What is the appropriate evaluation and management for a severe cough in an adult?

Evaluation and Management of Severe Cough in Adults

Immediate Classification by Duration

The single most important first step is to classify the cough by duration: acute (<3 weeks), subacute (3–8 weeks), or chronic (>8 weeks), because this classification immediately narrows your differential diagnosis and dictates the entire management pathway. 1, 2

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Red-Flag Assessment – Urgent Evaluation Required

Before proceeding with routine evaluation, actively screen for any of the following red-flag features that mandate immediate investigation:

• Hemoptysis – any blood in sputum requires urgent work-up for malignancy, tuberculosis, bronchiectasis, or pulmonary embolism 1, 2
• Unintentional weight loss – suggests malignancy, tuberculosis, or chronic infection 1, 2
• Fever >4 days or night sweats – indicates active infection or systemic disease 1, 2
• Significant dyspnea at rest or nocturnal dyspnea – may signal severe cardiopulmonary pathology 1, 2
• New cough in smoker >45 years or ≥30 pack-years – meets lung cancer screening criteria 2
• Recurrent pneumonia – points toward structural lung disease, immunodeficiency, or aspiration 2

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Mandatory Baseline Investigations for Chronic Cough (>8 weeks)

All adults with chronic cough require chest radiography and spirometry as non-negotiable baseline investigations. 1, 2

• Chest radiograph – excludes mass lesions, infiltrates, bronchiectasis, interstitial lung disease, and cardiac abnormalities 1, 2
• Spirometry with bronchodilator testing – detects airflow obstruction and assesses reversibility 1, 2
• Quantify cough severity – use visual analog scales or validated quality-of-life questionnaires to objectively monitor treatment response 1, 2

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Critical Medication and Exposure Review

• Discontinue any ACE inhibitor immediately – cough typically resolves within a median of 26 days (range up to 40 weeks) after cessation; no patient with troublesome cough should continue ACE inhibitors 1, 2
• Verify smoking status – smoking-related cough usually resolves within 4 weeks after cessation; prioritize smoking cessation as the primary intervention 1, 2
• Assess occupational and environmental exposures – systematically evaluate for workplace irritants, mold, dust, and indoor air quality 1, 2
• Consider sitagliptin – DPP-4 inhibitors can provoke cough and should be discontinued if suspected 1, 2

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Systematic Empiric Treatment Algorithm for Chronic Cough

The "Big Four" etiologies—upper airway cough syndrome (UACS), asthma, gastroesophageal reflux disease (GERD), and non-asthmatic eosinophilic bronchitis (NAEB)—account for >90% of chronic cough cases in non-smokers with normal or near-normal chest radiographs. 1, 2, 3

Step 1: Treat Upper Airway Cough Syndrome (UACS)

UACS is the single most frequent cause, accounting for 18.6%–81.8% of chronic cough cases. 1, 2

• Start a first-generation antihistamine-decongestant combination (e.g., brompheniramine/pseudoephedrine or chlorpheniramine/phenylephrine) 2
• Add intranasal corticosteroid spray (fluticasone or mometasone) 1, 2
• Expected response time: days to 1–2 weeks 2

Step 2: Evaluate and Treat Asthma (Including Cough-Variant Asthma)

Asthma accounts for 14.6%–41.3% of chronic cough; cough may be the sole manifestation, and normal spirometry does NOT exclude asthma. 1, 2, 3

• Perform methacholine bronchial provocation testing when spirometry is normal but clinical suspicion remains 1, 2
• No pulmonary function test can reliably exclude a cough that would respond to corticosteroids 1, 2
• Initiate inhaled corticosteroids (fluticasone 220 µg or budesonide 360 µg twice daily) with or without long-acting bronchodilators 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 1, 2
• Expected response time: up to 8 weeks for full effect 2

Step 3: Treat Gastroesophageal Reflux Disease (GERD)

GERD contributes to 4.6%–85.4% of chronic cough and often occurs without gastrointestinal symptoms; failure to consider GERD is a common reason for treatment failure. 1, 2

• Initiate intensive acid suppression with proton pump inhibitors (omeprazole 20–40 mg twice daily before meals) plus alginates for a minimum of 3 months 1, 2
• Implement dietary and lifestyle modifications – remove medications that aggravate reflux (bisphosphonates, nitrates, calcium-channel blockers, theophylline) 2
• Consider adding prokinetic agents (metoclopramide 10 mg three times daily) if response is inadequate 2
• Expected response time: 2 weeks to 12 weeks 2
• Note: Acid suppression alone is no longer recommended as definitive treatment 1, 2

Step 4: Consider Non-Asthmatic Eosinophilic Bronchitis (NAEB)

NAEB accounts for 6.4%–17.2% of chronic cough cases and is characterized by eosinophilic airway inflammation without airway hyperresponsiveness. 1, 2

• Request induced sputum analysis after exclusion of other common causes; sputum eosinophilia >3% has important treatment implications 1, 2
• Treat with inhaled corticosteroids 2

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Critical Management Principle: Multiple Simultaneous Etiologies

Up to 67% of chronic cough patients have multiple concurrent causes; cough resolves only after ALL contributing factors are addressed. 1, 2, 3

• Retain partially effective therapies and employ additive treatment strategies rather than stopping and switching 2
• Formally quantify treatment effects using validated cough severity measures at each step 1, 2

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Follow-Up and Advanced Evaluation

• Schedule follow-up within 4–6 weeks after initial evaluation to reassess cough severity and verify treatment adherence 1, 2
• If all empiric therapies fail after 8 weeks, obtain high-resolution CT chest to evaluate for bronchiectasis, interstitial lung disease, or occult masses 1, 2
• Consider bronchoscopy to assess for endobronchial lesions, sarcoidosis, eosinophilic bronchitis, or occult infection when comprehensive work-up remains inconclusive 2
• Refer to a specialist cough clinic for refractory unexplained chronic cough 1, 2

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Special Considerations for Acute and Subacute Cough

Acute Cough (<3 weeks)

• Most acute coughs are viral upper respiratory tract infections and resolve spontaneously 1
• Antibiotics are explicitly contraindicated unless there is documented bacterial pneumonia, sinusitis, or pertussis 4, 5
• Over-the-counter preparations (guaifenesin, honey-lemon) may provide subjective benefit 1, 4, 5
• Suspect pertussis when cough lasts ≥2 weeks with paroxysms, post-tussive vomiting, or inspiratory "whoop"; immediate macrolide therapy is indicated 2, 4, 5

Subacute (Post-Infectious) Cough (3–8 weeks)

Post-infectious cough is the most frequent cause of subacute cough (≈48% of cases) and typically resolves without specific therapy. 1, 4

• First-line treatment: Inhaled ipratropium bromide (2–3 puffs four times daily) has the strongest evidence for attenuating post-infectious cough, with response expected within 1–2 weeks 2, 4
• Second-line: Add inhaled corticosteroids (fluticasone 220 µg or budesonide 360 µg twice daily) if cough persists and adversely affects quality of life; allow up to 8 weeks for full response 2, 4
• Third-line: Oral prednisone (30–40 mg daily for 5–10 days) is reserved for severe paroxysms that significantly impair quality of life, and only after exclusion of UACS, asthma, and GERD 2, 4
• Antibiotics are contraindicated for post-infectious cough unless there is confirmed bacterial sinusitis or early pertussis 4, 5

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Common Pitfalls to Avoid

• Assuming a single etiology – up to 67% of chronic cough patients have multiple concurrent causes 1, 2
• Neglecting medication review – failure to discontinue ACE inhibitors before extensive work-up leads to unnecessary investigations 1, 2
• Relying solely on acid suppression for GERD-related cough – comprehensive management (lifestyle modification, dietary changes, possible prokinetics) is necessary 2
• Inadequate trial duration – empiric therapeutic trials should be maintained for 4–6 weeks before deeming them ineffective 1, 2
• Prescribing antibiotics for viral or post-infectious cough – provides no benefit, contributes to resistance, and causes adverse effects 4, 5

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Symptomatic Relief Options

• Benzonatate is FDA-approved for symptomatic relief of cough 6
• Guaifenesin (200–400 mg every 4 hours, up to 6 times daily) is FDA-approved to help loosen phlegm and thin bronchial secretions 4, 5
• Dextromethorphan (60 mg for maximum cough reflex suppression) may be considered for dry, bothersome cough 4
• Honey and lemon provide symptomatic relief through central modulation of the cough reflex 4