What is the appropriate diagnostic and management approach for a patient with chronic cough, considering potential underlying respiratory conditions such as asthma or COPD, and possible complicating factors like a history of smoking or exposure to pollutants?

Pulmonary Function Testing in Chronic Cough Evaluation

Spirometry with bronchodilator response testing should be performed early in all patients with chronic cough to identify asthma (including cough-variant asthma) and COPD, as these conditions frequently present with cough as the sole symptom and normal spirometry does not exclude asthma. 1, 2

Initial Diagnostic Approach

Begin with spirometry and chest radiograph immediately to characterize lung function and exclude serious pathology before proceeding with empiric treatment. 1

Key History Elements to Assess

• ACE inhibitor use: Discontinue immediately if present, as this resolves cough in days to 2 weeks (median 26 days) 2
• Smoking status: Current smoking requires cessation as the priority intervention, with most patients achieving resolution within 4 weeks 2
• Environmental exposures: Assess for occupational dusts, indoor fungal contamination (humidifiers, water damage, mold), or air pollutants 3, 4
• Red flag symptoms: Hemoptysis, significant dyspnea, fever, weight loss, or history of cancer/tuberculosis warrant direct investigation rather than empiric treatment 2

Role of Pulmonary Function Testing

Spirometry Interpretation

Spirometry identifies obstructive patterns (FEV₁/FVC < 70%) suggesting COPD or asthma, but normal spirometry does NOT rule out cough-variant asthma. 1, 2

• Bronchodilator reversibility: An increase in FEV₁ ≥12% AND ≥200 mL after bronchodilator administration confirms asthma 5
• Baseline FEV₁ < 60% predicted or < 1.5 L in adults: Contraindication to methacholine challenge testing 4
• Hyperinflation pattern: May indicate COPD, chronic HP with bronchiolitis, or air trapping from asthma 1, 3

Methacholine Challenge Testing

When spirometry is normal but asthma is suspected, methacholine challenge testing can diagnose cough-variant asthma by demonstrating bronchial hyperreactivity. 4, 6

• Positive test: ≥20% reduction in FEV₁ (PC₂₀) after methacholine inhalation 4
• False positives occur: After recent respiratory infections, immunizations, in smokers, patients with allergic rhinitis without asthma, or after air pollutant exposure 4
• Safety requirement: Must be performed in pulmonary function laboratory with emergency equipment immediately available; β-agonist must be administered after testing 4

Historical data demonstrates that pulmonary function testing (spirometry and bronchial challenge) diagnosed previously unrecognized asthma in 45% of patients with isolated chronic cough, while bronchoscopy had minimal diagnostic yield. 6

Sequential Empiric Treatment Algorithm

After obtaining spirometry, treat the three most common causes sequentially and additively, as multiple causes frequently coexist. 7, 1

Treatment Sequence

1. Upper Airway Cough Syndrome (UACS): Start with first-generation antihistamine-decongestant combination as UACS accounts for approximately 44% of cases 1, 2

2. Asthma/Cough-Variant Asthma: Initiate inhaled corticosteroids with or without bronchodilators even without spirometric obstruction, as many patients lack sufficient reversibility to meet traditional criteria 2

3. Gastroesophageal Reflux Disease (GERD): Begin intensive acid suppression therapy for at least 3 months, as GERD is frequently overlooked 2

Treatment must be sequential AND additive—do not stop one therapy when starting another, as 2-3 simultaneous causes are common. 7, 1

Advanced Testing Indications

High-Resolution CT Chest

Proceed to HRCT only after sequential empiric treatment for all three common causes has failed with adequate treatment duration (several weeks for UACS/asthma, ≥3 months for GERD). 2

• Bronchiectasis detection: HRCT identifies bronchiectasis in up to 8% of chronic cough cases; 34% of CT-proven bronchiectasis has normal chest radiographs 2
• Interstitial lung disease: Consider when DLCO is reduced (as in hypersensitivity pneumonitis) or ground-glass opacities are suspected 3
• Diagnostic yield: HRCT finds abnormalities in 42% of patients with presumed normal chest radiographs and is diagnostic in 24% who failed initial protocols 2

Bronchoscopy

Bronchoscopy should be reserved for patients who fail all empiric treatments and have completed HRCT, to evaluate for occult endobronchial disease (tumor, sarcoidosis, eosinophilic/lymphocytic bronchitis). 7

Special Considerations for Smoking and Pollutant Exposure

In patients with smoking history or pollutant exposure presenting with hyperinflation on imaging:

• Confirm COPD diagnosis: Spirometry showing FEV₁/FVC < 70% that is NOT reversible with bronchodilators establishes COPD 5
• Distinguish stable disease from exacerbation: Productive cough or recurrent infections warrant HRCT to evaluate for bronchiectasis 1
• Smoking cessation is mandatory: Most effective intervention for preventing disease progression 2, 8

Critical Pitfalls to Avoid

• Do not rely on PEF measurements alone: Peak flow has poor positive predictive value (36-67%) for bronchodilator response compared to FEV₁ testing 9
• Do not assume single etiology: Failing to treat all contributing causes simultaneously once identified leads to persistent symptoms 1
• Do not order extensive upfront testing: Sequential empiric treatment is more cost-effective than comprehensive initial investigation 2
• Do not skip adequate treatment duration: Insufficient treatment duration (especially for GERD requiring ≥3 months) leads to false treatment failures 2
• Do not perform methacholine challenge in patients with baseline FEV₁ < 60% predicted: This is an absolute contraindication due to severe bronchoconstriction risk 4