Management of Chronic Cough with Normal Investigations
For an adult patient with chronic cough lasting 1 year and completely normal chest X-ray, spirometry, and physical examination, you should proceed with empiric sequential treatment targeting the three most common causes: upper airway cough syndrome (UACS), asthma/eosinophilic bronchitis, and gastroesophageal reflux disease (GERD), in that order. 1, 2
Initial Diagnostic Considerations
Despite normal baseline investigations, the absence of abnormalities on chest X-ray and spirometry does not exclude disease—both tests are specific but not sensitive 1, 2. The three most common causes of chronic cough in adults with normal chest radiographs are UACS (most common), asthma, and GERD, accounting for the vast majority of cases 1, 3.
Critical First Steps Before Empiric Treatment
- Discontinue ACE inhibitors immediately if the patient is taking them, as they are a common and reversible cause of chronic cough 2
- Ensure smoking cessation if applicable, as tobacco exposure is a major contributor 2
- Review occupational and environmental exposures that may trigger cough 2
Algorithmic Approach to Empiric Treatment
Step 1: Trial for Upper Airway Cough Syndrome (UACS)
Begin with a first-generation antihistamine-decongestant combination as UACS is the most common cause 1. The typical response time is at least 1-2 weeks, though some patients may require longer 1. If cough resolves or partially resolves, continue treatment and consider UACS confirmed 1.
Step 2: Evaluate for Asthma/Eosinophilic Bronchitis
If UACS treatment fails, proceed with bronchial provocation testing (methacholine challenge) to assess for bronchial hyperresponsiveness, as cough-variant asthma commonly presents with normal spirometry 1, 2. A negative methacholine challenge essentially excludes asthma from the differential 1.
If methacholine testing is unavailable or positive, initiate a 2-week trial of oral corticosteroids (e.g., prednisone) 2. This approach serves dual purposes:
- Confirms eosinophilic airway inflammation if cough improves 1, 2
- Lack of response effectively rules out both asthma and non-asthmatic eosinophilic bronchitis (NAEB) 2
Important caveat: A positive methacholine test is consistent with but not diagnostic of cough-variant asthma—definitive diagnosis requires documented cough resolution with asthma-specific therapy 1.
Step 3: Address Gastroesophageal Reflux Disease (GERD)
If asthma/eosinophilic bronchitis is excluded, initiate empiric treatment for GERD with:
- High-dose proton pump inhibitor therapy 2
- Dietary modifications (eliminate high-fat foods, coffee, tea, soda, chocolate, mints, citrus, alcohol) 4
- Lifestyle changes (no smoking, elevate head of bed, avoid eating before bedtime) 4
Critical timing consideration: GERD-related cough requires at least 3 months of intensive acid suppression for adequate therapeutic trial 2. This is a common pitfall—inadequate trial duration leads to premature abandonment of effective therapy 2.
Key clinical pearl: GERD-associated cough frequently occurs without typical gastrointestinal symptoms like heartburn, so absence of reflux symptoms does not exclude this diagnosis 2.
Multifactorial Cough Recognition
Chronic cough is frequently multifactorial—patients commonly have two or even all three of the common diagnoses (UACS, asthma, GERD) simultaneously 1. The cough will not resolve until all contributing factors are effectively treated 1. If partial improvement occurs with one treatment, continue that therapy while adding treatment for the next most likely cause 1.
When to Pursue Additional Investigation
Consider further diagnostic workup if:
- Red flags are present: hemoptysis, significant weight loss, fever, night sweats, or systemic symptoms 2, 3
- No response after 4-6 weeks of empiric treatment for all three common causes 3
- Patient is immunocompromised or from tuberculosis-endemic area 1
Additional investigations may include:
- High-resolution CT chest to evaluate for bronchiectasis, interstitial lung disease, or occult malignancy 1, 2
- 24-hour esophageal pH monitoring if GERD treatment fails despite adequate trial 2
- Bronchoscopy if structural abnormalities or endobronchial lesions are suspected 1
Refractory Chronic Cough Management
Only after thorough evaluation at a specialist cough clinic should cough be labeled as idiopathic 2. For truly refractory cases unresponsive to specific treatments, consider: