPI x 2 / 3 months Therapy failure  24 hour intraesophageal pHmetry ( pharyngeal pHmetry )  GERD (+) High dose PPI + H2 blocker agent Surgery(Fundoplication) Pulmonary and Crit Care Update 1994; Vol 9 Morice AH. ERJ 2004;24:481-492 Weeks of antireflux therapy Patients responded No No (%) 2 16 (41) 4 38 (86) 6 42 (95) 8 43 (99) 12 weeks 44 (100) Poe RH.Chest 2003;123:679-684 Cumulative Response to GERD Therapy Preop pH <4: %23.6 De Meester: 85 Postop pH <4: %2.4 De Meester: 9.9 1. Chronic cough for at least 2 months 2. Immunocompetent patients 3. Chest radiograph is normal 4. Not exposed to enviromental irritants nor a present smoker 5. Not taking an ACE inhibitor 6. Symptomatic asthma has been ruled out 7. Rhinosinus diseases has been ruled out: 8. ‘Silent sinusitis’ has been ruled out 9. Nonasthmatic eosinophilic bronchitis has been ruled out: BPT is negative Cough has not improved with asthma therapy First generation H1 antagonists has been used Eo 3% in induced sputum Cough has not improved with steroids Irwin RS. Chest 2006;129:80S-94S İrwin RS. AJRCCM Vol 165; 1469-1474, 2002 Clinical Profile That Chronic Cough İs Likely Due To ‘Silent GERD’ Postnasal Drip Syndrome (PNDS) Prevalence : 8 – 87% Pathogenesis : The sensation of drainage of secretions from the nose or paranasal sinuses into the pharynx Clinical Presentation: Dripping sensation Tickle in the throat Nasal congestion Mucus in oropharynx Cobblestone appearence of oropharynx ACCP consensus. CHEST 1998; 114: 133-181 ERS Task Force. ERS Journal ; 24: 553-566 Pathogenic Triad in Chronic Cough. CHEST 1999; 116: 279-284 Evaluation of chronic cough. UPTODATE 2005 Chest 2006;129:63S-71S In patient with chronic cough that is related to upper airway abnormalities Upper Airway Cough Syndrome UACS Treatment Antihistamines / decongestant combinations - “Older” sedating antihistamines more effective - Treatment effect should be observed in 1 week Additional / Alternative treatments : Ipratropium nasal spray : 2-7 days Nasal steroids (such as BDP, FP,BUD) : 2-3 days - 2 week 3 months prescribed Eosinophilic Eronchitis Airway obstruction Bronchial hyperreactivity NO YES YES NO Asthmatic Coughs Cough Variant Asthma Asthma Cough Variant Asthma Prevalence : 24 – 59% Clinical Diagnosis Gold standard  History - Episodic symptoms, Family history Reversibility testing PEF monitoring Bronchoprovocation test Differential Diagnosis: Decreased of cough with classical asthma therapy ACCP consensus. CHEST 1998; 114: 133-181 ERS Task Force. ERS Journal ; 24: 553-566 The Journal of Respiratory Disease; 25; 310-315 THORAX 59; 342-346 Middle age patients Smoking is unusual, occupational ? Prevalence of atopy similar population Good respond to inhaled steroids Gibson et al. Lancet 1989 Chest 2006;129:116S-121S Eosinophilic Bronchitis Isolated chronic cough,  productive of sputum Normal lung function without variable airflow limitation Airway hyperresponsiveness absent Eosinophilia in sputum and BAL Cough reflex to capsaicin increased Normal daily variability in peak expiratory flow (<20%) 1)Kim et al AJRCCM 2003; 2) Brightling et al AJRCCM 1999;160:406-10, 3) Joo Korean JIM 2002;17:31-7, 4) Carney et al AJRCCM 1997; 156:211-6, 5) Ma et al Zhongua 2003;26:362-5, 6) Ayik, Erdinc et al Respir Med 2003;97:695-701 Eosinophilic Bronchitis A Worldwide Disease Causes of chronic cough Ayık SÖ, Başoğlu ÖK, Erdinç M. Respir Med Vol. 97 (2003) 695-701 Causes of Isolated Chronic Cough Brightling CE et al. AJRCCM 1999 Asthmatic Cough Airway obstruction Reversibility PEF değişkenliği Increased NO all of them PEF monitoring Prevalence: 0-50% More agressive diagnosis and treatments UACS, GERD and postinfectious cough leads to lower incidence ‘unexplained’. Airway inflammation Mast cell, histamin, cysteinil LTs, PD2, PE2 Irwin RS,et al. Chest 2006;130:362-370 Chronic Unexplained (Idiopathic) Cough Important missed history (smoking,ACEI,enviromental,drugs,allergy) Failure to do correct diagnostic tests Failure to use ‘empiric’ treatment Failure to use effective therapy Unknown disease process Potential Reasons Chronic Unexplained (Idiopathic) Cough « Truly idiopathic cough is rare and misdiagnosis very common, especially if cough is provoked by sites outside the airways » Eur Respir J 24: 481-492 2004 Idiopathic cough % ? Studies in the 1980’s % patients 1990-1995 Idiopathic cough % ? % patients Idiopathic cough % ? 1996-1999 % patients Idiopathic cough % ? 2000  % patients Haque et al Chest 2005;127:1710-1713 Chronic Idiopathic Cough

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CHRONIC COUGH MÜNEVVER ERDİNÇ Department of Chest Diseases Ege University Faculty of Medicine Differential Diagnosis And Treatment In Adults Acute Cough lasting less than 3 weeks Subacute Cough lasting 3 to 8 weeks Chronic Cough Lasting more than 8 weeks Morice AH.Eur Respir J 2004 :24:481-492 Fontana GA.Thorax 2003;58:1092-1095 Irwin RS.NEJM 343(23): 1715-1721,2000 Irwin RS. Chest 1998; 114(suppl1) :133S-181S Differantial Diagnosis of Chronic Cough in Adults PNDS Allergic rhinitis Chronic sinusitis GERD Cough variant asthma ACEI induced cough Pertusis Neurogenic Traumatic Postinfectious cough Phychogenic cough Chronic aspiration Zenker diverticulosis Foreign body Chronic bronchitis Bronchiectasis Lung cancer Subglottic stenosis Tracheomalasie Tracheoesophageal fistul Tuerculosis Sarcoidosis Congestive heart failure Simpson CB. Otolaryngology–Head Neck Surg 2006; 134: 693-700 In prospective studies in adults, chronic cough is most commonly due to 6 disorders : Upper Airway Cough Syndrome (UACS) Asthma GERD Chronic Bronchitis Bronchiectasis Non-asthmatic Eosinophilic Bronchitis Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S New Considerations Eosinophilic bronchitis Atopic cough Non acid(volume)/ weakly acid reflux Idiopathic (unexplained) öksürük Diagnosis and Management of Cough ACCP Evidence-Based CPG 2006 Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S Plevkova, et al. Respir Physiol Neurobiol 2004; 142: 225-235 Postnasal drip syndrome (PNDS) renamed upper airway cough syndrome (UACS) Upper airway afferents may reflexly enhance coughing Nonasthmatic eosinophilic bronchitis recognized as a common cause of chronic cough Idiopathic cough renamed unexplained cough The term acid reflux disease, unless it can be definitively shown to apply, replaced by reflux disease Update of current diagnostic and therapeutic approaches Common diseases, Uncommon diseases New algorithms for the management of cough in adults and children An empiric integrative approach is recommended 10 12 13 12 16 6 4 ASTHMA PNDS GERD Chest 1999;116:279-284 1. Gastroesophageal reflux disease (21-41%) 2. Cough variant asthma (24-59%) 3. Postnasal drip syndrome (41-58%) Chest 1999;116:279-281 Percentage of Cases Presenting 1,2,3, and 4 Causative Factors İmmunocompetent patients Not exposed to enviromental irritants Chest radiograph is normal Not taking an ACE inhibitor Not a current smoker Asthma and/or GERD, PNDS responsible for 93.6% of the cases of chronic cough Harding SM .Chest 2003;123:659-660 Changing Trends in Diagnosis Percentage of Diagnosis (%) GERD ASTHMA RHINITIS Impaired esophageal clearance Functional defect in LES syphincter Hiatal hernia Delayed gastric emptying İncreased intra-abdominal pressure GERD ? Decreased saliva Heartburn (pyrosis) and regurgitation At least weekly symptoms extraesophageal reflux symptoms and/or esophageal mucosal damage / Katzka & DiMarino 1995 FLR Signs Edema and hyperemia of larynx Vocal cord erythema, polyps, granulomas, ulcers Hyperemia and lymphoid hyperplasia of posterior pharynx Interarytenoid changes Subglottic stenosis GERD-related cough incidence 5 - 55% May be the sole presenting symptom(1/3) Thorax 2003:58;1092-1095) (Chest 1997; 111: 1389-1402) Irwin RS. Chest 2006;129:80S-94S Association between cough and reflux is important Esophageal-tracheal-bronchial reflex Microaspiration Pathogenesis ARRD 1981;123:413-417 Arch Intern Med 1996;156:997 Chest 1993;104:1511-1517 El Hennawi, 2004 OHNS Nonacidic factors? Esophageal dismotility? . Mediator Release . Inflammation . Edema . Mucus . Smooth Muscle Microaspiration REFLUX Esophageal Vagal Afferents Bronchial Hyperreactivity Airway Vagal Afferents CNS Stein MR.Am J Med 2003 Chest 1997;111: 1389-1402 Airway Airway Vagal Efferents Esophagus Tracheobronchial Tree Stomach Oesophagus Pharyngeal pHmetry + - Not GERD Clinical GERD symptoms ? Nonacid, weakly acid reflux? Increase dose PPI + alginate İmproved Not improved Continue pHmetry under treatment Consider  Simultaneously dual probes 24 hours pHmonitoring and intraesophageal impedance Irwin RS.AJRCCM 165:1469-74,2002 McGarvey LPA.Thorax 59:342-346,2004 15 cm 17 cm 6 impedance channels 1 pH electrode + Adult Standard Model ZAN-S61C01E Multichannel intraluminal impedance-pH catheter Non acid reflux On going reflux of ‘non-acid’ material may be responsible for continuing symptoms while on acid-suppressing medications Therapy in Esophageal-pulmonary reflux Conservative and lifestyle measures Ampirical therapy: Acid suppression Proton pump inhibitors  PPI x 2 / 3 months Therapy failure  24 hour intraesophageal pHmetry ( pharyngeal pHmetry )  GERD (+) High dose PPI + H2 blocker agent Surgery(Fundoplication) Pulmonary and Crit Care Update 1994; Vol 9 Morice AH. ERJ 2004;24:481-492 Weeks of antireflux therapy Patients responded No No (%) 2 16 (41) 4 38 (86) 6 42 (95) 8 43 (99) 12 weeks 44 (100) Poe RH.Chest 2003;123:679-684 Cumulative Response to GERD Therapy Preop pH <4: %23.6 De Meester: 85 Postop pH <4: %2.4 De Meester: 9.9 1. Chronic cough for at least 2 months 2. Immunocompetent patients 3. Chest radiograph is normal 4. Not exposed to enviromental irritants nor a present smoker 5. Not taking an ACE inhibitor 6. Symptomatic asthma has been ruled out 7. Rhinosinus diseases has been ruled out: 8. ‘Silent sinusitis’ has been ruled out 9. Nonasthmatic eosinophilic bronchitis has been ruled out: BPT is negative Cough has not improved with asthma therapy First generation H1 antagonists has been used Eo 3% in induced sputum Cough has not improved with steroids Irwin RS. Chest 2006;129:80S-94S İrwin RS. AJRCCM Vol 165; 1469-1474, 2002 Clinical Profile That Chronic Cough İs Likely Due To ‘Silent GERD’ Postnasal Drip Syndrome (PNDS) Prevalence : 8 – 87% Pathogenesis : The sensation of drainage of secretions from the nose or paranasal sinuses into the pharynx Clinical Presentation: Dripping sensation Tickle in the throat Nasal congestion Mucus in oropharynx Cobblestone appearence of oropharynx ACCP consensus. CHEST 1998; 114: 133-181 ERS Task Force. ERS Journal ; 24: 553-566 Pathogenic Triad in Chronic Cough. CHEST 1999; 116: 279-284 Evaluation of chronic cough. UPTODATE 2005 Chest 2006;129:63S-71S In patient with chronic cough that is related to upper airway abnormalities Upper Airway Cough Syndrome UACS Treatment Antihistamines / decongestant combinations - “Older” sedating antihistamines more effective - Treatment effect should be observed in 1 week Additional / Alternative treatments : Ipratropium nasal spray : 2-7 days Nasal steroids (such as BDP, FP,BUD) : 2-3 days - 2 week 3 months prescribed Eosinophilic Eronchitis Airway obstruction Bronchial hyperreactivity NO YES YES NO Asthmatic Coughs Cough Variant Asthma Asthma Cough Variant Asthma Prevalence : 24 – 59% Clinical Diagnosis Gold standard  History - Episodic symptoms, Family history Reversibility testing PEF monitoring Bronchoprovocation test Differential Diagnosis: Decreased of cough with classical asthma therapy ACCP consensus. CHEST 1998; 114: 133-181 ERS Task Force. ERS Journal ; 24: 553-566 The Journal of Respiratory Disease; 25; 310-315 THORAX 59; 342-346 Middle age patients Smoking is unusual, occupational ? Prevalence of atopy similar population Good respond to inhaled steroids Gibson et al. Lancet 1989 Chest 2006;129:116S-121S Eosinophilic Bronchitis Isolated chronic cough,  productive of sputum Normal lung function without variable airflow limitation Airway hyperresponsiveness absent Eosinophilia in sputum and BAL Cough reflex to capsaicin increased Normal daily variability in peak expiratory flow (<20%) 1)Kim et al AJRCCM 2003; 2) Brightling et al AJRCCM 1999;160:406-10, 3) Joo Korean JIM 2002;17:31-7, 4) Carney et al AJRCCM 1997; 156:211-6, 5) Ma et al Zhongua 2003;26:362-5, 6) Ayik, Erdinc et al Respir Med 2003;97:695-701 Eosinophilic Bronchitis A Worldwide Disease Causes of chronic cough Ayık SÖ, Başoğlu ÖK, Erdinç M. Respir Med Vol. 97 (2003) 695-701 Causes of Isolated Chronic Cough Brightling CE et al. AJRCCM 1999 Asthmatic Cough Airway obstruction Reversibility PEF değişkenliği Increased NO all of them PEF monitoring Prevalence: 0-50% More agressive diagnosis and treatments UACS, GERD and postinfectious cough leads to lower incidence ‘unexplained’. Airway inflammation Mast cell, histamin, cysteinil LTs, PD2, PE2 Irwin RS,et al. Chest 2006;130:362-370 Chronic Unexplained (Idiopathic) Cough Important missed history (smoking,ACEI,enviromental,drugs,allergy) Failure to do correct diagnostic tests Failure to use ‘empiric’ treatment Failure to use effective therapy Unknown disease process Potential Reasons Chronic Unexplained (Idiopathic) Cough « Truly idiopathic cough is rare and misdiagnosis very common, especially if cough is provoked by sites outside the airways » Eur Respir J 24: 481-492 2004 Idiopathic cough % ? Studies in the 1980’s % patients 1990-1995 Idiopathic cough % ? % patients Idiopathic cough % ? 1996-1999 % patients Idiopathic cough % ? 2000  % patients Haque et al Chest 2005;127:1710-1713 Chronic Idiopathic Cough Predominantly female and associated with BAL lymphocytosis Raising the possibility of a link between autoimmune diseases Surinder S. Et al. Respir Med 98:242-246;2004 Chronic Idiopathic Cough *OR: 8.8

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CHRONIC COUGH MÜNEVVER ERDİNÇ Department of Chest Diseases Ege University Faculty of Medicine Differential Diagnosis And Treatment In Adults Acute Cough lasting less than 3 weeks Subacute Cough lasting 3 to 8 weeks Chronic Cough Lasting more than 8 weeks Morice AH.Eur Respir J 2004 :24:481-492 Fontana GA.Thorax 2003;58:1092-1095 Irwin RS.NEJM 343(23): 1715-1721,2000 Irwin RS. Chest 1998; 114(suppl1) :133S-181S Differantial Diagnosis of Chronic Cough in Adults PNDS Allergic rhinitis Chronic sinusitis GERD Cough variant asthma ACEI induced cough Pertusis Neurogenic Traumatic Postinfectious cough Phychogenic cough Chronic aspiration Zenker diverticulosis Foreign body Chronic bronchitis Bronchiectasis Lung cancer Subglottic stenosis Tracheomalasie Tracheoesophageal fistul Tuerculosis Sarcoidosis Congestive heart failure Simpson CB. Otolaryngology–Head Neck Surg 2006; 134: 693-700 In prospective studies in adults, chronic cough is most commonly due to 6 disorders : Upper Airway Cough Syndrome (UACS) Asthma GERD Chronic Bronchitis Bronchiectasis Non-asthmatic Eosinophilic Bronchitis Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S New Considerations Eosinophilic bronchitis Atopic cough Non acid(volume)/ weakly acid reflux Idiopathic (unexplained) öksürük Diagnosis and Management of Cough ACCP Evidence-Based CPG 2006 Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S Plevkova, et al. Respir Physiol Neurobiol 2004; 142: 225-235 Postnasal drip syndrome (PNDS) renamed upper airway cough syndrome (UACS) Upper airway afferents may reflexly enhance coughing Nonasthmatic eosinophilic bronchitis recognized as a common cause of chronic cough Idiopathic cough renamed unexplained cough The term acid reflux disease, unless it can be definitively shown to apply, replaced by reflux disease Update of current diagnostic and therapeutic approaches Common diseases, Uncommon diseases New algorithms for the management of cough in adults and children An empiric integrative approach is recommended 10 12 13 12 16 6 4 ASTHMA PNDS GERD Chest 1999;116:279-284 1. Gastroesophageal reflux disease (21-41%) 2. Cough variant asthma (24-59%) 3. Postnasal drip syndrome (41-58%) Chest 1999;116:279-281 Percentage of Cases Presenting 1,2,3, and 4 Causative Factors İmmunocompetent patients Not exposed to enviromental irritants Chest radiograph is normal Not taking an ACE inhibitor Not a current smoker Asthma and/or GERD, PNDS responsible for 93.6% of the cases of chronic cough Harding SM .Chest 2003;123:659-660 Changing Trends in Diagnosis Percentage of Diagnosis (%) GERD ASTHMA RHINITIS Impaired esophageal clearance Functional defect in LES syphincter Hiatal hernia Delayed gastric emptying İncreased intra-abdominal pressure GERD ? Decreased saliva Heartburn (pyrosis) and regurgitation At least weekly symptoms extraesophageal reflux symptoms and/or esophageal mucosal damage / Katzka & DiMarino 1995 FLR Signs Edema and hyperemia of larynx Vocal cord erythema, polyps, granulomas, ulcers Hyperemia and lymphoid hyperplasia of posterior pharynx Interarytenoid changes Subglottic stenosis GERD-related cough incidence 5 - 55% May be the sole presenting symptom(1/3) Thorax 2003:58;1092-1095) (Chest 1997; 111: 1389-1402) Irwin RS. Chest 2006;129:80S-94S Association between cough and reflux is important Esophageal-tracheal-bronchial reflex Microaspiration Pathogenesis ARRD 1981;123:413-417 Arch Intern Med 1996;156:997 Chest 1993;104:1511-1517 El Hennawi, 2004 OHNS Nonacidic factors? Esophageal dismotility? . Mediator Release . Inflammation . Edema . Mucus . Smooth Muscle Microaspiration REFLUX Esophageal Vagal Afferents Bronchial Hyperreactivity Airway Vagal Afferents CNS Stein MR.Am J Med 2003 Chest 1997;111: 1389-1402 Airway Airway Vagal Efferents Esophagus Tracheobronchial Tree Stomach Oesophagus Pharyngeal pHmetry + - Not GERD Clinical GERD symptoms ? Nonacid, weakly acid reflux? Increase dose PPI + alginate İmproved Not improved Continue pHmetry under treatment Consider  Simultaneously dual probes 24 hours pHmonitoring and intraesophageal impedance Irwin RS.AJRCCM 165:1469-74,2002 McGarvey LPA.Thorax 59:342-346,2004 15 cm 17 cm 6 impedance channels 1 pH electrode + Adult Standard Model ZAN-S61C01E Multichannel intraluminal impedance-pH catheter Non acid reflux On going reflux of ‘non-acid’ material may be responsible for continuing symptoms while on acid-suppressing medications Therapy in Esophageal-pulmonary reflux Conservative and lifestyle measures Ampirical therapy: Acid suppression Proton pump inhibitors  PPI x 2 / 3 months Therapy failure  24 hour intraesophageal pHmetry ( pharyngeal pHmetry )  GERD (+) High dose PPI + H2 blocker agent Surgery(Fundoplication) Pulmonary and Crit Care Update 1994; Vol 9 Morice AH. ERJ 2004;24:481-492 Weeks of antireflux therapy Patients responded No No (%) 2 16 (41) 4 38 (86) 6 42 (95) 8 43 (99) 12 weeks 44 (100) Poe RH.Chest 2003;123:679-684 Cumulative Response to GERD Therapy Preop pH <4: %23.6 De Meester: 85 Postop pH <4: %2.4 De Meester: 9.9 1. Chronic cough for at least 2 months 2. Immunocompetent patients 3. Chest radiograph is normal 4. Not exposed to enviromental irritants nor a present smoker 5. Not taking an ACE inhibitor 6. Symptomatic asthma has been ruled out 7. Rhinosinus diseases has been ruled out: 8. ‘Silent sinusitis’ has been ruled out 9. Nonasthmatic eosinophilic bronchitis has been ruled out: BPT is negative Cough has not improved with asthma therapy First generation H1 antagonists has been used Eo 3% in induced sputum Cough has not improved with steroids Irwin RS. Chest 2006;129:80S-94S İrwin RS. AJRCCM Vol 165; 1469-1474, 2002 Clinical Profile That Chronic Cough İs Likely Due To ‘Silent GERD’ Postnasal Drip Syndrome (PNDS) Prevalence : 8 – 87% Pathogenesis : The sensation of drainage of secretions from the nose or paranasal sinuses into the pharynx Clinical Presentation: Dripping sensation Tickle in the throat Nasal congestion Mucus in oropharynx Cobblestone appearence of oropharynx ACCP consensus. CHEST 1998; 114: 133-181 ERS Task Force. ERS Journal ; 24: 553-566 Pathogenic Triad in Chronic Cough. CHEST 1999; 116: 279-284 Evaluation of chronic cough. UPTODATE 2005 Chest 2006;129:63S-71S In patient with chronic cough that is related to upper airway abnormalities Upper Airway Cough Syndrome UACS Treatment Antihistamines / decongestant combinations - “Older” sedating antihistamines more effective - Treatment effect should be observed in 1 week Additional / Alternative treatments : Ipratropium nasal spray : 2-7 days Nasal steroids (such as BDP, FP,BUD) : 2-3 days - 2 week 3 months prescribed Eosinophilic Eronchitis Airway obstruction Bronchial hyperreactivity NO YES YES NO Asthmatic Coughs Cough Variant Asthma Asthma Cough Variant Asthma Prevalence : 24 – 59% Clinical Diagnosis Gold standard  History - Episodic symptoms, Family history Reversibility testing PEF monitoring Bronchoprovocation test Differential Diagnosis: Decreased of cough with classical asthma therapy ACCP consensus. CHEST 1998; 114: 133-181 ERS Task Force. ERS Journal ; 24: 553-566 The Journal of Respiratory Disease; 25; 310-315 THORAX 59; 342-346 Middle age patients Smoking is unusual, occupational ? Prevalence of atopy similar population Good respond to inhaled steroids Gibson et al. Lancet 1989 Chest 2006;129:116S-121S Eosinophilic Bronchitis Isolated chronic cough,  productive of sputum Normal lung function without variable airflow limitation Airway hyperresponsiveness absent Eosinophilia in sputum and BAL Cough reflex to capsaicin increased Normal daily variability in peak expiratory flow (<20%) 1)Kim et al AJRCCM 2003; 2) Brightling et al AJRCCM 1999;160:406-10, 3) Joo Korean JIM 2002;17:31-7, 4) Carney et al AJRCCM 1997; 156:211-6, 5) Ma et al Zhongua 2003;26:362-5, 6) Ayik, Erdinc et al Respir Med 2003;97:695-701 Eosinophilic Bronchitis A Worldwide Disease Causes of chronic cough Ayık SÖ, Başoğlu ÖK, Erdinç M. Respir Med Vol. 97 (2003) 695-701 Causes of Isolated Chronic Cough Brightling CE et al. AJRCCM 1999 Asthmatic Cough Airway obstruction Reversibility PEF değişkenliği Increased NO all of them PEF monitoring Prevalence: 0-50% More agressive diagnosis and treatments UACS, GERD and postinfectious cough leads to lower incidence ‘unexplained’. Airway inflammation Mast cell, histamin, cysteinil LTs, PD2, PE2 Irwin RS,et al. Chest 2006;130:362-370 Chronic Unexplained (Idiopathic) Cough Important missed history (smoking,ACEI,enviromental,drugs,allergy) Failure to do correct diagnostic tests Failure to use ‘empiric’ treatment Failure to use effective therapy Unknown disease process Potential Reasons Chronic Unexplained (Idiopathic) Cough « Truly idiopathic cough is rare and misdiagnosis very common, especially if cough is provoked by sites outside the airways » Eur Respir J 24: 481-492 2004 Idiopathic cough % ? Studies in the 1980’s % patients 1990-1995 Idiopathic cough % ? % patients Idiopathic cough % ? 1996-1999 % patients Idiopathic cough % ? 2000  % patients Haque et al Chest 2005;127:1710-1713 Chronic Idiopathic Cough Predominantly female and associated with BAL lymphocytosis Raising the possibility of a link between autoimmune diseases Surinder S. Et al. Respir Med 98:242-246;2004 Chronic Idiopathic Cough *OR: 8.8 Inflammation Chronic Idiopathic Cough Birring et al AJRCM 2004

Slide 43 -

CHRONIC COUGH MÜNEVVER ERDİNÇ Department of Chest Diseases Ege University Faculty of Medicine Differential Diagnosis And Treatment In Adults Acute Cough lasting less than 3 weeks Subacute Cough lasting 3 to 8 weeks Chronic Cough Lasting more than 8 weeks Morice AH.Eur Respir J 2004 :24:481-492 Fontana GA.Thorax 2003;58:1092-1095 Irwin RS.NEJM 343(23): 1715-1721,2000 Irwin RS. Chest 1998; 114(suppl1) :133S-181S Differantial Diagnosis of Chronic Cough in Adults PNDS Allergic rhinitis Chronic sinusitis GERD Cough variant asthma ACEI induced cough Pertusis Neurogenic Traumatic Postinfectious cough Phychogenic cough Chronic aspiration Zenker diverticulosis Foreign body Chronic bronchitis Bronchiectasis Lung cancer Subglottic stenosis Tracheomalasie Tracheoesophageal fistul Tuerculosis Sarcoidosis Congestive heart failure Simpson CB. Otolaryngology–Head Neck Surg 2006; 134: 693-700 In prospective studies in adults, chronic cough is most commonly due to 6 disorders : Upper Airway Cough Syndrome (UACS) Asthma GERD Chronic Bronchitis Bronchiectasis Non-asthmatic Eosinophilic Bronchitis Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S New Considerations Eosinophilic bronchitis Atopic cough Non acid(volume)/ weakly acid reflux Idiopathic (unexplained) öksürük Diagnosis and Management of Cough ACCP Evidence-Based CPG 2006 Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S Plevkova, et al. Respir Physiol Neurobiol 2004; 142: 225-235 Postnasal drip syndrome (PNDS) renamed upper airway cough syndrome (UACS) Upper airway afferents may reflexly enhance coughing Nonasthmatic eosinophilic bronchitis recognized as a common cause of chronic cough Idiopathic cough renamed unexplained cough The term acid reflux disease, unless it can be definitively shown to apply, replaced by reflux disease Update of current diagnostic and therapeutic approaches Common diseases, Uncommon diseases New algorithms for the management of cough in adults and children An empiric integrative approach is recommended 10 12 13 12 16 6 4 ASTHMA PNDS GERD Chest 1999;116:279-284 1. Gastroesophageal reflux disease (21-41%) 2. Cough variant asthma (24-59%) 3. Postnasal drip syndrome (41-58%) Chest 1999;116:279-281 Percentage of Cases Presenting 1,2,3, and 4 Causative Factors İmmunocompetent patients Not exposed to enviromental irritants Chest radiograph is normal Not taking an ACE inhibitor Not a current smoker Asthma and/or GERD, PNDS responsible for 93.6% of the cases of chronic cough Harding SM .Chest 2003;123:659-660 Changing Trends in Diagnosis Percentage of Diagnosis (%) GERD ASTHMA RHINITIS Impaired esophageal clearance Functional defect in LES syphincter Hiatal hernia Delayed gastric emptying İncreased intra-abdominal pressure GERD ? Decreased saliva Heartburn (pyrosis) and regurgitation At least weekly symptoms extraesophageal reflux symptoms and/or esophageal mucosal damage / Katzka & DiMarino 1995 FLR Signs Edema and hyperemia of larynx Vocal cord erythema, polyps, granulomas, ulcers Hyperemia and lymphoid hyperplasia of posterior pharynx Interarytenoid changes Subglottic stenosis GERD-related cough incidence 5 - 55% May be the sole presenting symptom(1/3) Thorax 2003:58;1092-1095) (Chest 1997; 111: 1389-1402) Irwin RS. Chest 2006;129:80S-94S Association between cough and reflux is important Esophageal-tracheal-bronchial reflex Microaspiration Pathogenesis ARRD 1981;123:413-417 Arch Intern Med 1996;156:997 Chest 1993;104:1511-1517 El Hennawi, 2004 OHNS Nonacidic factors? Esophageal dismotility? . Mediator Release . Inflammation . Edema . Mucus . Smooth Muscle Microaspiration REFLUX Esophageal Vagal Afferents Bronchial Hyperreactivity Airway Vagal Afferents CNS Stein MR.Am J Med 2003 Chest 1997;111: 1389-1402 Airway Airway Vagal Efferents Esophagus Tracheobronchial Tree Stomach Oesophagus Pharyngeal pHmetry + - Not GERD Clinical GERD symptoms ? Nonacid, weakly acid reflux? Increase dose PPI + alginate İmproved Not improved Continue pHmetry under treatment Consider  Simultaneously dual probes 24 hours pHmonitoring and intraesophageal impedance Irwin RS.AJRCCM 165:1469-74,2002 McGarvey LPA.Thorax 59:342-346,2004 15 cm 17 cm 6 impedance channels 1 pH electrode + Adult Standard Model ZAN-S61C01E Multichannel intraluminal impedance-pH catheter Non acid reflux On going reflux of ‘non-acid’ material may be responsible for continuing symptoms while on acid-suppressing medications Therapy in Esophageal-pulmonary reflux Conservative and lifestyle measures Ampirical therapy: Acid suppression Proton pump inhibitors  PPI x 2 / 3 months Therapy failure  24 hour intraesophageal pHmetry ( pharyngeal pHmetry )  GERD (+) High dose PPI + H2 blocker agent Surgery(Fundoplication) Pulmonary and Crit Care Update 1994; Vol 9 Morice AH. ERJ 2004;24:481-492 Weeks of antireflux therapy Patients responded No No (%) 2 16 (41) 4 38 (86) 6 42 (95) 8 43 (99) 12 weeks 44 (100) Poe RH.Chest 2003;123:679-684 Cumulative Response to GERD Therapy Preop pH <4: %23.6 De Meester: 85 Postop pH <4: %2.4 De Meester: 9.9 1. Chronic cough for at least 2 months 2. Immunocompetent patients 3. Chest radiograph is normal 4. Not exposed to enviromental irritants nor a present smoker 5. Not taking an ACE inhibitor 6. Symptomatic asthma has been ruled out 7. Rhinosinus diseases has been ruled out: 8. ‘Silent sinusitis’ has been ruled out 9. Nonasthmatic eosinophilic bronchitis has been ruled out: BPT is negative Cough has not improved with asthma therapy First generation H1 antagonists has been used Eo 3% in induced sputum Cough has not improved with steroids Irwin RS. Chest 2006;129:80S-94S İrwin RS. AJRCCM Vol 165; 1469-1474, 2002 Clinical Profile That Chronic Cough İs Likely Due To ‘Silent GERD’ Postnasal Drip Syndrome (PNDS) Prevalence : 8 – 87% Pathogenesis : The sensation of drainage of secretions from the nose or paranasal sinuses into the pharynx Clinical Presentation: Dripping sensation Tickle in the throat Nasal congestion Mucus in oropharynx Cobblestone appearence of oropharynx ACCP consensus. CHEST 1998; 114: 133-181 ERS Task Force. ERS Journal ; 24: 553-566 Pathogenic Triad in Chronic Cough. CHEST 1999; 116: 279-284 Evaluation of chronic cough. UPTODATE 2005 Chest 2006;129:63S-71S In patient with chronic cough that is related to upper airway abnormalities Upper Airway Cough Syndrome UACS Treatment Antihistamines / decongestant combinations - “Older” sedating antihistamines more effective - Treatment effect should be observed in 1 week Additional / Alternative treatments : Ipratropium nasal spray : 2-7 days Nasal steroids (such as BDP, FP,BUD) : 2-3 days - 2 week 3 months prescribed Eosinophilic Eronchitis Airway obstruction Bronchial hyperreactivity NO YES YES NO Asthmatic Coughs Cough Variant Asthma Asthma Cough Variant Asthma Prevalence : 24 – 59% Clinical Diagnosis Gold standard  History - Episodic symptoms, Family history Reversibility testing PEF monitoring Bronchoprovocation test Differential Diagnosis: Decreased of cough with classical asthma therapy ACCP consensus. CHEST 1998; 114: 133-181 ERS Task Force. ERS Journal ; 24: 553-566 The Journal of Respiratory Disease; 25; 310-315 THORAX 59; 342-346 Middle age patients Smoking is unusual, occupational ? Prevalence of atopy similar population Good respond to inhaled steroids Gibson et al. Lancet 1989 Chest 2006;129:116S-121S Eosinophilic Bronchitis Isolated chronic cough,  productive of sputum Normal lung function without variable airflow limitation Airway hyperresponsiveness absent Eosinophilia in sputum and BAL Cough reflex to capsaicin increased Normal daily variability in peak expiratory flow (<20%) 1)Kim et al AJRCCM 2003; 2) Brightling et al AJRCCM 1999;160:406-10, 3) Joo Korean JIM 2002;17:31-7, 4) Carney et al AJRCCM 1997; 156:211-6, 5) Ma et al Zhongua 2003;26:362-5, 6) Ayik, Erdinc et al Respir Med 2003;97:695-701 Eosinophilic Bronchitis A Worldwide Disease Causes of chronic cough Ayık SÖ, Başoğlu ÖK, Erdinç M. Respir Med Vol. 97 (2003) 695-701 Causes of Isolated Chronic Cough Brightling CE et al. AJRCCM 1999 Asthmatic Cough Airway obstruction Reversibility PEF değişkenliği Increased NO all of them PEF monitoring Prevalence: 0-50% More agressive diagnosis and treatments UACS, GERD and postinfectious cough leads to lower incidence ‘unexplained’. Airway inflammation Mast cell, histamin, cysteinil LTs, PD2, PE2 Irwin RS,et al. Chest 2006;130:362-370 Chronic Unexplained (Idiopathic) Cough Important missed history (smoking,ACEI,enviromental,drugs,allergy) Failure to do correct diagnostic tests Failure to use ‘empiric’ treatment Failure to use effective therapy Unknown disease process Potential Reasons Chronic Unexplained (Idiopathic) Cough « Truly idiopathic cough is rare and misdiagnosis very common, especially if cough is provoked by sites outside the airways » Eur Respir J 24: 481-492 2004 Idiopathic cough % ? Studies in the 1980’s % patients 1990-1995 Idiopathic cough % ? % patients Idiopathic cough % ? 1996-1999 % patients Idiopathic cough % ? 2000  % patients Haque et al Chest 2005;127:1710-1713 Chronic Idiopathic Cough Predominantly female and associated with BAL lymphocytosis Raising the possibility of a link between autoimmune diseases Surinder S. Et al. Respir Med 98:242-246;2004 Chronic Idiopathic Cough *OR: 8.8 Inflammation Chronic Idiopathic Cough Birring et al AJRCM 2004 + BAL lymphocytosis Sarcoidosis Hypersensitivity pneumonitis Rheumatoid Arthritis Sjögren’s syndrome Lung tx Inflammatory bowel disease Hypothyroidism Autoimmune disorders (SLE, RA) Pernisious anemia DM Thorax 2003;58:1066-1070 Chronic Idiopathic Cough

Slide 44 -

CHRONIC COUGH MÜNEVVER ERDİNÇ Department of Chest Diseases Ege University Faculty of Medicine Differential Diagnosis And Treatment In Adults Acute Cough lasting less than 3 weeks Subacute Cough lasting 3 to 8 weeks Chronic Cough Lasting more than 8 weeks Morice AH.Eur Respir J 2004 :24:481-492 Fontana GA.Thorax 2003;58:1092-1095 Irwin RS.NEJM 343(23): 1715-1721,2000 Irwin RS. Chest 1998; 114(suppl1) :133S-181S Differantial Diagnosis of Chronic Cough in Adults PNDS Allergic rhinitis Chronic sinusitis GERD Cough variant asthma ACEI induced cough Pertusis Neurogenic Traumatic Postinfectious cough Phychogenic cough Chronic aspiration Zenker diverticulosis Foreign body Chronic bronchitis Bronchiectasis Lung cancer Subglottic stenosis Tracheomalasie Tracheoesophageal fistul Tuerculosis Sarcoidosis Congestive heart failure Simpson CB. Otolaryngology–Head Neck Surg 2006; 134: 693-700 In prospective studies in adults, chronic cough is most commonly due to 6 disorders : Upper Airway Cough Syndrome (UACS) Asthma GERD Chronic Bronchitis Bronchiectasis Non-asthmatic Eosinophilic Bronchitis Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S New Considerations Eosinophilic bronchitis Atopic cough Non acid(volume)/ weakly acid reflux Idiopathic (unexplained) öksürük Diagnosis and Management of Cough ACCP Evidence-Based CPG 2006 Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S Plevkova, et al. Respir Physiol Neurobiol 2004; 142: 225-235 Postnasal drip syndrome (PNDS) renamed upper airway cough syndrome (UACS) Upper airway afferents may reflexly enhance coughing Nonasthmatic eosinophilic bronchitis recognized as a common cause of chronic cough Idiopathic cough renamed unexplained cough The term acid reflux disease, unless it can be definitively shown to apply, replaced by reflux disease Update of current diagnostic and therapeutic approaches Common diseases, Uncommon diseases New algorithms for the management of cough in adults and children An empiric integrative approach is recommended 10 12 13 12 16 6 4 ASTHMA PNDS GERD Chest 1999;116:279-284 1. Gastroesophageal reflux disease (21-41%) 2. Cough variant asthma (24-59%) 3. Postnasal drip syndrome (41-58%) Chest 1999;116:279-281 Percentage of Cases Presenting 1,2,3, and 4 Causative Factors İmmunocompetent patients Not exposed to enviromental irritants Chest radiograph is normal Not taking an ACE inhibitor Not a current smoker Asthma and/or GERD, PNDS responsible for 93.6% of the cases of chronic cough Harding SM .Chest 2003;123:659-660 Changing Trends in Diagnosis Percentage of Diagnosis (%) GERD ASTHMA RHINITIS Impaired esophageal clearance Functional defect in LES syphincter Hiatal hernia Delayed gastric emptying İncreased intra-abdominal pressure GERD ? Decreased saliva Heartburn (pyrosis) and regurgitation At least weekly symptoms extraesophageal reflux symptoms and/or esophageal mucosal damage / Katzka & DiMarino 1995 FLR Signs Edema and hyperemia of larynx Vocal cord erythema, polyps, granulomas, ulcers Hyperemia and lymphoid hyperplasia of posterior pharynx Interarytenoid changes Subglottic stenosis GERD-related cough incidence 5 - 55% May be the sole presenting symptom(1/3) Thorax 2003:58;1092-1095) (Chest 1997; 111: 1389-1402) Irwin RS. Chest 2006;129:80S-94S Association between cough and reflux is important Esophageal-tracheal-bronchial reflex Microaspiration Pathogenesis ARRD 1981;123:413-417 Arch Intern Med 1996;156:997 Chest 1993;104:1511-1517 El Hennawi, 2004 OHNS Nonacidic factors? Esophageal dismotility? . Mediator Release . Inflammation . Edema . Mucus . Smooth Muscle Microaspiration REFLUX Esophageal Vagal Afferents Bronchial Hyperreactivity Airway Vagal Afferents CNS Stein MR.Am J Med 2003 Chest 1997;111: 1389-1402 Airway Airway Vagal Efferents Esophagus Tracheobronchial Tree Stomach Oesophagus Pharyngeal pHmetry + - Not GERD Clinical GERD symptoms ? Nonacid, weakly acid reflux? Increase dose PPI + alginate İmproved Not improved Continue pHmetry under treatment Consider  Simultaneously dual probes 24 hours pHmonitoring and intraesophageal impedance Irwin RS.AJRCCM 165:1469-74,2002 McGarvey LPA.Thorax 59:342-346,2004 15 cm 17 cm 6 impedance channels 1 pH electrode + Adult Standard Model ZAN-S61C01E Multichannel intraluminal impedance-pH catheter Non acid reflux On going reflux of ‘non-acid’ material may be responsible for continuing symptoms while on acid-suppressing medications Therapy in Esophageal-pulmonary reflux Conservative and lifestyle measures Ampirical therapy: Acid suppression Proton pump inhibitors  PPI x 2 / 3 months Therapy failure  24 hour intraesophageal pHmetry ( pharyngeal pHmetry )  GERD (+) High dose PPI + H2 blocker agent Surgery(Fundoplication) Pulmonary and Crit Care Update 1994; Vol 9 Morice AH. ERJ 2004;24:481-492 Weeks of antireflux therapy Patients responded No No (%) 2 16 (41) 4 38 (86) 6 42 (95) 8 43 (99) 12 weeks 44 (100) Poe RH.Chest 2003;123:679-684 Cumulative Response to GERD Therapy Preop pH <4: %23.6 De Meester: 85 Postop pH <4: %2.4 De Meester: 9.9 1. Chronic cough for at least 2 months 2. Immunocompetent patients 3. Chest radiograph is normal 4. Not exposed to enviromental irritants nor a present smoker 5. Not taking an ACE inhibitor 6. Symptomatic asthma has been ruled out 7. Rhinosinus diseases has been ruled out: 8. ‘Silent sinusitis’ has been ruled out 9. Nonasthmatic eosinophilic bronchitis has been ruled out: BPT is negative Cough has not improved with asthma therapy First generation H1 antagonists has been used Eo 3% in induced sputum Cough has not improved with steroids Irwin RS. Chest 2006;129:80S-94S İrwin RS. AJRCCM Vol 165; 1469-1474, 2002 Clinical Profile That Chronic Cough İs Likely Due To ‘Silent GERD’ Postnasal Drip Syndrome (PNDS) Prevalence : 8 – 87% Pathogenesis : The sensation of drainage of secretions from the nose or paranasal sinuses into the pharynx Clinical Presentation: Dripping sensation Tickle in the throat Nasal congestion Mucus in oropharynx Cobblestone appearence of oropharynx ACCP consensus. CHEST 1998; 114: 133-181 ERS Task Force. ERS Journal ; 24: 553-566 Pathogenic Triad in Chronic Cough. CHEST 1999; 116: 279-284 Evaluation of chronic cough. UPTODATE 2005 Chest 2006;129:63S-71S In patient with chronic cough that is related to upper airway abnormalities Upper Airway Cough Syndrome UACS Treatment Antihistamines / decongestant combinations - “Older” sedating antihistamines more effective - Treatment effect should be observed in 1 week Additional / Alternative treatments : Ipratropium nasal spray : 2-7 days Nasal steroids (such as BDP, FP,BUD) : 2-3 days - 2 week 3 months prescribed Eosinophilic Eronchitis Airway obstruction Bronchial hyperreactivity NO YES YES NO Asthmatic Coughs Cough Variant Asthma Asthma Cough Variant Asthma Prevalence : 24 – 59% Clinical Diagnosis Gold standard  History - Episodic symptoms, Family history Reversibility testing PEF monitoring Bronchoprovocation test Differential Diagnosis: Decreased of cough with classical asthma therapy ACCP consensus. CHEST 1998; 114: 133-181 ERS Task Force. ERS Journal ; 24: 553-566 The Journal of Respiratory Disease; 25; 310-315 THORAX 59; 342-346 Middle age patients Smoking is unusual, occupational ? Prevalence of atopy similar population Good respond to inhaled steroids Gibson et al. Lancet 1989 Chest 2006;129:116S-121S Eosinophilic Bronchitis Isolated chronic cough,  productive of sputum Normal lung function without variable airflow limitation Airway hyperresponsiveness absent Eosinophilia in sputum and BAL Cough reflex to capsaicin increased Normal daily variability in peak expiratory flow (<20%) 1)Kim et al AJRCCM 2003; 2) Brightling et al AJRCCM 1999;160:406-10, 3) Joo Korean JIM 2002;17:31-7, 4) Carney et al AJRCCM 1997; 156:211-6, 5) Ma et al Zhongua 2003;26:362-5, 6) Ayik, Erdinc et al Respir Med 2003;97:695-701 Eosinophilic Bronchitis A Worldwide Disease Causes of chronic cough Ayık SÖ, Başoğlu ÖK, Erdinç M. Respir Med Vol. 97 (2003) 695-701 Causes of Isolated Chronic Cough Brightling CE et al. AJRCCM 1999 Asthmatic Cough Airway obstruction Reversibility PEF değişkenliği Increased NO all of them PEF monitoring Prevalence: 0-50% More agressive diagnosis and treatments UACS, GERD and postinfectious cough leads to lower incidence ‘unexplained’. Airway inflammation Mast cell, histamin, cysteinil LTs, PD2, PE2 Irwin RS,et al. Chest 2006;130:362-370 Chronic Unexplained (Idiopathic) Cough Important missed history (smoking,ACEI,enviromental,drugs,allergy) Failure to do correct diagnostic tests Failure to use ‘empiric’ treatment Failure to use effective therapy Unknown disease process Potential Reasons Chronic Unexplained (Idiopathic) Cough « Truly idiopathic cough is rare and misdiagnosis very common, especially if cough is provoked by sites outside the airways » Eur Respir J 24: 481-492 2004 Idiopathic cough % ? Studies in the 1980’s % patients 1990-1995 Idiopathic cough % ? % patients Idiopathic cough % ? 1996-1999 % patients Idiopathic cough % ? 2000  % patients Haque et al Chest 2005;127:1710-1713 Chronic Idiopathic Cough Predominantly female and associated with BAL lymphocytosis Raising the possibility of a link between autoimmune diseases Surinder S. Et al. Respir Med 98:242-246;2004 Chronic Idiopathic Cough *OR: 8.8 Inflammation Chronic Idiopathic Cough Birring et al AJRCM 2004 + BAL lymphocytosis Sarcoidosis Hypersensitivity pneumonitis Rheumatoid Arthritis Sjögren’s syndrome Lung tx Inflammatory bowel disease Hypothyroidism Autoimmune disorders (SLE, RA) Pernisious anemia DM Thorax 2003;58:1066-1070 Chronic Idiopathic Cough Irwin RS,et al. Chest 2006;130:362-370 It is not correct to state that “a typical lymphocytic airways inflammation is seen in idiopathic cough” because lymphocytic or lymphoplasmacytic inflammation a non-specific finding related to trauma of coughing Chronic Idiopathic Cough

Slide 45 -

CHRONIC COUGH MÜNEVVER ERDİNÇ Department of Chest Diseases Ege University Faculty of Medicine Differential Diagnosis And Treatment In Adults Acute Cough lasting less than 3 weeks Subacute Cough lasting 3 to 8 weeks Chronic Cough Lasting more than 8 weeks Morice AH.Eur Respir J 2004 :24:481-492 Fontana GA.Thorax 2003;58:1092-1095 Irwin RS.NEJM 343(23): 1715-1721,2000 Irwin RS. Chest 1998; 114(suppl1) :133S-181S Differantial Diagnosis of Chronic Cough in Adults PNDS Allergic rhinitis Chronic sinusitis GERD Cough variant asthma ACEI induced cough Pertusis Neurogenic Traumatic Postinfectious cough Phychogenic cough Chronic aspiration Zenker diverticulosis Foreign body Chronic bronchitis Bronchiectasis Lung cancer Subglottic stenosis Tracheomalasie Tracheoesophageal fistul Tuerculosis Sarcoidosis Congestive heart failure Simpson CB. Otolaryngology–Head Neck Surg 2006; 134: 693-700 In prospective studies in adults, chronic cough is most commonly due to 6 disorders : Upper Airway Cough Syndrome (UACS) Asthma GERD Chronic Bronchitis Bronchiectasis Non-asthmatic Eosinophilic Bronchitis Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S New Considerations Eosinophilic bronchitis Atopic cough Non acid(volume)/ weakly acid reflux Idiopathic (unexplained) öksürük Diagnosis and Management of Cough ACCP Evidence-Based CPG 2006 Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S Plevkova, et al. Respir Physiol Neurobiol 2004; 142: 225-235 Postnasal drip syndrome (PNDS) renamed upper airway cough syndrome (UACS) Upper airway afferents may reflexly enhance coughing Nonasthmatic eosinophilic bronchitis recognized as a common cause of chronic cough Idiopathic cough renamed unexplained cough The term acid reflux disease, unless it can be definitively shown to apply, replaced by reflux disease Update of current diagnostic and therapeutic approaches Common diseases, Uncommon diseases New algorithms for the management of cough in adults and children An empiric integrative approach is recommended 10 12 13 12 16 6 4 ASTHMA PNDS GERD Chest 1999;116:279-284 1. Gastroesophageal reflux disease (21-41%) 2. Cough variant asthma (24-59%) 3. Postnasal drip syndrome (41-58%) Chest 1999;116:279-281 Percentage of Cases Presenting 1,2,3, and 4 Causative Factors İmmunocompetent patients Not exposed to enviromental irritants Chest radiograph is normal Not taking an ACE inhibitor Not a current smoker Asthma and/or GERD, PNDS responsible for 93.6% of the cases of chronic cough Harding SM .Chest 2003;123:659-660 Changing Trends in Diagnosis Percentage of Diagnosis (%) GERD ASTHMA RHINITIS Impaired esophageal clearance Functional defect in LES syphincter Hiatal hernia Delayed gastric emptying İncreased intra-abdominal pressure GERD ? Decreased saliva Heartburn (pyrosis) and regurgitation At least weekly symptoms extraesophageal reflux symptoms and/or esophageal mucosal damage / Katzka & DiMarino 1995 FLR Signs Edema and hyperemia of larynx Vocal cord erythema, polyps, granulomas, ulcers Hyperemia and lymphoid hyperplasia of posterior pharynx Interarytenoid changes Subglottic stenosis GERD-related cough incidence 5 - 55% May be the sole presenting symptom(1/3) Thorax 2003:58;1092-1095) (Chest 1997; 111: 1389-1402) Irwin RS. Chest 2006;129:80S-94S Association between cough and reflux is important Esophageal-tracheal-bronchial reflex Microaspiration Pathogenesis ARRD 1981;123:413-417 Arch Intern Med 1996;156:997 Chest 1993;104:1511-1517 El Hennawi, 2004 OHNS Nonacidic factors? Esophageal dismotility? . Mediator Release . Inflammation . Edema . Mucus . Smooth Muscle Microaspiration REFLUX Esophageal Vagal Afferents Bronchial Hyperreactivity Airway Vagal Afferents CNS Stein MR.Am J Med 2003 Chest 1997;111: 1389-1402 Airway Airway Vagal Efferents Esophagus Tracheobronchial Tree Stomach Oesophagus Pharyngeal pHmetry + - Not GERD Clinical GERD symptoms ? Nonacid, weakly acid reflux? Increase dose PPI + alginate İmproved Not improved Continue pHmetry under treatment Consider  Simultaneously dual probes 24 hours pHmonitoring and intraesophageal impedance Irwin RS.AJRCCM 165:1469-74,2002 McGarvey LPA.Thorax 59:342-346,2004 15 cm 17 cm 6 impedance channels 1 pH electrode + Adult Standard Model ZAN-S61C01E Multichannel intraluminal impedance-pH catheter Non acid reflux On going reflux of ‘non-acid’ material may be responsible for continuing symptoms while on acid-suppressing medications Therapy in Esophageal-pulmonary reflux Conservative and lifestyle measures Ampirical therapy: Acid suppression Proton pump inhibitors  PPI x 2 / 3 months Therapy failure  24 hour intraesophageal pHmetry ( pharyngeal pHmetry )  GERD (+) High dose PPI + H2 blocker agent Surgery(Fundoplication) Pulmonary and Crit Care Update 1994; Vol 9 Morice AH. ERJ 2004;24:481-492 Weeks of antireflux therapy Patients responded No No (%) 2 16 (41) 4 38 (86) 6 42 (95) 8 43 (99) 12 weeks 44 (100) Poe RH.Chest 2003;123:679-684 Cumulative Response to GERD Therapy Preop pH <4: %23.6 De Meester: 85 Postop pH <4: %2.4 De Meester: 9.9 1. Chronic cough for at least 2 months 2. Immunocompetent patients 3. Chest radiograph is normal 4. Not exposed to enviromental irritants nor a present smoker 5. Not taking an ACE inhibitor 6. Symptomatic asthma has been ruled out 7. Rhinosinus diseases has been ruled out: 8. ‘Silent sinusitis’ has been ruled out 9. Nonasthmatic eosinophilic bronchitis has been ruled out: BPT is negative Cough has not improved with asthma therapy First generation H1 antagonists has been used Eo 3% in induced sputum Cough has not improved with steroids Irwin RS. Chest 2006;129:80S-94S İrwin RS. AJRCCM Vol 165; 1469-1474, 2002 Clinical Profile That Chronic Cough İs Likely Due To ‘Silent GERD’ Postnasal Drip Syndrome (PNDS) Prevalence : 8 – 87% Pathogenesis : The sensation of drainage of secretions from the nose or paranasal sinuses into the pharynx Clinical Presentation: Dripping sensation Tickle in the throat Nasal congestion Mucus in oropharynx Cobblestone appearence of oropharynx ACCP consensus. CHEST 1998; 114: 133-181 ERS Task Force. ERS Journal ; 24: 553-566 Pathogenic Triad in Chronic Cough. CHEST 1999; 116: 279-284 Evaluation of chronic cough. UPTODATE 2005 Chest 2006;129:63S-71S In patient with chronic cough that is related to upper airway abnormalities Upper Airway Cough Syndrome UACS Treatment Antihistamines / decongestant combinations - “Older” sedating antihistamines more effective - Treatment effect should be observed in 1 week Additional / Alternative treatments : Ipratropium nasal spray : 2-7 days Nasal steroids (such as BDP, FP,BUD) : 2-3 days - 2 week 3 months prescribed Eosinophilic Eronchitis Airway obstruction Bronchial hyperreactivity NO YES YES NO Asthmatic Coughs Cough Variant Asthma Asthma Cough Variant Asthma Prevalence : 24 – 59% Clinical Diagnosis Gold standard  History - Episodic symptoms, Family history Reversibility testing PEF monitoring Bronchoprovocation test Differential Diagnosis: Decreased of cough with classical asthma therapy ACCP consensus. CHEST 1998; 114: 133-181 ERS Task Force. ERS Journal ; 24: 553-566 The Journal of Respiratory Disease; 25; 310-315 THORAX 59; 342-346 Middle age patients Smoking is unusual, occupational ? Prevalence of atopy similar population Good respond to inhaled steroids Gibson et al. Lancet 1989 Chest 2006;129:116S-121S Eosinophilic Bronchitis Isolated chronic cough,  productive of sputum Normal lung function without variable airflow limitation Airway hyperresponsiveness absent Eosinophilia in sputum and BAL Cough reflex to capsaicin increased Normal daily variability in peak expiratory flow (<20%) 1)Kim et al AJRCCM 2003; 2) Brightling et al AJRCCM 1999;160:406-10, 3) Joo Korean JIM 2002;17:31-7, 4) Carney et al AJRCCM 1997; 156:211-6, 5) Ma et al Zhongua 2003;26:362-5, 6) Ayik, Erdinc et al Respir Med 2003;97:695-701 Eosinophilic Bronchitis A Worldwide Disease Causes of chronic cough Ayık SÖ, Başoğlu ÖK, Erdinç M. Respir Med Vol. 97 (2003) 695-701 Causes of Isolated Chronic Cough Brightling CE et al. AJRCCM 1999 Asthmatic Cough Airway obstruction Reversibility PEF değişkenliği Increased NO all of them PEF monitoring Prevalence: 0-50% More agressive diagnosis and treatments UACS, GERD and postinfectious cough leads to lower incidence ‘unexplained’. Airway inflammation Mast cell, histamin, cysteinil LTs, PD2, PE2 Irwin RS,et al. Chest 2006;130:362-370 Chronic Unexplained (Idiopathic) Cough Important missed history (smoking,ACEI,enviromental,drugs,allergy) Failure to do correct diagnostic tests Failure to use ‘empiric’ treatment Failure to use effective therapy Unknown disease process Potential Reasons Chronic Unexplained (Idiopathic) Cough « Truly idiopathic cough is rare and misdiagnosis very common, especially if cough is provoked by sites outside the airways » Eur Respir J 24: 481-492 2004 Idiopathic cough % ? Studies in the 1980’s % patients 1990-1995 Idiopathic cough % ? % patients Idiopathic cough % ? 1996-1999 % patients Idiopathic cough % ? 2000  % patients Haque et al Chest 2005;127:1710-1713 Chronic Idiopathic Cough Predominantly female and associated with BAL lymphocytosis Raising the possibility of a link between autoimmune diseases Surinder S. Et al. Respir Med 98:242-246;2004 Chronic Idiopathic Cough *OR: 8.8 Inflammation Chronic Idiopathic Cough Birring et al AJRCM 2004 + BAL lymphocytosis Sarcoidosis Hypersensitivity pneumonitis Rheumatoid Arthritis Sjögren’s syndrome Lung tx Inflammatory bowel disease Hypothyroidism Autoimmune disorders (SLE, RA) Pernisious anemia DM Thorax 2003;58:1066-1070 Chronic Idiopathic Cough Irwin RS,et al. Chest 2006;130:362-370 It is not correct to state that “a typical lymphocytic airways inflammation is seen in idiopathic cough” because lymphocytic or lymphoplasmacytic inflammation a non-specific finding related to trauma of coughing Chronic Idiopathic Cough Psychogenic Cough Cough is often triggered by a common cold Usually dissapears during sleep Like a dog barking The diagnosis of psychogenic cough is one of exclusion, after ruling out an organic or functional cause of cough. Specific or empiric treatment Antitussives are usually ineffective. Respirology 2006;Suppl 4 ;S160-S174 Irwin RS et al. Chest 1998, 114:2 suppl ERS Task Force: Eur Respir J 2004, 24:481-492

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CHRONIC COUGH MÜNEVVER ERDİNÇ Department of Chest Diseases Ege University Faculty of Medicine Differential Diagnosis And Treatment In Adults Acute Cough lasting less than 3 weeks Subacute Cough lasting 3 to 8 weeks Chronic Cough Lasting more than 8 weeks Morice AH.Eur Respir J 2004 :24:481-492 Fontana GA.Thorax 2003;58:1092-1095 Irwin RS.NEJM 343(23): 1715-1721,2000 Irwin RS. Chest 1998; 114(suppl1) :133S-181S Differantial Diagnosis of Chronic Cough in Adults PNDS Allergic rhinitis Chronic sinusitis GERD Cough variant asthma ACEI induced cough Pertusis Neurogenic Traumatic Postinfectious cough Phychogenic cough Chronic aspiration Zenker diverticulosis Foreign body Chronic bronchitis Bronchiectasis Lung cancer Subglottic stenosis Tracheomalasie Tracheoesophageal fistul Tuerculosis Sarcoidosis Congestive heart failure Simpson CB. Otolaryngology–Head Neck Surg 2006; 134: 693-700 In prospective studies in adults, chronic cough is most commonly due to 6 disorders : Upper Airway Cough Syndrome (UACS) Asthma GERD Chronic Bronchitis Bronchiectasis Non-asthmatic Eosinophilic Bronchitis Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S New Considerations Eosinophilic bronchitis Atopic cough Non acid(volume)/ weakly acid reflux Idiopathic (unexplained) öksürük Diagnosis and Management of Cough ACCP Evidence-Based CPG 2006 Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S Plevkova, et al. Respir Physiol Neurobiol 2004; 142: 225-235 Postnasal drip syndrome (PNDS) renamed upper airway cough syndrome (UACS) Upper airway afferents may reflexly enhance coughing Nonasthmatic eosinophilic bronchitis recognized as a common cause of chronic cough Idiopathic cough renamed unexplained cough The term acid reflux disease, unless it can be definitively shown to apply, replaced by reflux disease Update of current diagnostic and therapeutic approaches Common diseases, Uncommon diseases New algorithms for the management of cough in adults and children An empiric integrative approach is recommended 10 12 13 12 16 6 4 ASTHMA PNDS GERD Chest 1999;116:279-284 1. Gastroesophageal reflux disease (21-41%) 2. Cough variant asthma (24-59%) 3. Postnasal drip syndrome (41-58%) Chest 1999;116:279-281 Percentage of Cases Presenting 1,2,3, and 4 Causative Factors İmmunocompetent patients Not exposed to enviromental irritants Chest radiograph is normal Not taking an ACE inhibitor Not a current smoker Asthma and/or GERD, PNDS responsible for 93.6% of the cases of chronic cough Harding SM .Chest 2003;123:659-660 Changing Trends in Diagnosis Percentage of Diagnosis (%) GERD ASTHMA RHINITIS Impaired esophageal clearance Functional defect in LES syphincter Hiatal hernia Delayed gastric emptying İncreased intra-abdominal pressure GERD ? Decreased saliva Heartburn (pyrosis) and regurgitation At least weekly symptoms extraesophageal reflux symptoms and/or esophageal mucosal damage / Katzka & DiMarino 1995 FLR Signs Edema and hyperemia of larynx Vocal cord erythema, polyps, granulomas, ulcers Hyperemia and lymphoid hyperplasia of posterior pharynx Interarytenoid changes Subglottic stenosis GERD-related cough incidence 5 - 55% May be the sole presenting symptom(1/3) Thorax 2003:58;1092-1095) (Chest 1997; 111: 1389-1402) Irwin RS. Chest 2006;129:80S-94S Association between cough and reflux is important Esophageal-tracheal-bronchial reflex Microaspiration Pathogenesis ARRD 1981;123:413-417 Arch Intern Med 1996;156:997 Chest 1993;104:1511-1517 El Hennawi, 2004 OHNS Nonacidic factors? Esophageal dismotility? . Mediator Release . Inflammation . Edema . Mucus . Smooth Muscle Microaspiration REFLUX Esophageal Vagal Afferents Bronchial Hyperreactivity Airway Vagal Afferents CNS Stein MR.Am J Med 2003 Chest 1997;111: 1389-1402 Airway Airway Vagal Efferents Esophagus Tracheobronchial Tree Stomach Oesophagus Pharyngeal pHmetry + - Not GERD Clinical GERD symptoms ? Nonacid, weakly acid reflux? Increase dose PPI + alginate İmproved Not improved Continue pHmetry under treatment Consider  Simultaneously dual probes 24 hours pHmonitoring and intraesophageal impedance Irwin RS.AJRCCM 165:1469-74,2002 McGarvey LPA.Thorax 59:342-346,2004 15 cm 17 cm 6 impedance channels 1 pH electrode + Adult Standard Model ZAN-S61C01E Multichannel intraluminal impedance-pH catheter Non acid reflux On going reflux of ‘non-acid’ material may be responsible for continuing symptoms while on acid-suppressing medications Therapy in Esophageal-pulmonary reflux Conservative and lifestyle measures Ampirical therapy: Acid suppression Proton pump inhibitors  PPI x 2 / 3 months Therapy failure  24 hour intraesophageal pHmetry ( pharyngeal pHmetry )  GERD (+) High dose PPI + H2 blocker agent Surgery(Fundoplication) Pulmonary and Crit Care Update 1994; Vol 9 Morice AH. ERJ 2004;24:481-492 Weeks of antireflux therapy Patients responded No No (%) 2 16 (41) 4 38 (86) 6 42 (95) 8 43 (99) 12 weeks 44 (100) Poe RH.Chest 2003;123:679-684 Cumulative Response to GERD Therapy Preop pH <4: %23.6 De Meester: 85 Postop pH <4: %2.4 De Meester: 9.9 1. Chronic cough for at least 2 months 2. Immunocompetent patients 3. Chest radiograph is normal 4. Not exposed to enviromental irritants nor a present smoker 5. Not taking an ACE inhibitor 6. Symptomatic asthma has been ruled out 7. Rhinosinus diseases has been ruled out: 8. ‘Silent sinusitis’ has been ruled out 9. Nonasthmatic eosinophilic bronchitis has been ruled out: BPT is negative Cough has not improved with asthma therapy First generation H1 antagonists has been used Eo 3% in induced sputum Cough has not improved with steroids Irwin RS. Chest 2006;129:80S-94S İrwin RS. AJRCCM Vol 165; 1469-1474, 2002 Clinical Profile That Chronic Cough İs Likely Due To ‘Silent GERD’ Postnasal Drip Syndrome (PNDS) Prevalence : 8 – 87% Pathogenesis : The sensation of drainage of secretions from the nose or paranasal sinuses into the pharynx Clinical Presentation: Dripping sensation Tickle in the throat Nasal congestion Mucus in oropharynx Cobblestone appearence of oropharynx ACCP consensus. CHEST 1998; 114: 133-181 ERS Task Force. ERS Journal ; 24: 553-566 Pathogenic Triad in Chronic Cough. CHEST 1999; 116: 279-284 Evaluation of chronic cough. UPTODATE 2005 Chest 2006;129:63S-71S In patient with chronic cough that is related to upper airway abnormalities Upper Airway Cough Syndrome UACS Treatment Antihistamines / decongestant combinations - “Older” sedating antihistamines more effective - Treatment effect should be observed in 1 week Additional / Alternative treatments : Ipratropium nasal spray : 2-7 days Nasal steroids (such as BDP, FP,BUD) : 2-3 days - 2 week 3 months prescribed Eosinophilic Eronchitis Airway obstruction Bronchial hyperreactivity NO YES YES NO Asthmatic Coughs Cough Variant Asthma Asthma Cough Variant Asthma Prevalence : 24 – 59% Clinical Diagnosis Gold standard  History - Episodic symptoms, Family history Reversibility testing PEF monitoring Bronchoprovocation test Differential Diagnosis: Decreased of cough with classical asthma therapy ACCP consensus. CHEST 1998; 114: 133-181 ERS Task Force. ERS Journal ; 24: 553-566 The Journal of Respiratory Disease; 25; 310-315 THORAX 59; 342-346 Middle age patients Smoking is unusual, occupational ? Prevalence of atopy similar population Good respond to inhaled steroids Gibson et al. Lancet 1989 Chest 2006;129:116S-121S Eosinophilic Bronchitis Isolated chronic cough,  productive of sputum Normal lung function without variable airflow limitation Airway hyperresponsiveness absent Eosinophilia in sputum and BAL Cough reflex to capsaicin increased Normal daily variability in peak expiratory flow (<20%) 1)Kim et al AJRCCM 2003; 2) Brightling et al AJRCCM 1999;160:406-10, 3) Joo Korean JIM 2002;17:31-7, 4) Carney et al AJRCCM 1997; 156:211-6, 5) Ma et al Zhongua 2003;26:362-5, 6) Ayik, Erdinc et al Respir Med 2003;97:695-701 Eosinophilic Bronchitis A Worldwide Disease Causes of chronic cough Ayık SÖ, Başoğlu ÖK, Erdinç M. Respir Med Vol. 97 (2003) 695-701 Causes of Isolated Chronic Cough Brightling CE et al. AJRCCM 1999 Asthmatic Cough Airway obstruction Reversibility PEF değişkenliği Increased NO all of them PEF monitoring Prevalence: 0-50% More agressive diagnosis and treatments UACS, GERD and postinfectious cough leads to lower incidence ‘unexplained’. Airway inflammation Mast cell, histamin, cysteinil LTs, PD2, PE2 Irwin RS,et al. Chest 2006;130:362-370 Chronic Unexplained (Idiopathic) Cough Important missed history (smoking,ACEI,enviromental,drugs,allergy) Failure to do correct diagnostic tests Failure to use ‘empiric’ treatment Failure to use effective therapy Unknown disease process Potential Reasons Chronic Unexplained (Idiopathic) Cough « Truly idiopathic cough is rare and misdiagnosis very common, especially if cough is provoked by sites outside the airways » Eur Respir J 24: 481-492 2004 Idiopathic cough % ? Studies in the 1980’s % patients 1990-1995 Idiopathic cough % ? % patients Idiopathic cough % ? 1996-1999 % patients Idiopathic cough % ? 2000  % patients Haque et al Chest 2005;127:1710-1713 Chronic Idiopathic Cough Predominantly female and associated with BAL lymphocytosis Raising the possibility of a link between autoimmune diseases Surinder S. Et al. Respir Med 98:242-246;2004 Chronic Idiopathic Cough *OR: 8.8 Inflammation Chronic Idiopathic Cough Birring et al AJRCM 2004 + BAL lymphocytosis Sarcoidosis Hypersensitivity pneumonitis Rheumatoid Arthritis Sjögren’s syndrome Lung tx Inflammatory bowel disease Hypothyroidism Autoimmune disorders (SLE, RA) Pernisious anemia DM Thorax 2003;58:1066-1070 Chronic Idiopathic Cough Irwin RS,et al. Chest 2006;130:362-370 It is not correct to state that “a typical lymphocytic airways inflammation is seen in idiopathic cough” because lymphocytic or lymphoplasmacytic inflammation a non-specific finding related to trauma of coughing Chronic Idiopathic Cough Psychogenic Cough Cough is often triggered by a common cold Usually dissapears during sleep Like a dog barking The diagnosis of psychogenic cough is one of exclusion, after ruling out an organic or functional cause of cough. Specific or empiric treatment Antitussives are usually ineffective. Respirology 2006;Suppl 4 ;S160-S174 Irwin RS et al. Chest 1998, 114:2 suppl ERS Task Force: Eur Respir J 2004, 24:481-492 Prevalence: 11-25 % History: After a respiratory tract infection Diagnosis: Spasmodic cough Normal chest radiograph, with/without ronchii Respiratory viruses, m.pneumoniae, c.pneumoniae, B.pertussis Serum acute IgA antibody ELISA Rarely lymphocytosis Airway inflammation +/- Airway hyperresponsivenes Irwin RS et al. Chest 1998, 114:2 suppl ACCP consensus. CHEST 1998; 114: 133-181 ERS Task Force. ERS Journal ; 24: 553-566 Postinfectious Cough

Slide 47 -

CHRONIC COUGH MÜNEVVER ERDİNÇ Department of Chest Diseases Ege University Faculty of Medicine Differential Diagnosis And Treatment In Adults Acute Cough lasting less than 3 weeks Subacute Cough lasting 3 to 8 weeks Chronic Cough Lasting more than 8 weeks Morice AH.Eur Respir J 2004 :24:481-492 Fontana GA.Thorax 2003;58:1092-1095 Irwin RS.NEJM 343(23): 1715-1721,2000 Irwin RS. Chest 1998; 114(suppl1) :133S-181S Differantial Diagnosis of Chronic Cough in Adults PNDS Allergic rhinitis Chronic sinusitis GERD Cough variant asthma ACEI induced cough Pertusis Neurogenic Traumatic Postinfectious cough Phychogenic cough Chronic aspiration Zenker diverticulosis Foreign body Chronic bronchitis Bronchiectasis Lung cancer Subglottic stenosis Tracheomalasie Tracheoesophageal fistul Tuerculosis Sarcoidosis Congestive heart failure Simpson CB. Otolaryngology–Head Neck Surg 2006; 134: 693-700 In prospective studies in adults, chronic cough is most commonly due to 6 disorders : Upper Airway Cough Syndrome (UACS) Asthma GERD Chronic Bronchitis Bronchiectasis Non-asthmatic Eosinophilic Bronchitis Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S New Considerations Eosinophilic bronchitis Atopic cough Non acid(volume)/ weakly acid reflux Idiopathic (unexplained) öksürük Diagnosis and Management of Cough ACCP Evidence-Based CPG 2006 Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S Plevkova, et al. Respir Physiol Neurobiol 2004; 142: 225-235 Postnasal drip syndrome (PNDS) renamed upper airway cough syndrome (UACS) Upper airway afferents may reflexly enhance coughing Nonasthmatic eosinophilic bronchitis recognized as a common cause of chronic cough Idiopathic cough renamed unexplained cough The term acid reflux disease, unless it can be definitively shown to apply, replaced by reflux disease Update of current diagnostic and therapeutic approaches Common diseases, Uncommon diseases New algorithms for the management of cough in adults and children An empiric integrative approach is recommended 10 12 13 12 16 6 4 ASTHMA PNDS GERD Chest 1999;116:279-284 1. Gastroesophageal reflux disease (21-41%) 2. Cough variant asthma (24-59%) 3. Postnasal drip syndrome (41-58%) Chest 1999;116:279-281 Percentage of Cases Presenting 1,2,3, and 4 Causative Factors İmmunocompetent patients Not exposed to enviromental irritants Chest radiograph is normal Not taking an ACE inhibitor Not a current smoker Asthma and/or GERD, PNDS responsible for 93.6% of the cases of chronic cough Harding SM .Chest 2003;123:659-660 Changing Trends in Diagnosis Percentage of Diagnosis (%) GERD ASTHMA RHINITIS Impaired esophageal clearance Functional defect in LES syphincter Hiatal hernia Delayed gastric emptying İncreased intra-abdominal pressure GERD ? Decreased saliva Heartburn (pyrosis) and regurgitation At least weekly symptoms extraesophageal reflux symptoms and/or esophageal mucosal damage / Katzka & DiMarino 1995 FLR Signs Edema and hyperemia of larynx Vocal cord erythema, polyps, granulomas, ulcers Hyperemia and lymphoid hyperplasia of posterior pharynx Interarytenoid changes Subglottic stenosis GERD-related cough incidence 5 - 55% May be the sole presenting symptom(1/3) Thorax 2003:58;1092-1095) (Chest 1997; 111: 1389-1402) Irwin RS. Chest 2006;129:80S-94S Association between cough and reflux is important Esophageal-tracheal-bronchial reflex Microaspiration Pathogenesis ARRD 1981;123:413-417 Arch Intern Med 1996;156:997 Chest 1993;104:1511-1517 El Hennawi, 2004 OHNS Nonacidic factors? Esophageal dismotility? . Mediator Release . Inflammation . Edema . Mucus . Smooth Muscle Microaspiration REFLUX Esophageal Vagal Afferents Bronchial Hyperreactivity Airway Vagal Afferents CNS Stein MR.Am J Med 2003 Chest 1997;111: 1389-1402 Airway Airway Vagal Efferents Esophagus Tracheobronchial Tree Stomach Oesophagus Pharyngeal pHmetry + - Not GERD Clinical GERD symptoms ? Nonacid, weakly acid reflux? Increase dose PPI + alginate İmproved Not improved Continue pHmetry under treatment Consider  Simultaneously dual probes 24 hours pHmonitoring and intraesophageal impedance Irwin RS.AJRCCM 165:1469-74,2002 McGarvey LPA.Thorax 59:342-346,2004 15 cm 17 cm 6 impedance channels 1 pH electrode + Adult Standard Model ZAN-S61C01E Multichannel intraluminal impedance-pH catheter Non acid reflux On going reflux of ‘non-acid’ material may be responsible for continuing symptoms while on acid-suppressing medications Therapy in Esophageal-pulmonary reflux Conservative and lifestyle measures Ampirical therapy: Acid suppression Proton pump inhibitors  PPI x 2 / 3 months Therapy failure  24 hour intraesophageal pHmetry ( pharyngeal pHmetry )  GERD (+) High dose PPI + H2 blocker agent Surgery(Fundoplication) Pulmonary and Crit Care Update 1994; Vol 9 Morice AH. ERJ 2004;24:481-492 Weeks of antireflux therapy Patients responded No No (%) 2 16 (41) 4 38 (86) 6 42 (95) 8 43 (99) 12 weeks 44 (100) Poe RH.Chest 2003;123:679-684 Cumulative Response to GERD Therapy Preop pH <4: %23.6 De Meester: 85 Postop pH <4: %2.4 De Meester: 9.9 1. Chronic cough for at least 2 months 2. Immunocompetent patients 3. Chest radiograph is normal 4. Not exposed to enviromental irritants nor a present smoker 5. Not taking an ACE inhibitor 6. Symptomatic asthma has been ruled out 7. Rhinosinus diseases has been ruled out: 8. ‘Silent sinusitis’ has been ruled out 9. Nonasthmatic eosinophilic bronchitis has been ruled out: BPT is negative Cough has not improved with asthma therapy First generation H1 antagonists has been used Eo 3% in induced sputum Cough has not improved with steroids Irwin RS. Chest 2006;129:80S-94S İrwin RS. AJRCCM Vol 165; 1469-1474, 2002 Clinical Profile That Chronic Cough İs Likely Due To ‘Silent GERD’ Postnasal Drip Syndrome (PNDS) Prevalence : 8 – 87% Pathogenesis : The sensation of drainage of secretions from the nose or paranasal sinuses into the pharynx Clinical Presentation: Dripping sensation Tickle in the throat Nasal congestion Mucus in oropharynx Cobblestone appearence of oropharynx ACCP consensus. CHEST 1998; 114: 133-181 ERS Task Force. ERS Journal ; 24: 553-566 Pathogenic Triad in Chronic Cough. CHEST 1999; 116: 279-284 Evaluation of chronic cough. UPTODATE 2005 Chest 2006;129:63S-71S In patient with chronic cough that is related to upper airway abnormalities Upper Airway Cough Syndrome UACS Treatment Antihistamines / decongestant combinations - “Older” sedating antihistamines more effective - Treatment effect should be observed in 1 week Additional / Alternative treatments : Ipratropium nasal spray : 2-7 days Nasal steroids (such as BDP, FP,BUD) : 2-3 days - 2 week 3 months prescribed Eosinophilic Eronchitis Airway obstruction Bronchial hyperreactivity NO YES YES NO Asthmatic Coughs Cough Variant Asthma Asthma Cough Variant Asthma Prevalence : 24 – 59% Clinical Diagnosis Gold standard  History - Episodic symptoms, Family history Reversibility testing PEF monitoring Bronchoprovocation test Differential Diagnosis: Decreased of cough with classical asthma therapy ACCP consensus. CHEST 1998; 114: 133-181 ERS Task Force. ERS Journal ; 24: 553-566 The Journal of Respiratory Disease; 25; 310-315 THORAX 59; 342-346 Middle age patients Smoking is unusual, occupational ? Prevalence of atopy similar population Good respond to inhaled steroids Gibson et al. Lancet 1989 Chest 2006;129:116S-121S Eosinophilic Bronchitis Isolated chronic cough,  productive of sputum Normal lung function without variable airflow limitation Airway hyperresponsiveness absent Eosinophilia in sputum and BAL Cough reflex to capsaicin increased Normal daily variability in peak expiratory flow (<20%) 1)Kim et al AJRCCM 2003; 2) Brightling et al AJRCCM 1999;160:406-10, 3) Joo Korean JIM 2002;17:31-7, 4) Carney et al AJRCCM 1997; 156:211-6, 5) Ma et al Zhongua 2003;26:362-5, 6) Ayik, Erdinc et al Respir Med 2003;97:695-701 Eosinophilic Bronchitis A Worldwide Disease Causes of chronic cough Ayık SÖ, Başoğlu ÖK, Erdinç M. Respir Med Vol. 97 (2003) 695-701 Causes of Isolated Chronic Cough Brightling CE et al. AJRCCM 1999 Asthmatic Cough Airway obstruction Reversibility PEF değişkenliği Increased NO all of them PEF monitoring Prevalence: 0-50% More agressive diagnosis and treatments UACS, GERD and postinfectious cough leads to lower incidence ‘unexplained’. Airway inflammation Mast cell, histamin, cysteinil LTs, PD2, PE2 Irwin RS,et al. Chest 2006;130:362-370 Chronic Unexplained (Idiopathic) Cough Important missed history (smoking,ACEI,enviromental,drugs,allergy) Failure to do correct diagnostic tests Failure to use ‘empiric’ treatment Failure to use effective therapy Unknown disease process Potential Reasons Chronic Unexplained (Idiopathic) Cough « Truly idiopathic cough is rare and misdiagnosis very common, especially if cough is provoked by sites outside the airways » Eur Respir J 24: 481-492 2004 Idiopathic cough % ? Studies in the 1980’s % patients 1990-1995 Idiopathic cough % ? % patients Idiopathic cough % ? 1996-1999 % patients Idiopathic cough % ? 2000  % patients Haque et al Chest 2005;127:1710-1713 Chronic Idiopathic Cough Predominantly female and associated with BAL lymphocytosis Raising the possibility of a link between autoimmune diseases Surinder S. Et al. Respir Med 98:242-246;2004 Chronic Idiopathic Cough *OR: 8.8 Inflammation Chronic Idiopathic Cough Birring et al AJRCM 2004 + BAL lymphocytosis Sarcoidosis Hypersensitivity pneumonitis Rheumatoid Arthritis Sjögren’s syndrome Lung tx Inflammatory bowel disease Hypothyroidism Autoimmune disorders (SLE, RA) Pernisious anemia DM Thorax 2003;58:1066-1070 Chronic Idiopathic Cough Irwin RS,et al. Chest 2006;130:362-370 It is not correct to state that “a typical lymphocytic airways inflammation is seen in idiopathic cough” because lymphocytic or lymphoplasmacytic inflammation a non-specific finding related to trauma of coughing Chronic Idiopathic Cough Psychogenic Cough Cough is often triggered by a common cold Usually dissapears during sleep Like a dog barking The diagnosis of psychogenic cough is one of exclusion, after ruling out an organic or functional cause of cough. Specific or empiric treatment Antitussives are usually ineffective. Respirology 2006;Suppl 4 ;S160-S174 Irwin RS et al. Chest 1998, 114:2 suppl ERS Task Force: Eur Respir J 2004, 24:481-492 Prevalence: 11-25 % History: After a respiratory tract infection Diagnosis: Spasmodic cough Normal chest radiograph, with/without ronchii Respiratory viruses, m.pneumoniae, c.pneumoniae, B.pertussis Serum acute IgA antibody ELISA Rarely lymphocytosis Airway inflammation +/- Airway hyperresponsivenes Irwin RS et al. Chest 1998, 114:2 suppl ACCP consensus. CHEST 1998; 114: 133-181 ERS Task Force. ERS Journal ; 24: 553-566 Postinfectious Cough Oral and/or inhaled steroid (2-3 weeks) Antibiyotic : Macrolides (Chlamydia, mycoplasma) TMP/SMX : Pertusis (3-6 weeks) Ipatropium bromid decrease efferent limb of the cough reflex decrease stimulation of cough receptors Antitussive therapy Irwin RS et al. Chest 1998,114:2 suppl Miyashita N. J Med Microbiol 2003, 52:3,265-269 Postinfectious Cough

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CHRONIC COUGH MÜNEVVER ERDİNÇ Department of Chest Diseases Ege University Faculty of Medicine Differential Diagnosis And Treatment In Adults Acute Cough lasting less than 3 weeks Subacute Cough lasting 3 to 8 weeks Chronic Cough Lasting more than 8 weeks Morice AH.Eur Respir J 2004 :24:481-492 Fontana GA.Thorax 2003;58:1092-1095 Irwin RS.NEJM 343(23): 1715-1721,2000 Irwin RS. Chest 1998; 114(suppl1) :133S-181S Differantial Diagnosis of Chronic Cough in Adults PNDS Allergic rhinitis Chronic sinusitis GERD Cough variant asthma ACEI induced cough Pertusis Neurogenic Traumatic Postinfectious cough Phychogenic cough Chronic aspiration Zenker diverticulosis Foreign body Chronic bronchitis Bronchiectasis Lung cancer Subglottic stenosis Tracheomalasie Tracheoesophageal fistul Tuerculosis Sarcoidosis Congestive heart failure Simpson CB. Otolaryngology–Head Neck Surg 2006; 134: 693-700 In prospective studies in adults, chronic cough is most commonly due to 6 disorders : Upper Airway Cough Syndrome (UACS) Asthma GERD Chronic Bronchitis Bronchiectasis Non-asthmatic Eosinophilic Bronchitis Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S New Considerations Eosinophilic bronchitis Atopic cough Non acid(volume)/ weakly acid reflux Idiopathic (unexplained) öksürük Diagnosis and Management of Cough ACCP Evidence-Based CPG 2006 Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S Plevkova, et al. Respir Physiol Neurobiol 2004; 142: 225-235 Postnasal drip syndrome (PNDS) renamed upper airway cough syndrome (UACS) Upper airway afferents may reflexly enhance coughing Nonasthmatic eosinophilic bronchitis recognized as a common cause of chronic cough Idiopathic cough renamed unexplained cough The term acid reflux disease, unless it can be definitively shown to apply, replaced by reflux disease Update of current diagnostic and therapeutic approaches Common diseases, Uncommon diseases New algorithms for the management of cough in adults and children An empiric integrative approach is recommended 10 12 13 12 16 6 4 ASTHMA PNDS GERD Chest 1999;116:279-284 1. Gastroesophageal reflux disease (21-41%) 2. Cough variant asthma (24-59%) 3. Postnasal drip syndrome (41-58%) Chest 1999;116:279-281 Percentage of Cases Presenting 1,2,3, and 4 Causative Factors İmmunocompetent patients Not exposed to enviromental irritants Chest radiograph is normal Not taking an ACE inhibitor Not a current smoker Asthma and/or GERD, PNDS responsible for 93.6% of the cases of chronic cough Harding SM .Chest 2003;123:659-660 Changing Trends in Diagnosis Percentage of Diagnosis (%) GERD ASTHMA RHINITIS Impaired esophageal clearance Functional defect in LES syphincter Hiatal hernia Delayed gastric emptying İncreased intra-abdominal pressure GERD ? Decreased saliva Heartburn (pyrosis) and regurgitation At least weekly symptoms extraesophageal reflux symptoms and/or esophageal mucosal damage / Katzka & DiMarino 1995 FLR Signs Edema and hyperemia of larynx Vocal cord erythema, polyps, granulomas, ulcers Hyperemia and lymphoid hyperplasia of posterior pharynx Interarytenoid changes Subglottic stenosis GERD-related cough incidence 5 - 55% May be the sole presenting symptom(1/3) Thorax 2003:58;1092-1095) (Chest 1997; 111: 1389-1402) Irwin RS. Chest 2006;129:80S-94S Association between cough and reflux is important Esophageal-tracheal-bronchial reflex Microaspiration Pathogenesis ARRD 1981;123:413-417 Arch Intern Med 1996;156:997 Chest 1993;104:1511-1517 El Hennawi, 2004 OHNS Nonacidic factors? Esophageal dismotility? . Mediator Release . Inflammation . Edema . Mucus . Smooth Muscle Microaspiration REFLUX Esophageal Vagal Afferents Bronchial Hyperreactivity Airway Vagal Afferents CNS Stein MR.Am J Med 2003 Chest 1997;111: 1389-1402 Airway Airway Vagal Efferents Esophagus Tracheobronchial Tree Stomach Oesophagus Pharyngeal pHmetry + - Not GERD Clinical GERD symptoms ? Nonacid, weakly acid reflux? Increase dose PPI + alginate İmproved Not improved Continue pHmetry under treatment Consider  Simultaneously dual probes 24 hours pHmonitoring and intraesophageal impedance Irwin RS.AJRCCM 165:1469-74,2002 McGarvey LPA.Thorax 59:342-346,2004 15 cm 17 cm 6 impedance channels 1 pH electrode + Adult Standard Model ZAN-S61C01E Multichannel intraluminal impedance-pH catheter Non acid reflux On going reflux of ‘non-acid’ material may be responsible for continuing symptoms while on acid-suppressing medications Therapy in Esophageal-pulmonary reflux Conservative and lifestyle measures Ampirical therapy: Acid suppression Proton pump inhibitors  PPI x 2 / 3 months Therapy failure  24 hour intraesophageal pHmetry ( pharyngeal pHmetry )  GERD (+) High dose PPI + H2 blocker agent Surgery(Fundoplication) Pulmonary and Crit Care Update 1994; Vol 9 Morice AH. ERJ 2004;24:481-492 Weeks of antireflux therapy Patients responded No No (%) 2 16 (41) 4 38 (86) 6 42 (95) 8 43 (99) 12 weeks 44 (100) Poe RH.Chest 2003;123:679-684 Cumulative Response to GERD Therapy Preop pH <4: %23.6 De Meester: 85 Postop pH <4: %2.4 De Meester: 9.9 1. Chronic cough for at least 2 months 2. Immunocompetent patients 3. Chest radiograph is normal 4. Not exposed to enviromental irritants nor a present smoker 5. Not taking an ACE inhibitor 6. Symptomatic asthma has been ruled out 7. Rhinosinus diseases has been ruled out: 8. ‘Silent sinusitis’ has been ruled out 9. Nonasthmatic eosinophilic bronchitis has been ruled out: BPT is negative Cough has not improved with asthma therapy First generation H1 antagonists has been used Eo 3% in induced sputum Cough has not improved with steroids Irwin RS. Chest 2006;129:80S-94S İrwin RS. AJRCCM Vol 165; 1469-1474, 2002 Clinical Profile That Chronic Cough İs Likely Due To ‘Silent GERD’ Postnasal Drip Syndrome (PNDS) Prevalence : 8 – 87% Pathogenesis : The sensation of drainage of secretions from the nose or paranasal sinuses into the pharynx Clinical Presentation: Dripping sensation Tickle in the throat Nasal congestion Mucus in oropharynx Cobblestone appearence of oropharynx ACCP consensus. CHEST 1998; 114: 133-181 ERS Task Force. ERS Journal ; 24: 553-566 Pathogenic Triad in Chronic Cough. CHEST 1999; 116: 279-284 Evaluation of chronic cough. UPTODATE 2005 Chest 2006;129:63S-71S In patient with chronic cough that is related to upper airway abnormalities Upper Airway Cough Syndrome UACS Treatment Antihistamines / decongestant combinations - “Older” sedating antihistamines more effective - Treatment effect should be observed in 1 week Additional / Alternative treatments : Ipratropium nasal spray : 2-7 days Nasal steroids (such as BDP, FP,BUD) : 2-3 days - 2 week 3 months prescribed Eosinophilic Eronchitis Airway obstruction Bronchial hyperreactivity NO YES YES NO Asthmatic Coughs Cough Variant Asthma Asthma Cough Variant Asthma Prevalence : 24 – 59% Clinical Diagnosis Gold standard  History - Episodic symptoms, Family history Reversibility testing PEF monitoring Bronchoprovocation test Differential Diagnosis: Decreased of cough with classical asthma therapy ACCP consensus. CHEST 1998; 114: 133-181 ERS Task Force. ERS Journal ; 24: 553-566 The Journal of Respiratory Disease; 25; 310-315 THORAX 59; 342-346 Middle age patients Smoking is unusual, occupational ? Prevalence of atopy similar population Good respond to inhaled steroids Gibson et al. Lancet 1989 Chest 2006;129:116S-121S Eosinophilic Bronchitis Isolated chronic cough,  productive of sputum Normal lung function without variable airflow limitation Airway hyperresponsiveness absent Eosinophilia in sputum and BAL Cough reflex to capsaicin increased Normal daily variability in peak expiratory flow (<20%) 1)Kim et al AJRCCM 2003; 2) Brightling et al AJRCCM 1999;160:406-10, 3) Joo Korean JIM 2002;17:31-7, 4) Carney et al AJRCCM 1997; 156:211-6, 5) Ma et al Zhongua 2003;26:362-5, 6) Ayik, Erdinc et al Respir Med 2003;97:695-701 Eosinophilic Bronchitis A Worldwide Disease Causes of chronic cough Ayık SÖ, Başoğlu ÖK, Erdinç M. Respir Med Vol. 97 (2003) 695-701 Causes of Isolated Chronic Cough Brightling CE et al. AJRCCM 1999 Asthmatic Cough Airway obstruction Reversibility PEF değişkenliği Increased NO all of them PEF monitoring Prevalence: 0-50% More agressive diagnosis and treatments UACS, GERD and postinfectious cough leads to lower incidence ‘unexplained’. Airway inflammation Mast cell, histamin, cysteinil LTs, PD2, PE2 Irwin RS,et al. Chest 2006;130:362-370 Chronic Unexplained (Idiopathic) Cough Important missed history (smoking,ACEI,enviromental,drugs,allergy) Failure to do correct diagnostic tests Failure to use ‘empiric’ treatment Failure to use effective therapy Unknown disease process Potential Reasons Chronic Unexplained (Idiopathic) Cough « Truly idiopathic cough is rare and misdiagnosis very common, especially if cough is provoked by sites outside the airways » Eur Respir J 24: 481-492 2004 Idiopathic cough % ? Studies in the 1980’s % patients 1990-1995 Idiopathic cough % ? % patients Idiopathic cough % ? 1996-1999 % patients Idiopathic cough % ? 2000  % patients Haque et al Chest 2005;127:1710-1713 Chronic Idiopathic Cough Predominantly female and associated with BAL lymphocytosis Raising the possibility of a link between autoimmune diseases Surinder S. Et al. Respir Med 98:242-246;2004 Chronic Idiopathic Cough *OR: 8.8 Inflammation Chronic Idiopathic Cough Birring et al AJRCM 2004 + BAL lymphocytosis Sarcoidosis Hypersensitivity pneumonitis Rheumatoid Arthritis Sjögren’s syndrome Lung tx Inflammatory bowel disease Hypothyroidism Autoimmune disorders (SLE, RA) Pernisious anemia DM Thorax 2003;58:1066-1070 Chronic Idiopathic Cough Irwin RS,et al. Chest 2006;130:362-370 It is not correct to state that “a typical lymphocytic airways inflammation is seen in idiopathic cough” because lymphocytic or lymphoplasmacytic inflammation a non-specific finding related to trauma of coughing Chronic Idiopathic Cough Psychogenic Cough Cough is often triggered by a common cold Usually dissapears during sleep Like a dog barking The diagnosis of psychogenic cough is one of exclusion, after ruling out an organic or functional cause of cough. Specific or empiric treatment Antitussives are usually ineffective. Respirology 2006;Suppl 4 ;S160-S174 Irwin RS et al. Chest 1998, 114:2 suppl ERS Task Force: Eur Respir J 2004, 24:481-492 Prevalence: 11-25 % History: After a respiratory tract infection Diagnosis: Spasmodic cough Normal chest radiograph, with/without ronchii Respiratory viruses, m.pneumoniae, c.pneumoniae, B.pertussis Serum acute IgA antibody ELISA Rarely lymphocytosis Airway inflammation +/- Airway hyperresponsivenes Irwin RS et al. Chest 1998, 114:2 suppl ACCP consensus. CHEST 1998; 114: 133-181 ERS Task Force. ERS Journal ; 24: 553-566 Postinfectious Cough Oral and/or inhaled steroid (2-3 weeks) Antibiyotic : Macrolides (Chlamydia, mycoplasma) TMP/SMX : Pertusis (3-6 weeks) Ipatropium bromid decrease efferent limb of the cough reflex decrease stimulation of cough receptors Antitussive therapy Irwin RS et al. Chest 1998,114:2 suppl Miyashita N. J Med Microbiol 2003, 52:3,265-269 Postinfectious Cough ACEI Induced Chronic Cough Frequency: 0.2-33% Predominantly female Not dose related Appears within hours, weeks, months Pathogenesis: Neurokinin, Substance P, Prostoglandins, stimulates afferent C-fibers in the airway  increased cough reflex sensitivity Prefer Angiotensin II receptör antagonists

Slide 49 -

CHRONIC COUGH MÜNEVVER ERDİNÇ Department of Chest Diseases Ege University Faculty of Medicine Differential Diagnosis And Treatment In Adults Acute Cough lasting less than 3 weeks Subacute Cough lasting 3 to 8 weeks Chronic Cough Lasting more than 8 weeks Morice AH.Eur Respir J 2004 :24:481-492 Fontana GA.Thorax 2003;58:1092-1095 Irwin RS.NEJM 343(23): 1715-1721,2000 Irwin RS. Chest 1998; 114(suppl1) :133S-181S Differantial Diagnosis of Chronic Cough in Adults PNDS Allergic rhinitis Chronic sinusitis GERD Cough variant asthma ACEI induced cough Pertusis Neurogenic Traumatic Postinfectious cough Phychogenic cough Chronic aspiration Zenker diverticulosis Foreign body Chronic bronchitis Bronchiectasis Lung cancer Subglottic stenosis Tracheomalasie Tracheoesophageal fistul Tuerculosis Sarcoidosis Congestive heart failure Simpson CB. Otolaryngology–Head Neck Surg 2006; 134: 693-700 In prospective studies in adults, chronic cough is most commonly due to 6 disorders : Upper Airway Cough Syndrome (UACS) Asthma GERD Chronic Bronchitis Bronchiectasis Non-asthmatic Eosinophilic Bronchitis Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S New Considerations Eosinophilic bronchitis Atopic cough Non acid(volume)/ weakly acid reflux Idiopathic (unexplained) öksürük Diagnosis and Management of Cough ACCP Evidence-Based CPG 2006 Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S Plevkova, et al. Respir Physiol Neurobiol 2004; 142: 225-235 Postnasal drip syndrome (PNDS) renamed upper airway cough syndrome (UACS) Upper airway afferents may reflexly enhance coughing Nonasthmatic eosinophilic bronchitis recognized as a common cause of chronic cough Idiopathic cough renamed unexplained cough The term acid reflux disease, unless it can be definitively shown to apply, replaced by reflux disease Update of current diagnostic and therapeutic approaches Common diseases, Uncommon diseases New algorithms for the management of cough in adults and children An empiric integrative approach is recommended 10 12 13 12 16 6 4 ASTHMA PNDS GERD Chest 1999;116:279-284 1. Gastroesophageal reflux disease (21-41%) 2. Cough variant asthma (24-59%) 3. Postnasal drip syndrome (41-58%) Chest 1999;116:279-281 Percentage of Cases Presenting 1,2,3, and 4 Causative Factors İmmunocompetent patients Not exposed to enviromental irritants Chest radiograph is normal Not taking an ACE inhibitor Not a current smoker Asthma and/or GERD, PNDS responsible for 93.6% of the cases of chronic cough Harding SM .Chest 2003;123:659-660 Changing Trends in Diagnosis Percentage of Diagnosis (%) GERD ASTHMA RHINITIS Impaired esophageal clearance Functional defect in LES syphincter Hiatal hernia Delayed gastric emptying İncreased intra-abdominal pressure GERD ? Decreased saliva Heartburn (pyrosis) and regurgitation At least weekly symptoms extraesophageal reflux symptoms and/or esophageal mucosal damage / Katzka & DiMarino 1995 FLR Signs Edema and hyperemia of larynx Vocal cord erythema, polyps, granulomas, ulcers Hyperemia and lymphoid hyperplasia of posterior pharynx Interarytenoid changes Subglottic stenosis GERD-related cough incidence 5 - 55% May be the sole presenting symptom(1/3) Thorax 2003:58;1092-1095) (Chest 1997; 111: 1389-1402) Irwin RS. Chest 2006;129:80S-94S Association between cough and reflux is important Esophageal-tracheal-bronchial reflex Microaspiration Pathogenesis ARRD 1981;123:413-417 Arch Intern Med 1996;156:997 Chest 1993;104:1511-1517 El Hennawi, 2004 OHNS Nonacidic factors? Esophageal dismotility? . Mediator Release . Inflammation . Edema . Mucus . Smooth Muscle Microaspiration REFLUX Esophageal Vagal Afferents Bronchial Hyperreactivity Airway Vagal Afferents CNS Stein MR.Am J Med 2003 Chest 1997;111: 1389-1402 Airway Airway Vagal Efferents Esophagus Tracheobronchial Tree Stomach Oesophagus Pharyngeal pHmetry + - Not GERD Clinical GERD symptoms ? Nonacid, weakly acid reflux? Increase dose PPI + alginate İmproved Not improved Continue pHmetry under treatment Consider  Simultaneously dual probes 24 hours pHmonitoring and intraesophageal impedance Irwin RS.AJRCCM 165:1469-74,2002 McGarvey LPA.Thorax 59:342-346,2004 15 cm 17 cm 6 impedance channels 1 pH electrode + Adult Standard Model ZAN-S61C01E Multichannel intraluminal impedance-pH catheter Non acid reflux On going reflux of ‘non-acid’ material may be responsible for continuing symptoms while on acid-suppressing medications Therapy in Esophageal-pulmonary reflux Conservative and lifestyle measures Ampirical therapy: Acid suppression Proton pump inhibitors  PPI x 2 / 3 months Therapy failure  24 hour intraesophageal pHmetry ( pharyngeal pHmetry )  GERD (+) High dose PPI + H2 blocker agent Surgery(Fundoplication) Pulmonary and Crit Care Update 1994; Vol 9 Morice AH. ERJ 2004;24:481-492 Weeks of antireflux therapy Patients responded No No (%) 2 16 (41) 4 38 (86) 6 42 (95) 8 43 (99) 12 weeks 44 (100) Poe RH.Chest 2003;123:679-684 Cumulative Response to GERD Therapy Preop pH <4: %23.6 De Meester: 85 Postop pH <4: %2.4 De Meester: 9.9 1. Chronic cough for at least 2 months 2. Immunocompetent patients 3. Chest radiograph is normal 4. Not exposed to enviromental irritants nor a present smoker 5. Not taking an ACE inhibitor 6. Symptomatic asthma has been ruled out 7. Rhinosinus diseases has been ruled out: 8. ‘Silent sinusitis’ has been ruled out 9. Nonasthmatic eosinophilic bronchitis has been ruled out: BPT is negative Cough has not improved with asthma therapy First generation H1 antagonists has been used Eo 3% in induced sputum Cough has not improved with steroids Irwin RS. Chest 2006;129:80S-94S İrwin RS. AJRCCM Vol 165; 1469-1474, 2002 Clinical Profile That Chronic Cough İs Likely Due To ‘Silent GERD’ Postnasal Drip Syndrome (PNDS) Prevalence : 8 – 87% Pathogenesis : The sensation of drainage of secretions from the nose or paranasal sinuses into the pharynx Clinical Presentation: Dripping sensation Tickle in the throat Nasal congestion Mucus in oropharynx Cobblestone appearence of oropharynx ACCP consensus. CHEST 1998; 114: 133-181 ERS Task Force. ERS Journal ; 24: 553-566 Pathogenic Triad in Chronic Cough. CHEST 1999; 116: 279-284 Evaluation of chronic cough. UPTODATE 2005 Chest 2006;129:63S-71S In patient with chronic cough that is related to upper airway abnormalities Upper Airway Cough Syndrome UACS Treatment Antihistamines / decongestant combinations - “Older” sedating antihistamines more effective - Treatment effect should be observed in 1 week Additional / Alternative treatments : Ipratropium nasal spray : 2-7 days Nasal steroids (such as BDP, FP,BUD) : 2-3 days - 2 week 3 months prescribed Eosinophilic Eronchitis Airway obstruction Bronchial hyperreactivity NO YES YES NO Asthmatic Coughs Cough Variant Asthma Asthma Cough Variant Asthma Prevalence : 24 – 59% Clinical Diagnosis Gold standard  History - Episodic symptoms, Family history Reversibility testing PEF monitoring Bronchoprovocation test Differential Diagnosis: Decreased of cough with classical asthma therapy ACCP consensus. CHEST 1998; 114: 133-181 ERS Task Force. ERS Journal ; 24: 553-566 The Journal of Respiratory Disease; 25; 310-315 THORAX 59; 342-346 Middle age patients Smoking is unusual, occupational ? Prevalence of atopy similar population Good respond to inhaled steroids Gibson et al. Lancet 1989 Chest 2006;129:116S-121S Eosinophilic Bronchitis Isolated chronic cough,  productive of sputum Normal lung function without variable airflow limitation Airway hyperresponsiveness absent Eosinophilia in sputum and BAL Cough reflex to capsaicin increased Normal daily variability in peak expiratory flow (<20%) 1)Kim et al AJRCCM 2003; 2) Brightling et al AJRCCM 1999;160:406-10, 3) Joo Korean JIM 2002;17:31-7, 4) Carney et al AJRCCM 1997; 156:211-6, 5) Ma et al Zhongua 2003;26:362-5, 6) Ayik, Erdinc et al Respir Med 2003;97:695-701 Eosinophilic Bronchitis A Worldwide Disease Causes of chronic cough Ayık SÖ, Başoğlu ÖK, Erdinç M. Respir Med Vol. 97 (2003) 695-701 Causes of Isolated Chronic Cough Brightling CE et al. AJRCCM 1999 Asthmatic Cough Airway obstruction Reversibility PEF değişkenliği Increased NO all of them PEF monitoring Prevalence: 0-50% More agressive diagnosis and treatments UACS, GERD and postinfectious cough leads to lower incidence ‘unexplained’. Airway inflammation Mast cell, histamin, cysteinil LTs, PD2, PE2 Irwin RS,et al. Chest 2006;130:362-370 Chronic Unexplained (Idiopathic) Cough Important missed history (smoking,ACEI,enviromental,drugs,allergy) Failure to do correct diagnostic tests Failure to use ‘empiric’ treatment Failure to use effective therapy Unknown disease process Potential Reasons Chronic Unexplained (Idiopathic) Cough « Truly idiopathic cough is rare and misdiagnosis very common, especially if cough is provoked by sites outside the airways » Eur Respir J 24: 481-492 2004 Idiopathic cough % ? Studies in the 1980’s % patients 1990-1995 Idiopathic cough % ? % patients Idiopathic cough % ? 1996-1999 % patients Idiopathic cough % ? 2000  % patients Haque et al Chest 2005;127:1710-1713 Chronic Idiopathic Cough Predominantly female and associated with BAL lymphocytosis Raising the possibility of a link between autoimmune diseases Surinder S. Et al. Respir Med 98:242-246;2004 Chronic Idiopathic Cough *OR: 8.8 Inflammation Chronic Idiopathic Cough Birring et al AJRCM 2004 + BAL lymphocytosis Sarcoidosis Hypersensitivity pneumonitis Rheumatoid Arthritis Sjögren’s syndrome Lung tx Inflammatory bowel disease Hypothyroidism Autoimmune disorders (SLE, RA) Pernisious anemia DM Thorax 2003;58:1066-1070 Chronic Idiopathic Cough Irwin RS,et al. Chest 2006;130:362-370 It is not correct to state that “a typical lymphocytic airways inflammation is seen in idiopathic cough” because lymphocytic or lymphoplasmacytic inflammation a non-specific finding related to trauma of coughing Chronic Idiopathic Cough Psychogenic Cough Cough is often triggered by a common cold Usually dissapears during sleep Like a dog barking The diagnosis of psychogenic cough is one of exclusion, after ruling out an organic or functional cause of cough. Specific or empiric treatment Antitussives are usually ineffective. Respirology 2006;Suppl 4 ;S160-S174 Irwin RS et al. Chest 1998, 114:2 suppl ERS Task Force: Eur Respir J 2004, 24:481-492 Prevalence: 11-25 % History: After a respiratory tract infection Diagnosis: Spasmodic cough Normal chest radiograph, with/without ronchii Respiratory viruses, m.pneumoniae, c.pneumoniae, B.pertussis Serum acute IgA antibody ELISA Rarely lymphocytosis Airway inflammation +/- Airway hyperresponsivenes Irwin RS et al. Chest 1998, 114:2 suppl ACCP consensus. CHEST 1998; 114: 133-181 ERS Task Force. ERS Journal ; 24: 553-566 Postinfectious Cough Oral and/or inhaled steroid (2-3 weeks) Antibiyotic : Macrolides (Chlamydia, mycoplasma) TMP/SMX : Pertusis (3-6 weeks) Ipatropium bromid decrease efferent limb of the cough reflex decrease stimulation of cough receptors Antitussive therapy Irwin RS et al. Chest 1998,114:2 suppl Miyashita N. J Med Microbiol 2003, 52:3,265-269 Postinfectious Cough ACEI Induced Chronic Cough Frequency: 0.2-33% Predominantly female Not dose related Appears within hours, weeks, months Pathogenesis: Neurokinin, Substance P, Prostoglandins, stimulates afferent C-fibers in the airway  increased cough reflex sensitivity Prefer Angiotensin II receptör antagonists Treatment Irwin RS et al. Chest 1998, 114:2

Slide 50 -

CHRONIC COUGH MÜNEVVER ERDİNÇ Department of Chest Diseases Ege University Faculty of Medicine Differential Diagnosis And Treatment In Adults Acute Cough lasting less than 3 weeks Subacute Cough lasting 3 to 8 weeks Chronic Cough Lasting more than 8 weeks Morice AH.Eur Respir J 2004 :24:481-492 Fontana GA.Thorax 2003;58:1092-1095 Irwin RS.NEJM 343(23): 1715-1721,2000 Irwin RS. Chest 1998; 114(suppl1) :133S-181S Differantial Diagnosis of Chronic Cough in Adults PNDS Allergic rhinitis Chronic sinusitis GERD Cough variant asthma ACEI induced cough Pertusis Neurogenic Traumatic Postinfectious cough Phychogenic cough Chronic aspiration Zenker diverticulosis Foreign body Chronic bronchitis Bronchiectasis Lung cancer Subglottic stenosis Tracheomalasie Tracheoesophageal fistul Tuerculosis Sarcoidosis Congestive heart failure Simpson CB. Otolaryngology–Head Neck Surg 2006; 134: 693-700 In prospective studies in adults, chronic cough is most commonly due to 6 disorders : Upper Airway Cough Syndrome (UACS) Asthma GERD Chronic Bronchitis Bronchiectasis Non-asthmatic Eosinophilic Bronchitis Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S New Considerations Eosinophilic bronchitis Atopic cough Non acid(volume)/ weakly acid reflux Idiopathic (unexplained) öksürük Diagnosis and Management of Cough ACCP Evidence-Based CPG 2006 Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S Plevkova, et al. Respir Physiol Neurobiol 2004; 142: 225-235 Postnasal drip syndrome (PNDS) renamed upper airway cough syndrome (UACS) Upper airway afferents may reflexly enhance coughing Nonasthmatic eosinophilic bronchitis recognized as a common cause of chronic cough Idiopathic cough renamed unexplained cough The term acid reflux disease, unless it can be definitively shown to apply, replaced by reflux disease Update of current diagnostic and therapeutic approaches Common diseases, Uncommon diseases New algorithms for the management of cough in adults and children An empiric integrative approach is recommended 10 12 13 12 16 6 4 ASTHMA PNDS GERD Chest 1999;116:279-284 1. Gastroesophageal reflux disease (21-41%) 2. Cough variant asthma (24-59%) 3. Postnasal drip syndrome (41-58%) Chest 1999;116:279-281 Percentage of Cases Presenting 1,2,3, and 4 Causative Factors İmmunocompetent patients Not exposed to enviromental irritants Chest radiograph is normal Not taking an ACE inhibitor Not a current smoker Asthma and/or GERD, PNDS responsible for 93.6% of the cases of chronic cough Harding SM .Chest 2003;123:659-660 Changing Trends in Diagnosis Percentage of Diagnosis (%) GERD ASTHMA RHINITIS Impaired esophageal clearance Functional defect in LES syphincter Hiatal hernia Delayed gastric emptying İncreased intra-abdominal pressure GERD ? Decreased saliva Heartburn (pyrosis) and regurgitation At least weekly symptoms extraesophageal reflux symptoms and/or esophageal mucosal damage / Katzka & DiMarino 1995 FLR Signs Edema and hyperemia of larynx Vocal cord erythema, polyps, granulomas, ulcers Hyperemia and lymphoid hyperplasia of posterior pharynx Interarytenoid changes Subglottic stenosis GERD-related cough incidence 5 - 55% May be the sole presenting symptom(1/3) Thorax 2003:58;1092-1095) (Chest 1997; 111: 1389-1402) Irwin RS. Chest 2006;129:80S-94S Association between cough and reflux is important Esophageal-tracheal-bronchial reflex Microaspiration Pathogenesis ARRD 1981;123:413-417 Arch Intern Med 1996;156:997 Chest 1993;104:1511-1517 El Hennawi, 2004 OHNS Nonacidic factors? Esophageal dismotility? . Mediator Release . Inflammation . Edema . Mucus . Smooth Muscle Microaspiration REFLUX Esophageal Vagal Afferents Bronchial Hyperreactivity Airway Vagal Afferents CNS Stein MR.Am J Med 2003 Chest 1997;111: 1389-1402 Airway Airway Vagal Efferents Esophagus Tracheobronchial Tree Stomach Oesophagus Pharyngeal pHmetry + - Not GERD Clinical GERD symptoms ? Nonacid, weakly acid reflux? Increase dose PPI + alginate İmproved Not improved Continue pHmetry under treatment Consider  Simultaneously dual probes 24 hours pHmonitoring and intraesophageal impedance Irwin RS.AJRCCM 165:1469-74,2002 McGarvey LPA.Thorax 59:342-346,2004 15 cm 17 cm 6 impedance channels 1 pH electrode + Adult Standard Model ZAN-S61C01E Multichannel intraluminal impedance-pH catheter Non acid reflux On going reflux of ‘non-acid’ material may be responsible for continuing symptoms while on acid-suppressing medications Therapy in Esophageal-pulmonary reflux Conservative and lifestyle measures Ampirical therapy: Acid suppression Proton pump inhibitors  PPI x 2 / 3 months Therapy failure  24 hour intraesophageal pHmetry ( pharyngeal pHmetry )  GERD (+) High dose PPI + H2 blocker agent Surgery(Fundoplication) Pulmonary and Crit Care Update 1994; Vol 9 Morice AH. ERJ 2004;24:481-492 Weeks of antireflux therapy Patients responded No No (%) 2 16 (41) 4 38 (86) 6 42 (95) 8 43 (99) 12 weeks 44 (100) Poe RH.Chest 2003;123:679-684 Cumulative Response to GERD Therapy Preop pH <4: %23.6 De Meester: 85 Postop pH <4: %2.4 De Meester: 9.9 1. Chronic cough for at least 2 months 2. Immunocompetent patients 3. Chest radiograph is normal 4. Not exposed to enviromental irritants nor a present smoker 5. Not taking an ACE inhibitor 6. Symptomatic asthma has been ruled out 7. Rhinosinus diseases has been ruled out: 8. ‘Silent sinusitis’ has been ruled out 9. Nonasthmatic eosinophilic bronchitis has been ruled out: BPT is negative Cough has not improved with asthma therapy First generation H1 antagonists has been used Eo 3% in induced sputum Cough has not improved with steroids Irwin RS. Chest 2006;129:80S-94S İrwin RS. AJRCCM Vol 165; 1469-1474, 2002 Clinical Profile That Chronic Cough İs Likely Due To ‘Silent GERD’ Postnasal Drip Syndrome (PNDS) Prevalence : 8 – 87% Pathogenesis : The sensation of drainage of secretions from the nose or paranasal sinuses into the pharynx Clinical Presentation: Dripping sensation Tickle in the throat Nasal congestion Mucus in oropharynx Cobblestone appearence of oropharynx ACCP consensus. CHEST 1998; 114: 133-181 ERS Task Force. ERS Journal ; 24: 553-566 Pathogenic Triad in Chronic Cough. CHEST 1999; 116: 279-284 Evaluation of chronic cough. UPTODATE 2005 Chest 2006;129:63S-71S In patient with chronic cough that is related to upper airway abnormalities Upper Airway Cough Syndrome UACS Treatment Antihistamines / decongestant combinations - “Older” sedating antihistamines more effective - Treatment effect should be observed in 1 week Additional / Alternative treatments : Ipratropium nasal spray : 2-7 days Nasal steroids (such as BDP, FP,BUD) : 2-3 days - 2 week 3 months prescribed Eosinophilic Eronchitis Airway obstruction Bronchial hyperreactivity NO YES YES NO Asthmatic Coughs Cough Variant Asthma Asthma Cough Variant Asthma Prevalence : 24 – 59% Clinical Diagnosis Gold standard  History - Episodic symptoms, Family history Reversibility testing PEF monitoring Bronchoprovocation test Differential Diagnosis: Decreased of cough with classical asthma therapy ACCP consensus. CHEST 1998; 114: 133-181 ERS Task Force. ERS Journal ; 24: 553-566 The Journal of Respiratory Disease; 25; 310-315 THORAX 59; 342-346 Middle age patients Smoking is unusual, occupational ? Prevalence of atopy similar population Good respond to inhaled steroids Gibson et al. Lancet 1989 Chest 2006;129:116S-121S Eosinophilic Bronchitis Isolated chronic cough,  productive of sputum Normal lung function without variable airflow limitation Airway hyperresponsiveness absent Eosinophilia in sputum and BAL Cough reflex to capsaicin increased Normal daily variability in peak expiratory flow (<20%) 1)Kim et al AJRCCM 2003; 2) Brightling et al AJRCCM 1999;160:406-10, 3) Joo Korean JIM 2002;17:31-7, 4) Carney et al AJRCCM 1997; 156:211-6, 5) Ma et al Zhongua 2003;26:362-5, 6) Ayik, Erdinc et al Respir Med 2003;97:695-701 Eosinophilic Bronchitis A Worldwide Disease Causes of chronic cough Ayık SÖ, Başoğlu ÖK, Erdinç M. Respir Med Vol. 97 (2003) 695-701 Causes of Isolated Chronic Cough Brightling CE et al. AJRCCM 1999 Asthmatic Cough Airway obstruction Reversibility PEF değişkenliği Increased NO all of them PEF monitoring Prevalence: 0-50% More agressive diagnosis and treatments UACS, GERD and postinfectious cough leads to lower incidence ‘unexplained’. Airway inflammation Mast cell, histamin, cysteinil LTs, PD2, PE2 Irwin RS,et al. Chest 2006;130:362-370 Chronic Unexplained (Idiopathic) Cough Important missed history (smoking,ACEI,enviromental,drugs,allergy) Failure to do correct diagnostic tests Failure to use ‘empiric’ treatment Failure to use effective therapy Unknown disease process Potential Reasons Chronic Unexplained (Idiopathic) Cough « Truly idiopathic cough is rare and misdiagnosis very common, especially if cough is provoked by sites outside the airways » Eur Respir J 24: 481-492 2004 Idiopathic cough % ? Studies in the 1980’s % patients 1990-1995 Idiopathic cough % ? % patients Idiopathic cough % ? 1996-1999 % patients Idiopathic cough % ? 2000  % patients Haque et al Chest 2005;127:1710-1713 Chronic Idiopathic Cough Predominantly female and associated with BAL lymphocytosis Raising the possibility of a link between autoimmune diseases Surinder S. Et al. Respir Med 98:242-246;2004 Chronic Idiopathic Cough *OR: 8.8 Inflammation Chronic Idiopathic Cough Birring et al AJRCM 2004 + BAL lymphocytosis Sarcoidosis Hypersensitivity pneumonitis Rheumatoid Arthritis Sjögren’s syndrome Lung tx Inflammatory bowel disease Hypothyroidism Autoimmune disorders (SLE, RA) Pernisious anemia DM Thorax 2003;58:1066-1070 Chronic Idiopathic Cough Irwin RS,et al. Chest 2006;130:362-370 It is not correct to state that “a typical lymphocytic airways inflammation is seen in idiopathic cough” because lymphocytic or lymphoplasmacytic inflammation a non-specific finding related to trauma of coughing Chronic Idiopathic Cough Psychogenic Cough Cough is often triggered by a common cold Usually dissapears during sleep Like a dog barking The diagnosis of psychogenic cough is one of exclusion, after ruling out an organic or functional cause of cough. Specific or empiric treatment Antitussives are usually ineffective. Respirology 2006;Suppl 4 ;S160-S174 Irwin RS et al. Chest 1998, 114:2 suppl ERS Task Force: Eur Respir J 2004, 24:481-492 Prevalence: 11-25 % History: After a respiratory tract infection Diagnosis: Spasmodic cough Normal chest radiograph, with/without ronchii Respiratory viruses, m.pneumoniae, c.pneumoniae, B.pertussis Serum acute IgA antibody ELISA Rarely lymphocytosis Airway inflammation +/- Airway hyperresponsivenes Irwin RS et al. Chest 1998, 114:2 suppl ACCP consensus. CHEST 1998; 114: 133-181 ERS Task Force. ERS Journal ; 24: 553-566 Postinfectious Cough Oral and/or inhaled steroid (2-3 weeks) Antibiyotic : Macrolides (Chlamydia, mycoplasma) TMP/SMX : Pertusis (3-6 weeks) Ipatropium bromid decrease efferent limb of the cough reflex decrease stimulation of cough receptors Antitussive therapy Irwin RS et al. Chest 1998,114:2 suppl Miyashita N. J Med Microbiol 2003, 52:3,265-269 Postinfectious Cough ACEI Induced Chronic Cough Frequency: 0.2-33% Predominantly female Not dose related Appears within hours, weeks, months Pathogenesis: Neurokinin, Substance P, Prostoglandins, stimulates afferent C-fibers in the airway  increased cough reflex sensitivity Prefer Angiotensin II receptör antagonists Treatment Irwin RS et al. Chest 1998, 114:2 Capsaicin type I Vanilloid receptor antagonists Selective opioid receptor agonists Opioid-like receptor agonists Tachykinin receptor antagonists Endogenous cannabinoids 5-HT receptor agonists Large-conductance calcium-activated potassium channel openers Dicpinigaitis PV.Chest 2006 ;129:284S-286S Future Therapies

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CHRONIC COUGH MÜNEVVER ERDİNÇ Department of Chest Diseases Ege University Faculty of Medicine Differential Diagnosis And Treatment In Adults Acute Cough lasting less than 3 weeks Subacute Cough lasting 3 to 8 weeks Chronic Cough Lasting more than 8 weeks Morice AH.Eur Respir J 2004 :24:481-492 Fontana GA.Thorax 2003;58:1092-1095 Irwin RS.NEJM 343(23): 1715-1721,2000 Irwin RS. Chest 1998; 114(suppl1) :133S-181S Differantial Diagnosis of Chronic Cough in Adults PNDS Allergic rhinitis Chronic sinusitis GERD Cough variant asthma ACEI induced cough Pertusis Neurogenic Traumatic Postinfectious cough Phychogenic cough Chronic aspiration Zenker diverticulosis Foreign body Chronic bronchitis Bronchiectasis Lung cancer Subglottic stenosis Tracheomalasie Tracheoesophageal fistul Tuerculosis Sarcoidosis Congestive heart failure Simpson CB. Otolaryngology–Head Neck Surg 2006; 134: 693-700 In prospective studies in adults, chronic cough is most commonly due to 6 disorders : Upper Airway Cough Syndrome (UACS) Asthma GERD Chronic Bronchitis Bronchiectasis Non-asthmatic Eosinophilic Bronchitis Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S New Considerations Eosinophilic bronchitis Atopic cough Non acid(volume)/ weakly acid reflux Idiopathic (unexplained) öksürük Diagnosis and Management of Cough ACCP Evidence-Based CPG 2006 Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S Plevkova, et al. Respir Physiol Neurobiol 2004; 142: 225-235 Postnasal drip syndrome (PNDS) renamed upper airway cough syndrome (UACS) Upper airway afferents may reflexly enhance coughing Nonasthmatic eosinophilic bronchitis recognized as a common cause of chronic cough Idiopathic cough renamed unexplained cough The term acid reflux disease, unless it can be definitively shown to apply, replaced by reflux disease Update of current diagnostic and therapeutic approaches Common diseases, Uncommon diseases New algorithms for the management of cough in adults and children An empiric integrative approach is recommended 10 12 13 12 16 6 4 ASTHMA PNDS GERD Chest 1999;116:279-284 1. Gastroesophageal reflux disease (21-41%) 2. Cough variant asthma (24-59%) 3. Postnasal drip syndrome (41-58%) Chest 1999;116:279-281 Percentage of Cases Presenting 1,2,3, and 4 Causative Factors İmmunocompetent patients Not exposed to enviromental irritants Chest radiograph is normal Not taking an ACE inhibitor Not a current smoker Asthma and/or GERD, PNDS responsible for 93.6% of the cases of chronic cough Harding SM .Chest 2003;123:659-660 Changing Trends in Diagnosis Percentage of Diagnosis (%) GERD ASTHMA RHINITIS Impaired esophageal clearance Functional defect in LES syphincter Hiatal hernia Delayed gastric emptying İncreased intra-abdominal pressure GERD ? Decreased saliva Heartburn (pyrosis) and regurgitation At least weekly symptoms extraesophageal reflux symptoms and/or esophageal mucosal damage / Katzka & DiMarino 1995 FLR Signs Edema and hyperemia of larynx Vocal cord erythema, polyps, granulomas, ulcers Hyperemia and lymphoid hyperplasia of posterior pharynx Interarytenoid changes Subglottic stenosis GERD-related cough incidence 5 - 55% May be the sole presenting symptom(1/3) Thorax 2003:58;1092-1095) (Chest 1997; 111: 1389-1402) Irwin RS. Chest 2006;129:80S-94S Association between cough and reflux is important Esophageal-tracheal-bronchial reflex Microaspiration Pathogenesis ARRD 1981;123:413-417 Arch Intern Med 1996;156:997 Chest 1993;104:1511-1517 El Hennawi, 2004 OHNS Nonacidic factors? Esophageal dismotility? . Mediator Release . Inflammation . Edema . Mucus . Smooth Muscle Microaspiration REFLUX Esophageal Vagal Afferents Bronchial Hyperreactivity Airway Vagal Afferents CNS Stein MR.Am J Med 2003 Chest 1997;111: 1389-1402 Airway Airway Vagal Efferents Esophagus Tracheobronchial Tree Stomach Oesophagus Pharyngeal pHmetry + - Not GERD Clinical GERD symptoms ? Nonacid, weakly acid reflux? Increase dose PPI + alginate İmproved Not improved Continue pHmetry under treatment Consider  Simultaneously dual probes 24 hours pHmonitoring and intraesophageal impedance Irwin RS.AJRCCM 165:1469-74,2002 McGarvey LPA.Thorax 59:342-346,2004 15 cm 17 cm 6 impedance channels 1 pH electrode + Adult Standard Model ZAN-S61C01E Multichannel intraluminal impedance-pH catheter Non acid reflux On going reflux of ‘non-acid’ material may be responsible for continuing symptoms while on acid-suppressing medications Therapy in Esophageal-pulmonary reflux Conservative and lifestyle measures Ampirical therapy: Acid suppression Proton pump inhibitors  PPI x 2 / 3 months Therapy failure  24 hour intraesophageal pHmetry ( pharyngeal pHmetry )  GERD (+) High dose PPI + H2 blocker agent Surgery(Fundoplication) Pulmonary and Crit Care Update 1994; Vol 9 Morice AH. ERJ 2004;24:481-492 Weeks of antireflux therapy Patients responded No No (%) 2 16 (41) 4 38 (86) 6 42 (95) 8 43 (99) 12 weeks 44 (100) Poe RH.Chest 2003;123:679-684 Cumulative Response to GERD Therapy Preop pH <4: %23.6 De Meester: 85 Postop pH <4: %2.4 De Meester: 9.9 1. Chronic cough for at least 2 months 2. Immunocompetent patients 3. Chest radiograph is normal 4. Not exposed to enviromental irritants nor a present smoker 5. Not taking an ACE inhibitor 6. Symptomatic asthma has been ruled out 7. Rhinosinus diseases has been ruled out: 8. ‘Silent sinusitis’ has been ruled out 9. Nonasthmatic eosinophilic bronchitis has been ruled out: BPT is negative Cough has not improved with asthma therapy First generation H1 antagonists has been used Eo 3% in induced sputum Cough has not improved with steroids Irwin RS. Chest 2006;129:80S-94S İrwin RS. AJRCCM Vol 165; 1469-1474, 2002 Clinical Profile That Chronic Cough İs Likely Due To ‘Silent GERD’ Postnasal Drip Syndrome (PNDS) Prevalence : 8 – 87% Pathogenesis : The sensation of drainage of secretions from the nose or paranasal sinuses into the pharynx Clinical Presentation: Dripping sensation Tickle in the throat Nasal congestion Mucus in oropharynx Cobblestone appearence of oropharynx ACCP consensus. CHEST 1998; 114: 133-181 ERS Task Force. ERS Journal ; 24: 553-566 Pathogenic Triad in Chronic Cough. CHEST 1999; 116: 279-284 Evaluation of chronic cough. UPTODATE 2005 Chest 2006;129:63S-71S In patient with chronic cough that is related to upper airway abnormalities Upper Airway Cough Syndrome UACS Treatment Antihistamines / decongestant combinations - “Older” sedating antihistamines more effective - Treatment effect should be observed in 1 week Additional / Alternative treatments : Ipratropium nasal spray : 2-7 days Nasal steroids (such as BDP, FP,BUD) : 2-3 days - 2 week 3 months prescribed Eosinophilic Eronchitis Airway obstruction Bronchial hyperreactivity NO YES YES NO Asthmatic Coughs Cough Variant Asthma Asthma Cough Variant Asthma Prevalence : 24 – 59% Clinical Diagnosis Gold standard  History - Episodic symptoms, Family history Reversibility testing PEF monitoring Bronchoprovocation test Differential Diagnosis: Decreased of cough with classical asthma therapy ACCP consensus. CHEST 1998; 114: 133-181 ERS Task Force. ERS Journal ; 24: 553-566 The Journal of Respiratory Disease; 25; 310-315 THORAX 59; 342-346 Middle age patients Smoking is unusual, occupational ? Prevalence of atopy similar population Good respond to inhaled steroids Gibson et al. Lancet 1989 Chest 2006;129:116S-121S Eosinophilic Bronchitis Isolated chronic cough,  productive of sputum Normal lung function without variable airflow limitation Airway hyperresponsiveness absent Eosinophilia in sputum and BAL Cough reflex to capsaicin increased Normal daily variability in peak expiratory flow (<20%) 1)Kim et al AJRCCM 2003; 2) Brightling et al AJRCCM 1999;160:406-10, 3) Joo Korean JIM 2002;17:31-7, 4) Carney et al AJRCCM 1997; 156:211-6, 5) Ma et al Zhongua 2003;26:362-5, 6) Ayik, Erdinc et al Respir Med 2003;97:695-701 Eosinophilic Bronchitis A Worldwide Disease Causes of chronic cough Ayık SÖ, Başoğlu ÖK, Erdinç M. Respir Med Vol. 97 (2003) 695-701 Causes of Isolated Chronic Cough Brightling CE et al. AJRCCM 1999 Asthmatic Cough Airway obstruction Reversibility PEF değişkenliği Increased NO all of them PEF monitoring Prevalence: 0-50% More agressive diagnosis and treatments UACS, GERD and postinfectious cough leads to lower incidence ‘unexplained’. Airway inflammation Mast cell, histamin, cysteinil LTs, PD2, PE2 Irwin RS,et al. Chest 2006;130:362-370 Chronic Unexplained (Idiopathic) Cough Important missed history (smoking,ACEI,enviromental,drugs,allergy) Failure to do correct diagnostic tests Failure to use ‘empiric’ treatment Failure to use effective therapy Unknown disease process Potential Reasons Chronic Unexplained (Idiopathic) Cough « Truly idiopathic cough is rare and misdiagnosis very common, especially if cough is provoked by sites outside the airways » Eur Respir J 24: 481-492 2004 Idiopathic cough % ? Studies in the 1980’s % patients 1990-1995 Idiopathic cough % ? % patients Idiopathic cough % ? 1996-1999 % patients Idiopathic cough % ? 2000  % patients Haque et al Chest 2005;127:1710-1713 Chronic Idiopathic Cough Predominantly female and associated with BAL lymphocytosis Raising the possibility of a link between autoimmune diseases Surinder S. Et al. Respir Med 98:242-246;2004 Chronic Idiopathic Cough *OR: 8.8 Inflammation Chronic Idiopathic Cough Birring et al AJRCM 2004 + BAL lymphocytosis Sarcoidosis Hypersensitivity pneumonitis Rheumatoid Arthritis Sjögren’s syndrome Lung tx Inflammatory bowel disease Hypothyroidism Autoimmune disorders (SLE, RA) Pernisious anemia DM Thorax 2003;58:1066-1070 Chronic Idiopathic Cough Irwin RS,et al. Chest 2006;130:362-370 It is not correct to state that “a typical lymphocytic airways inflammation is seen in idiopathic cough” because lymphocytic or lymphoplasmacytic inflammation a non-specific finding related to trauma of coughing Chronic Idiopathic Cough Psychogenic Cough Cough is often triggered by a common cold Usually dissapears during sleep Like a dog barking The diagnosis of psychogenic cough is one of exclusion, after ruling out an organic or functional cause of cough. Specific or empiric treatment Antitussives are usually ineffective. Respirology 2006;Suppl 4 ;S160-S174 Irwin RS et al. Chest 1998, 114:2 suppl ERS Task Force: Eur Respir J 2004, 24:481-492 Prevalence: 11-25 % History: After a respiratory tract infection Diagnosis: Spasmodic cough Normal chest radiograph, with/without ronchii Respiratory viruses, m.pneumoniae, c.pneumoniae, B.pertussis Serum acute IgA antibody ELISA Rarely lymphocytosis Airway inflammation +/- Airway hyperresponsivenes Irwin RS et al. Chest 1998, 114:2 suppl ACCP consensus. CHEST 1998; 114: 133-181 ERS Task Force. ERS Journal ; 24: 553-566 Postinfectious Cough Oral and/or inhaled steroid (2-3 weeks) Antibiyotic : Macrolides (Chlamydia, mycoplasma) TMP/SMX : Pertusis (3-6 weeks) Ipatropium bromid decrease efferent limb of the cough reflex decrease stimulation of cough receptors Antitussive therapy Irwin RS et al. Chest 1998,114:2 suppl Miyashita N. J Med Microbiol 2003, 52:3,265-269 Postinfectious Cough ACEI Induced Chronic Cough Frequency: 0.2-33% Predominantly female Not dose related Appears within hours, weeks, months Pathogenesis: Neurokinin, Substance P, Prostoglandins, stimulates afferent C-fibers in the airway  increased cough reflex sensitivity Prefer Angiotensin II receptör antagonists Treatment Irwin RS et al. Chest 1998, 114:2 Capsaicin type I Vanilloid receptor antagonists Selective opioid receptor agonists Opioid-like receptor agonists Tachykinin receptor antagonists Endogenous cannabinoids 5-HT receptor agonists Large-conductance calcium-activated potassium channel openers Dicpinigaitis PV.Chest 2006 ;129:284S-286S Future Therapies Chronic cough History,Examination, Chest X-Ray, PFT Normal Abnormal Sputum, bronchoscopy,CT, Cardiac tests Smoking, ACEI , Irritants ? Specific diagnosis - treatment Stop 4 weeks yes Chronic Cough Algoritm For the Management of Adults

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CHRONIC COUGH MÜNEVVER ERDİNÇ Department of Chest Diseases Ege University Faculty of Medicine Differential Diagnosis And Treatment In Adults Acute Cough lasting less than 3 weeks Subacute Cough lasting 3 to 8 weeks Chronic Cough Lasting more than 8 weeks Morice AH.Eur Respir J 2004 :24:481-492 Fontana GA.Thorax 2003;58:1092-1095 Irwin RS.NEJM 343(23): 1715-1721,2000 Irwin RS. Chest 1998; 114(suppl1) :133S-181S Differantial Diagnosis of Chronic Cough in Adults PNDS Allergic rhinitis Chronic sinusitis GERD Cough variant asthma ACEI induced cough Pertusis Neurogenic Traumatic Postinfectious cough Phychogenic cough Chronic aspiration Zenker diverticulosis Foreign body Chronic bronchitis Bronchiectasis Lung cancer Subglottic stenosis Tracheomalasie Tracheoesophageal fistul Tuerculosis Sarcoidosis Congestive heart failure Simpson CB. Otolaryngology–Head Neck Surg 2006; 134: 693-700 In prospective studies in adults, chronic cough is most commonly due to 6 disorders : Upper Airway Cough Syndrome (UACS) Asthma GERD Chronic Bronchitis Bronchiectasis Non-asthmatic Eosinophilic Bronchitis Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S New Considerations Eosinophilic bronchitis Atopic cough Non acid(volume)/ weakly acid reflux Idiopathic (unexplained) öksürük Diagnosis and Management of Cough ACCP Evidence-Based CPG 2006 Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S Plevkova, et al. Respir Physiol Neurobiol 2004; 142: 225-235 Postnasal drip syndrome (PNDS) renamed upper airway cough syndrome (UACS) Upper airway afferents may reflexly enhance coughing Nonasthmatic eosinophilic bronchitis recognized as a common cause of chronic cough Idiopathic cough renamed unexplained cough The term acid reflux disease, unless it can be definitively shown to apply, replaced by reflux disease Update of current diagnostic and therapeutic approaches Common diseases, Uncommon diseases New algorithms for the management of cough in adults and children An empiric integrative approach is recommended 10 12 13 12 16 6 4 ASTHMA PNDS GERD Chest 1999;116:279-284 1. Gastroesophageal reflux disease (21-41%) 2. Cough variant asthma (24-59%) 3. Postnasal drip syndrome (41-58%) Chest 1999;116:279-281 Percentage of Cases Presenting 1,2,3, and 4 Causative Factors İmmunocompetent patients Not exposed to enviromental irritants Chest radiograph is normal Not taking an ACE inhibitor Not a current smoker Asthma and/or GERD, PNDS responsible for 93.6% of the cases of chronic cough Harding SM .Chest 2003;123:659-660 Changing Trends in Diagnosis Percentage of Diagnosis (%) GERD ASTHMA RHINITIS Impaired esophageal clearance Functional defect in LES syphincter Hiatal hernia Delayed gastric emptying İncreased intra-abdominal pressure GERD ? Decreased saliva Heartburn (pyrosis) and regurgitation At least weekly symptoms extraesophageal reflux symptoms and/or esophageal mucosal damage / Katzka & DiMarino 1995 FLR Signs Edema and hyperemia of larynx Vocal cord erythema, polyps, granulomas, ulcers Hyperemia and lymphoid hyperplasia of posterior pharynx Interarytenoid changes Subglottic stenosis GERD-related cough incidence 5 - 55% May be the sole presenting symptom(1/3) Thorax 2003:58;1092-1095) (Chest 1997; 111: 1389-1402) Irwin RS. Chest 2006;129:80S-94S Association between cough and reflux is important Esophageal-tracheal-bronchial reflex Microaspiration Pathogenesis ARRD 1981;123:413-417 Arch Intern Med 1996;156:997 Chest 1993;104:1511-1517 El Hennawi, 2004 OHNS Nonacidic factors? Esophageal dismotility? . Mediator Release . Inflammation . Edema . Mucus . Smooth Muscle Microaspiration REFLUX Esophageal Vagal Afferents Bronchial Hyperreactivity Airway Vagal Afferents CNS Stein MR.Am J Med 2003 Chest 1997;111: 1389-1402 Airway Airway Vagal Efferents Esophagus Tracheobronchial Tree Stomach Oesophagus Pharyngeal pHmetry + - Not GERD Clinical GERD symptoms ? Nonacid, weakly acid reflux? Increase dose PPI + alginate İmproved Not improved Continue pHmetry under treatment Consider  Simultaneously dual probes 24 hours pHmonitoring and intraesophageal impedance Irwin RS.AJRCCM 165:1469-74,2002 McGarvey LPA.Thorax 59:342-346,2004 15 cm 17 cm 6 impedance channels 1 pH electrode + Adult Standard Model ZAN-S61C01E Multichannel intraluminal impedance-pH catheter Non acid reflux On going reflux of ‘non-acid’ material may be responsible for continuing symptoms while on acid-suppressing medications Therapy in Esophageal-pulmonary reflux Conservative and lifestyle measures Ampirical therapy: Acid suppression Proton pump inhibitors  PPI x 2 / 3 months Therapy failure  24 hour intraesophageal pHmetry ( pharyngeal pHmetry )  GERD (+) High dose PPI + H2 blocker agent Surgery(Fundoplication) Pulmonary and Crit Care Update 1994; Vol 9 Morice AH. ERJ 2004;24:481-492 Weeks of antireflux therapy Patients responded No No (%) 2 16 (41) 4 38 (86) 6 42 (95) 8 43 (99) 12 weeks 44 (100) Poe RH.Chest 2003;123:679-684 Cumulative Response to GERD Therapy Preop pH <4: %23.6 De Meester: 85 Postop pH <4: %2.4 De Meester: 9.9 1. Chronic cough for at least 2 months 2. Immunocompetent patients 3. Chest radiograph is normal 4. Not exposed to enviromental irritants nor a present smoker 5. Not taking an ACE inhibitor 6. Symptomatic asthma has been ruled out 7. Rhinosinus diseases has been ruled out: 8. ‘Silent sinusitis’ has been ruled out 9. Nonasthmatic eosinophilic bronchitis has been ruled out: BPT is negative Cough has not improved with asthma therapy First generation H1 antagonists has been used Eo 3% in induced sputum Cough has not improved with steroids Irwin RS. Chest 2006;129:80S-94S İrwin RS. AJRCCM Vol 165; 1469-1474, 2002 Clinical Profile That Chronic Cough İs Likely Due To ‘Silent GERD’ Postnasal Drip Syndrome (PNDS) Prevalence : 8 – 87% Pathogenesis : The sensation of drainage of secretions from the nose or paranasal sinuses into the pharynx Clinical Presentation: Dripping sensation Tickle in the throat Nasal congestion Mucus in oropharynx Cobblestone appearence of oropharynx ACCP consensus. CHEST 1998; 114: 133-181 ERS Task Force. ERS Journal ; 24: 553-566 Pathogenic Triad in Chronic Cough. CHEST 1999; 116: 279-284 Evaluation of chronic cough. UPTODATE 2005 Chest 2006;129:63S-71S In patient with chronic cough that is related to upper airway abnormalities Upper Airway Cough Syndrome UACS Treatment Antihistamines / decongestant combinations - “Older” sedating antihistamines more effective - Treatment effect should be observed in 1 week Additional / Alternative treatments : Ipratropium nasal spray : 2-7 days Nasal steroids (such as BDP, FP,BUD) : 2-3 days - 2 week 3 months prescribed Eosinophilic Eronchitis Airway obstruction Bronchial hyperreactivity NO YES YES NO Asthmatic Coughs Cough Variant Asthma Asthma Cough Variant Asthma Prevalence : 24 – 59% Clinical Diagnosis Gold standard  History - Episodic symptoms, Family history Reversibility testing PEF monitoring Bronchoprovocation test Differential Diagnosis: Decreased of cough with classical asthma therapy ACCP consensus. CHEST 1998; 114: 133-181 ERS Task Force. ERS Journal ; 24: 553-566 The Journal of Respiratory Disease; 25; 310-315 THORAX 59; 342-346 Middle age patients Smoking is unusual, occupational ? Prevalence of atopy similar population Good respond to inhaled steroids Gibson et al. Lancet 1989 Chest 2006;129:116S-121S Eosinophilic Bronchitis Isolated chronic cough,  productive of sputum Normal lung function without variable airflow limitation Airway hyperresponsiveness absent Eosinophilia in sputum and BAL Cough reflex to capsaicin increased Normal daily variability in peak expiratory flow (<20%) 1)Kim et al AJRCCM 2003; 2) Brightling et al AJRCCM 1999;160:406-10, 3) Joo Korean JIM 2002;17:31-7, 4) Carney et al AJRCCM 1997; 156:211-6, 5) Ma et al Zhongua 2003;26:362-5, 6) Ayik, Erdinc et al Respir Med 2003;97:695-701 Eosinophilic Bronchitis A Worldwide Disease Causes of chronic cough Ayık SÖ, Başoğlu ÖK, Erdinç M. Respir Med Vol. 97 (2003) 695-701 Causes of Isolated Chronic Cough Brightling CE et al. AJRCCM 1999 Asthmatic Cough Airway obstruction Reversibility PEF değişkenliği Increased NO all of them PEF monitoring Prevalence: 0-50% More agressive diagnosis and treatments UACS, GERD and postinfectious cough leads to lower incidence ‘unexplained’. Airway inflammation Mast cell, histamin, cysteinil LTs, PD2, PE2 Irwin RS,et al. Chest 2006;130:362-370 Chronic Unexplained (Idiopathic) Cough Important missed history (smoking,ACEI,enviromental,drugs,allergy) Failure to do correct diagnostic tests Failure to use ‘empiric’ treatment Failure to use effective therapy Unknown disease process Potential Reasons Chronic Unexplained (Idiopathic) Cough « Truly idiopathic cough is rare and misdiagnosis very common, especially if cough is provoked by sites outside the airways » Eur Respir J 24: 481-492 2004 Idiopathic cough % ? Studies in the 1980’s % patients 1990-1995 Idiopathic cough % ? % patients Idiopathic cough % ? 1996-1999 % patients Idiopathic cough % ? 2000  % patients Haque et al Chest 2005;127:1710-1713 Chronic Idiopathic Cough Predominantly female and associated with BAL lymphocytosis Raising the possibility of a link between autoimmune diseases Surinder S. Et al. Respir Med 98:242-246;2004 Chronic Idiopathic Cough *OR: 8.8 Inflammation Chronic Idiopathic Cough Birring et al AJRCM 2004 + BAL lymphocytosis Sarcoidosis Hypersensitivity pneumonitis Rheumatoid Arthritis Sjögren’s syndrome Lung tx Inflammatory bowel disease Hypothyroidism Autoimmune disorders (SLE, RA) Pernisious anemia DM Thorax 2003;58:1066-1070 Chronic Idiopathic Cough Irwin RS,et al. Chest 2006;130:362-370 It is not correct to state that “a typical lymphocytic airways inflammation is seen in idiopathic cough” because lymphocytic or lymphoplasmacytic inflammation a non-specific finding related to trauma of coughing Chronic Idiopathic Cough Psychogenic Cough Cough is often triggered by a common cold Usually dissapears during sleep Like a dog barking The diagnosis of psychogenic cough is one of exclusion, after ruling out an organic or functional cause of cough. Specific or empiric treatment Antitussives are usually ineffective. Respirology 2006;Suppl 4 ;S160-S174 Irwin RS et al. Chest 1998, 114:2 suppl ERS Task Force: Eur Respir J 2004, 24:481-492 Prevalence: 11-25 % History: After a respiratory tract infection Diagnosis: Spasmodic cough Normal chest radiograph, with/without ronchii Respiratory viruses, m.pneumoniae, c.pneumoniae, B.pertussis Serum acute IgA antibody ELISA Rarely lymphocytosis Airway inflammation +/- Airway hyperresponsivenes Irwin RS et al. Chest 1998, 114:2 suppl ACCP consensus. CHEST 1998; 114: 133-181 ERS Task Force. ERS Journal ; 24: 553-566 Postinfectious Cough Oral and/or inhaled steroid (2-3 weeks) Antibiyotic : Macrolides (Chlamydia, mycoplasma) TMP/SMX : Pertusis (3-6 weeks) Ipatropium bromid decrease efferent limb of the cough reflex decrease stimulation of cough receptors Antitussive therapy Irwin RS et al. Chest 1998,114:2 suppl Miyashita N. J Med Microbiol 2003, 52:3,265-269 Postinfectious Cough ACEI Induced Chronic Cough Frequency: 0.2-33% Predominantly female Not dose related Appears within hours, weeks, months Pathogenesis: Neurokinin, Substance P, Prostoglandins, stimulates afferent C-fibers in the airway  increased cough reflex sensitivity Prefer Angiotensin II receptör antagonists Treatment Irwin RS et al. Chest 1998, 114:2 Capsaicin type I Vanilloid receptor antagonists Selective opioid receptor agonists Opioid-like receptor agonists Tachykinin receptor antagonists Endogenous cannabinoids 5-HT receptor agonists Large-conductance calcium-activated potassium channel openers Dicpinigaitis PV.Chest 2006 ;129:284S-286S Future Therapies Chronic cough History,Examination, Chest X-Ray, PFT Normal Abnormal Sputum, bronchoscopy,CT, Cardiac tests Smoking, ACEI , Irritants ? Specific diagnosis - treatment Stop 4 weeks yes Chronic Cough Algoritm For the Management of Adults Chronic cough History,Examination, Chest X-Ray, PFT Normal Abnormal Sputum, bronchoscopy,CT, Cardiac tests Smoking, ACEI, Irritants ? Specific diagnosis - Treatment Cough? Yes No UACS,GERD, Asthma, NAEB ? No Yes Stop 4 weeks İmproved? Chronic Cough Algoritm For the Management of Adults

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CHRONIC COUGH MÜNEVVER ERDİNÇ Department of Chest Diseases Ege University Faculty of Medicine Differential Diagnosis And Treatment In Adults Acute Cough lasting less than 3 weeks Subacute Cough lasting 3 to 8 weeks Chronic Cough Lasting more than 8 weeks Morice AH.Eur Respir J 2004 :24:481-492 Fontana GA.Thorax 2003;58:1092-1095 Irwin RS.NEJM 343(23): 1715-1721,2000 Irwin RS. Chest 1998; 114(suppl1) :133S-181S Differantial Diagnosis of Chronic Cough in Adults PNDS Allergic rhinitis Chronic sinusitis GERD Cough variant asthma ACEI induced cough Pertusis Neurogenic Traumatic Postinfectious cough Phychogenic cough Chronic aspiration Zenker diverticulosis Foreign body Chronic bronchitis Bronchiectasis Lung cancer Subglottic stenosis Tracheomalasie Tracheoesophageal fistul Tuerculosis Sarcoidosis Congestive heart failure Simpson CB. Otolaryngology–Head Neck Surg 2006; 134: 693-700 In prospective studies in adults, chronic cough is most commonly due to 6 disorders : Upper Airway Cough Syndrome (UACS) Asthma GERD Chronic Bronchitis Bronchiectasis Non-asthmatic Eosinophilic Bronchitis Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S New Considerations Eosinophilic bronchitis Atopic cough Non acid(volume)/ weakly acid reflux Idiopathic (unexplained) öksürük Diagnosis and Management of Cough ACCP Evidence-Based CPG 2006 Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S Plevkova, et al. Respir Physiol Neurobiol 2004; 142: 225-235 Postnasal drip syndrome (PNDS) renamed upper airway cough syndrome (UACS) Upper airway afferents may reflexly enhance coughing Nonasthmatic eosinophilic bronchitis recognized as a common cause of chronic cough Idiopathic cough renamed unexplained cough The term acid reflux disease, unless it can be definitively shown to apply, replaced by reflux disease Update of current diagnostic and therapeutic approaches Common diseases, Uncommon diseases New algorithms for the management of cough in adults and children An empiric integrative approach is recommended 10 12 13 12 16 6 4 ASTHMA PNDS GERD Chest 1999;116:279-284 1. Gastroesophageal reflux disease (21-41%) 2. Cough variant asthma (24-59%) 3. Postnasal drip syndrome (41-58%) Chest 1999;116:279-281 Percentage of Cases Presenting 1,2,3, and 4 Causative Factors İmmunocompetent patients Not exposed to enviromental irritants Chest radiograph is normal Not taking an ACE inhibitor Not a current smoker Asthma and/or GERD, PNDS responsible for 93.6% of the cases of chronic cough Harding SM .Chest 2003;123:659-660 Changing Trends in Diagnosis Percentage of Diagnosis (%) GERD ASTHMA RHINITIS Impaired esophageal clearance Functional defect in LES syphincter Hiatal hernia Delayed gastric emptying İncreased intra-abdominal pressure GERD ? Decreased saliva Heartburn (pyrosis) and regurgitation At least weekly symptoms extraesophageal reflux symptoms and/or esophageal mucosal damage / Katzka & DiMarino 1995 FLR Signs Edema and hyperemia of larynx Vocal cord erythema, polyps, granulomas, ulcers Hyperemia and lymphoid hyperplasia of posterior pharynx Interarytenoid changes Subglottic stenosis GERD-related cough incidence 5 - 55% May be the sole presenting symptom(1/3) Thorax 2003:58;1092-1095) (Chest 1997; 111: 1389-1402) Irwin RS. Chest 2006;129:80S-94S Association between cough and reflux is important Esophageal-tracheal-bronchial reflex Microaspiration Pathogenesis ARRD 1981;123:413-417 Arch Intern Med 1996;156:997 Chest 1993;104:1511-1517 El Hennawi, 2004 OHNS Nonacidic factors? Esophageal dismotility? . Mediator Release . Inflammation . Edema . Mucus . Smooth Muscle Microaspiration REFLUX Esophageal Vagal Afferents Bronchial Hyperreactivity Airway Vagal Afferents CNS Stein MR.Am J Med 2003 Chest 1997;111: 1389-1402 Airway Airway Vagal Efferents Esophagus Tracheobronchial Tree Stomach Oesophagus Pharyngeal pHmetry + - Not GERD Clinical GERD symptoms ? Nonacid, weakly acid reflux? Increase dose PPI + alginate İmproved Not improved Continue pHmetry under treatment Consider  Simultaneously dual probes 24 hours pHmonitoring and intraesophageal impedance Irwin RS.AJRCCM 165:1469-74,2002 McGarvey LPA.Thorax 59:342-346,2004 15 cm 17 cm 6 impedance channels 1 pH electrode + Adult Standard Model ZAN-S61C01E Multichannel intraluminal impedance-pH catheter Non acid reflux On going reflux of ‘non-acid’ material may be responsible for continuing symptoms while on acid-suppressing medications Therapy in Esophageal-pulmonary reflux Conservative and lifestyle measures Ampirical therapy: Acid suppression Proton pump inhibitors  PPI x 2 / 3 months Therapy failure  24 hour intraesophageal pHmetry ( pharyngeal pHmetry )  GERD (+) High dose PPI + H2 blocker agent Surgery(Fundoplication) Pulmonary and Crit Care Update 1994; Vol 9 Morice AH. ERJ 2004;24:481-492 Weeks of antireflux therapy Patients responded No No (%) 2 16 (41) 4 38 (86) 6 42 (95) 8 43 (99) 12 weeks 44 (100) Poe RH.Chest 2003;123:679-684 Cumulative Response to GERD Therapy Preop pH <4: %23.6 De Meester: 85 Postop pH <4: %2.4 De Meester: 9.9 1. Chronic cough for at least 2 months 2. Immunocompetent patients 3. Chest radiograph is normal 4. Not exposed to enviromental irritants nor a present smoker 5. Not taking an ACE inhibitor 6. Symptomatic asthma has been ruled out 7. Rhinosinus diseases has been ruled out: 8. ‘Silent sinusitis’ has been ruled out 9. Nonasthmatic eosinophilic bronchitis has been ruled out: BPT is negative Cough has not improved with asthma therapy First generation H1 antagonists has been used Eo 3% in induced sputum Cough has not improved with steroids Irwin RS. Chest 2006;129:80S-94S İrwin RS. AJRCCM Vol 165; 1469-1474, 2002 Clinical Profile That Chronic Cough İs Likely Due To ‘Silent GERD’ Postnasal Drip Syndrome (PNDS) Prevalence : 8 – 87% Pathogenesis : The sensation of drainage of secretions from the nose or paranasal sinuses into the pharynx Clinical Presentation: Dripping sensation Tickle in the throat Nasal congestion Mucus in oropharynx Cobblestone appearence of oropharynx ACCP consensus. CHEST 1998; 114: 133-181 ERS Task Force. ERS Journal ; 24: 553-566 Pathogenic Triad in Chronic Cough. CHEST 1999; 116: 279-284 Evaluation of chronic cough. UPTODATE 2005 Chest 2006;129:63S-71S In patient with chronic cough that is related to upper airway abnormalities Upper Airway Cough Syndrome UACS Treatment Antihistamines / decongestant combinations - “Older” sedating antihistamines more effective - Treatment effect should be observed in 1 week Additional / Alternative treatments : Ipratropium nasal spray : 2-7 days Nasal steroids (such as BDP, FP,BUD) : 2-3 days - 2 week 3 months prescribed Eosinophilic Eronchitis Airway obstruction Bronchial hyperreactivity NO YES YES NO Asthmatic Coughs Cough Variant Asthma Asthma Cough Variant Asthma Prevalence : 24 – 59% Clinical Diagnosis Gold standard  History - Episodic symptoms, Family history Reversibility testing PEF monitoring Bronchoprovocation test Differential Diagnosis: Decreased of cough with classical asthma therapy ACCP consensus. CHEST 1998; 114: 133-181 ERS Task Force. ERS Journal ; 24: 553-566 The Journal of Respiratory Disease; 25; 310-315 THORAX 59; 342-346 Middle age patients Smoking is unusual, occupational ? Prevalence of atopy similar population Good respond to inhaled steroids Gibson et al. Lancet 1989 Chest 2006;129:116S-121S Eosinophilic Bronchitis Isolated chronic cough,  productive of sputum Normal lung function without variable airflow limitation Airway hyperresponsiveness absent Eosinophilia in sputum and BAL Cough reflex to capsaicin increased Normal daily variability in peak expiratory flow (<20%) 1)Kim et al AJRCCM 2003; 2) Brightling et al AJRCCM 1999;160:406-10, 3) Joo Korean JIM 2002;17:31-7, 4) Carney et al AJRCCM 1997; 156:211-6, 5) Ma et al Zhongua 2003;26:362-5, 6) Ayik, Erdinc et al Respir Med 2003;97:695-701 Eosinophilic Bronchitis A Worldwide Disease Causes of chronic cough Ayık SÖ, Başoğlu ÖK, Erdinç M. Respir Med Vol. 97 (2003) 695-701 Causes of Isolated Chronic Cough Brightling CE et al. AJRCCM 1999 Asthmatic Cough Airway obstruction Reversibility PEF değişkenliği Increased NO all of them PEF monitoring Prevalence: 0-50% More agressive diagnosis and treatments UACS, GERD and postinfectious cough leads to lower incidence ‘unexplained’. Airway inflammation Mast cell, histamin, cysteinil LTs, PD2, PE2 Irwin RS,et al. Chest 2006;130:362-370 Chronic Unexplained (Idiopathic) Cough Important missed history (smoking,ACEI,enviromental,drugs,allergy) Failure to do correct diagnostic tests Failure to use ‘empiric’ treatment Failure to use effective therapy Unknown disease process Potential Reasons Chronic Unexplained (Idiopathic) Cough « Truly idiopathic cough is rare and misdiagnosis very common, especially if cough is provoked by sites outside the airways » Eur Respir J 24: 481-492 2004 Idiopathic cough % ? Studies in the 1980’s % patients 1990-1995 Idiopathic cough % ? % patients Idiopathic cough % ? 1996-1999 % patients Idiopathic cough % ? 2000  % patients Haque et al Chest 2005;127:1710-1713 Chronic Idiopathic Cough Predominantly female and associated with BAL lymphocytosis Raising the possibility of a link between autoimmune diseases Surinder S. Et al. Respir Med 98:242-246;2004 Chronic Idiopathic Cough *OR: 8.8 Inflammation Chronic Idiopathic Cough Birring et al AJRCM 2004 + BAL lymphocytosis Sarcoidosis Hypersensitivity pneumonitis Rheumatoid Arthritis Sjögren’s syndrome Lung tx Inflammatory bowel disease Hypothyroidism Autoimmune disorders (SLE, RA) Pernisious anemia DM Thorax 2003;58:1066-1070 Chronic Idiopathic Cough Irwin RS,et al. Chest 2006;130:362-370 It is not correct to state that “a typical lymphocytic airways inflammation is seen in idiopathic cough” because lymphocytic or lymphoplasmacytic inflammation a non-specific finding related to trauma of coughing Chronic Idiopathic Cough Psychogenic Cough Cough is often triggered by a common cold Usually dissapears during sleep Like a dog barking The diagnosis of psychogenic cough is one of exclusion, after ruling out an organic or functional cause of cough. Specific or empiric treatment Antitussives are usually ineffective. Respirology 2006;Suppl 4 ;S160-S174 Irwin RS et al. Chest 1998, 114:2 suppl ERS Task Force: Eur Respir J 2004, 24:481-492 Prevalence: 11-25 % History: After a respiratory tract infection Diagnosis: Spasmodic cough Normal chest radiograph, with/without ronchii Respiratory viruses, m.pneumoniae, c.pneumoniae, B.pertussis Serum acute IgA antibody ELISA Rarely lymphocytosis Airway inflammation +/- Airway hyperresponsivenes Irwin RS et al. Chest 1998, 114:2 suppl ACCP consensus. CHEST 1998; 114: 133-181 ERS Task Force. ERS Journal ; 24: 553-566 Postinfectious Cough Oral and/or inhaled steroid (2-3 weeks) Antibiyotic : Macrolides (Chlamydia, mycoplasma) TMP/SMX : Pertusis (3-6 weeks) Ipatropium bromid decrease efferent limb of the cough reflex decrease stimulation of cough receptors Antitussive therapy Irwin RS et al. Chest 1998,114:2 suppl Miyashita N. J Med Microbiol 2003, 52:3,265-269 Postinfectious Cough ACEI Induced Chronic Cough Frequency: 0.2-33% Predominantly female Not dose related Appears within hours, weeks, months Pathogenesis: Neurokinin, Substance P, Prostoglandins, stimulates afferent C-fibers in the airway  increased cough reflex sensitivity Prefer Angiotensin II receptör antagonists Treatment Irwin RS et al. Chest 1998, 114:2 Capsaicin type I Vanilloid receptor antagonists Selective opioid receptor agonists Opioid-like receptor agonists Tachykinin receptor antagonists Endogenous cannabinoids 5-HT receptor agonists Large-conductance calcium-activated potassium channel openers Dicpinigaitis PV.Chest 2006 ;129:284S-286S Future Therapies Chronic cough History,Examination, Chest X-Ray, PFT Normal Abnormal Sputum, bronchoscopy,CT, Cardiac tests Smoking, ACEI , Irritants ? Specific diagnosis - treatment Stop 4 weeks yes Chronic Cough Algoritm For the Management of Adults Chronic cough History,Examination, Chest X-Ray, PFT Normal Abnormal Sputum, bronchoscopy,CT, Cardiac tests Smoking, ACEI, Irritants ? Specific diagnosis - Treatment Cough? Yes No UACS,GERD, Asthma, NAEB ? No Yes Stop 4 weeks İmproved? Chronic Cough Algoritm For the Management of Adults Chronic cough Normal Abnormal Cough? Yes Yok No Yes Improved Cough? No Yes Empiric/ Specific Therapy History,Examination, Chest X-Ray, PFT Sputum, Bronchoscopy,CT, Cardiac tests Specific diagnosis - treatment Smoking, ACEI ?, Irritants? UACS,GERD, Asthma, NAEB Stop 4 weeks Chronic Cough Algoritm

Slide 54 -

CHRONIC COUGH MÜNEVVER ERDİNÇ Department of Chest Diseases Ege University Faculty of Medicine Differential Diagnosis And Treatment In Adults Acute Cough lasting less than 3 weeks Subacute Cough lasting 3 to 8 weeks Chronic Cough Lasting more than 8 weeks Morice AH.Eur Respir J 2004 :24:481-492 Fontana GA.Thorax 2003;58:1092-1095 Irwin RS.NEJM 343(23): 1715-1721,2000 Irwin RS. Chest 1998; 114(suppl1) :133S-181S Differantial Diagnosis of Chronic Cough in Adults PNDS Allergic rhinitis Chronic sinusitis GERD Cough variant asthma ACEI induced cough Pertusis Neurogenic Traumatic Postinfectious cough Phychogenic cough Chronic aspiration Zenker diverticulosis Foreign body Chronic bronchitis Bronchiectasis Lung cancer Subglottic stenosis Tracheomalasie Tracheoesophageal fistul Tuerculosis Sarcoidosis Congestive heart failure Simpson CB. Otolaryngology–Head Neck Surg 2006; 134: 693-700 In prospective studies in adults, chronic cough is most commonly due to 6 disorders : Upper Airway Cough Syndrome (UACS) Asthma GERD Chronic Bronchitis Bronchiectasis Non-asthmatic Eosinophilic Bronchitis Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S New Considerations Eosinophilic bronchitis Atopic cough Non acid(volume)/ weakly acid reflux Idiopathic (unexplained) öksürük Diagnosis and Management of Cough ACCP Evidence-Based CPG 2006 Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S Plevkova, et al. Respir Physiol Neurobiol 2004; 142: 225-235 Postnasal drip syndrome (PNDS) renamed upper airway cough syndrome (UACS) Upper airway afferents may reflexly enhance coughing Nonasthmatic eosinophilic bronchitis recognized as a common cause of chronic cough Idiopathic cough renamed unexplained cough The term acid reflux disease, unless it can be definitively shown to apply, replaced by reflux disease Update of current diagnostic and therapeutic approaches Common diseases, Uncommon diseases New algorithms for the management of cough in adults and children An empiric integrative approach is recommended 10 12 13 12 16 6 4 ASTHMA PNDS GERD Chest 1999;116:279-284 1. Gastroesophageal reflux disease (21-41%) 2. Cough variant asthma (24-59%) 3. Postnasal drip syndrome (41-58%) Chest 1999;116:279-281 Percentage of Cases Presenting 1,2,3, and 4 Causative Factors İmmunocompetent patients Not exposed to enviromental irritants Chest radiograph is normal Not taking an ACE inhibitor Not a current smoker Asthma and/or GERD, PNDS responsible for 93.6% of the cases of chronic cough Harding SM .Chest 2003;123:659-660 Changing Trends in Diagnosis Percentage of Diagnosis (%) GERD ASTHMA RHINITIS Impaired esophageal clearance Functional defect in LES syphincter Hiatal hernia Delayed gastric emptying İncreased intra-abdominal pressure GERD ? Decreased saliva Heartburn (pyrosis) and regurgitation At least weekly symptoms extraesophageal reflux symptoms and/or esophageal mucosal damage / Katzka & DiMarino 1995 FLR Signs Edema and hyperemia of larynx Vocal cord erythema, polyps, granulomas, ulcers Hyperemia and lymphoid hyperplasia of posterior pharynx Interarytenoid changes Subglottic stenosis GERD-related cough incidence 5 - 55% May be the sole presenting symptom(1/3) Thorax 2003:58;1092-1095) (Chest 1997; 111: 1389-1402) Irwin RS. Chest 2006;129:80S-94S Association between cough and reflux is important Esophageal-tracheal-bronchial reflex Microaspiration Pathogenesis ARRD 1981;123:413-417 Arch Intern Med 1996;156:997 Chest 1993;104:1511-1517 El Hennawi, 2004 OHNS Nonacidic factors? Esophageal dismotility? . Mediator Release . Inflammation . Edema . Mucus . Smooth Muscle Microaspiration REFLUX Esophageal Vagal Afferents Bronchial Hyperreactivity Airway Vagal Afferents CNS Stein MR.Am J Med 2003 Chest 1997;111: 1389-1402 Airway Airway Vagal Efferents Esophagus Tracheobronchial Tree Stomach Oesophagus Pharyngeal pHmetry + - Not GERD Clinical GERD symptoms ? Nonacid, weakly acid reflux? Increase dose PPI + alginate İmproved Not improved Continue pHmetry under treatment Consider  Simultaneously dual probes 24 hours pHmonitoring and intraesophageal impedance Irwin RS.AJRCCM 165:1469-74,2002 McGarvey LPA.Thorax 59:342-346,2004 15 cm 17 cm 6 impedance channels 1 pH electrode + Adult Standard Model ZAN-S61C01E Multichannel intraluminal impedance-pH catheter Non acid reflux On going reflux of ‘non-acid’ material may be responsible for continuing symptoms while on acid-suppressing medications Therapy in Esophageal-pulmonary reflux Conservative and lifestyle measures Ampirical therapy: Acid suppression Proton pump inhibitors  PPI x 2 / 3 months Therapy failure  24 hour intraesophageal pHmetry ( pharyngeal pHmetry )  GERD (+) High dose PPI + H2 blocker agent Surgery(Fundoplication) Pulmonary and Crit Care Update 1994; Vol 9 Morice AH. ERJ 2004;24:481-492 Weeks of antireflux therapy Patients responded No No (%) 2 16 (41) 4 38 (86) 6 42 (95) 8 43 (99) 12 weeks 44 (100) Poe RH.Chest 2003;123:679-684 Cumulative Response to GERD Therapy Preop pH <4: %23.6 De Meester: 85 Postop pH <4: %2.4 De Meester: 9.9 1. Chronic cough for at least 2 months 2. Immunocompetent patients 3. Chest radiograph is normal 4. Not exposed to enviromental irritants nor a present smoker 5. Not taking an ACE inhibitor 6. Symptomatic asthma has been ruled out 7. Rhinosinus diseases has been ruled out: 8. ‘Silent sinusitis’ has been ruled out 9. Nonasthmatic eosinophilic bronchitis has been ruled out: BPT is negative Cough has not improved with asthma therapy First generation H1 antagonists has been used Eo 3% in induced sputum Cough has not improved with steroids Irwin RS. Chest 2006;129:80S-94S İrwin RS. AJRCCM Vol 165; 1469-1474, 2002 Clinical Profile That Chronic Cough İs Likely Due To ‘Silent GERD’ Postnasal Drip Syndrome (PNDS) Prevalence : 8 – 87% Pathogenesis : The sensation of drainage of secretions from the nose or paranasal sinuses into the pharynx Clinical Presentation: Dripping sensation Tickle in the throat Nasal congestion Mucus in oropharynx Cobblestone appearence of oropharynx ACCP consensus. CHEST 1998; 114: 133-181 ERS Task Force. ERS Journal ; 24: 553-566 Pathogenic Triad in Chronic Cough. CHEST 1999; 116: 279-284 Evaluation of chronic cough. UPTODATE 2005 Chest 2006;129:63S-71S In patient with chronic cough that is related to upper airway abnormalities Upper Airway Cough Syndrome UACS Treatment Antihistamines / decongestant combinations - “Older” sedating antihistamines more effective - Treatment effect should be observed in 1 week Additional / Alternative treatments : Ipratropium nasal spray : 2-7 days Nasal steroids (such as BDP, FP,BUD) : 2-3 days - 2 week 3 months prescribed Eosinophilic Eronchitis Airway obstruction Bronchial hyperreactivity NO YES YES NO Asthmatic Coughs Cough Variant Asthma Asthma Cough Variant Asthma Prevalence : 24 – 59% Clinical Diagnosis Gold standard  History - Episodic symptoms, Family history Reversibility testing PEF monitoring Bronchoprovocation test Differential Diagnosis: Decreased of cough with classical asthma therapy ACCP consensus. CHEST 1998; 114: 133-181 ERS Task Force. ERS Journal ; 24: 553-566 The Journal of Respiratory Disease; 25; 310-315 THORAX 59; 342-346 Middle age patients Smoking is unusual, occupational ? Prevalence of atopy similar population Good respond to inhaled steroids Gibson et al. Lancet 1989 Chest 2006;129:116S-121S Eosinophilic Bronchitis Isolated chronic cough,  productive of sputum Normal lung function without variable airflow limitation Airway hyperresponsiveness absent Eosinophilia in sputum and BAL Cough reflex to capsaicin increased Normal daily variability in peak expiratory flow (<20%) 1)Kim et al AJRCCM 2003; 2) Brightling et al AJRCCM 1999;160:406-10, 3) Joo Korean JIM 2002;17:31-7, 4) Carney et al AJRCCM 1997; 156:211-6, 5) Ma et al Zhongua 2003;26:362-5, 6) Ayik, Erdinc et al Respir Med 2003;97:695-701 Eosinophilic Bronchitis A Worldwide Disease Causes of chronic cough Ayık SÖ, Başoğlu ÖK, Erdinç M. Respir Med Vol. 97 (2003) 695-701 Causes of Isolated Chronic Cough Brightling CE et al. AJRCCM 1999 Asthmatic Cough Airway obstruction Reversibility PEF değişkenliği Increased NO all of them PEF monitoring Prevalence: 0-50% More agressive diagnosis and treatments UACS, GERD and postinfectious cough leads to lower incidence ‘unexplained’. Airway inflammation Mast cell, histamin, cysteinil LTs, PD2, PE2 Irwin RS,et al. Chest 2006;130:362-370 Chronic Unexplained (Idiopathic) Cough Important missed history (smoking,ACEI,enviromental,drugs,allergy) Failure to do correct diagnostic tests Failure to use ‘empiric’ treatment Failure to use effective therapy Unknown disease process Potential Reasons Chronic Unexplained (Idiopathic) Cough « Truly idiopathic cough is rare and misdiagnosis very common, especially if cough is provoked by sites outside the airways » Eur Respir J 24: 481-492 2004 Idiopathic cough % ? Studies in the 1980’s % patients 1990-1995 Idiopathic cough % ? % patients Idiopathic cough % ? 1996-1999 % patients Idiopathic cough % ? 2000  % patients Haque et al Chest 2005;127:1710-1713 Chronic Idiopathic Cough Predominantly female and associated with BAL lymphocytosis Raising the possibility of a link between autoimmune diseases Surinder S. Et al. Respir Med 98:242-246;2004 Chronic Idiopathic Cough *OR: 8.8 Inflammation Chronic Idiopathic Cough Birring et al AJRCM 2004 + BAL lymphocytosis Sarcoidosis Hypersensitivity pneumonitis Rheumatoid Arthritis Sjögren’s syndrome Lung tx Inflammatory bowel disease Hypothyroidism Autoimmune disorders (SLE, RA) Pernisious anemia DM Thorax 2003;58:1066-1070 Chronic Idiopathic Cough Irwin RS,et al. Chest 2006;130:362-370 It is not correct to state that “a typical lymphocytic airways inflammation is seen in idiopathic cough” because lymphocytic or lymphoplasmacytic inflammation a non-specific finding related to trauma of coughing Chronic Idiopathic Cough Psychogenic Cough Cough is often triggered by a common cold Usually dissapears during sleep Like a dog barking The diagnosis of psychogenic cough is one of exclusion, after ruling out an organic or functional cause of cough. Specific or empiric treatment Antitussives are usually ineffective. Respirology 2006;Suppl 4 ;S160-S174 Irwin RS et al. Chest 1998, 114:2 suppl ERS Task Force: Eur Respir J 2004, 24:481-492 Prevalence: 11-25 % History: After a respiratory tract infection Diagnosis: Spasmodic cough Normal chest radiograph, with/without ronchii Respiratory viruses, m.pneumoniae, c.pneumoniae, B.pertussis Serum acute IgA antibody ELISA Rarely lymphocytosis Airway inflammation +/- Airway hyperresponsivenes Irwin RS et al. Chest 1998, 114:2 suppl ACCP consensus. CHEST 1998; 114: 133-181 ERS Task Force. ERS Journal ; 24: 553-566 Postinfectious Cough Oral and/or inhaled steroid (2-3 weeks) Antibiyotic : Macrolides (Chlamydia, mycoplasma) TMP/SMX : Pertusis (3-6 weeks) Ipatropium bromid decrease efferent limb of the cough reflex decrease stimulation of cough receptors Antitussive therapy Irwin RS et al. Chest 1998,114:2 suppl Miyashita N. J Med Microbiol 2003, 52:3,265-269 Postinfectious Cough ACEI Induced Chronic Cough Frequency: 0.2-33% Predominantly female Not dose related Appears within hours, weeks, months Pathogenesis: Neurokinin, Substance P, Prostoglandins, stimulates afferent C-fibers in the airway  increased cough reflex sensitivity Prefer Angiotensin II receptör antagonists Treatment Irwin RS et al. Chest 1998, 114:2 Capsaicin type I Vanilloid receptor antagonists Selective opioid receptor agonists Opioid-like receptor agonists Tachykinin receptor antagonists Endogenous cannabinoids 5-HT receptor agonists Large-conductance calcium-activated potassium channel openers Dicpinigaitis PV.Chest 2006 ;129:284S-286S Future Therapies Chronic cough History,Examination, Chest X-Ray, PFT Normal Abnormal Sputum, bronchoscopy,CT, Cardiac tests Smoking, ACEI , Irritants ? Specific diagnosis - treatment Stop 4 weeks yes Chronic Cough Algoritm For the Management of Adults Chronic cough History,Examination, Chest X-Ray, PFT Normal Abnormal Sputum, bronchoscopy,CT, Cardiac tests Smoking, ACEI, Irritants ? Specific diagnosis - Treatment Cough? Yes No UACS,GERD, Asthma, NAEB ? No Yes Stop 4 weeks İmproved? Chronic Cough Algoritm For the Management of Adults Chronic cough Normal Abnormal Cough? Yes Yok No Yes Improved Cough? No Yes Empiric/ Specific Therapy History,Examination, Chest X-Ray, PFT Sputum, Bronchoscopy,CT, Cardiac tests Specific diagnosis - treatment Smoking, ACEI ?, Irritants? UACS,GERD, Asthma, NAEB Stop 4 weeks Chronic Cough Algoritm Chronic cough History,Examination, Chest X-Ray, PFT Normal Abnormal Sputum, Bronchoscopy,CT, Cardiac tests Smoking, ACEI ?, Irritants? Cough? Yes No UACS,GERD, Asthma, NAEB No Yes Stop 4 weeks Improved Empiric Therapy ENT, Sinus CT BPT,PEF monit., NO Esophageal tests No response Specific diagnosis - treatment Specific Diagnosis - Treatment Chronic Cough Algoritm

Slide 55 -

CHRONIC COUGH MÜNEVVER ERDİNÇ Department of Chest Diseases Ege University Faculty of Medicine Differential Diagnosis And Treatment In Adults Acute Cough lasting less than 3 weeks Subacute Cough lasting 3 to 8 weeks Chronic Cough Lasting more than 8 weeks Morice AH.Eur Respir J 2004 :24:481-492 Fontana GA.Thorax 2003;58:1092-1095 Irwin RS.NEJM 343(23): 1715-1721,2000 Irwin RS. Chest 1998; 114(suppl1) :133S-181S Differantial Diagnosis of Chronic Cough in Adults PNDS Allergic rhinitis Chronic sinusitis GERD Cough variant asthma ACEI induced cough Pertusis Neurogenic Traumatic Postinfectious cough Phychogenic cough Chronic aspiration Zenker diverticulosis Foreign body Chronic bronchitis Bronchiectasis Lung cancer Subglottic stenosis Tracheomalasie Tracheoesophageal fistul Tuerculosis Sarcoidosis Congestive heart failure Simpson CB. Otolaryngology–Head Neck Surg 2006; 134: 693-700 In prospective studies in adults, chronic cough is most commonly due to 6 disorders : Upper Airway Cough Syndrome (UACS) Asthma GERD Chronic Bronchitis Bronchiectasis Non-asthmatic Eosinophilic Bronchitis Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S New Considerations Eosinophilic bronchitis Atopic cough Non acid(volume)/ weakly acid reflux Idiopathic (unexplained) öksürük Diagnosis and Management of Cough ACCP Evidence-Based CPG 2006 Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S Plevkova, et al. Respir Physiol Neurobiol 2004; 142: 225-235 Postnasal drip syndrome (PNDS) renamed upper airway cough syndrome (UACS) Upper airway afferents may reflexly enhance coughing Nonasthmatic eosinophilic bronchitis recognized as a common cause of chronic cough Idiopathic cough renamed unexplained cough The term acid reflux disease, unless it can be definitively shown to apply, replaced by reflux disease Update of current diagnostic and therapeutic approaches Common diseases, Uncommon diseases New algorithms for the management of cough in adults and children An empiric integrative approach is recommended 10 12 13 12 16 6 4 ASTHMA PNDS GERD Chest 1999;116:279-284 1. Gastroesophageal reflux disease (21-41%) 2. Cough variant asthma (24-59%) 3. Postnasal drip syndrome (41-58%) Chest 1999;116:279-281 Percentage of Cases Presenting 1,2,3, and 4 Causative Factors İmmunocompetent patients Not exposed to enviromental irritants Chest radiograph is normal Not taking an ACE inhibitor Not a current smoker Asthma and/or GERD, PNDS responsible for 93.6% of the cases of chronic cough Harding SM .Chest 2003;123:659-660 Changing Trends in Diagnosis Percentage of Diagnosis (%) GERD ASTHMA RHINITIS Impaired esophageal clearance Functional defect in LES syphincter Hiatal hernia Delayed gastric emptying İncreased intra-abdominal pressure GERD ? Decreased saliva Heartburn (pyrosis) and regurgitation At least weekly symptoms extraesophageal reflux symptoms and/or esophageal mucosal damage / Katzka & DiMarino 1995 FLR Signs Edema and hyperemia of larynx Vocal cord erythema, polyps, granulomas, ulcers Hyperemia and lymphoid hyperplasia of posterior pharynx Interarytenoid changes Subglottic stenosis GERD-related cough incidence 5 - 55% May be the sole presenting symptom(1/3) Thorax 2003:58;1092-1095) (Chest 1997; 111: 1389-1402) Irwin RS. Chest 2006;129:80S-94S Association between cough and reflux is important Esophageal-tracheal-bronchial reflex Microaspiration Pathogenesis ARRD 1981;123:413-417 Arch Intern Med 1996;156:997 Chest 1993;104:1511-1517 El Hennawi, 2004 OHNS Nonacidic factors? Esophageal dismotility? . Mediator Release . Inflammation . Edema . Mucus . Smooth Muscle Microaspiration REFLUX Esophageal Vagal Afferents Bronchial Hyperreactivity Airway Vagal Afferents CNS Stein MR.Am J Med 2003 Chest 1997;111: 1389-1402 Airway Airway Vagal Efferents Esophagus Tracheobronchial Tree Stomach Oesophagus Pharyngeal pHmetry + - Not GERD Clinical GERD symptoms ? Nonacid, weakly acid reflux? Increase dose PPI + alginate İmproved Not improved Continue pHmetry under treatment Consider  Simultaneously dual probes 24 hours pHmonitoring and intraesophageal impedance Irwin RS.AJRCCM 165:1469-74,2002 McGarvey LPA.Thorax 59:342-346,2004 15 cm 17 cm 6 impedance channels 1 pH electrode + Adult Standard Model ZAN-S61C01E Multichannel intraluminal impedance-pH catheter Non acid reflux On going reflux of ‘non-acid’ material may be responsible for continuing symptoms while on acid-suppressing medications Therapy in Esophageal-pulmonary reflux Conservative and lifestyle measures Ampirical therapy: Acid suppression Proton pump inhibitors  PPI x 2 / 3 months Therapy failure  24 hour intraesophageal pHmetry ( pharyngeal pHmetry )  GERD (+) High dose PPI + H2 blocker agent Surgery(Fundoplication) Pulmonary and Crit Care Update 1994; Vol 9 Morice AH. ERJ 2004;24:481-492 Weeks of antireflux therapy Patients responded No No (%) 2 16 (41) 4 38 (86) 6 42 (95) 8 43 (99) 12 weeks 44 (100) Poe RH.Chest 2003;123:679-684 Cumulative Response to GERD Therapy Preop pH <4: %23.6 De Meester: 85 Postop pH <4: %2.4 De Meester: 9.9 1. Chronic cough for at least 2 months 2. Immunocompetent patients 3. Chest radiograph is normal 4. Not exposed to enviromental irritants nor a present smoker 5. Not taking an ACE inhibitor 6. Symptomatic asthma has been ruled out 7. Rhinosinus diseases has been ruled out: 8. ‘Silent sinusitis’ has been ruled out 9. Nonasthmatic eosinophilic bronchitis has been ruled out: BPT is negative Cough has not improved with asthma therapy First generation H1 antagonists has been used Eo 3% in induced sputum Cough has not improved with steroids Irwin RS. Chest 2006;129:80S-94S İrwin RS. AJRCCM Vol 165; 1469-1474, 2002 Clinical Profile That Chronic Cough İs Likely Due To ‘Silent GERD’ Postnasal Drip Syndrome (PNDS) Prevalence : 8 – 87% Pathogenesis : The sensation of drainage of secretions from the nose or paranasal sinuses into the pharynx Clinical Presentation: Dripping sensation Tickle in the throat Nasal congestion Mucus in oropharynx Cobblestone appearence of oropharynx ACCP consensus. CHEST 1998; 114: 133-181 ERS Task Force. ERS Journal ; 24: 553-566 Pathogenic Triad in Chronic Cough. CHEST 1999; 116: 279-284 Evaluation of chronic cough. UPTODATE 2005 Chest 2006;129:63S-71S In patient with chronic cough that is related to upper airway abnormalities Upper Airway Cough Syndrome UACS Treatment Antihistamines / decongestant combinations - “Older” sedating antihistamines more effective - Treatment effect should be observed in 1 week Additional / Alternative treatments : Ipratropium nasal spray : 2-7 days Nasal steroids (such as BDP, FP,BUD) : 2-3 days - 2 week 3 months prescribed Eosinophilic Eronchitis Airway obstruction Bronchial hyperreactivity NO YES YES NO Asthmatic Coughs Cough Variant Asthma Asthma Cough Variant Asthma Prevalence : 24 – 59% Clinical Diagnosis Gold standard  History - Episodic symptoms, Family history Reversibility testing PEF monitoring Bronchoprovocation test Differential Diagnosis: Decreased of cough with classical asthma therapy ACCP consensus. CHEST 1998; 114: 133-181 ERS Task Force. ERS Journal ; 24: 553-566 The Journal of Respiratory Disease; 25; 310-315 THORAX 59; 342-346 Middle age patients Smoking is unusual, occupational ? Prevalence of atopy similar population Good respond to inhaled steroids Gibson et al. Lancet 1989 Chest 2006;129:116S-121S Eosinophilic Bronchitis Isolated chronic cough,  productive of sputum Normal lung function without variable airflow limitation Airway hyperresponsiveness absent Eosinophilia in sputum and BAL Cough reflex to capsaicin increased Normal daily variability in peak expiratory flow (<20%) 1)Kim et al AJRCCM 2003; 2) Brightling et al AJRCCM 1999;160:406-10, 3) Joo Korean JIM 2002;17:31-7, 4) Carney et al AJRCCM 1997; 156:211-6, 5) Ma et al Zhongua 2003;26:362-5, 6) Ayik, Erdinc et al Respir Med 2003;97:695-701 Eosinophilic Bronchitis A Worldwide Disease Causes of chronic cough Ayık SÖ, Başoğlu ÖK, Erdinç M. Respir Med Vol. 97 (2003) 695-701 Causes of Isolated Chronic Cough Brightling CE et al. AJRCCM 1999 Asthmatic Cough Airway obstruction Reversibility PEF değişkenliği Increased NO all of them PEF monitoring Prevalence: 0-50% More agressive diagnosis and treatments UACS, GERD and postinfectious cough leads to lower incidence ‘unexplained’. Airway inflammation Mast cell, histamin, cysteinil LTs, PD2, PE2 Irwin RS,et al. Chest 2006;130:362-370 Chronic Unexplained (Idiopathic) Cough Important missed history (smoking,ACEI,enviromental,drugs,allergy) Failure to do correct diagnostic tests Failure to use ‘empiric’ treatment Failure to use effective therapy Unknown disease process Potential Reasons Chronic Unexplained (Idiopathic) Cough « Truly idiopathic cough is rare and misdiagnosis very common, especially if cough is provoked by sites outside the airways » Eur Respir J 24: 481-492 2004 Idiopathic cough % ? Studies in the 1980’s % patients 1990-1995 Idiopathic cough % ? % patients Idiopathic cough % ? 1996-1999 % patients Idiopathic cough % ? 2000  % patients Haque et al Chest 2005;127:1710-1713 Chronic Idiopathic Cough Predominantly female and associated with BAL lymphocytosis Raising the possibility of a link between autoimmune diseases Surinder S. Et al. Respir Med 98:242-246;2004 Chronic Idiopathic Cough *OR: 8.8 Inflammation Chronic Idiopathic Cough Birring et al AJRCM 2004 + BAL lymphocytosis Sarcoidosis Hypersensitivity pneumonitis Rheumatoid Arthritis Sjögren’s syndrome Lung tx Inflammatory bowel disease Hypothyroidism Autoimmune disorders (SLE, RA) Pernisious anemia DM Thorax 2003;58:1066-1070 Chronic Idiopathic Cough Irwin RS,et al. Chest 2006;130:362-370 It is not correct to state that “a typical lymphocytic airways inflammation is seen in idiopathic cough” because lymphocytic or lymphoplasmacytic inflammation a non-specific finding related to trauma of coughing Chronic Idiopathic Cough Psychogenic Cough Cough is often triggered by a common cold Usually dissapears during sleep Like a dog barking The diagnosis of psychogenic cough is one of exclusion, after ruling out an organic or functional cause of cough. Specific or empiric treatment Antitussives are usually ineffective. Respirology 2006;Suppl 4 ;S160-S174 Irwin RS et al. Chest 1998, 114:2 suppl ERS Task Force: Eur Respir J 2004, 24:481-492 Prevalence: 11-25 % History: After a respiratory tract infection Diagnosis: Spasmodic cough Normal chest radiograph, with/without ronchii Respiratory viruses, m.pneumoniae, c.pneumoniae, B.pertussis Serum acute IgA antibody ELISA Rarely lymphocytosis Airway inflammation +/- Airway hyperresponsivenes Irwin RS et al. Chest 1998, 114:2 suppl ACCP consensus. CHEST 1998; 114: 133-181 ERS Task Force. ERS Journal ; 24: 553-566 Postinfectious Cough Oral and/or inhaled steroid (2-3 weeks) Antibiyotic : Macrolides (Chlamydia, mycoplasma) TMP/SMX : Pertusis (3-6 weeks) Ipatropium bromid decrease efferent limb of the cough reflex decrease stimulation of cough receptors Antitussive therapy Irwin RS et al. Chest 1998,114:2 suppl Miyashita N. J Med Microbiol 2003, 52:3,265-269 Postinfectious Cough ACEI Induced Chronic Cough Frequency: 0.2-33% Predominantly female Not dose related Appears within hours, weeks, months Pathogenesis: Neurokinin, Substance P, Prostoglandins, stimulates afferent C-fibers in the airway  increased cough reflex sensitivity Prefer Angiotensin II receptör antagonists Treatment Irwin RS et al. Chest 1998, 114:2 Capsaicin type I Vanilloid receptor antagonists Selective opioid receptor agonists Opioid-like receptor agonists Tachykinin receptor antagonists Endogenous cannabinoids 5-HT receptor agonists Large-conductance calcium-activated potassium channel openers Dicpinigaitis PV.Chest 2006 ;129:284S-286S Future Therapies Chronic cough History,Examination, Chest X-Ray, PFT Normal Abnormal Sputum, bronchoscopy,CT, Cardiac tests Smoking, ACEI , Irritants ? Specific diagnosis - treatment Stop 4 weeks yes Chronic Cough Algoritm For the Management of Adults Chronic cough History,Examination, Chest X-Ray, PFT Normal Abnormal Sputum, bronchoscopy,CT, Cardiac tests Smoking, ACEI, Irritants ? Specific diagnosis - Treatment Cough? Yes No UACS,GERD, Asthma, NAEB ? No Yes Stop 4 weeks İmproved? Chronic Cough Algoritm For the Management of Adults Chronic cough Normal Abnormal Cough? Yes Yok No Yes Improved Cough? No Yes Empiric/ Specific Therapy History,Examination, Chest X-Ray, PFT Sputum, Bronchoscopy,CT, Cardiac tests Specific diagnosis - treatment Smoking, ACEI ?, Irritants? UACS,GERD, Asthma, NAEB Stop 4 weeks Chronic Cough Algoritm Chronic cough History,Examination, Chest X-Ray, PFT Normal Abnormal Sputum, Bronchoscopy,CT, Cardiac tests Smoking, ACEI ?, Irritants? Cough? Yes No UACS,GERD, Asthma, NAEB No Yes Stop 4 weeks Improved Empiric Therapy ENT, Sinus CT BPT,PEF monit., NO Esophageal tests No response Specific diagnosis - treatment Specific Diagnosis - Treatment Chronic Cough Algoritm UACS,GERD, Asthma, NAEB Empiric or Specific Diagnosis and Treatment Cough ? No Sputum, HRCT, Bronchoscopy Improved Yes Post infectious? Yes Consider uncommon causes Cough ? No Yes Physcogenic cough? Specific diagnosis - Treatment

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CHRONIC COUGH MÜNEVVER ERDİNÇ Department of Chest Diseases Ege University Faculty of Medicine Differential Diagnosis And Treatment In Adults Acute Cough lasting less than 3 weeks Subacute Cough lasting 3 to 8 weeks Chronic Cough Lasting more than 8 weeks Morice AH.Eur Respir J 2004 :24:481-492 Fontana GA.Thorax 2003;58:1092-1095 Irwin RS.NEJM 343(23): 1715-1721,2000 Irwin RS. Chest 1998; 114(suppl1) :133S-181S Differantial Diagnosis of Chronic Cough in Adults PNDS Allergic rhinitis Chronic sinusitis GERD Cough variant asthma ACEI induced cough Pertusis Neurogenic Traumatic Postinfectious cough Phychogenic cough Chronic aspiration Zenker diverticulosis Foreign body Chronic bronchitis Bronchiectasis Lung cancer Subglottic stenosis Tracheomalasie Tracheoesophageal fistul Tuerculosis Sarcoidosis Congestive heart failure Simpson CB. Otolaryngology–Head Neck Surg 2006; 134: 693-700 In prospective studies in adults, chronic cough is most commonly due to 6 disorders : Upper Airway Cough Syndrome (UACS) Asthma GERD Chronic Bronchitis Bronchiectasis Non-asthmatic Eosinophilic Bronchitis Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S New Considerations Eosinophilic bronchitis Atopic cough Non acid(volume)/ weakly acid reflux Idiopathic (unexplained) öksürük Diagnosis and Management of Cough ACCP Evidence-Based CPG 2006 Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S Plevkova, et al. Respir Physiol Neurobiol 2004; 142: 225-235 Postnasal drip syndrome (PNDS) renamed upper airway cough syndrome (UACS) Upper airway afferents may reflexly enhance coughing Nonasthmatic eosinophilic bronchitis recognized as a common cause of chronic cough Idiopathic cough renamed unexplained cough The term acid reflux disease, unless it can be definitively shown to apply, replaced by reflux disease Update of current diagnostic and therapeutic approaches Common diseases, Uncommon diseases New algorithms for the management of cough in adults and children An empiric integrative approach is recommended 10 12 13 12 16 6 4 ASTHMA PNDS GERD Chest 1999;116:279-284 1. Gastroesophageal reflux disease (21-41%) 2. Cough variant asthma (24-59%) 3. Postnasal drip syndrome (41-58%) Chest 1999;116:279-281 Percentage of Cases Presenting 1,2,3, and 4 Causative Factors İmmunocompetent patients Not exposed to enviromental irritants Chest radiograph is normal Not taking an ACE inhibitor Not a current smoker Asthma and/or GERD, PNDS responsible for 93.6% of the cases of chronic cough Harding SM .Chest 2003;123:659-660 Changing Trends in Diagnosis Percentage of Diagnosis (%) GERD ASTHMA RHINITIS Impaired esophageal clearance Functional defect in LES syphincter Hiatal hernia Delayed gastric emptying İncreased intra-abdominal pressure GERD ? Decreased saliva Heartburn (pyrosis) and regurgitation At least weekly symptoms extraesophageal reflux symptoms and/or esophageal mucosal damage / Katzka & DiMarino 1995 FLR Signs Edema and hyperemia of larynx Vocal cord erythema, polyps, granulomas, ulcers Hyperemia and lymphoid hyperplasia of posterior pharynx Interarytenoid changes Subglottic stenosis GERD-related cough incidence 5 - 55% May be the sole presenting symptom(1/3) Thorax 2003:58;1092-1095) (Chest 1997; 111: 1389-1402) Irwin RS. Chest 2006;129:80S-94S Association between cough and reflux is important Esophageal-tracheal-bronchial reflex Microaspiration Pathogenesis ARRD 1981;123:413-417 Arch Intern Med 1996;156:997 Chest 1993;104:1511-1517 El Hennawi, 2004 OHNS Nonacidic factors? Esophageal dismotility? . Mediator Release . Inflammation . Edema . Mucus . Smooth Muscle Microaspiration REFLUX Esophageal Vagal Afferents Bronchial Hyperreactivity Airway Vagal Afferents CNS Stein MR.Am J Med 2003 Chest 1997;111: 1389-1402 Airway Airway Vagal Efferents Esophagus Tracheobronchial Tree Stomach Oesophagus Pharyngeal pHmetry + - Not GERD Clinical GERD symptoms ? Nonacid, weakly acid reflux? Increase dose PPI + alginate İmproved Not improved Continue pHmetry under treatment Consider  Simultaneously dual probes 24 hours pHmonitoring and intraesophageal impedance Irwin RS.AJRCCM 165:1469-74,2002 McGarvey LPA.Thorax 59:342-346,2004 15 cm 17 cm 6 impedance channels 1 pH electrode + Adult Standard Model ZAN-S61C01E Multichannel intraluminal impedance-pH catheter Non acid reflux On going reflux of ‘non-acid’ material may be responsible for continuing symptoms while on acid-suppressing medications Therapy in Esophageal-pulmonary reflux Conservative and lifestyle measures Ampirical therapy: Acid suppression Proton pump inhibitors  PPI x 2 / 3 months Therapy failure  24 hour intraesophageal pHmetry ( pharyngeal pHmetry )  GERD (+) High dose PPI + H2 blocker agent Surgery(Fundoplication) Pulmonary and Crit Care Update 1994; Vol 9 Morice AH. ERJ 2004;24:481-492 Weeks of antireflux therapy Patients responded No No (%) 2 16 (41) 4 38 (86) 6 42 (95) 8 43 (99) 12 weeks 44 (100) Poe RH.Chest 2003;123:679-684 Cumulative Response to GERD Therapy Preop pH <4: %23.6 De Meester: 85 Postop pH <4: %2.4 De Meester: 9.9 1. Chronic cough for at least 2 months 2. Immunocompetent patients 3. Chest radiograph is normal 4. Not exposed to enviromental irritants nor a present smoker 5. Not taking an ACE inhibitor 6. Symptomatic asthma has been ruled out 7. Rhinosinus diseases has been ruled out: 8. ‘Silent sinusitis’ has been ruled out 9. Nonasthmatic eosinophilic bronchitis has been ruled out: BPT is negative Cough has not improved with asthma therapy First generation H1 antagonists has been used Eo 3% in induced sputum Cough has not improved with steroids Irwin RS. Chest 2006;129:80S-94S İrwin RS. AJRCCM Vol 165; 1469-1474, 2002 Clinical Profile That Chronic Cough İs Likely Due To ‘Silent GERD’ Postnasal Drip Syndrome (PNDS) Prevalence : 8 – 87% Pathogenesis : The sensation of drainage of secretions from the nose or paranasal sinuses into the pharynx Clinical Presentation: Dripping sensation Tickle in the throat Nasal congestion Mucus in oropharynx Cobblestone appearence of oropharynx ACCP consensus. CHEST 1998; 114: 133-181 ERS Task Force. ERS Journal ; 24: 553-566 Pathogenic Triad in Chronic Cough. CHEST 1999; 116: 279-284 Evaluation of chronic cough. UPTODATE 2005 Chest 2006;129:63S-71S In patient with chronic cough that is related to upper airway abnormalities Upper Airway Cough Syndrome UACS Treatment Antihistamines / decongestant combinations - “Older” sedating antihistamines more effective - Treatment effect should be observed in 1 week Additional / Alternative treatments : Ipratropium nasal spray : 2-7 days Nasal steroids (such as BDP, FP,BUD) : 2-3 days - 2 week 3 months prescribed Eosinophilic Eronchitis Airway obstruction Bronchial hyperreactivity NO YES YES NO Asthmatic Coughs Cough Variant Asthma Asthma Cough Variant Asthma Prevalence : 24 – 59% Clinical Diagnosis Gold standard  History - Episodic symptoms, Family history Reversibility testing PEF monitoring Bronchoprovocation test Differential Diagnosis: Decreased of cough with classical asthma therapy ACCP consensus. CHEST 1998; 114: 133-181 ERS Task Force. ERS Journal ; 24: 553-566 The Journal of Respiratory Disease; 25; 310-315 THORAX 59; 342-346 Middle age patients Smoking is unusual, occupational ? Prevalence of atopy similar population Good respond to inhaled steroids Gibson et al. Lancet 1989 Chest 2006;129:116S-121S Eosinophilic Bronchitis Isolated chronic cough,  productive of sputum Normal lung function without variable airflow limitation Airway hyperresponsiveness absent Eosinophilia in sputum and BAL Cough reflex to capsaicin increased Normal daily variability in peak expiratory flow (<20%) 1)Kim et al AJRCCM 2003; 2) Brightling et al AJRCCM 1999;160:406-10, 3) Joo Korean JIM 2002;17:31-7, 4) Carney et al AJRCCM 1997; 156:211-6, 5) Ma et al Zhongua 2003;26:362-5, 6) Ayik, Erdinc et al Respir Med 2003;97:695-701 Eosinophilic Bronchitis A Worldwide Disease Causes of chronic cough Ayık SÖ, Başoğlu ÖK, Erdinç M. Respir Med Vol. 97 (2003) 695-701 Causes of Isolated Chronic Cough Brightling CE et al. AJRCCM 1999 Asthmatic Cough Airway obstruction Reversibility PEF değişkenliği Increased NO all of them PEF monitoring Prevalence: 0-50% More agressive diagnosis and treatments UACS, GERD and postinfectious cough leads to lower incidence ‘unexplained’. Airway inflammation Mast cell, histamin, cysteinil LTs, PD2, PE2 Irwin RS,et al. Chest 2006;130:362-370 Chronic Unexplained (Idiopathic) Cough Important missed history (smoking,ACEI,enviromental,drugs,allergy) Failure to do correct diagnostic tests Failure to use ‘empiric’ treatment Failure to use effective therapy Unknown disease process Potential Reasons Chronic Unexplained (Idiopathic) Cough « Truly idiopathic cough is rare and misdiagnosis very common, especially if cough is provoked by sites outside the airways » Eur Respir J 24: 481-492 2004 Idiopathic cough % ? Studies in the 1980’s % patients 1990-1995 Idiopathic cough % ? % patients Idiopathic cough % ? 1996-1999 % patients Idiopathic cough % ? 2000  % patients Haque et al Chest 2005;127:1710-1713 Chronic Idiopathic Cough Predominantly female and associated with BAL lymphocytosis Raising the possibility of a link between autoimmune diseases Surinder S. Et al. Respir Med 98:242-246;2004 Chronic Idiopathic Cough *OR: 8.8 Inflammation Chronic Idiopathic Cough Birring et al AJRCM 2004 + BAL lymphocytosis Sarcoidosis Hypersensitivity pneumonitis Rheumatoid Arthritis Sjögren’s syndrome Lung tx Inflammatory bowel disease Hypothyroidism Autoimmune disorders (SLE, RA) Pernisious anemia DM Thorax 2003;58:1066-1070 Chronic Idiopathic Cough Irwin RS,et al. Chest 2006;130:362-370 It is not correct to state that “a typical lymphocytic airways inflammation is seen in idiopathic cough” because lymphocytic or lymphoplasmacytic inflammation a non-specific finding related to trauma of coughing Chronic Idiopathic Cough Psychogenic Cough Cough is often triggered by a common cold Usually dissapears during sleep Like a dog barking The diagnosis of psychogenic cough is one of exclusion, after ruling out an organic or functional cause of cough. Specific or empiric treatment Antitussives are usually ineffective. Respirology 2006;Suppl 4 ;S160-S174 Irwin RS et al. Chest 1998, 114:2 suppl ERS Task Force: Eur Respir J 2004, 24:481-492 Prevalence: 11-25 % History: After a respiratory tract infection Diagnosis: Spasmodic cough Normal chest radiograph, with/without ronchii Respiratory viruses, m.pneumoniae, c.pneumoniae, B.pertussis Serum acute IgA antibody ELISA Rarely lymphocytosis Airway inflammation +/- Airway hyperresponsivenes Irwin RS et al. Chest 1998, 114:2 suppl ACCP consensus. CHEST 1998; 114: 133-181 ERS Task Force. ERS Journal ; 24: 553-566 Postinfectious Cough Oral and/or inhaled steroid (2-3 weeks) Antibiyotic : Macrolides (Chlamydia, mycoplasma) TMP/SMX : Pertusis (3-6 weeks) Ipatropium bromid decrease efferent limb of the cough reflex decrease stimulation of cough receptors Antitussive therapy Irwin RS et al. Chest 1998,114:2 suppl Miyashita N. J Med Microbiol 2003, 52:3,265-269 Postinfectious Cough ACEI Induced Chronic Cough Frequency: 0.2-33% Predominantly female Not dose related Appears within hours, weeks, months Pathogenesis: Neurokinin, Substance P, Prostoglandins, stimulates afferent C-fibers in the airway  increased cough reflex sensitivity Prefer Angiotensin II receptör antagonists Treatment Irwin RS et al. Chest 1998, 114:2 Capsaicin type I Vanilloid receptor antagonists Selective opioid receptor agonists Opioid-like receptor agonists Tachykinin receptor antagonists Endogenous cannabinoids 5-HT receptor agonists Large-conductance calcium-activated potassium channel openers Dicpinigaitis PV.Chest 2006 ;129:284S-286S Future Therapies Chronic cough History,Examination, Chest X-Ray, PFT Normal Abnormal Sputum, bronchoscopy,CT, Cardiac tests Smoking, ACEI , Irritants ? Specific diagnosis - treatment Stop 4 weeks yes Chronic Cough Algoritm For the Management of Adults Chronic cough History,Examination, Chest X-Ray, PFT Normal Abnormal Sputum, bronchoscopy,CT, Cardiac tests Smoking, ACEI, Irritants ? Specific diagnosis - Treatment Cough? Yes No UACS,GERD, Asthma, NAEB ? No Yes Stop 4 weeks İmproved? Chronic Cough Algoritm For the Management of Adults Chronic cough Normal Abnormal Cough? Yes Yok No Yes Improved Cough? No Yes Empiric/ Specific Therapy History,Examination, Chest X-Ray, PFT Sputum, Bronchoscopy,CT, Cardiac tests Specific diagnosis - treatment Smoking, ACEI ?, Irritants? UACS,GERD, Asthma, NAEB Stop 4 weeks Chronic Cough Algoritm Chronic cough History,Examination, Chest X-Ray, PFT Normal Abnormal Sputum, Bronchoscopy,CT, Cardiac tests Smoking, ACEI ?, Irritants? Cough? Yes No UACS,GERD, Asthma, NAEB No Yes Stop 4 weeks Improved Empiric Therapy ENT, Sinus CT BPT,PEF monit., NO Esophageal tests No response Specific diagnosis - treatment Specific Diagnosis - Treatment Chronic Cough Algoritm UACS,GERD, Asthma, NAEB Empiric or Specific Diagnosis and Treatment Cough ? No Sputum, HRCT, Bronchoscopy Improved Yes Post infectious? Yes Consider uncommon causes Cough ? No Yes Physcogenic cough? Specific diagnosis - Treatment UACS,GERD, Asthma, NAEB Empiric or Specific Diagnosis and Treatment Cough ? No Sputum, HRCT, Bronchoscopy Improved Yes Post infectious? Yes Consider uncommon causes Cough ? No Yes Physcogenic cough? Specific diagnosis - Treatment Specific diagnosis - Treatment Improved Chronic idiopathic cough No

Slide 57 -

CHRONIC COUGH MÜNEVVER ERDİNÇ Department of Chest Diseases Ege University Faculty of Medicine Differential Diagnosis And Treatment In Adults Acute Cough lasting less than 3 weeks Subacute Cough lasting 3 to 8 weeks Chronic Cough Lasting more than 8 weeks Morice AH.Eur Respir J 2004 :24:481-492 Fontana GA.Thorax 2003;58:1092-1095 Irwin RS.NEJM 343(23): 1715-1721,2000 Irwin RS. Chest 1998; 114(suppl1) :133S-181S Differantial Diagnosis of Chronic Cough in Adults PNDS Allergic rhinitis Chronic sinusitis GERD Cough variant asthma ACEI induced cough Pertusis Neurogenic Traumatic Postinfectious cough Phychogenic cough Chronic aspiration Zenker diverticulosis Foreign body Chronic bronchitis Bronchiectasis Lung cancer Subglottic stenosis Tracheomalasie Tracheoesophageal fistul Tuerculosis Sarcoidosis Congestive heart failure Simpson CB. Otolaryngology–Head Neck Surg 2006; 134: 693-700 In prospective studies in adults, chronic cough is most commonly due to 6 disorders : Upper Airway Cough Syndrome (UACS) Asthma GERD Chronic Bronchitis Bronchiectasis Non-asthmatic Eosinophilic Bronchitis Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S New Considerations Eosinophilic bronchitis Atopic cough Non acid(volume)/ weakly acid reflux Idiopathic (unexplained) öksürük Diagnosis and Management of Cough ACCP Evidence-Based CPG 2006 Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S Plevkova, et al. Respir Physiol Neurobiol 2004; 142: 225-235 Postnasal drip syndrome (PNDS) renamed upper airway cough syndrome (UACS) Upper airway afferents may reflexly enhance coughing Nonasthmatic eosinophilic bronchitis recognized as a common cause of chronic cough Idiopathic cough renamed unexplained cough The term acid reflux disease, unless it can be definitively shown to apply, replaced by reflux disease Update of current diagnostic and therapeutic approaches Common diseases, Uncommon diseases New algorithms for the management of cough in adults and children An empiric integrative approach is recommended 10 12 13 12 16 6 4 ASTHMA PNDS GERD Chest 1999;116:279-284 1. Gastroesophageal reflux disease (21-41%) 2. Cough variant asthma (24-59%) 3. Postnasal drip syndrome (41-58%) Chest 1999;116:279-281 Percentage of Cases Presenting 1,2,3, and 4 Causative Factors İmmunocompetent patients Not exposed to enviromental irritants Chest radiograph is normal Not taking an ACE inhibitor Not a current smoker Asthma and/or GERD, PNDS responsible for 93.6% of the cases of chronic cough Harding SM .Chest 2003;123:659-660 Changing Trends in Diagnosis Percentage of Diagnosis (%) GERD ASTHMA RHINITIS Impaired esophageal clearance Functional defect in LES syphincter Hiatal hernia Delayed gastric emptying İncreased intra-abdominal pressure GERD ? Decreased saliva Heartburn (pyrosis) and regurgitation At least weekly symptoms extraesophageal reflux symptoms and/or esophageal mucosal damage / Katzka & DiMarino 1995 FLR Signs Edema and hyperemia of larynx Vocal cord erythema, polyps, granulomas, ulcers Hyperemia and lymphoid hyperplasia of posterior pharynx Interarytenoid changes Subglottic stenosis GERD-related cough incidence 5 - 55% May be the sole presenting symptom(1/3) Thorax 2003:58;1092-1095) (Chest 1997; 111: 1389-1402) Irwin RS. Chest 2006;129:80S-94S Association between cough and reflux is important Esophageal-tracheal-bronchial reflex Microaspiration Pathogenesis ARRD 1981;123:413-417 Arch Intern Med 1996;156:997 Chest 1993;104:1511-1517 El Hennawi, 2004 OHNS Nonacidic factors? Esophageal dismotility? . Mediator Release . Inflammation . Edema . Mucus . Smooth Muscle Microaspiration REFLUX Esophageal Vagal Afferents Bronchial Hyperreactivity Airway Vagal Afferents CNS Stein MR.Am J Med 2003 Chest 1997;111: 1389-1402 Airway Airway Vagal Efferents Esophagus Tracheobronchial Tree Stomach Oesophagus Pharyngeal pHmetry + - Not GERD Clinical GERD symptoms ? Nonacid, weakly acid reflux? Increase dose PPI + alginate İmproved Not improved Continue pHmetry under treatment Consider  Simultaneously dual probes 24 hours pHmonitoring and intraesophageal impedance Irwin RS.AJRCCM 165:1469-74,2002 McGarvey LPA.Thorax 59:342-346,2004 15 cm 17 cm 6 impedance channels 1 pH electrode + Adult Standard Model ZAN-S61C01E Multichannel intraluminal impedance-pH catheter Non acid reflux On going reflux of ‘non-acid’ material may be responsible for continuing symptoms while on acid-suppressing medications Therapy in Esophageal-pulmonary reflux Conservative and lifestyle measures Ampirical therapy: Acid suppression Proton pump inhibitors  PPI x 2 / 3 months Therapy failure  24 hour intraesophageal pHmetry ( pharyngeal pHmetry )  GERD (+) High dose PPI + H2 blocker agent Surgery(Fundoplication) Pulmonary and Crit Care Update 1994; Vol 9 Morice AH. ERJ 2004;24:481-492 Weeks of antireflux therapy Patients responded No No (%) 2 16 (41) 4 38 (86) 6 42 (95) 8 43 (99) 12 weeks 44 (100) Poe RH.Chest 2003;123:679-684 Cumulative Response to GERD Therapy Preop pH <4: %23.6 De Meester: 85 Postop pH <4: %2.4 De Meester: 9.9 1. Chronic cough for at least 2 months 2. Immunocompetent patients 3. Chest radiograph is normal 4. Not exposed to enviromental irritants nor a present smoker 5. Not taking an ACE inhibitor 6. Symptomatic asthma has been ruled out 7. Rhinosinus diseases has been ruled out: 8. ‘Silent sinusitis’ has been ruled out 9. Nonasthmatic eosinophilic bronchitis has been ruled out: BPT is negative Cough has not improved with asthma therapy First generation H1 antagonists has been used Eo 3% in induced sputum Cough has not improved with steroids Irwin RS. Chest 2006;129:80S-94S İrwin RS. AJRCCM Vol 165; 1469-1474, 2002 Clinical Profile That Chronic Cough İs Likely Due To ‘Silent GERD’ Postnasal Drip Syndrome (PNDS) Prevalence : 8 – 87% Pathogenesis : The sensation of drainage of secretions from the nose or paranasal sinuses into the pharynx Clinical Presentation: Dripping sensation Tickle in the throat Nasal congestion Mucus in oropharynx Cobblestone appearence of oropharynx ACCP consensus. CHEST 1998; 114: 133-181 ERS Task Force. ERS Journal ; 24: 553-566 Pathogenic Triad in Chronic Cough. CHEST 1999; 116: 279-284 Evaluation of chronic cough. UPTODATE 2005 Chest 2006;129:63S-71S In patient with chronic cough that is related to upper airway abnormalities Upper Airway Cough Syndrome UACS Treatment Antihistamines / decongestant combinations - “Older” sedating antihistamines more effective - Treatment effect should be observed in 1 week Additional / Alternative treatments : Ipratropium nasal spray : 2-7 days Nasal steroids (such as BDP, FP,BUD) : 2-3 days - 2 week 3 months prescribed Eosinophilic Eronchitis Airway obstruction Bronchial hyperreactivity NO YES YES NO Asthmatic Coughs Cough Variant Asthma Asthma Cough Variant Asthma Prevalence : 24 – 59% Clinical Diagnosis Gold standard  History - Episodic symptoms, Family history Reversibility testing PEF monitoring Bronchoprovocation test Differential Diagnosis: Decreased of cough with classical asthma therapy ACCP consensus. CHEST 1998; 114: 133-181 ERS Task Force. ERS Journal ; 24: 553-566 The Journal of Respiratory Disease; 25; 310-315 THORAX 59; 342-346 Middle age patients Smoking is unusual, occupational ? Prevalence of atopy similar population Good respond to inhaled steroids Gibson et al. Lancet 1989 Chest 2006;129:116S-121S Eosinophilic Bronchitis Isolated chronic cough,  productive of sputum Normal lung function without variable airflow limitation Airway hyperresponsiveness absent Eosinophilia in sputum and BAL Cough reflex to capsaicin increased Normal daily variability in peak expiratory flow (<20%) 1)Kim et al AJRCCM 2003; 2) Brightling et al AJRCCM 1999;160:406-10, 3) Joo Korean JIM 2002;17:31-7, 4) Carney et al AJRCCM 1997; 156:211-6, 5) Ma et al Zhongua 2003;26:362-5, 6) Ayik, Erdinc et al Respir Med 2003;97:695-701 Eosinophilic Bronchitis A Worldwide Disease Causes of chronic cough Ayık SÖ, Başoğlu ÖK, Erdinç M. Respir Med Vol. 97 (2003) 695-701 Causes of Isolated Chronic Cough Brightling CE et al. AJRCCM 1999 Asthmatic Cough Airway obstruction Reversibility PEF değişkenliği Increased NO all of them PEF monitoring Prevalence: 0-50% More agressive diagnosis and treatments UACS, GERD and postinfectious cough leads to lower incidence ‘unexplained’. Airway inflammation Mast cell, histamin, cysteinil LTs, PD2, PE2 Irwin RS,et al. Chest 2006;130:362-370 Chronic Unexplained (Idiopathic) Cough Important missed history (smoking,ACEI,enviromental,drugs,allergy) Failure to do correct diagnostic tests Failure to use ‘empiric’ treatment Failure to use effective therapy Unknown disease process Potential Reasons Chronic Unexplained (Idiopathic) Cough « Truly idiopathic cough is rare and misdiagnosis very common, especially if cough is provoked by sites outside the airways » Eur Respir J 24: 481-492 2004 Idiopathic cough % ? Studies in the 1980’s % patients 1990-1995 Idiopathic cough % ? % patients Idiopathic cough % ? 1996-1999 % patients Idiopathic cough % ? 2000  % patients Haque et al Chest 2005;127:1710-1713 Chronic Idiopathic Cough Predominantly female and associated with BAL lymphocytosis Raising the possibility of a link between autoimmune diseases Surinder S. Et al. Respir Med 98:242-246;2004 Chronic Idiopathic Cough *OR: 8.8 Inflammation Chronic Idiopathic Cough Birring et al AJRCM 2004 + BAL lymphocytosis Sarcoidosis Hypersensitivity pneumonitis Rheumatoid Arthritis Sjögren’s syndrome Lung tx Inflammatory bowel disease Hypothyroidism Autoimmune disorders (SLE, RA) Pernisious anemia DM Thorax 2003;58:1066-1070 Chronic Idiopathic Cough Irwin RS,et al. Chest 2006;130:362-370 It is not correct to state that “a typical lymphocytic airways inflammation is seen in idiopathic cough” because lymphocytic or lymphoplasmacytic inflammation a non-specific finding related to trauma of coughing Chronic Idiopathic Cough Psychogenic Cough Cough is often triggered by a common cold Usually dissapears during sleep Like a dog barking The diagnosis of psychogenic cough is one of exclusion, after ruling out an organic or functional cause of cough. Specific or empiric treatment Antitussives are usually ineffective. Respirology 2006;Suppl 4 ;S160-S174 Irwin RS et al. Chest 1998, 114:2 suppl ERS Task Force: Eur Respir J 2004, 24:481-492 Prevalence: 11-25 % History: After a respiratory tract infection Diagnosis: Spasmodic cough Normal chest radiograph, with/without ronchii Respiratory viruses, m.pneumoniae, c.pneumoniae, B.pertussis Serum acute IgA antibody ELISA Rarely lymphocytosis Airway inflammation +/- Airway hyperresponsivenes Irwin RS et al. Chest 1998, 114:2 suppl ACCP consensus. CHEST 1998; 114: 133-181 ERS Task Force. ERS Journal ; 24: 553-566 Postinfectious Cough Oral and/or inhaled steroid (2-3 weeks) Antibiyotic : Macrolides (Chlamydia, mycoplasma) TMP/SMX : Pertusis (3-6 weeks) Ipatropium bromid decrease efferent limb of the cough reflex decrease stimulation of cough receptors Antitussive therapy Irwin RS et al. Chest 1998,114:2 suppl Miyashita N. J Med Microbiol 2003, 52:3,265-269 Postinfectious Cough ACEI Induced Chronic Cough Frequency: 0.2-33% Predominantly female Not dose related Appears within hours, weeks, months Pathogenesis: Neurokinin, Substance P, Prostoglandins, stimulates afferent C-fibers in the airway  increased cough reflex sensitivity Prefer Angiotensin II receptör antagonists Treatment Irwin RS et al. Chest 1998, 114:2 Capsaicin type I Vanilloid receptor antagonists Selective opioid receptor agonists Opioid-like receptor agonists Tachykinin receptor antagonists Endogenous cannabinoids 5-HT receptor agonists Large-conductance calcium-activated potassium channel openers Dicpinigaitis PV.Chest 2006 ;129:284S-286S Future Therapies Chronic cough History,Examination, Chest X-Ray, PFT Normal Abnormal Sputum, bronchoscopy,CT, Cardiac tests Smoking, ACEI , Irritants ? Specific diagnosis - treatment Stop 4 weeks yes Chronic Cough Algoritm For the Management of Adults Chronic cough History,Examination, Chest X-Ray, PFT Normal Abnormal Sputum, bronchoscopy,CT, Cardiac tests Smoking, ACEI, Irritants ? Specific diagnosis - Treatment Cough? Yes No UACS,GERD, Asthma, NAEB ? No Yes Stop 4 weeks İmproved? Chronic Cough Algoritm For the Management of Adults Chronic cough Normal Abnormal Cough? Yes Yok No Yes Improved Cough? No Yes Empiric/ Specific Therapy History,Examination, Chest X-Ray, PFT Sputum, Bronchoscopy,CT, Cardiac tests Specific diagnosis - treatment Smoking, ACEI ?, Irritants? UACS,GERD, Asthma, NAEB Stop 4 weeks Chronic Cough Algoritm Chronic cough History,Examination, Chest X-Ray, PFT Normal Abnormal Sputum, Bronchoscopy,CT, Cardiac tests Smoking, ACEI ?, Irritants? Cough? Yes No UACS,GERD, Asthma, NAEB No Yes Stop 4 weeks Improved Empiric Therapy ENT, Sinus CT BPT,PEF monit., NO Esophageal tests No response Specific diagnosis - treatment Specific Diagnosis - Treatment Chronic Cough Algoritm UACS,GERD, Asthma, NAEB Empiric or Specific Diagnosis and Treatment Cough ? No Sputum, HRCT, Bronchoscopy Improved Yes Post infectious? Yes Consider uncommon causes Cough ? No Yes Physcogenic cough? Specific diagnosis - Treatment UACS,GERD, Asthma, NAEB Empiric or Specific Diagnosis and Treatment Cough ? No Sputum, HRCT, Bronchoscopy Improved Yes Post infectious? Yes Consider uncommon causes Cough ? No Yes Physcogenic cough? Specific diagnosis - Treatment Specific diagnosis - Treatment Improved Chronic idiopathic cough No THANK YOU…