CHRONIC COUGH 2014

Mandel Sher, MDClinical Professor of Medicine and Pediatrics

Division of Allergy and ImmunologyMorsani College of MedicineUniversity of South Florida

www.centerforcough.com

Cough

• Defense mechanism to clear secretions and foreign materials from airways

• Convert dysrhythmias and maintain consciousness during severe dysrhythmias

• Factor in spread of infection• Common symptom prompting medical

attention

Cough

• Acute cough- less than three weeks– Common cold

• Subacute cough- three to eight weeks– Post infectious cough

• Chronic cough- greater than eight weeks

Acute Cough

• Common cold• Viral bronchitis• Non- viral infection

– Pertussis, Chlamydia, mycoplasma• Environmental irritant• Foreign body aspiration• Pneumonia• CHF

Postinfectious Cough

• Diagnosis of exclusion• Prolonged cough after URI with normal chest

radiograph• Resolves over time e.g. multiple months• Oral steroids, inhaled steroids, ipratropium

bromide therapies• ?role of leukotriene inhibitors

Braman, SS Chest 2006;129(suppl),138S-146S

Chronic CoughCase

• 61 y/o non smoking female with ten years of continuous cough with onset after URI. Dry cough prompted by throat tickle and triggered by talking, scents/odors, and by changes in temperatures. Cough can induce incontinence. Feels socially isolated, anxious, and can be depressed. Family members and co-workers have expressed annoyance. Finds throat lozenges and sipping on water helpful. Evaluated by primary care MD, two ENT’s, GI, Pulmonary and Allergy. Unresponsive to multiple therapies .

The Key to Chronic CoughAnatomic Approach

• In the non smoker, without ACE inhibitors, and a normal chest x-ray• GERD

– NERD• POST NASAL DRIP(Upper Airway Cough Syndrome)- allergic rhinitis,

vasomotor rhinitis, sinusitis• COUGH VARIANT ASTHMA

– Non Asthmatic Eosinophilic Bronchitis• Idiopathic cough

Irwin etal. Diagnosis and Management of Cough AACP Evidence

basedClinical Practice Guidelines.Chest.2006; S1-S237

.

It’s the Cough Reflex, Stupid!

Chronic cough is the result of cough reflex hypersensitivity with triggers from associated anatomic entities

Anatomy of Cough

• Afferent stimulus, central processing and control, and efferent output– Complex and not well understood

• Cough is involuntary to protect from inhaled, aspirated and intrapulmonary

• Cough can be voluntary• The “Urge to Cough” irritant type cough

Canning, B. J. Chest 2006;129:33S-47S

Anatomy Of Cough

• Mechanosensory cough– “true cough receptor”– Protect against aspiration of objects and acid– Conscious and anesthetized in Guinea pigs not

human– Involves vagal/Alpha delta myelinated pathways– RAR and SAR receptors

Brooks. Cough. 2011, 7:10Mazzone.Cough.1;2doi:10.1186/1745-9974-1-

Anatomy of Cough• Chemicosensory cough

–Chemical , irritants and lung inflammation–Conscious but not anesthetized–Nociceptive Type C unmyelinated fibers–TRPV1 and TRPA1 receptors

• Also in pain and itch pathways• Capsaicin- irritant• bradykinin & tachykinin(inflammation)

Brooks. Cough. 2011, 7:10Mazzone.Cough.1;2doi:10.1186/1745-9974-1-

Anatomy of Cough• Poorly defined, diffuse “cough center” in medulla

separate from breathing center• Possible state of “excitability’ from different

afferent pathways – Esophageal, upper and lower respiratory

• Heightened responses to innocuous stimuli eg perfume or cold air, laughing or talking

• Anti-tussive effects of opiates, N-methyl-D-aspartate and possibly anti-histamines

Canning, B. J. Chest 2006;129:33S-47S

Cough reflex after URI McGarvey etal:oi:10.1016/j.pupt.2008.11.003

d

Capsaicin Cough Challenge• Women have increased sensitivity• Smokers have decreased sensitivity• URI has transient increase sensitivity• Allergic rhinitis> normals• Stable asthmatics=normals• Cough asthma> non cough asthma• Acid in distal esophagus increases sensitivity

Dicpingaitis:Pulmonary Pharmacology & TherapeuticsVolume 20, Issue 4, August 2007, Pages 319-324

Confessions of a Cough Doctor

• Chronic coughers have heightened Cough Reflex Sensitivity(CRS)

• CRS has variable inflammatory, neurogenic and behavioral components

• UACS, GERD, and asthma associated with chronic cough– Direct activation of cough– By increasing CRS– Innocent bystander

• Diagnostics studies-specificity/sensitivity?

Upper Airway Cough Syndrome• A major contributor to chronic cough

– Allergic rhinitis, vasomotor rhinitis, sinusitis• Mechanisms

– Nasal inflammation from allergy and infection causes CRS– Vasomotor neuropathy causes CRS– Post nasal drip- causative or associated only?• Symptoms can be “silent” in 20%(based on response to

therapy with first generation antihistamines)• A sensation of post nasal drip, nasal discharge, or throat

clearing• First generation antihistamines more effective than new

non sedating antihistamines. Act as antitussive via anticholinergic or TRPV1 receptors

Rhinitis Treatment• Nasal steroids

– Allergic rhinitis(AR) and non allergic rhinitis(NAR• *Intranasal anti-histamines

– Both for AR and NAR(helps congestion)– May be additive to nasal steroids

• Anti-histamines– AR only*Classical anti-histamines in chronic cough

• *Ipratropium bromide– NAR(rhinorrhea)

• Nasal saline

Laryngopharyngeal RefluxVocal Cord Hyperfunction

GERD and Chronic Cough• Proximal vs Distal GERD/NERD as trigger/cause of cough?

– Hoarseness, throat clear, and sore throat imply LPR– Microaspiration probably not common

• Possibly in elderly?– GERD symptoms– Asymptomatic

• Mechansims– Direct acid, pepsin, gas– Esophageal activation of cough reflex– Associative but not causative

Woodcock etal. British Medical Bulletin 2010;96:61-73

GERD and Chronic Cough

• Cough triggers GERD/NERD– Most chronic coughers probably have GERD/NERD

• Esophageal dysmotility– Possible rational of response to macrolide antibioticcs

• Diagnostics have poor specificity/ sensitivity– EGD to identify Barrett’s, strictures, eosinophilic

esophagitis– pH probe, manometry and multichannel intraluminal

impedance

GERD and Chronic CoughDiagnosis and Treatment

• Coughing decreasing with PPI and/or dietary therapy

• Response to PPI therapy may takes months• Not all PPI’s are alike and benefit from twice daily

dosing• PPI therapy should not be indefinite due to

potential side effects• Dietary therapy

Cough Variant Asthma and Chronic Cough

• Clinical characteristics– With or without wheezing, SOB, chest findings– Generally increases with exercise, laughter, cold exposure and

middle night(all non specific)– PFT’s generally normal– Allergy/atopy in 40-80%– Bronchial hyperreactivity is hallmark

• Non Asthma Eosinophilic Bronchitis– Absence of variable airway obstruction and bronchial

hyperreactivity– Sputum eosinophils with mast cells in airway epithelium rather

than smooth muscle– Both respond inhaled and oral corticosteroids

Diagnosis of “Chest Cough”

• Expired nitric oxide(eNO) predicted positive response to ICS in chronic cough with a cut off of 38ppm

• 36/41 positive response to ICS high eNO• 2/24 positive response to ICS – low eNO• Methacholine challenge less sensitive/spec.• Cough asthma and eosinophilic bronchitis

Hahn PY - Mayo Clin Proc - 01-NOV-2007; 82(11): 1350-5

Cough Variant Asthma and Chronic Cough

• Response to therapy can be diagnostic• Traditional asthma treatment

– ICS +/- LABA– May take 6-8 weeks for maximal response– Inhalers may be irritating– Use MDI with spacers– Value of oral corticosteroid trial

Chronic CoughCough Reflex Treatment

• Oral corticosteroids– Peripheral and ??central

• Opiates-central– NDMA-dextromethorphan

• Classical antihistamines– Oral-central and peripheral e.g. chlorpheniramine– Intranasal-peripheral

• Benzonatate, menthol drops-peripheral• Amitryptylline, gabapentin, pregabalin• Speech therapy

Refractory Chronic Cough

• BREAK THE COUGH CYCLE• Concurrent Therapy

– GERD- Diet +/- PPI– UACS- INS, INA, chlorpheniramine– Asthma/eosinophilic bronchitis if indicated

• MDI ICS with spacer– Cough suppression

• Pharmacologic- opiate, antihistamines, benzonatate• exercises

– Cough inflammation• Oral corticosteroids

– Cough neuropathy• Gabapentin, amitriptylline