CHRONIC COUGH

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

2. 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

3. 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

4. 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-asthmaticEosinophilic Bronchitis Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S

5. New Considerations • Eosinophilic bronchitis • Atopic cough • Non acid(volume)/ weakly acid reflux • Idiopathic (unexplained) öksürük

6. Diagnosis and Management of Cough ACCP Evidence-Based CPG 2006 • 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 Guidelines Writing Committee. Chest 2006; 129 (Suppl. 1): 1S-292S Plevkova, et al. Respir Physiol Neurobiol 2004; 142: 225-235

7. PNDS 12 ASTHMA 16 13 12 6 4 10 GERD 1.Gastroesophageal reflux disease(21-41%) 2. Cough variant asthma (24-59%) 3.Postnasal drip syndrome(41-58%) Chest 1999;116:279-284

8. Percentage of Cases Presenting 1,2,3, and 4 Causative Factors Chest 1999;116:279-281

9. Asthma and/or GERD, PNDS responsible for 93.6% of the cases of chronic cough • İmmunocompetent patients • Not exposed to enviromental irritants • Chest radiograph is normal • Not taking an ACE inhibitor • Not a current smoker Harding SM .Chest 2003;123:659-660

10. Changing Trends in Diagnosis GERD ASTHMA RHINITIS Percentage of Diagnosis (%)

11. GERD ? Heartburn (pyrosis) and regurgitation At least weekly symptoms extraesophageal reflux symptoms and/or esophageal mucosal damage / Decreased saliva Impaired esophageal clearance Functional defect in LES syphincter Hiatal hernia Delayed gastric emptying İncreased intra-abdominal pressure Katzka & DiMarino 1995

12. Edema and hyperemia of larynx • Vocal cord erythema, polyps, granulomas, ulcers • Hyperemia and lymphoid hyperplasia • of posterior pharynx • Interarytenoid changes • Subglottic stenosis FLR Signs

13. GERD-related cough incidence 5 - 55% May be the sole presenting symptom(1/3) ARRD 1981;123:413-417 Arch Intern Med 1996;156:997 Chest 1993;104:1511-1517 El Hennawi, 2004 OHNS Association between cough andreflux is important • Esophageal-tracheal-bronchial reflex • Microaspiration Pathogenesis Nonacidic factors? Esophageal dismotility? Thorax 2003:58;1092-1095) (Chest 1997; 111: 1389-1402) Irwin RS. Chest 2006;129:80S-94S

14. Esophagus Tracheobronchial Tree Airway REFLUX Microaspiration .Mediator Release . Inflammation . Edema .Mucus . Smooth Muscle Airway Vagal Afferents Esophageal Vagal Afferents CNS Airway Vagal Efferents Bronchial Hyperreactivity Stein MR.Am J Med 2003 Chest 1997;111: 1389-1402

15. Oesophagus Stomach

16. Pharyngeal pHmetry - + Increase dose PPI + alginate Not GERD Clinical GERD symptoms ? Nonacid, weakly acid reflux? İmproved Not improved Consider  Simultaneously dual probes 24 hours pHmonitoring and intraesophageal impedance Continue pHmetry under treatment Irwin RS.AJRCCM 165:1469-74,2002 McGarvey LPA.Thorax 59:342-346,2004

17. 17 cm 15 cm 9 cm 7 cm pH - 5 cm 5 cm 6 impedance channels 3 cm + 1 pH electrode Multichannel intraluminal impedance-pH catheter Adult Standard Model ZAN-S61C01E

18. Non acid reflux On going reflux of ‘non-acid’ material may be responsible for continuing symptoms while on acid-suppressing medications

19. 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

20. Cumulative Response to GERD Therapy 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

21. Preop pH <4: %23.6 De Meester: 85 Postop pH <4: %2.4 De Meester: 9.9

22. Clinical Profile That Chronic Cough İs Likely Due To‘Silent GERD’ 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

23. 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

24. In patient with chronic cough that is related to upper airway abnormalities Upper Airway Cough Syndrome Chest 2006;129:63S-71S

25. 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

26. Asthmatic Coughs Eosinophilic Eronchitis Bronchial hyperreactivity YES NO Cough Variant Asthma Asthma NO YES Airway obstruction

27. 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

28. 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%) 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

29. 13% UK 91patients, 19992 15% Korea 92 patients, 20023 14% USA 37patients 20031 33% Turkey 36 patients, 20036 20% China 86 patients 20035 10% Australia 30 patients, 20004 Eosinophilic BronchitisA Worldwide Disease 1)Kim et al AJRCCM 2003; 2) Brightling et al AJRCCM 1999;160:406-10, 3) JooKorean 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, Erdincet al Respir Med 2003;97:695-701

30. Causes of chronic cough Ayık SÖ, Başoğlu ÖK, Erdinç M. Respir Med Vol. 97 (2003) 695-701

31. Causes of Isolated Chronic Cough Brightling CE et al. AJRCCM 1999

32. Asthma İnhaled steroid β2-agonist Yes No Bronchial provocation test Eosinophilic Bronchitis İnhaled steroid Negative Cough Variant Asthma İnhaled steroid β2-agonist Positive Induced sputum (3%  eosinophilia Asthmatic Cough Airway obstruction Reversibility PEF değişkenliği PEF monitoring Increased NO all of them

34. Chronic Unexplained (Idiopathic) Cough • 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

35. Chronic Unexplained (Idiopathic) Cough Potential Reasons • 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 « 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

36. Idiopathic cough% ? Studies in the 1980’s % patients

37. Idiopathic cough% ? 1990-1995 % patients

38. Idiopathic cough% ? 1996-1999 % patients

39. Idiopathic cough% ? 2000  % patients

40. Chronic Idiopathic Cough Haque et al Chest 2005;127:1710-1713

41. Chronic Idiopathic Cough • Predominantly female and associated with BAL lymphocytosis • Raising the possibility of a link between autoimmune diseases *OR: 8.8 Surinder S. Et al. Respir Med 98:242-246;2004

42. Chronic Idiopathic Cough Inflammation Birring et al AJRCM 2004

43. Chronic Idiopathic Cough • + 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

44. Chronic Idiopathic Cough • 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 Irwin RS,et al. Chest 2006;130:362-370

45. 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

46. Postinfectious Cough • 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

47. 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

48. 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

49. NONSPECIFIC SPECIFIC Antitussive Protussive Causative treatment Codein Dextromethorphan Difenhidramin Pseudoephedrine Dekstrobromfeniramin Ipatropium Bromide Naproksen Hypertonic saline Erdostein Amilorid N asetilsistein Terbutalin Physiotherapy Postural drainage Treatment Irwin RS et al. Chest 1998, 114:2

50. Future Therapies • 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