What is the approach to assessing chronic cough, including differential diagnosis, history, physical examination, and investigations?

Approach to Assessment of Chronic Cough

Chronic cough is defined as cough lasting ≥8 weeks in adults, and the assessment should follow a systematic algorithmic approach starting with mandatory baseline investigations (chest X-ray and spirometry), followed by targeted evaluation for the three most common causes: upper airway cough syndrome (UACS), asthma, and gastroesophageal reflux disease (GERD). 1

Definition and Initial Screening

• Duration: Cough lasting >8 weeks in adults (>4 weeks in children) 1, 2, 3
• Exception: In high TB prevalence areas, define chronic cough as ≥2-3 weeks duration 1

Differential Diagnosis (Most Common to Rare)

Most Common Causes (Account for ~90% of cases)

• Upper Airway Cough Syndrome (UACS) - most common, due to rhinosinus conditions 1
• Asthma (including cough-variant asthma) 1
• Gastroesophageal Reflux Disease (GERD) 1
• Nonasthmatic Eosinophilic Bronchitis (NAEB) 1

Smoking-Related

• Chronic bronchitis/COPD - defined as cough and sputum on most days for ≥3 months over ≥2 consecutive years 1
• Smoking-related chronic cough - resolves within 4 weeks of cessation in most cases 1

Medication-Induced

• ACE inhibitor-induced cough - must be excluded early 4, 3

Infectious Causes (Geographic/Population-Specific)

• Tuberculosis - especially in endemic areas, prisons, nursing homes, immunocompromised 1
• Endemic mycoses - geographic predilection 1
• Post-infectious cough 5

Less Common but Important

• Bronchiectasis 1
• Lung cancer - especially with abnormal chest X-ray 1
• Interstitial lung disease 1
• Congestive heart failure 1

Refractory/Unexplained

• Cough hypersensitivity syndrome - when cough persists after guideline-based assessment and treatment 1, 2

History: Specific Elements to Assess

Cough Characteristics

• Duration and progression of symptoms 5
• Quality: dry vs. productive (sputum color, consistency, amount) 1, 5
• Timing: diurnal variation (worse at night, morning, after meals) 5
• Paroxysmal nature - suggests pertussis or asthma 5

Associated Symptoms

• UACS indicators: postnasal drip sensation, throat clearing, nasal discharge 1
• Asthma indicators: wheezing, chest tightness, dyspnea, nocturnal symptoms 5
• GERD indicators: heartburn, regurgitation, dysphagia (note: cough may occur WITHOUT typical GI symptoms) 1, 4
• Constitutional symptoms: fever, night sweats, weight loss (suggests TB, malignancy) 1, 5

Red Flag Symptoms Requiring Urgent Investigation

• Hemoptysis 5, 2
• Persistent hoarseness 5
• Recurrent pneumonia 5, 2
• Unexplained weight loss 1, 5
• Digital clubbing 5
• Dysphagia 5

Exposure and Risk Factor History

• Smoking status (current, former, pack-years) - critical first question 1
• Occupational exposures to respiratory irritants 1, 4
• Medication history: ACE inhibitors must be identified 4, 3
• Geographic/travel history: TB endemic areas, fungal endemic regions 1
• Environmental triggers: cold air, exercise, pollutants, allergens 5
• Past medical history: TB, cancer, AIDS, immunodeficiency 1

Impact Assessment

• Severity and quality of life impact using validated tools (cough visual analogue scores, cough-specific QOL questionnaires) 4

Physical Examination: Key Findings

• Nasal examination: discharge, mucosal edema, polyps (suggests UACS) 1
• Oropharyngeal examination: cobblestoning, postnasal drainage 1
• Lung auscultation: wheezing (asthma), crackles (interstitial disease, CHF), prolonged expiration (COPD) 1
• Digital clubbing: suggests chronic lung disease 5
• Signs of heart failure: elevated JVP, peripheral edema 1

Investigations: Algorithmic Approach

Mandatory Initial Investigations (All Patients)

• Chest radiograph - required to rule out malignancy, infection, structural abnormalities 4, 2, 3
• Spirometry with bronchodilator response - essential to identify airflow obstruction and reversibility 4, 2, 6

Additional First-Line Tests (Based on Availability)

• Exhaled nitric oxide (FeNO) - helps identify eosinophilic inflammation 6
• Blood eosinophil count - supports diagnosis of eosinophilic conditions 6

If Chest X-Ray is Abnormal: Pursue Specific Finding

• Mass/nodule: CT chest → bronchoscopy or transthoracic biopsy or PET scan 1
• Interstitial pattern: High-resolution CT → bronchoscopy with transbronchoscopic biopsy or VATS biopsy 1
• Infiltrate: Consider infection (TB sputum cultures, bronchoscopy if needed) 1
• Cardiomegaly/pulmonary edema: Cardiovascular evaluation, trial of diuresis 1
• Mediastinal mass: Biopsy for diagnosis 1

Second-Line Investigations (If Initial Tests Normal)

For Suspected Asthma/Eosinophilic Bronchitis

• Bronchial provocation testing (methacholine challenge) - if spirometry normal 4, 6
• Trial of oral corticosteroids (2 weeks) - lack of response effectively rules out eosinophilic inflammation 4
• Induced sputum for eosinophils - if available 1

For Suspected GERD

• Empiric treatment trial preferred over testing as initial approach 4, 3
• 24-hour esophageal pH monitoring - only if empiric treatment fails 4
• Note: Requires ≥3 months of intensive acid suppression for adequate therapeutic trial 4

For Suspected TB (High-Risk Populations)

• Sputum smears and cultures for acid-fast bacilli 1
• Chest radiograph (if not already done) 1

For Suspected UACS

• Empiric trial of first-generation antihistamine-decongestant - diagnostic and therapeutic 1, 3
• Sinus imaging - only if empiric treatment fails 1

Advanced/Specialist Investigations (Refractory Cases)

• High-resolution CT chest - if initial evaluation unrevealing 1, 2
• Bronchoscopy - reserved for patients without diagnosis after stepwise evaluation 1
• Low-dose CT chest - validated for lung cancer screening in appropriate populations 1

Critical Pitfalls to Avoid

• Overlooking GERD as a cause - reflux-associated cough frequently occurs WITHOUT typical heartburn or regurgitation 1, 4
• Inadequate treatment trial duration - GERD requires ≥3 months of intensive therapy; UACS requires several weeks 1, 4
• Relying solely on spirometry for asthma diagnosis - cough-variant asthma often presents with normal spirometry; bronchial provocation testing is essential 4, 6
• Missing ACE inhibitor as culprit - all patients on ACE inhibitors must discontinue and observe for resolution 4, 3
• Failing to recognize multifactorial etiology - 25% of patients have multiple simultaneous causes; cough won't resolve until ALL causes are treated 1
• Premature labeling as "idiopathic" - should only occur after thorough specialist assessment following published guidelines 1, 4
• Inadequate TB screening in high-risk populations - prisons, nursing homes, endemic areas, immunocompromised patients require specific screening protocols 1
• Ignoring smoking cessation - must be addressed early as it can resolve cough within 4 weeks in many cases 1, 4

Sequential Empiric Treatment Approach (When Initial Tests Normal)

The algorithmic approach prioritizes treating the most common causes sequentially, starting with UACS, then asthma, then GERD, as this is more cost-effective than extensive upfront testing. 1

1. First: Trial of antihistamine-decongestant for UACS (several weeks) 1
2. Second: If partial/no response, add asthma treatment (inhaled corticosteroids ± bronchodilators) 1
3. Third: If still unresolved, add GERD treatment (intensive acid suppression for ≥3 months) 1, 4
4. Reassess: If no response after treating all three common causes, refer to specialist for advanced evaluation 1, 4