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. Estimated 28 million outpatient visits annually (2002)
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% of all doctor visits are for cough.
More than 20% of all OTC medications purchased were for cough and colds symptoms.

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

4. Why We Cough Adaptive Maladaptive 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 Respir Crit Care Med (2004); 170:

11. Cough Freebies Smoking
ACE (angiotensin converting enzyme) inhibitor therapy for hypertension
Incidence %
Timing: hours - months after 1st dose
Resolution with cessation:
Typical 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 (1), 169S-173S

12. These 3 causes are said to cause 90% of all chronic cough
“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. Distinguished by treatment
Cough and Asthma
Roughly 30% of all cough
Several variants:
Classical asthma
Cough-variant
Eosinophilic bronchitis
Atopic cough
Described by Glauser.
Corrao confirmed improvement in cough with inhaled bronchodilator therapy.
Up to 1/3 of all cough variant asthma patients go onto classical asthma
Eosinophilic bronchitis and atopic cough may be same clinical entity.
Distinguished by treatment
Pavord, ID. Pulm Pharm Ther. 2004, 17,

15. Cough and Asthma + + / - - Airway Hyper – Responsiveness
Eosinophilic Airway Inflammation
BAL Eosinophilia
Response to Bronchodilator
Response to Inhaled Steroids
Atopy
Classical Asthma +
+ / -
Cough Variant Asthma
Eosinophilic Bronchitis -
Atopic Cough
Both cough variant asthma and eosinophilic bronchitis respond to leukotriene inhibitor therapy.
Pavord, I.D. Pulm Pharm Ther. 2004, 17,

16. Cough and Asthma Evaluation Management CXR
Spirometry +/- bronchodilator
Methacholine challenge
Allergy testing
Management
Bronchodilator / inhaled steroid/ leukotriene inhibitor therapy
Antihistamine / desensitization
Both cough variant asthma and eosinophilic bronchitis respond to leukotriene inhibitor therapy.

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 %

19. Difference felt to be labeling /marketing
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 pathognomonic findings 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 Respir Crit Care Med. 1994, 149,

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

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. Oropharyngeal pH montoring
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 Otol Rhinol Laryngol. 2005, 114,

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 Otol Rhinol Laryngol. 2005, 114,

31. Behavior Modification
Cortical control is evident
Voluntary cough
Placebo-mediated cough suppression
Eccles R; Pulm Pharmacol Ther. 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,

33. Uncommon Causes of Cough
Pulmonary Disorders:
Tracheobronchomalacia
Airway stenosis / strictures
Tracheobronchopathia osteoplastica
Mounier-Kuhn Syndrome
(Tracheobronchomegaly)
Tracheobroncial amyloidosis
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. Retrospective chart review 132 patients (2005-2010)
OHSU and Chronic Cough
Retrospective chart review
132 patients ( )
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