What is the appropriate workup for a 40-year-old non-smoker with a cough but no fever and no significant medical history?

Workup for Cough Without Fever in a 40-Year-Old Non-Smoker

Begin with a detailed history focusing on cough duration, medication review (especially ACE inhibitors), and symptoms of upper airway disease, asthma, or reflux, followed immediately by chest radiograph and spirometry as mandatory baseline investigations. 1, 2

Initial Clinical Assessment

Duration Classification

• Classify the cough as acute (<3 weeks), subacute (3–8 weeks), or chronic (>8 weeks), as this single determination immediately narrows your differential diagnosis and dictates the entire management pathway. 1

Red-Flag Screening

Even in a 40-year-old without fever, actively inquire about:

• Hemoptysis – any blood in sputum mandates urgent evaluation for malignancy, tuberculosis, or pulmonary embolism. 1
• Unintentional weight loss – suggests malignancy or chronic infection. 1
• Significant dyspnea at rest or nocturnal dyspnea – may indicate serious cardiopulmonary pathology. 1
• Recurrent pneumonia – points toward structural lung disease or immunodeficiency. 1

Medication and Exposure Review

• Review all medications and discontinue any ACE inhibitor immediately, as drug-induced cough typically resolves within a median of 26 days (up to 40 weeks) after cessation. 1
• Verify smoking status (including vaping and secondhand exposure at home or work), as tobacco exposure is a dominant cause of chronic cough. 1
• Systematically assess occupational and environmental irritant exposures (dust, chemicals, fumes, cold air). 1

Mandatory Baseline Investigations

All adults with cough lasting >8 weeks require:

• Chest radiograph – to exclude mass lesions, infiltrates, bronchiectasis, interstitial lung disease, and cardiac abnormalities. 1, 2
• Spirometry with bronchodilator testing – to detect airflow obstruction and assess reversibility. 1, 2
• Cough severity quantification using visual analog scales or validated quality-of-life questionnaires. 1

Targeted History for Common Etiologies

Upper Airway Cough Syndrome (UACS)

• Probe for frequent throat clearing, post-nasal drip sensation, nasal congestion, or chronic rhinitis, as UACS accounts for approximately 19%–82% of chronic cough cases and may present as "silent post-nasal drip" without overt nasal complaints. 1

Asthma (Including Cough-Variant)

• Ask about wheezing, chest tightness, and dyspnea that worsen with exercise, cold air, or allergens, recognizing that asthma is responsible for about 15%–41% of chronic cough and cough may be the sole manifestation. 1
• Document atopic background (personal or family history of asthma, allergic rhinitis, food or drug allergies). 1

Gastroesophageal Reflux Disease (GERD)

• Query about heartburn, regurgitation, sour taste, throat burning, and hoarseness, but recognize that GERD-related cough frequently occurs without classic gastrointestinal symptoms ("silent GERD"). 1
• Ask about post-meal or recumbent cough, as worsening after meals or when lying down supports a reflux-related etiology. 1

Physical Examination Focus

Upper Airway Examination

• Inspect nasal mucosa: pale, boggy turbinates suggest allergic rhinitis; erythematous turbinates suggest infectious rhinitis; nasal polyps may support chronic rhinosinusitis. 1
• Examine oropharynx: cobblestoning of the posterior pharynx is classic for post-nasal drip/UACS. 1

Chest Auscultation

• Auscultate during forced expiration and immediately after coughing; wheezes that appear only with these maneuvers are characteristic of cough-variant asthma. 1
• Listen for crackles, which may indicate interstitial lung disease, bronchiectasis, or heart failure. 1

General Inspection

• Assess for peripheral edema and weight gain, which are clinical clues suggestive of heart failure. 1
• Examine for finger clubbing, which together with cough should prompt evaluation for bronchiectasis, interstitial lung disease, or malignancy. 1

Algorithmic Approach Based on Duration

Acute Cough (<3 weeks)

• Most acute coughs are viral upper respiratory tract infections and resolve spontaneously without specific treatment. 3
• Obtain chest radiograph only if hemoptysis, prominent systemic illness, suspicion of inhaled foreign body, or suspicion of lung cancer is present. 3
• Supportive care with over-the-counter preparations (e.g., honey and lemon, guaifenesin) is appropriate. 3, 4

Subacute Cough (3–8 weeks)

• The most frequent cause is postinfectious cough (≈48% of cases), which typically resolves without specific therapy. 1
• Inhaled ipratropium bromide (2–3 puffs four times daily) has the strongest evidence for attenuating postinfectious cough, with clinical improvement typically seen within 1–2 weeks. 4
• If cough persists beyond 8 weeks, reclassify as chronic cough and systematically evaluate for UACS, asthma, and GERD. 1, 4

Chronic Cough (>8 weeks)

In non-smokers with normal or near-normal chest radiographs, four conditions (UACS, asthma, GERD, and non-asthmatic eosinophilic bronchitis) account for >90% of chronic cough cases. 1

Step 1: Empiric Treatment for UACS

• Begin with a first-generation antihistamine-decongestant combination (e.g., brompheniramine/pseudoephedrine or chlorpheniramine/phenylephrine) plus an intranasal corticosteroid spray (e.g., fluticasone or mometasone). 1
• Expected response time: days to 1–2 weeks. 1

Step 2: Evaluate for Asthma

• If UACS treatment fails, perform 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. 2
• If methacholine testing is unavailable, a 2-week trial of oral prednisone (30–40 mg daily) can confirm eosinophilic airway inflammation if cough improves. 1
• Initiate inhaled corticosteroids (e.g., fluticasone 220 µg or budesonide 360 µg twice daily) if asthma is confirmed; complete resolution may require up to 8 weeks. 1

Step 3: Treat for GERD

• Initiate intensive acid suppression with omeprazole 20–40 mg twice daily before meals for ≥8 weeks, combined with dietary and lifestyle modifications. 1
• Clinical response may require 2 weeks to several months. 1
• Failure to consider GERD is a frequent cause of therapeutic failure, and reflux-associated cough may occur without typical gastrointestinal symptoms. 1, 2

Critical Management Principles

Multifactorial Etiology

• Up to 67% of chronic cough patients have multiple concurrent causes (e.g., UACS, asthma, GERD); cough resolves only after all contributing factors are addressed. 1
• When partial improvement occurs with one treatment, continue that therapy and add the next intervention rather than stopping and switching. 4

Adequate Trial Duration

• Maintain empiric therapeutic trials for 4–6 weeks before deeming them ineffective, and schedule formal re-evaluation at this interval using validated cough-severity instruments. 1

Common Pitfalls to Avoid

• Relying solely on spirometry to diagnose asthma, as cough-variant asthma may present with normal spirometry. 1, 2
• Inadequate trial periods for GERD therapy, as treatment requires at least 3 months of intensive acid suppression for proper evaluation. 1, 2
• Assuming a single etiology when up to 67% of patients have multiple concurrent causes. 1

Advanced Evaluation When Empiric Therapy Fails

If all empiric therapies are ineffective after 8 weeks:

• Obtain high-resolution CT of the chest to evaluate for bronchiectasis, interstitial lung disease, or occult masses. 3, 1
• Consider bronchoscopy to assess for endobronchial lesions, sarcoidosis, eosinophilic bronchitis, or occult infection. 3, 1
• Refer to a specialist cough clinic, as chronic cough should only be labeled as idiopathic after thorough assessment by a specialist. 1, 2