Chronic Cough

Reviewed 06/2017
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Subject: Chronic Cough

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BASICS

DESCRIPTION

  • Chronic cough is defined as a cough that persists for >8 weeks in adults.

  • In children, chronic cough is often defined as a cough of >4 weeks in duration.

  • Subacute cough describes a cough lasting 3 to 8 weeks.

  • Patients present because of fear of the causative illness (e.g., cancer) as well as annoyance, self-consciousness, and hoarseness.

  • System(s) affected: gastrointestinal (GI), pulmonary

EPIDEMIOLOGY

  • Predominant age: all age groups

  • Predominant sex: male = female, with females more likely to seek out medical attention

Incidence

Recurrent cough has been reported at 3-40% by various population estimates. 

Prevalence

Chronic cough is one of the most common reasons for primary care visits. 

ETIOLOGY AND PATHOPHYSIOLOGY

Varies with findings and disorders implicated 
  • Often multiple etiologies, but most are related to bronchial irritation. Most frequent etiologies (account for >90% of cases) in nonsmokers include the following:

    • ▪ Upper airway cough syndrome (UACS) (formerly referred to as postnasal drip syndrome) and other upper airway abnormalities, including allergic and vasomotor rhinitis syndromes
    • ▪ Asthma
    • ▪ Gastroesophageal reflux disease (GERD)
  • Other causes:

    • ▪ ACE inhibitors
    • ▪ Chronic smoking or exposure to smoke or pollutants
    • ▪ Aspiration
    • ▪ Bronchiectasis
    • ▪ Infections (e.g., pertussis, tuberculosis)
    • ▪ Nonasthmatic eosinophilic bronchitis (NAEB)
    • ▪ Cystic fibrosis
    • ▪ Sleep apnea
    • ▪ Restrictive lung diseases (e.g., chronic interstitial lung disease)
    • ▪ Neoplasms: bronchogenic or laryngeal
    • ▪ Psychogenic (habit cough)
  • Cough reflex hypersensitivity or cough hypersensitivity syndrome define a syndrome of cough with characteristic trigger symptoms not adequately explained by other medical conditions 1.

RISK FACTORS

Although various conditions may contribute to chronic cough, the main causes include smoking and pulmonary diseases. 

COMMONLY ASSOCIATED CONDITIONS

Patients with UACS, asthma, and GERD may present with chronic cough as the only symptom and not the usual symptoms associated with the diagnoses. 

DIAGNOSIS

HISTORY

  • Patient age, associated signs/symptoms, medical history, medication history (i.e., ACE inhibitors), environmental and occupational exposures, potential for aspiration, and smoking history may make some causes more likely.

  • The character of cough or description of sputum quality is rarely helpful in predicting the underlying cause.

  • Cough diaries have not correlated well with objective measures.

  • Hemoptysis or signs of systemic illness preclude empiric therapy.

PHYSICAL EXAM

  • Signs and symptoms are variable and related to the underlying cause; usually, a nonproductive cough with no other signs or symptoms.

  • Possible signs and symptoms of UACS, sinusitis, GERD, congestive heart failure, chronic stressors

  • Absence of additional signs/symptoms of a particular condition not necessarily helpful

    • ▪ For example, 5% of patients with GERD have no other signs or symptoms and sometimes have poor response to empiric proton pump inhibitor (PPI) trials.

DIAGNOSTIC TESTS & INTERPRETATION

  • Evaluation often starts with empiric therapy directed at likely underlying etiology and/or simple testing such as a chest x-ray (CXR).

  • Extensive testing only if indicated by the history and physical

Pediatric Considerations

Children with chronic cough not responsive to an inhaled β-agonist and without overt stressors should undergo spirometry (if age-appropriate) and foreign body evaluation (CXR). 

Initial Tests (lab, imaging)

  • Evaluation will be dictated by findings in the comprehensive history and physical.

  • Evaluation of peak flow may be indicated.

  • If considering neoplasm, heart failure, or infectious etiologies, CXR or B-type natriuretic peptide (BNP) may be indicated.

  • In cases of failure to respond to initial trial of empiric therapy, CXR may also be beneficial.

Follow-Up Tests & Special Considerations
  • Examples:

    • ▪ If considering chronic obstructive pulmonary disease (COPD), asthma, or restrictive lung disease: spirometry
    • ▪ If suspicious of cystic fibrosis: sweat chloride testing
    • ▪ If suspicious of hypereosinophilic syndrome, tuberculosis, or malignancy: sputum for eosinophils and cytology
  • If abnormal CXR, suspected neoplasm, or underlying pulmonary disorder, consider a chest CT.

  • Consider pulmonary consultation.

  • Refer to gastroenterologist for endoscopy.

Diagnostic Procedures/Other

If diagnosis suggested and inadequate response to initial measures, other procedures can be considered: 
  • Pulmonary function testing

  • Purified protein derivative (PPD) skin testing

  • Allergen testing

  • 24-hour esophageal pH monitor

  • Bronchoscopy, if history of hemoptysis or smoking with normal CXR

  • Endoscopic or video fluoroscopic swallow evaluation or barium esophagram

  • Sinus CT

  • Ambulatory cough monitoring and cough challenge with citric acid, capsaicin, or other bronchodilator (at specialized cough clinic)

  • Echocardiogram

Test Interpretation

Specific to underlying cause 

TREATMENT

  • With chronic cough, empiric treatment should be directed at the most common causes as clinically indicated (UACS, asthma, GERD) 2[C].

  • Oral antihistamine/decongestant therapy with a 1st-generation antihistamine or nasal steroid spray can be used as initial empiric treatment 2[C].

  • In patients with cough associated with the common cold, nonsedating antihistamines were not found to be effective in reducing cough 2[C].

  • In stable patients with chronic bronchitis, therapy with ipratropium bromide may reduce chronic cough 3[C].

  • Centrally acting antitussive drugs (dextromethorphan, hydrocodone) may be used for short-term symptomatic relief of coughing in patients with chronic bronchitis but have limited efficacy in cough due to upper respiratory infections 3[C].

  • For cough associated with lung cancer, narcotic cough suppressants are recommended 3[C].

  • The American Academy of Pediatrics does not recommend central cough suppressants for treating any kind of cough 2[B].

  • In children ≪14 years, when pediatric recommendations are not available, adult recommendations should be used with caution 2[C].

  • Some children with recurrent cough and no evidence of airway obstruction may benefit from an inhaled β-agonist 4[C].

  • In infants and children with nonspecific chronic cough, trials of empiric PPI therapy were not effective 5[C].

GENERAL MEASURES

  • In patients with chronic cough, considerations for potential etiology should include asthma 2[B] or UACS 2[C].

  • With concomitant complaints of heartburn and regurgitation, GERD should be considered as a potential etiology 2[C].

  • 90% of patients will have resolution of cough after smoking cessation 2[A].

  • When indicated, ACE inhibitor therapy should be switched in patients in whom intolerable cough occurs 3[A]. It may take several days or weeks for cough to resolve after stopping ACE inhibitor therapy.

  • Empirically treat postnasal drip and GERD.

  • Consider nonpharmacologic options, such as warm fluids, hard candy, or nasal drops. In infants and children, try clearing secretions with a bulb syringe.

  • Attempt maximal therapy for single most likely cause for several weeks, then search for coexistent etiologies.

MEDICATION

  • Treatments (nasal steroids, classic antihistamines, antacids, bronchodilators, inhaled corticosteroids, PPIs, antibiotics) should be directed at the specific cause of cough.

  • If history and physical exam suggest GERD, may want to trial H2 blocker or PPI therapy prior to further diagnostic testing.

  • A comparative effectiveness review of 49 studies with common opioid and nonanesthetic antitussives stated there is some efficiency for treating cough in adults, but evidence is limited 6[C].

  • The FDA issued a public health advisory stating that OTC cough and cold medicines, including antitussives, expectorants, nasal decongestants, antihistamines, or combinations, should not be given to children ≪2 years. Subsequently, manufacturers have changed labeling to state “do not use” in children ≪4 years. National estimates have shown a decline in emergency department visits in children ≪2 years related to adverse events from cough and cold medicine ingestion 7.

  • Routine empiric treatment of children with chronic cough with leukotriene receptor antagonists lacks evidence and cannot be recommended 8[C]. A small pilot study with montelukast in adults demonstrated some symptom relief after 2 weeks of treatment 9[A].

First Line

  • In adults, oral antihistamine/decongestant therapy can be empiric treatment. Multiple formulations are available OTC in combination with other ingredients. Advise patients to review labels carefully or consult pharmacist:

  • Central cough suppressants for short-term symptomatic relief of nonproductive cough

    • Dextromethorphan 10 to 20 mg PO q4h for patients >12 years; use 5 to 10 mg PO q4h for patients 6 to 12 years
      • * Concomitant use of dextromethorphan and agents with serotonergic activity (e.g., SSRIs) should be avoided due to risk of serotonin syndrome.
    • ▪ Narcotics: codeine 15 to 30 mg PO q6h; hydrocodone/acetaminophen (Vicodin) 5 mg PO q6h; hydrocodone/chlorpheniramine (Tussionex Pennkinetic) 10 mg (5 mL) PO q12h for patients ≥12 years (no benefit in children; no good efficacy data in adults)

Second Line

  • A peripherally acting antitussive agent has been used:

    • ▪ In patients >10 years, benzonatate (Tessalon Perles) 100 to 200 mg PO TID as needed (maximum 600 mg/day)
  • Results from a small randomized placebo-controlled trial (n = 27) demonstrated subjective cough score improvement in patients using slow-release morphine sulfate. Patients had failed with other antitussive therapies. Side effects included constipation and drowsiness, and there were no discontinuations due to adverse events 10[A].

    • Morphine was administered 5 to 10 mg PO BID.
  • An analysis of studies evaluating inhaled corticosteroid use in chronic cough for patients without additional indication such as asthma did not show consistent benefits 11[C].

ISSUES FOR REFERRAL

Patients with chronic cough may benefit from evaluation by pulmonary, gastroenterology, ear-nose-and-throat (ENT), and/or allergy specialists. 

SURGERY/OTHER PROCEDURES

Fundoplication may be effective for cough secondary to refractory GERD. 

ONGOING CARE

FOLLOW-UP RECOMMENDATIONS

Consider stepwise withdrawal of medications after resolution of cough. 

Patient Monitoring

Frequent follow-up is necessary to assess the effectiveness of treatment 

DIET

Dietary modification: Patients with GERD may benefit by avoiding ethanol, caffeine, nicotine, citrus, tomatoes, chocolate, and fatty foods. 

PATIENT EDUCATION

  • Reassure patient that most cases of chronic cough are not life-threatening and that the condition can usually be managed effectively.

  • Counsel that several weeks to a month may be needed for significant reduction or elimination of cough

  • Prepare the patient for the possibility of multiple diagnostic tests and therapeutic regimens because the treatment is very often empiric.

PROGNOSIS

  • >80% of patients can be effectively diagnosed and treated using a systematic approach.

  • Cough from any cause may take weeks to months until resolution, and resolution depends greatly on efficacy of treatment directed at underlying etiology.

COMPLICATIONS

  • Cardiovascular: arrhythmias, syncope

  • Stress urinary incontinence

  • Abdominal and intercostal muscle strain

  • GI: emesis, hemorrhage, herniation

  • Neurologic: dizziness, headache, seizures

  • Respiratory: pneumothorax, laryngeal, or tracheobronchial trauma

  • Skin: petechiae, purpura, disruption of surgical wounds

  • Medication side effects

  • Other: negative impact on quality of life

REFERENCES

Morice  AH, Millqvist  E, Belvisi  MG, et al. Expert opinion on the cough hypersensitivity syndrome in respiratory medicine. Eur Respir J.  2014;44(5): 1132–1148.  [View Abstract]
Irwin  RS, Baumann  MH, Bolser  DC, et al. Diagnosis and management of cough executive summary: ACCP evidence-based clinical practice guidelines. Chest.  2006;129(1)(Suppl):1S–23S.  [View Abstract]
Bolser  DC. Cough suppressant and pharmacologic protussive therapy: ACCP evidence-based clinical practice guidelines. Chest.  2006;129(1)(Suppl): 238S–249S.  [View Abstract]
Gupta  A, McKean  M, Chang  AB. Management of chronic non-specific cough in childhood: an evidence-based review. Arch Dis Child Educ Pract Ed.  2007;92(2):33–39.  [View Abstract]
Chang  AB, Lasserson  TJ, Gaffney  J, et al. Gastrooesophageal reflux treatment for prolonged non-specific cough in children and adults. Cochrane Database Syst Rev.  2011;(1):CD004823.  [View Abstract]
Yancy  WS Jr, McCrory  DC, Coeytaux  RR, et al. Efficacy and tolerability of treatments for chronic cough: a systematic review and meta-analysis. Chest.  2013;144(6):1827–1838.  [View Abstract]
Hampton  LM, Nguyen  DB, Edwards  JR, et al. Cough and cold medication adverse events after market withdrawal and labeling revision. Pediatrics.  2013;132(6):1047–1054.  [View Abstract]
Chang  AB, Winter  D, Acworth  JP. Leukotriene receptor antagonist for prolonged non-specific cough in children. Cochrane Database Syst Rev.  2006;(2):CD005602.  [View Abstract]
Mincheva  RK, Kralimarkova  TZ, Rasheva  M, et al. A real-life observational pilot study to evaluate the effects of two-week treatment with montelukast in patients with chronic cough. Cough.  2014;10(1):2.  [View Abstract]
Morice  AH, Menon  MS, Mulrennan  SA, et al. Opiate therapy in chronic cough. Am J Respir Crit Care Med.  2007;175(4):312–315.  [View Abstract]
Johnstone  KJ, Chang  AB, Fong  KM, et al. Inhaled corticosteroids for subacute and chronic cough in adults. Cochrane Database Syst Rev.  2013;(3):CD009305.  [View Abstract]

ADDITIONAL READING

Dicpinigaitis PV, Morice AH, Birring SS, et al. Antitussive drugs—past, present, and future. Pharmacol Rev.  2014;66(2):468–512.  

SEE ALSO

  • Asthma; Bronchiectasis; Congestive Heart Failure; Eosinophilic Pneumonias; Gastroesophageal Reflux Disease; Laryngeal Cancer; Lung, Primary Malignancies; Pertussis; Pulmonary Edema; Rhinitis, Allergic; Sinusitis; Tuberculosis

  • Algorithm: Cough, Chronic

CODES

ICD10

  • R05 Cough

  • J44.9 Chronic obstructive pulmonary disease, unspecified

  • J41.0 Simple chronic bronchitis

ICD9

  • 786.2 Cough

  • 496 Chronic airway obstruction, not elsewhere classified

  • 491.0 Simple chronic bronchitis

SNOMED

  • 68154008 Chronic cough (finding)

  • 13645005 Chronic obstructive lung disease (disorder)

  • 46802002 smokers' cough (disorder)

CLINICAL PEARLS

  • Chronic cough is defined as a cough that persists for >8 weeks in adults.

  • In patients with chronic cough, most frequent etiologies include a history of smoking, asthma, UACS, and GERD.

  • The FDA issued a public health advisory stating that OTC cough and cold medicines should not be given to children ≪2 years. OTC cough expectorant and suppressant product labels state “do not use” in children ≪4 years.

 
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