How should a persistent cough lasting more than three weeks be evaluated and managed?

Evaluation and Management of Persistent Cough Lasting More Than Three Weeks

Immediate Assessment: Rule Out Life-Threatening Conditions First

Before assuming this is a benign post-infectious cough, actively screen for red-flag features that demand urgent investigation, including hemoptysis, unintentional weight loss, fever, night sweats, prominent dyspnea, hoarseness, and smoking history in adults over 45 years. 1, 2, 3

Critical Red Flags Requiring Immediate Chest Radiography:

• Hemoptysis (any amount) 1, 2, 3
• Vital sign abnormalities: heart rate ≥100 bpm, respiratory rate ≥24 breaths/min, temperature ≥38°C 3
• Asymmetrical lung sounds or focal consolidation on examination 1, 3
• Systemic symptoms: fever, unintentional weight loss, night sweats 1, 2, 3
• Smoker over 45 years with new or changed cough 2, 3
• Recurrent pneumonia 2

Classification by Duration: The 3-Week Mark Matters

At 3 weeks duration, the cough is transitioning from acute to subacute (3-8 weeks), with the most likely diagnosis being postinfectious cough, which accounts for approximately 48% of subacute cough cases. 1, 4, 3

• Acute cough: <3 weeks 1
• Subacute cough: 3-8 weeks 1
• Chronic cough: >8 weeks 1, 2

Mandatory Baseline Investigations

Obtain a chest radiograph in all patients with cough lasting ≥3 weeks to exclude pneumonia, mass lesions, infiltrates, bronchiectasis, interstitial lung disease, and cardiac abnormalities. 1, 2

Perform spirometry with bronchodilator testing to detect airflow obstruction and assess reversibility, as normal spirometry does not exclude asthma-related cough. 1, 2

Quantify cough severity using visual-analog scales or validated quality-of-life questionnaires to objectively monitor treatment response. 1, 2

Critical Medication and Exposure Review

Immediately discontinue any ACE inhibitor, regardless of temporal relationship to cough onset, as drug-induced cough typically resolves within a median of 26 days (range up to 40 weeks) after cessation. 2, 4, 3

Verify current smoking status and advise immediate cessation; smoking-related chronic cough usually resolves within 4 weeks after quitting. 2

Systematically assess for occupational and environmental irritant exposures. 2

Evaluate for Pertussis Before Assuming Postinfectious Cough

Actively evaluate for pertussis, especially if the patient reports paroxysmal coughing episodes, post-tussive vomiting, or inspiratory whooping sound; if suspected, obtain nasopharyngeal culture or PCR and start azithromycin immediately without waiting for laboratory confirmation. 1, 4, 3

• Pertussis is the most virulent form of postinfectious cough 1
• Antibiotics have no role in postinfectious cough except for pertussis or bacterial sinusitis 1

First-Line Treatment for Postinfectious Cough (3-8 Weeks Duration)

Prescribe inhaled ipratropium bromide as the only evidence-based first-line therapy for postinfectious cough, with approximately 70% response rate. 1, 4, 3

• The pathogenesis involves extensive inflammation and disruption of airway epithelial integrity, often with mucus hypersecretion and transient airway hyperresponsiveness 1
• Antibiotics have no role unless pertussis or bacterial sinusitis is confirmed 1, 4, 3

Alternative Therapies if Ipratropium Fails:

• First-generation antihistamine-decongestant combination if upper airway symptoms are present 3
• Consider short course of oral corticosteroids (prednisone 30-40 mg/day) for severe symptoms 3

If Cough Persists Beyond 8 Weeks: Systematic Chronic Cough Evaluation

When cough persists beyond 8 weeks, it meets the definition of chronic cough and warrants comprehensive evaluation for the "Big Four" etiologies that account for >90% of cases in non-smokers with normal chest radiographs: upper airway cough syndrome (UACS), asthma/cough-variant asthma, gastroesophageal reflux disease (GERD), and non-asthmatic eosinophilic bronchitis (NAEB). 1, 2

Upper Airway Cough Syndrome (UACS):

• Accounts for 18.6%-81.8% of chronic cough cases 2
• Trial first-generation antihistamine-decongestant combination for 1-2 weeks 2, 3
• When prominent upper airway symptoms are present, add topical nasal corticosteroid 2

Asthma/Cough-Variant Asthma:

• Accounts for 14.6%-41.3% of chronic cough cases 2
• No pulmonary function test can reliably exclude a cough that would respond to corticosteroids; normal spirometry does not rule out asthma-related cough 2
• Perform methacholine bronchial provocation testing when spirometry is normal and no obvious etiology is found 1, 2
• A 2-week trial of oral prednisone (30-40 mg daily) helps differentiate eosinophilic airway inflammation; lack of improvement suggests a non-asthmatic cause 2
• Initiate inhaled corticosteroids according to national asthma guidelines 2

Gastroesophageal Reflux Disease (GERD):

• Accounts for 4.6%-85.4% of chronic cough cases 2
• Cough related to reflux can occur without any gastrointestinal symptoms 2
• Initiate intensive acid suppression with proton-pump inhibitor (omeprazole 20-40 mg twice daily before meals) plus alginates for a minimum of 3 months; clinical response may require 2-12 weeks 2
• Add dietary and lifestyle modifications, including removal of medications that may aggravate reflux (bisphosphonates, nitrates, calcium-channel blockers, theophylline, progesterone) 2
• Consider adding prokinetic agent (metoclopramide 10 mg three times daily) if inadequate response 2

Non-Asthmatic Eosinophilic Bronchitis (NAEB):

• Accounts for 6.4%-17.2% of chronic cough cases 2
• Characterized by eosinophilic airway inflammation without airway hyperresponsiveness or variable airflow obstruction 2
• Treat with inhaled corticosteroids 2

Critical Management Principle: Multiple Simultaneous Etiologies

Up to 67% of chronic cough patients have multiple concurrent causes; therefore, retain partially effective therapies and employ additive treatment strategies rather than sequential monotherapy. 2

• Failure to recognize multiple contributing causes is a common pitfall leading to unsuccessful treatment 5

Advanced Evaluation When Empiric Therapies Fail

If all empiric therapies are ineffective after 8 weeks, obtain high-resolution CT chest to evaluate for bronchiectasis, interstitial lung disease, or occult masses. 2

Consider bronchoscopy to assess for endobronchial lesions, sarcoidosis, eosinophilic bronchitis, or occult infection when the comprehensive work-up remains inconclusive. 2

Refer to a specialized cough clinic when the condition remains undiagnosed after systematic evaluation of UACS, asthma, GERD, and NAEB. 2

Follow-Up and Monitoring

Schedule follow-up in 4-6 weeks to reassess cough severity using validated instruments and verify treatment adherence before abandoning a therapeutic trial. 2, 4, 3

Formally quantify treatment effects using validated cough-severity measures rather than relying on subjective assessment alone. 1, 2

Common Pitfalls to Avoid

• Do not prescribe antibiotics for postinfectious cough unless pertussis or bacterial sinusitis is confirmed 1, 4, 3
• Do not assume a single etiology; up to 67% have multiple concurrent causes requiring combination therapy 2
• Do not rely solely on acid-suppression for GERD-related cough; comprehensive management including lifestyle modification is necessary 2
• Do not abandon therapeutic trials prematurely; maintain empiric treatments for 4-6 weeks before deeming them ineffective 2, 4, 3
• Do not neglect medication review; failure to discontinue ACE inhibitors before extensive work-up leads to unnecessary investigations 2, 4, 3