The Otolaryngologist and Chronic Cough

1. The Otolaryngologist and Chronic Cough Joshua Schindler, MD Medical Director Northwest Clinic for Voice and Swallowing Assistant Professor Department of Otolaryngology Oregon Health & Science University

2. Scope of the Problem Estimated 28 million outpatient visits annually (2002) • Most common condition for which patients seek medical treatment CDC: National Ambulatory Medical Care Survey: 2002 Summary (2004) US Retail sales of OTC medications was $15.1 billion in 2004(excluding Wal-Mart) • $3.6 billion in cough and cold medication Consumer Health Care Products Assn (2004)

3. Scope of the Problem CDC: National Ambulatory Medical Care Survey: 2002 Summary (2004)

4. Why We Cough Adaptive • Defensive mechanism • Protection from aspiration • Clearance of particulate debris Maladaptive • Upper Airway Digestive Tract (UADT) irritation • Inflammation • Hyperreflexia • Habit?

5. Complicated web

6. Targets for Cough Management

7. Otolaryngology Evaluation and Management of Chronic Cough

8. Definitions of Cough Acute Cough < 3weeks Subacute Cough 3 – 8 weeks Chronic Cough > 8 weeks

9. Nomenclature Post Nasal Drip Syndrome (PNDS) = Upper Airway Cough Syndrome (UACS) Idiopathic Cough = Unexplained Cough Gastroesophageal reflux disease (GERD) = Reflux disease Laryngopharyngeal reflux (LPR)

10. Vanilloid receptors in Chronic cough Laryngeal Epithelium Laryngeal Epithelium Control Chronic Cough Groneberg, DA, et al.; Am J RespirCrit Care Med (2004); 170: 1276-1280

11. Cough Freebies • Smoking • ACE (angiotensin converting enzyme) inhibitor therapy for hypertension • Incidence 5 - 35% • Timing: hours - months after 1st dose • Resolution with cessation: • Typical 1 - 4 weeks • Range to 3 months “In a patient with chronic cough, ACE inhibitors should be considered as wholly or partially causative, regardless of the temporal relation between initiation of ACE inhibitor therapy and the start of cough.” Dicpinigaitis, PV. Chest.2006. 129(1),169S-173S

12. “The Trifecta” • Asthma • UACS (PND) • GERD These 3 causes are said to cause 90% of all chronic cough

13. Algorithm for Management of Chronic Cough Diagnosis and Management of Cough Executive Summary. Chest. 2006, 129(1) suppl.

14. Cough and Asthma Roughly 30% of all cough • Several variants: • Classical asthma • Cough-variant • Eosinophilic bronchitis • Atopic cough Distinguished by treatment Pavord, ID. PulmPharmTher. 2004, 17,399-402

15. Cough and Asthma Pavord, I.D. PulmPharmTher. 2004, 17, 399-402.

16. Cough and Asthma Evaluation • CXR • Spirometry +/- bronchodilator • Methacholine challenge • Allergy testing Management • Bronchodilator / inhaled steroid/ leukotrieneinhibitor therapy • Antihistamine / desensitization

17. UACS (PND) and Cough What is post nasal drip? • Sensation something running down the back of the throat • Poor definition of syndrome • Usually no physical findings

18. UACS (PND) and Cough What is post nasal drip? • 2 liters secretions/day • 500 cc nasal secretions • Ability to localize symptoms to OP/NP is poor • Throat clearing • Globus sensation • Association with cough is 8 - 56%

19. UACS (PND) and Cough UACS is a US perception Proctor & Gamble: • US telephone interviews (892) • 50% in US suffer from “PND” • UK telephone interviews (1000) • < 25% in UK suffer from “PND” Difference felt to be labeling /marketing

20. UACS (PND) and Cough “In patients with chronic cough, the diagnosis of upper airway cough syndrome should be determined by considering a combination of criteria, including symptoms, physical examination findings, radiographic findings, and, ultimately, the response to specific therapy. Because it is a syndrome, no pathognomonicfindings exist.” Diagnosis and Management of Cough Executive Summary. Chest.2006, 129, 1 suppl.

21. GERD and Cough GERD • Prevalence as cause of cough 5 - 41% • Trend toward increasing association • Common GI symptoms • Heartburn • Regurgitation • Dysphagia • Wide spectrum of clinical manifestations • ? Distal acid exposure can cause cough Ing, A. Am J RespirCrit Care Med. 1994, 149, 160-7.

22. GERD vs. LPR Koufman 1991 – “reflux laryngitis” and “laryngopharyngeal reflux” Belafsky, PC, et al.Laryngoscope, 2001, 111, 1313-317

23. Profile of GERD / LPR American College of Chest Physicians CPG • Chronic cough • Not exposed to chemical irritants • No ACE-I use • Normal chest radiograph • Failure of asthma therapy / Normal methacholine • Failure of antihistamine • Normal / stable sinus imaging • No eosinophilia of induced sputum / failure to respond to inhaled corticosteroids Irwin, R.S. Chest. 2006, 129(1), 80S-94S.

24. LPR Evaluation and Management • Empiric treatment before testing • Omeprazole (Prilosec) 40 mg BID or equivalent • Treatment should continue for 3-6 months • No benefit expected for 3 months • Revisit diagnosis if no improvement at 6 months

25. LPR Evaluation and Management • Empiric treatment before testing • Omeprazole 40 mg BID or equivalent • Treatment should continue for 3-6 months • No benefit expected for 3 months • Revisit diagnosis if no improvement at 6 months • Esophagoscopy can be normal • 24-hour pH probe is “gold standard” • Conventional indices (DeMeester score) • Reflux induced coughs • Barium esophagography or impedance testing for non-acid reflux determination • Oropharyngeal acid studies

26. Problems with LPR / GERD Diagnosis • Definitions are unclear • Symptoms are poorly defined • Physical findings are vague • Poor “gold standard” • Poor correlation with histologic findings • High treatment failure rate • Remarkably poor studies

27. LPR Evaluation • Oropharyngeal pH montoring • Restech probe • Volatile acid • 24-48 monitoring

28. Oropharyngeal Ph Probe

29. Sensory Neuropahy Lee & Woo (2005) • 28 patients “cryptogenic” cough • Average duration of cough = 7 mo (range 2 wk – 20 yr) • 2/3 had “previous work-up” • 20/28 felt to have RLN/SLN neuropathy Lee, B.; Woo, P. Ann OtolRhinolLaryngol. 2005, 114,253-257.

30. Sensory Neuropahy “Cryptogenic Cough” Lee & Woo (2005) • Treated with gabapentin (Neurontin) • Started 100 mg/qd– increased to ~900 mg/qd • Dose titrated to effect/side effects • Results: • 68% overall improvement • 80% of those with L-EMG neuropathy Lee, B.; Woo, P. Ann OtolRhinolLaryngol. 2005, 114,253-257

31. Behavior Modification • Cortical control is evident • Voluntary cough • Placebo-mediated cough suppression Eccles R; PulmPharmacolTher. 2002, 15, 303 – 8.

32. Behavior Modification • Cortical control is evident • Voluntary cough • Placebo-mediated cough suppression • Cough depressed / absent in: • Coma • Left cortical stroke • Sleep / anesthesia • Cough Suppression • Capsaicin-induced cough can be suppressed in humans Hutchings, et al. Respir Med. 1993, 87, 379 - 382.

33. Uncommon Causes of Cough Pulmonary Disorders: Tracheobronchomalacia Airway stenosis / strictures Tracheobronchopathiaosteoplastica Mounier-Kuhn Syndrome (Tracheobronchomegaly) Tracheobroncialamyloidosis Airway foreign bodies Broncholithiasis Lymphangioleiomyomatosis Pulmonary Langerhans cell histiocytosis Pulmonary alveolar proteinosis Pulmonary alveolar microlithiasis High Altitude Tonsillar hypertrophy Mediastinal masses Pulmonary edema Pulmonary embolism Others (vocal cord dysfunction, surgical sutures in airway) Nonpulmonary Disorders: Connective tissue disorders Vasculitides (WG, GCA and RPC) Esophageal disorders (tracheoesophageal and bronchoesophageal fistula) Inflammatory bowel diseases (Crohn disease and ulcerative colitis) Thyroid disorders (goiter, thyroiditis) Others (Tourette Syndrome) Wegner’s Granulomatosis

34. OHSU and Chronic Cough • Retrospective chart review • 132 patients (2005-2010) • Cough greater than 10 weeks • Evaluate work up and interventions • Response to therapy • None • Partial response (therapy continued) • Complete response (>85% improved by report)

35. OHSU and Chronic Cough

36. diagnosis and Chronic Cough

37. lung sources and Chronic Cough

38. gi Problems and Chronic Cough

39. uacs and Chronic Cough

40. Larynx and Chronic Cough

41. Nervous System and Chronic Cough

42. other Diagnoses and Chronic Cough

43. management of Chronic Cough Patients with: Favorable response to Rx 77% Partial Response to Rx 31% Complete Response to Rx 46%

44. Cause-Directed Therapies Selection bias likely a strong contributor to results

45. Cause-independent Therapies Selection bias likely a strong contributor to results

46. Chronic Cough Algorithm

47. Take Home Points • The causes of cough are as myriad as the nerves that meditate them • Asthma and atopic/eosinophilic bronchitis probably account for the majority of chronic cough • Post-nasal drip / UACS is probably “Voodoo” • GERD / LPR is difficult to diagnose and expensive to treat • An otolaryngologist may be helpful in evaluating and managing chronic cough

48. KNOWLEDGE Pearls • Chronic cough is almost always multifactorial • Listen to patient’s symptoms • Optimize therapy and testing for each suspected diagnosis– use high yield definitive studies • Eliminate OTC medications / cough drops • Patience is critical • Behavioral cough suppression can be tremendously useful