What is the differential diagnosis and initial management approach for a patient presenting with a dry cough and normal respiratory findings?

Differential Diagnosis for Dry Cough with Normal Respiratory Findings

Most Likely Diagnoses

For a patient with dry cough and normal respiratory examination, the three most common causes are upper airway cough syndrome (UACS), asthma, and gastroesophageal reflux disease (GERD), in descending order of prevalence. 1 Non-asthmatic eosinophilic bronchitis (NAEB) should also be considered early in the evaluation. 1

Primary Differential Diagnosis:

• Upper Airway Cough Syndrome (UACS) - Most common cause, accounting for approximately 44% of chronic cough cases with normal chest radiographs 1
• Asthma - Second most common, may present without wheezing or abnormal lung sounds 1, 2
• Gastroesophageal Reflux Disease (GERD) - Third most common cause 1, 3
• Non-Asthmatic Eosinophilic Bronchitis (NAEB) - Frequent enough to warrant early consideration 1, 2

Critical Medication-Related Causes:

• ACE Inhibitor-Induced Cough - Must be excluded immediately; discontinue ACE inhibitor regardless of temporal relationship, as cough typically resolves within days to 2 weeks (median 26 days) 1, 2
• Beta-Blocker Exacerbation - May worsen underlying asthma 4

Other Important Considerations:

• Smoking-Related Chronic Bronchitis - 90-94% of smokers experience cough resolution within the first year of cessation 2
• Tuberculosis - Consider in patients from endemic areas or with systemic symptoms (fever, night sweats, weight loss) 1, 2
• Endobronchial Tumor - Rare with normal chest radiograph but must not be delayed if other causes are excluded 1

Initial Management Approach

Step 1: Immediate Actions

• Discontinue ACE inhibitors immediately if the patient is taking one, regardless of when the cough started 1, 2
• Counsel and assist with smoking cessation if applicable; most patients experience resolution within 4 weeks 1, 2
• Obtain chest radiograph to confirm normal findings and rule out structural abnormalities 2, 3
• Perform spirometry as part of basic evaluation, though utility is not clearly established 2

Step 2: Sequential Empiric Treatment

The algorithmic approach should start with treating the most common cause first, then add treatments sequentially if cough persists, as multiple causes frequently coexist. 1, 2

First-Line: Treat for UACS

• Use oral first-generation antihistamine/decongestant combination (not newer non-sedating antihistamines, which are ineffective) 2, 5
• Add topical nasal corticosteroid if prominent upper airway symptoms are present 2
• Trial duration: 4-6 weeks 2

Second-Line: Add Asthma Treatment

• Initiate inhaled bronchodilators and inhaled corticosteroids if spirometry shows reversible airflow obstruction 2, 5
• Consider bronchoprovocation challenge or empiric trial if spirometry is normal but asthma is suspected 2
• For refractory cases, add leukotriene receptor antagonist before escalating to systemic corticosteroids 5

Third-Line: Add GERD Treatment

• Initiate empiric treatment for patients with typical reflux symptoms before performing esophageal testing 2
• Continue for 4-6 weeks as part of additive therapy 2

Consider NAEB Early:

• Perform induced sputum test for eosinophils if available 2
• Use empiric inhaled corticosteroids if testing is unavailable 2

Step 3: Advanced Evaluation (If Cough Persists After 4-6 Weeks)

• Pursue high-resolution CT scan or bronchoscopic evaluation for uncommon causes 2, 6
• Consider referral to specialist cough clinic when diagnosis remains unclear 2

Critical Pitfalls to Avoid

• Do not rely on cough characteristics (timing, quality, sound) for diagnosis, as they have little diagnostic value 1, 2
• Do not treat only one cause - multiple factors often contribute simultaneously, requiring additive therapy rather than sequential replacement 1, 2
• Do not label as idiopathic until thorough assessment at a specialist clinic excludes uncommon causes 2
• Do not forget that cough is frequently multifactorial - it is not uncommon to find two or all three common diagnoses present, and cough will not resolve until all are effectively treated 1
• Do not use routine cough suppressants when cough clearance is important 2

Special Population Considerations

• Immunocompromised patients: Use the same initial algorithm but expand differential diagnosis based on immune defect type and severity 2, 5
• HIV patients with CD4+ <200 cells/μL: Suspect Pneumocystis pneumonia, tuberculosis, and opportunistic infections 2
• Endemic areas: Obtain sputum smears, cultures for acid-fast bacilli to evaluate for tuberculosis 2