THE OTOLARYNGOLOGIST AND CHRONIC COUGH

Joshua Schindler, MD

Medical DirectorNorthwest Clinic for Voice and Swallowing

Assistant ProfessorDepartment of Otolaryngology

Oregon Health & Science University

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)

SCOPE OF THE PROBLEM

CDC: National Ambulatory Medical Care Survey: 2002 Summary (2004)

WHY WE COUGH

Adaptive- Defensive mechanism

• Protection from aspiration• Clearance of particulate debris

Maladaptive- Upper Airway Digestive Tract (UADT)

irritation• Inflammation• Hyperreflexia

- Habit?

COMPLICATED WEB

TARGETS FOR COUGH MANAGEMENT

OTOLARYNGOLOGY EVALUATION AND MANAGEMENT OF CHRONIC COUGH

DEFINITIONS OF COUGH

Acute Cough< 3weeks

Subacute Cough3 – 8 weeks

Chronic Cough> 8 weeks

NOMENCLATUREPost Nasal Drip Syndrome (PNDS)

= Upper Airway Cough Syndrome (UACS)

Idiopathic Cough= Unexplained Cough

Gastroesophageal reflux disease (GERD)= Reflux disease

Laryngopharyngeal reflux (LPR)

VANILLOID RECEPTORS IN CHRONIC COUGH

Groneberg, DA, et al.; Am J Respir Crit Care Med (2004); 170: 1276-1280

Control Chronic Cough

Laryngeal Epithelium Laryngeal Epithelium

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

“THE TRIFECTA”

• Asthma

• UACS (PND)

• GERD

These 3 causes are said to cause 90% of all chronic cough

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

ALGORITHM FOR MANAGEMENT OF CHRONIC COUGH

COUGH AND ASTHMA

Roughly 30% of all cough

Pavord, ID. Pulm Pharm Ther. 2004, 17, 399-402

Distinguished by treatment

Several variants:

– Classical asthma– Cough-variant– Eosinophilic

bronchitis– Atopic cough

COUGH AND ASTHMA

Pavord, I.D. Pulm Pharm Ther. 2004, 17, 399-402.

Airway Hyper –

Responsiveness

Eosinophilic Airway

Inflammation

BAL Eosinophili

a

Response to Bronchodilat

or

Response to Inhaled Steroids

Atopy

Classical Asthma + + / - + + + + / -

Cough Variant Asthma + + / - + + + + / -

Eosinophilic

Bronchitis - + + - + + / -

Atopic Cough - + / - - - + +

COUGH AND ASTHMAEvaluation

- CXR- Spirometry +/- bronchodilator- Methacholine challenge- Allergy testing

Management- Bronchodilator / inhaled steroid/ leukotriene

inhibitor therapy- Antihistamine / desensitization

UACS (PND) AND COUGH

- Sensation something running down the back of the throat

- Poor definition of syndrome• Usually no physical

findings

What is post nasal drip?

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%

UACS (PND) AND COUGHUACS is a US

perceptionProctor & 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

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.

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, 160-7.

GERD vs. LPR

Koufman 1991 – “reflux laryngitis” and “laryngopharyngeal reflux”

Belafsky, PC, et al. Laryngoscope, 2001, 111, 1313-317

PROFILE OF GERD / LPR

•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.

American College of Chest Physicians CPG

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

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

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

LPR EVALUATION

• Oropharyngeal pH montoring- Restech probe- Volatile acid- 24-48

monitoring

OROPHARYNGEAL PH PROBE

SENSORY NEUROPAHYLee & 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, 253-257.

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, 253-257

BEHAVIOR MODIFICATION• Cortical control is evident

- Voluntary cough- Placebo-mediated cough suppression

Eccles R; Pulm Pharmacol Ther. 2002, 15, 303 – 8.

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.

UNCOMMON CAUSES OF COUGH

Wegner’s Granulomatosis

Pulmonary Disorders:TracheobronchomalaciaAirway stenosis / stricturesTracheobronchopathia osteoplasticaMounier-Kuhn Syndrome

(Tracheobronchomegaly)Tracheobroncial amyloidosisAirway foreign bodiesBroncholithiasisLymphangioleiomyomatosisPulmonary Langerhans cell histiocytosisPulmonary alveolar proteinosisPulmonary alveolar microlithiasisHigh AltitudeTonsillar hypertrophyMediastinal massesPulmonary edemaPulmonary embolismOthers (vocal cord dysfunction,

surgical sutures in airway)Nonpulmonary Disorders:

Connective tissue disordersVasculitides (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)

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)

OHSU AND CHRONIC COUGH

DIAGNOSIS AND CHRONIC COUGH

LUNG SOURCES AND CHRONIC COUGH

GI PROBLEMS AND CHRONIC COUGH

UACS AND CHRONIC COUGH

LARYNX AND CHRONIC COUGH

NERVOUS SYSTEM AND CHRONIC COUGH

OTHER DIAGNOSES AND CHRONIC COUGH

MANAGEMENT OF CHRONIC COUGH

Patients with:Favorable response to Rx 77%

Partial Response to Rx 31%Complete Response to Rx 46%

CAUSE-DIRECTED THERAPIES

Selection bias likely a strong contributor to results

CAUSE-INDEPENDENT THERAPIES

Selection bias likely a strong contributor to results

CHRONIC COUGH ALGORITHM

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

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