How should I evaluate and treat a persistent cough lasting more than eight weeks in an otherwise healthy adult?

Evaluation and Treatment of Persistent Cough Lasting More Than Eight Weeks

Begin with a chest radiograph and spirometry as mandatory baseline investigations, then initiate empiric treatment targeting the three most common causes—upper airway cough syndrome, asthma, and gastroesophageal reflux disease—which together account for more than 90% of chronic cough cases. 1

Initial Mandatory Investigations

• Obtain a chest radiograph in every adult with chronic cough (>8 weeks) to exclude infectious, inflammatory, or malignant thoracic disease. This is non-negotiable and must be performed before assuming a benign etiology. 1

• Perform spirometry with bronchodilator testing to detect obstructive airway pathology. Normal spirometry does not exclude asthma-related cough, as cough may be the sole manifestation of airway inflammation. 1

• Quantify cough severity using visual-analog scales or validated quality-of-life questionnaires to objectively monitor treatment response at follow-up. 1

Critical Red-Flag Assessment

Screen for features requiring urgent investigation before proceeding with empiric therapy: 1

• Hemoptysis – mandates immediate work-up for malignancy, tuberculosis, or pulmonary embolism
• New-onset cough in individuals >45 years who smoke – meets lung cancer screening criteria
• Significant resting or nocturnal dyspnea – suggests severe cardiopulmonary disease
• Unintentional weight loss or fever – indicates possible malignancy, tuberculosis, or systemic infection
• Hoarseness – may reflect laryngeal pathology or recurrent laryngeal nerve involvement
• Peripheral edema with weight gain – suggests heart failure

Medication and Exposure Review

• Discontinue any ACE-inhibitor immediately if the patient is taking one; cough typically resolves within a median of 26 days (range up to 40 weeks) after cessation. 1

• Verify current smoking status and prioritize smoking cessation as the primary intervention; most smoking-related coughs improve within 4 weeks of quitting. 1

• Systematically assess occupational and environmental exposures (dust, chemicals, fumes) that may perpetuate cough. 1

Empiric Treatment Algorithm for the "Big Three" Causes

Because up to 67% of chronic cough patients have multiple simultaneous etiologies, retain partially effective therapies and employ additive treatment strategies rather than sequential monotherapy. 1

First-Line: Upper Airway Cough Syndrome (UACS)

• UACS accounts for 18.6%–81.8% of chronic cough cases and is the single most frequent cause. 1

• Initiate a first-generation antihistamine-decongestant combination (e.g., brompheniramine/pseudoephedrine or chlorpheniramine/phenylephrine) plus an intranasal corticosteroid spray (fluticasone or mometasone). 1, 2

• Improvement typically occurs within days to 1–2 weeks. 1

• UACS may present without prominent nasal symptoms such as post-nasal drip, making clinical recognition challenging. 1

Second-Line: Asthma (Including Cough-Variant Asthma)

• Asthma underlies 14.6%–41.3% of chronic cough and may present as cough alone without wheezing or dyspnea. 1

• No pulmonary function test can reliably exclude a cough that would respond to corticosteroids; therefore, a therapeutic trial is required when asthma is suspected. 1

• Obtain methacholine bronchial provocation testing when spirometry is normal but clinical suspicion remains; a positive challenge confirms cough-variant asthma in approximately 88% of cases. 1

• Initiate inhaled corticosteroids (fluticasone 220 mcg or budesonide 360 mcg twice daily) according to national asthma guidelines. 1

• A 2-week trial of oral prednisone (30–40 mg daily) can differentiate eosinophilic airway inflammation; lack of improvement makes an eosinophilic mechanism unlikely. 1

• Complete resolution of asthmatic cough may require up to 8 weeks of inhaled corticosteroid therapy. 1

Third-Line: Gastroesophageal Reflux Disease (GERD)

• GERD contributes to 4.6%–85.4% of chronic cough and frequently occurs without typical gastrointestinal symptoms (heartburn, regurgitation). 1

• Initiate intensive acid suppression with omeprazole 20–40 mg twice daily before meals plus alginates for a minimum of 3 months. 1

• Combine pharmacologic therapy with dietary and lifestyle modifications, including removal of medications that may aggravate reflux (bisphosphonates, nitrates, calcium-channel blockers, theophylline, progesterone). 1

• Clinical response may require 2 weeks to 12 weeks, so maintain therapy for an adequate duration before deeming it ineffective. 1

• Failure to consider GERD is a frequent cause of therapeutic failure. 1

Additional Diagnostic Considerations

• Non-asthmatic eosinophilic bronchitis (NAEB) accounts for 6.4%–17.2% of cases and is characterized by eosinophilic airway inflammation without airway hyper-responsiveness or variable airflow obstruction. 1

• NAEB responds to inhaled corticosteroids, making a therapeutic trial appropriate when eosinophilic inflammation is suspected. 1

• Atopic cough is more prevalent in Asian populations and also responds to inhaled corticosteroid therapy. 1

Follow-Up and Reassessment

• Schedule systematic re-evaluation 4–6 weeks after the initial visit to assess cough severity using validated instruments and verify treatment adherence before abandoning a therapeutic trial. 1

• If cough persists beyond 8 weeks despite empiric treatment of UACS, asthma, and GERD, obtain high-resolution computed tomography to evaluate for bronchiectasis, interstitial lung disease, or occult masses. 1

• Consider bronchoscopy when comprehensive work-up remains inconclusive, to assess for endobronchial lesions, sarcoidosis, eosinophilic bronchitis, or occult infection. 1

• Refer to a specialized cough clinic when the condition remains undiagnosed after systematic evaluation of all common causes. 1

Common Pitfalls to Avoid

• Assuming a single etiology – Up to 67% of chronic cough patients have multiple concurrent causes; cough resolves only after all contributing factors are addressed. 1

• Neglecting medication review – Failure to discontinue ACE inhibitors before extensive work-up leads to unnecessary investigations. 1

• Inadequate trial duration – Empiric therapeutic trials should be maintained for 4–6 weeks before deeming them ineffective, as response times vary by condition. 1

• Relying solely on acid-suppression for GERD-related cough – Comprehensive management (lifestyle modification, dietary changes, possible prokinetics) is necessary. 1