What pharmacologic treatments are recommended for a persistent cough?

Pharmacologic Treatment of Persistent Cough

For persistent cough, the treatment depends critically on the underlying cause—upper airway cough syndrome (UACS), asthma, or gastroesophageal reflux disease (GERD)—and should follow a systematic, stepwise approach starting with first-generation antihistamine-decongestant combinations for UACS, inhaled corticosteroids for asthma, and high-dose proton pump inhibitors for GERD. 1

Initial Assessment and Medication Review

Before initiating pharmacologic therapy, two critical steps must be taken:

• Immediately discontinue ACE inhibitors if the patient is taking them, as they cause cough in up to 16% of patients through a class effect that increases cough reflex sensitivity; the median time to resolution after stopping is 26 days but may take up to 40 weeks. 1

• Encourage smoking cessation if applicable, as smoking is one of the most common causes of persistent cough and appears to be dose-related. 1

Stepwise Treatment Algorithm by Etiology

Upper Airway Cough Syndrome (UACS)

First-line therapy for UACS involves:

• Prescribe a first-generation antihistamine-decongestant combination (such as brompheniramine/pseudoephedrine or chlorpheniramine/phenylephrine), as these have sedating properties that suppress cough and are particularly beneficial for nocturnal symptoms. 2

• Add an intranasal corticosteroid spray (fluticasone 100-200 mcg daily or mometasone) to address upper airway inflammation. 2, 3

• Expected response time is days to 1-2 weeks; if no improvement occurs within this timeframe, proceed to evaluate for asthma. 2

Asthma and Cough-Variant Asthma

When asthma is suspected (accounting for 24-32% of chronic cough cases 1):

• Start inhaled corticosteroids (fluticasone 220 mcg or budesonide 360 mcg twice daily) plus inhaled beta-agonists as first-line therapy. 1, 2

• Add an oral leukotriene inhibitor (such as montelukast) before considering oral corticosteroids if response is inadequate. 4

• Allow up to 8 weeks for full therapeutic response to inhaled corticosteroids, as complete resolution of asthmatic cough may require this duration. 2

• A 2-week trial of oral prednisone (30 mg daily) can serve as both diagnostic and therapeutic for cough-variant asthma when the diagnosis is uncertain. 2

Gastroesophageal Reflux Disease (GERD)

GERD frequently presents as "silent GERD" with cough as the sole manifestation:

• Initiate high-dose proton pump inhibitor therapy (omeprazole 40 mg twice daily) with dietary modifications for a minimum of 3 months. 1, 2

• Response time ranges from 2 weeks to several months, requiring patience and adherence before declaring treatment failure. 2

• Failure to consider GERD even without gastrointestinal symptoms is a common reason for treatment failure. 1, 4

Postinfectious Cough (3-8 Weeks Duration)

For cough persisting 3-8 weeks after acute respiratory infection:

• Inhaled ipratropium bromide (2-3 puffs, 17-34 mcg per puff, four times daily) is first-line therapy with the strongest evidence for attenuating postinfectious cough, with response expected within 1-2 weeks. 2

• Antibiotics are explicitly contraindicated unless there is confirmed bacterial sinusitis or early pertussis infection, as postinfectious cough is driven by airway inflammation, not bacterial infection. 2

• If cough persists despite ipratropium and significantly impairs quality of life, add inhaled corticosteroids (fluticasone 220 mcg or budesonide 360 mcg twice daily), allowing up to 8 weeks for full response. 2

• Oral prednisone (30-40 mg daily for 5-10 days) is reserved only for severe paroxysms that substantially impair quality of life, and only after ruling out UACS, asthma, and GERD. 2

Symptomatic Antitussive Therapy

When symptomatic relief is needed while addressing underlying causes:

• Dextromethorphan 30-60 mg is the most effective antitussive with the best safety profile, providing cough reflex suppression without the sedation and addiction risk of opiates. 4, 5

• Codeine and other opiates have no greater efficacy than dextromethorphan but carry significantly more side effects (sedation, constipation, addiction potential) and should only be considered when other measures fail. 2, 6

• Honey and lemon provide symptomatic relief through central modulation of the cough reflex and represent a simple, inexpensive, and often effective option. 2, 4

• Guaifenesin (200-400 mg every 4 hours, up to 6 times daily) is FDA-approved to help loosen phlegm and thin bronchial secretions, making it appropriate for productive cough. 2

Critical Pitfalls to Avoid

• Do not prescribe antibiotics for postinfectious cough unless bacterial sinusitis or pertussis is documented; this provides no benefit, contributes to antimicrobial resistance, and adds adverse-effect risk. 2, 4

• Do not assume purulent sputum indicates bacterial infection requiring antibiotics in acute bronchitis, as most short-term coughs are viral even when producing colored phlegm. 2, 4

• Do not fail to recognize when cough persists beyond 8 weeks, which requires reclassification as chronic cough and systematic evaluation for UACS, asthma, and GERD. 2

• Chronic cough is frequently multifactorial; partial improvement with one treatment should prompt continuation of that therapy while adding the next intervention in the algorithm, rather than stopping and switching. 2

• Do not use multiple intranasal corticosteroids simultaneously, as this is redundant; select one agent (e.g., fluticasone) as first-line therapy. 3