What are the likely diagnoses and recommended evaluation for a 17‑year‑old male who, 2–3 weeks after a viral upper‑respiratory infection, presents with an intermittent productive cough with occasional blood‑streaked sputum, worse in the mornings, when supine, with nocturnal awakening, and a sibling with asthma?

Differential Diagnosis for Post-Viral Cough with Hemoptysis in a 17-Year-Old Male

The most likely diagnoses are post-viral cough (expected to resolve within 8 weeks), cough-variant asthma (given family history and exercise/cold-air triggers), and non-asthmatic eosinophilic bronchitis (NAEB), with the blood-streaked sputum representing airway inflammation rather than serious pathology.

Primary Differential Diagnoses

1. Post-Viral Cough (Most Likely)

• Post-viral cough is defined as persistent cough lasting 3-8 weeks following an acute respiratory infection, which precisely matches this patient's timeline of 2-3 weeks post-URI 1.
• The mechanism involves extensive disruption of epithelial integrity, widespread airway inflammation, mucus hypersecretion, impaired mucociliary clearance, and transient bronchial hyperresponsiveness 1, 2.
• Blood-streaked sputum in the mornings is consistent with vigorous coughing causing minor mucosal trauma, not indicative of serious pathology in this context 2.
• Post-viral cough affects 11-25% of adults and even higher rates in children due to frequent respiratory infections 1.

2. Cough-Variant Asthma (CVA) – High Suspicion

• The family history of asthma in a sibling, combined with triggers including cold air exposure, exercise, laughter, and nocturnal awakening, strongly suggests CVA 3, 4.
• CVA accounts for 14-24% of subacute cough cases following upper respiratory infection 3, 4.
• Asthma may present with cough as the sole symptom ("cough variant asthma") with no wheezing or dyspnea 3, 1.
• The patient's triggers (supine position, cold air, post-cardio exercise) are classic for bronchial hyperresponsiveness 2, 4.

3. Non-Asthmatic Eosinophilic Bronchitis (NAEB)

• NAEB is characterized by cough, eosinophilic infiltration of the bronchial tree, normal spirometry, and lack of bronchial hyperresponsiveness 3.
• NAEB accounts for 13-33% of chronic cough cases in some series and 18.5% of subacute cough following acute upper respiratory infection 3, 4.
• Eosinophilic airway inflammation is common in subacute cough following acute upper respiratory tract infection, occurring in 33.6% of patients 4.
• NAEB responds predictably to inhaled corticosteroid therapy 3, 5.

4. Upper Airway Cough Syndrome (UACS) – Less Likely

• UACS (formerly post-nasal drip syndrome) accounts for 10.1% of subacute cough cases 4.
• The patient denies sore throat and has no reported nasal symptoms beyond the initial URI, making this less likely 3, 2.
• However, UACS can present with cough as the only symptom ("silent PNDS") 3.

5. Gastroesophageal Reflux Disease (GERD) – Consider

• GERD can present with cough as the sole manifestation ("silent GERD") without typical GI symptoms 3, 2.
• The worsening when supine and morning productive cough could suggest nocturnal reflux 2.
• GERD-related cough accounts for only 3.4% of subacute cough following acute upper respiratory infection 4.

Critical Red Flags to Evaluate

Hemoptysis Assessment

• Blood-streaked sputum in the context of vigorous coughing post-URI is typically benign, but requires careful assessment 2.
• Red flags requiring immediate chest X-ray include: frank hemoptysis (more than streaks), fever development, weight loss, night sweats, or persistent hemoptysis beyond 1 week 2.
• In this case, occasional morning blood-streaked sputum for one week in the context of productive cough is consistent with mucosal irritation 1, 2.

Timeline Considerations

• If cough persists beyond 8 weeks, it must be reclassified as chronic cough and systematically evaluated for UACS, asthma, and GERD 1, 2.
• The patient is currently at 2-3 weeks, well within the expected post-viral cough window 1.

Recommended Diagnostic Evaluation

Initial Assessment (Now)

• Chest X-ray is indicated due to hemoptysis, even though blood-streaked sputum is likely benign, to rule out pneumonia, mass, or other pathology 2.
• Spirometry with bronchodilator response to assess for airflow obstruction and reversibility suggestive of asthma 2, 4.
• Consider methacholine challenge testing if spirometry is normal but CVA is suspected based on family history and triggers 4, 5.

Advanced Testing if Initial Workup Normal

• Induced sputum for differential cell count to identify eosinophilic inflammation (NAEB vs. CVA) 3, 4, 5.
  • Sputum eosinophilia >3% indicates eosinophilic airway inflammation 4, 5.
  • CVA typically shows higher eosinophil counts (median 20%) compared to NAEB (median 7.5%) 4.
• Peak expiratory flow variability monitoring if asthma is suspected 5.

If Cough Persists Beyond 8 Weeks

• Systematic evaluation for UACS, asthma, and GERD as these are the most common causes of chronic cough 3, 2.
• High-resolution CT chest if all empiric therapies fail and chest X-ray is normal 2.
• Consider bronchoscopy to evaluate for endobronchial lesions, sarcoidosis, or occult infection if complete workup fails 2.

Initial Management Approach

First-Line Treatment (Weeks 1-3)

• Inhaled ipratropium bromide 2-3 puffs (17-34 mcg per puff) four times daily is the recommended first-line pharmacologic treatment with the strongest evidence for post-viral cough 1, 2.
• Honey and lemon provide symptomatic relief and represent the simplest, most cost-effective approach 1, 2.
• Supportive care with guaifenesin (200-400 mg every 4 hours, up to 6 times daily) to help loosen phlegm 2.

Second-Line Treatment (If Quality of Life Affected)

• Inhaled corticosteroids (fluticasone 220 mcg or budesonide 360 mcg twice daily) if cough persists despite ipratropium and significantly affects quality of life 1, 2.
  • Allow up to 8 weeks for full response 2.
  • This is particularly appropriate given the suspicion for CVA or NAEB 4, 5.

Third-Line Treatment (Severe Cases Only)

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

Empiric Asthma Trial (If CVA Suspected)

• Given the family history and classic triggers, consider an empiric trial of inhaled corticosteroids plus beta-agonists 2.
• Response may take up to 8 weeks 2.
• A diagnostic-therapeutic trial of prednisone 30 mg daily for 2 weeks can establish the diagnosis of CVA 2.

Critical Management Pitfalls to Avoid

What NOT to Do

• Antibiotics are explicitly contraindicated for post-viral cough unless there is clear evidence of bacterial sinusitis or early pertussis infection 1, 2.
• Do not prescribe antibiotics – they provide no benefit, contribute to resistance, and cause adverse effects 2.
• Do not jump to prednisone for mild post-infectious cough; reserve it for severe cases that have failed other therapies 1, 2.

Pertussis Consideration

• Exclude pertussis infection when cough lasts ≥2 weeks with paroxysms, post-tussive vomiting, or inspiratory whooping sound 2.
• Early macrolide therapy is indicated when pertussis is confirmed 2.

Follow-Up Timeline

• Reassess at 3-5 days if symptoms worsen or new red flags develop 2.
• Clinical review at approximately 6 weeks to ensure resolution 2.
• If cough persists beyond 8 weeks, reclassify as chronic cough and initiate systematic evaluation 1, 2.

Summary of Most Likely Diagnoses (Ranked)

1. Post-viral cough (37.8% of subacute cough cases) – expected self-limited course 4
2. Cough-variant asthma (14.3% of cases) – family history and triggers make this highly likely 4
3. Non-asthmatic eosinophilic bronchitis (18.5% of cases) – common in post-viral setting 4
4. Upper airway cough syndrome (10.1% of cases) – less likely given lack of upper airway symptoms 4
5. GERD-related cough (3.4% of cases) – possible given supine worsening 4

The blood-streaked sputum is most likely due to vigorous coughing causing minor mucosal trauma in the setting of airway inflammation, but warrants chest X-ray to exclude other pathology 2.