• Chronic cough is defined as a cough that persists for >8 weeks in adults.
• Subacute cough describes a cough lasting 3–8 weeks.
• In children, chronic cough is defined as a cough for >4 weeks in duration.
• Patients present because of fear of the causative illness (e.g., cancer), as well as annoyance, self-consciousness, and hoarseness.
• Patients with stress urinary incontinence may find cough particularly troubling.
• At the primary care level, chronic obstructive pulmonary disease (COPD) and smoking-related cough are common causes of chronic cough.
• System(s) affected: Gastrointestinal; Pulmonary

• Predominant age: All age groups
• Predominant sex: Male = Female

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.

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

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:
  • Upper airway cough syndrome (UACS) (formerly referred to as postnasal drip syndrome) and other upper airway abnormalities including rhinitis syndromes
  • Asthma
  • Nonasthmatic eosinophilic bronchitis (NAEB)
  • Gastroesophageal reflux disease (GERD)
• Other causes:
  • Chronic smoking or exposure to smoke or pollutants
  • Aspiration
  • Bronchiectasis
  • ACE inhibitors
  • Infections (e.g., pertussis, tuberculosis)
  • Cystic fibrosis
  • Sleep apnea
  • Restrictive lung diseases (e.g., chronic interstitial lung disease)
  • Neoplasms: Lung or laryngeal cancer, other
  • Psychogenic (habit cough)
• Cough reflex hypersensitivity or cough hypersensitivity syndrome are new labels attempting to define a syndrome of cough with characteristic trigger symptoms but are not adequately explained by other medical conditions (1).

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

• The age of the patient, presence of associated signs/symptoms, medical history, medication history (especially use of 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.
• Various ambulatory systems for recording cough are under development.
• Hemoptysis or signs of systemic illness preclude empiric therapy.

• 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
• Absence of additional signs/symptoms of a particular condition not necessarily helpful:
  • For example, 5% of GERD patients have no other signs or symptoms and sometimes have poor response to empiric proton pump inhibitor trials.

• Often evaluation 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

ALERT
Pediatric Considerations
Children with chronic cough not responsive to an inhaled β-agonist should undergo, at a minimum, spirometry (if age-appropriate) and CXR.

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

Follow-Up and Special Considerations

• Examples:
  • If considering COPD, asthma, or restrictive lung disease: Spirometry
  • If suspect cystic fibrosis: Sweat chloride testing
  • If suspect hypereosinophilic syndrome, tuberculosis, or malignancy: Sputum for eosinophils and cytology

ImagingInitial Imaging Approach

• If considering neoplasm, heart failure, or infectious etiologies, CXR may be indicated
• In cases of failure to respond to initial trial of empiric therapy, CXR may also be beneficial

Follow-Up and Special Considerations

• 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 suspected 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 necessary
• Endoscopic or video fluoroscopic swallow evaluation or barium esophagram
• Sinus CT
• Ambulatory cough monitoring and cough challenge with citric acid or capsaicin (at specialized cough clinic)
• Echocardiogram

Pathological Findings Specific to underlying cause

• With chronic cough, empiric treatment should be directed at the most common causes (UACS, asthma, GERD, NAEB) (2)[C].
• Oral antihistamine/decongestant therapy with a first-generation antihistamine should be 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 (codeine, dextromethorphan) are recommended for short-term symptomatic relief of coughing in patients with chronic bronchitis (3)[C]:
  • These agents have limited efficacy in cough due to upper respiratory infections (3)[C].
• For cough associated with lung cancer, the use of narcotic cough suppressants is recommended (3)[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.
• The American Academy of Pediatrics does not recommend central cough suppressants for treating any kind of cough (2)[B].
• In children <14 years old, 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 proton pump inhibitor therapy were not effective (5)[C].

• Treatments (antacids, bronchodilators, inhaled corticosteroids, proton pump inhibitors, antibiotics) should be directed at the specific cause of cough.
• The FDA issued a public health advisory stating that OTC cough and cold medicines should not be given to children <2 years.
• Consumer Healthcare Products Association (CHPA) members have changed OTC cough expectorant and suppressant product labels to state “do not use” in children <4 years old.

First Line

• In adults, oral antihistamine/decongestant therapy should be empiric treatment. Multiple formulations are available OTC in combination with other ingredients. Advise patients to review labels carefully or consult pharmacist:
  • Chlorpheniramine 2 mg/phenylephrine 5 mg/Acetaminophen 325 mg (Tylenol Allergy Multi-Symptom) 2 caplets or gelcaps PO q4h (Maximum 12 caplets or gelcaps in 24 hours: Age >12 years)
• Central cough suppressants for short-term symptomatic relief of nonproductive cough:
  • Dextromethorphan 10–20 mg PO q4h: Age >12 years. Use 5–10 mg PO q4h for age 6–12 years:
    • Concomitant use of dextromethorphan and agents with serotonergic activity (such as SSRIs) should be avoided due to risk of serotonin syndrome.
  • Narcotics: Codeine 15–30 mg PO q6h; hydrocodone (Vicodin) 5 mg PO q6h; hydrocodone (Tussionex Pennkinetic) 10 mg (5 mL) PO q12h for ages 12 or over

Second Line

• A peripherally acting antitussive agent has been used:
  • In patients > age 10, Benzonatate (Tessalon Perles) 100–200 mg PO t.i.d. as needed (maximum 600 mg daily)
• 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 (6)[C]:
  • Morphine was administered 5–10 mg PO b.i.d.
• For patients with cystic fibrosis, amiloride may improve cough clearance of sputum.

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 (2)[A].
• Empiric treatment of postnasal drip and GERD.
• Consider nonpharmacological options such as warm fluids, hard candy, or nasal drops. In infants and children, can try clearing secretions with a bulb syringe.
• Attempt maximal therapy for single most-likely cause for several weeks, then search for coexistent etiologies.

Issue for Referral

• Refer as needed based on specific suspected diagnosis for cough.
• Patients with chronic cough may benefit from evaluation by pulmonary, gastroenterology, ear-nose-and-throat (ENT), and/or allergy specialists.

Fundoplication may be effective for cough secondary to refractory GERD.

Consider stepwise withdrawal of medications after resolution of cough.

Patient Monitoring Frequent follow-up is necessary to assess the effectiveness of the treatment and the addition of other medications as needed.

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

• Reassure patient that most cases of chronic cough do not have life-threatening causes and that the condition can usually be managed effectively.
• Counsel that several weeks to a month may be needed for significant reduction or total elimination of cough.
• Prepare the patient for the possibility of multiple diagnostic tests and therapeutic regimens, because the treatment is very often empiric.

• >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.

• 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

• Birring SS. Controversies in the evaluation and management of chronic cough. Am J Respir Crit Care Med. 2011;183:708–15.
• Pavord ID, Chung KF. Management of chronic cough. Lancet. 2008;371:1375–84.

• 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

• 496 Chronic airway obstruction, not elsewhere classified
• 786.2 Cough

• R05 Cough
• J44.9 Chronic obstructive pulmonary disease, unspecified

• 68154008 Chronic cough (finding)
• 13645005 chronic obstructive lung disease (disorder)

• 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.
• Consumer Healthcare Products Association (CHPA) members have changed OTC cough expectorant and suppressant product labels to state “do not use” in children <4 years old.

Jacqueline L. Olin, MS, PharmD, BCPS, CPP, CDE
Susan Ziglar, MD

1. Chung KF. Chronic 'cough hypersensitivity syndrome': A more precise label for chronic cough. Pulm Pharmacol Ther. 2011:24:267–71.  [PMID:21292019]
2. Irwin RS, Baumann MH, Bolser DC, et al. Diagnosis and management of cough executive summary: ACCP evidence-based clinical practice guidelines. Chest. 2006;129:1S–23S.  [PMID:16428686]
3. Bolser DC. Cough suppressant and pharmacologic protussive therapy: ACCP evidence-based clinical practice guidelines. Chest. 2006;129:238S–249S.  [PMID:16428717]
4. Gupta A, et al. Management of chronic non-specific cough in childhood: An evidence-based review. Arch Dis Child Educ Pract Ed. 2007;92:ep33–ep39.
5. Chang AB, Lasserson TJ, Gaffney J, et al. Gastro-oesophageal reflux treatment for prolonged non-specific cough in children and adults. Cochrane Database Syst Rev. 2011;CD004823.  [PMID:21249664]
6. Morice AH, Menon MS, Mulrennan SA, et al. Opiate therapy in chronic cough. Am J Respir Crit Care Med. 2007;175:312–5.  [PMID:17122382]

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