In an adult patient with a persistent cough after an upper‑respiratory viral infection, what are the diagnostic criteria and recommended management for post‑infectious cough and for upper‑airway cough syndrome (post‑nasal drip syndrome)?

Diagnostic Criteria and Management for Post-Infectious Cough and Upper Airway Cough Syndrome

Post-Infectious Cough: Diagnostic Criteria

Post-infectious cough is diagnosed when cough persists for 3 to 8 weeks following an acute respiratory infection, based purely on clinical timeline and exclusion of bacterial causes. 1, 2

Key Diagnostic Features:

• Timeline: Initial URI symptoms for approximately 3 days, followed by persistent cough lasting 3-8 weeks after the acute infection resolves 3
• Clinical presentation: Non-purulent sputum, absence of fever, clear lungs except transient wheezes that clear with coughing, no crackles suggesting pneumonia, in an otherwise healthy nonsmoker 3
• Pathophysiology: Driven by post-viral airway inflammation with bronchial hyperresponsiveness, mucus hypersecretion, impaired mucociliary clearance, and increased cough reflex sensitivity 1, 2

Critical Rule-Out: Pertussis

• Suspect pertussis when cough lasts ≥2 weeks with paroxysms, post-tussive vomiting, or inspiratory whooping sound 1, 3
• Obtain nasopharyngeal culture or swab immediately if pertussis is suspected 4
• Prescribe macrolide antibiotics (azithromycin or clarithromycin) immediately and isolate for 5 days if pertussis is confirmed 4

When to Reclassify as Chronic Cough:

• If cough persists beyond 8 weeks, it must be reclassified as chronic cough and systematically evaluated for upper airway cough syndrome (UACS), asthma, and gastroesophageal reflux disease (GERD) 2, 3
• Obtain chest radiograph at 8 weeks, especially in smokers and patients over 50 years 3

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Post-Infectious Cough: Treatment Algorithm

First-Line Treatment (Weeks 1-3):

Inhaled ipratropium bromide 2-3 puffs (17-34 mcg per puff) four times daily is the first-line pharmacologic intervention with the strongest evidence for attenuating post-infectious cough. 1, 2, 3

• Expected response within 1-2 weeks 2, 3
• Supportive measures include honey and lemon, adequate hydration, and voluntary cough suppression 2, 3

Second-Line Treatment:

If cough persists despite ipratropium and adversely affects quality of life, add inhaled corticosteroids (fluticasone 220 mcg or budesonide 360 mcg twice daily). 1, 2, 3

• Allow up to 8 weeks for full therapeutic response 2, 3
• Mechanism involves suppression of airway inflammation and bronchial hyperresponsiveness 2

Third-Line Treatment for Severe Cases:

Oral prednisone 30-40 mg daily for 5-10 days should be reserved exclusively for severe paroxysms that significantly impair quality of life, and only after ruling out UACS, asthma, and GERD. 1, 2, 3

Antitussive Agents (When Other Measures Fail):

• Dextromethorphan 60 mg provides maximum cough reflex suppression and is preferred over codeine due to fewer side effects 2
• Codeine and pholcodine have no greater efficacy than dextromethorphan but carry significantly more adverse effects (drowsiness, nausea, constipation, physical dependence) 2
• First-generation sedating antihistamines may be suitable specifically for nocturnal cough 2, 4

What NOT to Do:

Antibiotics are explicitly contraindicated for post-infectious cough, as the cause is not bacterial infection. 1, 2, 3

• Antibiotics provide no benefit, contribute to antimicrobial resistance, and cause adverse effects 3
• Exception: confirmed bacterial sinusitis or early pertussis infection 1, 3

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Upper Airway Cough Syndrome (UACS): Diagnostic Criteria

UACS, formerly known as postnasal drip syndrome, is a clinical diagnosis of exclusion with no objective diagnostic testing or pathognomonic findings. 5

Clinical Features:

• May present with or without associated rhinitis and chronic rhinosinusitis 5
• Can manifest as "silent post-nasal drip syndrome" where cough is the only symptom despite absence of overt nasal complaints 3
• Physical examination may reveal swollen turbinates and tonsils (non-erythematous), consistent with upper airway inflammation 3
• Sensation of throat clearing, nasal discharge (watery or purulent), or throat irritation may be present 3

Diagnostic Confirmation:

Diagnosis is confirmed when therapeutic intervention results in symptom resolution. 5

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Upper Airway Cough Syndrome: Treatment Algorithm

First-generation antihistamine-decongestant combination plus intranasal corticosteroid spray is the recommended dual therapy for UACS. 2, 3

Specific Regimen:

• First-generation antihistamine-decongestant: brompheniramine/pseudoephedrine or chlorpheniramine/phenylephrine 3
• Intranasal corticosteroid: fluticasone or mometasone 3
• Expected response within days to 1-2 weeks 3

Important Considerations:

• UACS accounts for a significant proportion of chronic cough cases (part of the 90% triad with asthma and GERD) 5, 6
• Treatment should be continued even if partial improvement occurs, as chronic cough is frequently multifactorial 3
• Do not stop and switch therapies; instead, continue effective treatment and add the next intervention in the algorithm 3

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Common Pitfalls to Avoid

Timing Errors:

• Failing to recognize when post-infectious cough has persisted beyond 8 weeks, which requires reclassification as chronic cough and systematic evaluation for UACS, asthma, and GERD 2, 3

Inappropriate Antibiotic Use:

• Prescribing antibiotics for non-bacterial post-infectious cough provides no benefit and contributes to resistance 1, 2, 3
• Green or colored sputum does NOT indicate bacterial infection in post-infectious cough 3

Premature Use of Oral Steroids:

• Jumping to prednisone for mild post-infectious cough without first trying ipratropium and inhaled corticosteroids 3
• Oral steroids should be reserved for severe cases that have failed other therapies 2, 3

Overlooking Underlying Conditions:

• Not systematically evaluating for UACS, asthma, and GERD when cough persists beyond the expected post-infectious timeline 1, 2, 3
• These conditions may coexist and require concurrent treatment for complete resolution 3

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Red Flags Requiring Advanced Evaluation

Immediate Re-evaluation Needed:

• Fever development or prolongation 3
• Hemoptysis 3
• Symptoms worsen despite treatment 3

Advanced Testing Indications (if cough persists beyond 8 weeks):

• High-resolution CT chest to evaluate for bronchiectasis, interstitial lung disease, or occult masses if all empiric therapies fail 3
• Bronchoscopy to evaluate for endobronchial lesions, sarcoidosis, eosinophilic bronchitis, or occult infection if complete workup fails 3
• Induced sputum analysis to detect eosinophilic airway inflammation (sputum eosinophil count >3%) to differentiate cough-variant asthma or non-asthmatic eosinophilic bronchitis 3

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Follow-Up Timeline

• Schedule follow-up in 4-6 weeks to reassess if cough persists 4
• Repeat chest radiograph at approximately 6 weeks for smokers and those over 50 years 3
• If no improvement after 3-5 days of treatment for UACS, reassess for alternative diagnoses 3