What are the differential diagnoses and initial management for an isolated dry (non‑productive) cough in an otherwise healthy adult?

Differential Diagnosis of Isolated Dry Cough in Adults

Immediate Medication Review

Discontinue any ACE inhibitor immediately, as this is the single most common reversible cause of isolated dry cough, affecting 5–35% of patients taking these medications. 1 Cough typically resolves within 1–4 weeks after cessation (though may persist up to 3 months), and substituting an angiotensin-receptor blocker is safe and does not provoke recurrence. 1

Primary Differential Diagnoses

The following four conditions account for >90% of chronic dry cough in non-smokers with normal chest radiographs: 2

1. Upper Airway Cough Syndrome (UACS)

• Prevalence: 18.6–81.8% of chronic cough cases 2
• Clinical clues: Post-nasal drip sensation, frequent throat clearing, nasal discharge, or cough triggered by phonation (talking, laughing, singing) 1
• Key point: UACS can occur without prominent nasal symptoms 3
• Diagnostic limitation: ENT examination and sinus CT have low positive predictive values (63% and 67% respectively), meaning upper airway disease frequently coexists but does not always cause the cough 4

2. Cough-Variant Asthma (CVA)

• Prevalence: 14.6–41.3% of chronic cough cases 2
• Critical feature: Cough may be the sole manifestation of asthma, occurring without wheeze or dyspnea 3, 1
• Diagnostic pitfall: Normal spirometry does not exclude asthma-related cough 3, 2
• Pathophysiology: Eosinophilic airway inflammation with bronchial hyperresponsiveness 3
• Natural history: 30–40% of untreated CVA patients progress to classic asthma 5

3. Non-Asthmatic Eosinophilic Bronchitis (NAEB)

• Prevalence: 6.4–17.2% of chronic cough cases 2
• Distinguishing feature: Eosinophilic airway inflammation without airway hyperresponsiveness or variable airflow obstruction 3, 2
• Histology: Median 12.0 eosinophils/mm² on bronchial biopsy (vs. 0.0 in healthy controls) 6

4. Gastro-Oesophageal Reflux Disease (GERD)

• Prevalence: 4.6–85.4% of chronic cough cases 2
• Critical pitfall: Reflux-related cough frequently occurs without gastrointestinal symptoms (heartburn, regurgitation) 3, 1
• Clinical clues: Cough triggered by eating, post-prandial timing, or phonation 1

Additional Causes to Consider

5. Lymphocytic Bronchitis

• Histology: Median 84.5 lymphocytes/mm² on bronchial biopsy (vs. 22.0 in healthy controls) 6
• Demographics: Predominantly middle-aged women, often starting around menopause 3
• Associated features: Organ-specific autoimmune disease in up to 30% (particularly hypothyroidism) 3

6. Atopic Cough

• Geographic variation: More prevalent in Asian populations 2
• Treatment: Responds to inhaled corticosteroids 3

7. Smoking-Related Cough

• Dose-related: One of the most common causes of persistent cough 3
• Resolution: Typically improves within 4 weeks after cessation 3, 2

Mandatory Baseline Investigations

All adults with chronic dry cough (>8 weeks) require: 3, 2

• Chest radiograph to exclude mass lesions, infiltrates, bronchiectasis, interstitial lung disease, and cardiac abnormalities
• Spirometry with bronchodilator testing to detect airflow obstruction and assess reversibility
• Cough severity quantification using visual-analog scales or validated quality-of-life questionnaires

Specialized Testing Algorithm

When Spirometry is Normal:

Perform methacholine bronchial provocation testing to detect airway hyperresponsiveness. 3, 2

• Positive test: Confirms CVA in 88% of cases 4
• Negative test: Excludes asthma but does not rule out steroid-responsive cough 3

When Empiric Therapies Fail:

• High-resolution CT chest to evaluate for bronchiectasis, interstitial lung disease, or occult masses 2
• Bronchoscopy to assess for endobronchial lesions, sarcoidosis, eosinophilic bronchitis, or occult infection 2
• 24-hour esophageal pH monitoring when GERD is suspected but empiric therapy has failed 1

Red-Flag Symptoms Requiring Urgent Investigation

The following mandate immediate work-up for malignancy, tuberculosis, or serious infection: 3, 2

• Hemoptysis
• Unintentional weight loss
• Fever or night sweats
• Significant resting or nocturnal dyspnea
• Hoarseness
• New-onset cough in individuals >45 years who smoke
• Recurrent pneumonia

Critical Management Principle

Up to 67% of chronic cough patients have multiple simultaneous etiologies, requiring combination therapy rather than sequential monotherapy. 2 Continue partially effective therapies while adding the next empiric intervention. 1

Idiopathic Cough

Diagnosis of exclusion: Should be made only after comprehensive evaluation in a specialized cough clinic. 3, 2 Represents up to 20% of referrals to cough clinics after extensive investigation. 3