What lab tests should be ordered for the evaluation of chronic cough?

Laboratory Tests for Chronic Cough Evaluation

Essential Initial Laboratory Tests

For adults with chronic cough, the initial laboratory evaluation should be limited to spirometry with bronchodilator response and a chest radiograph—routine blood work is not indicated unless specific clinical features suggest an underlying systemic disease. 1, 2

Mandatory First-Line Tests

• Chest radiograph (posteroanterior view) is required for all patients to exclude malignancy, infection, bronchiectasis, interstitial lung disease, and structural abnormalities 3, 1, 4

  • Abnormal radiography has a positive likelihood ratio of infinity for detecting primary pulmonary pathology and is associated with an odds ratio of 7.7 for underlying disease other than asthma 3
  • However, normal chest radiography does not rule out significant pathology—in one series, 8 of 266 patients with normal radiographs had serious diagnoses including malignancy and bronchiectasis 3

• Spirometry with pre- and post-bronchodilator testing is essential to identify airflow obstruction and assess reversibility suggestive of asthma 1, 4, 2

  • Abnormal spirometry with bronchodilator reversibility provides objective evidence consistent with asthma 3
  • Normal spirometry does not exclude asthma, as cough-variant asthma frequently presents with normal baseline spirometry 1

Additional First-Line Measurements (When Available)

• Fractional exhaled nitric oxide (FeNO) helps identify eosinophilic airway inflammation 2
• Blood eosinophil count assists in detecting nonasthmatic eosinophilic bronchitis 2
• Validated cough severity and quality of life questionnaires should be used to objectively measure disease burden 1, 2

Second-Line Laboratory Tests (Based on Clinical Suspicion)

For Suspected Asthma or Eosinophilic Bronchitis

• Bronchial provocation testing (methacholine challenge) should be performed when asthma is suspected but spirometry is normal 1, 5

  • This is particularly important in patients with history of wheeze, exertional dyspnea, or atopy 3

• Two-week trial of oral corticosteroids serves as both diagnostic test and treatment—lack of response effectively rules out eosinophilic airway inflammation 1

For Suspected GERD

• 24-hour esophageal pH monitoring is the most sensitive and specific test for acid reflux 3

  • Results should only be interpreted as normal when conventional acid reflux indices are normal AND no reflux-induced coughs appear during monitoring 3
  • This test is recommended when empiric treatment fails, not as initial evaluation 3, 1
  • A low percentage of coughs associated with reflux does not exclude GERD as the diagnosis 3

• Barium esophagography may be the only available test to reveal non-acid gastroesophageal reflux of pathologic significance 3

For Suspected Pertussis

• Bordetella pertussis testing (culture, PCR, or serology depending on symptom duration and patient age) should be performed when clinically suspected—particularly with paroxysmal cough, post-tussive vomiting, or inspiratory whoop 3

Tests NOT Routinely Recommended

The following tests should not be routinely ordered as they lack evidence of benefit: 3

• Lipid-laden macrophages in BAL fluid or induced sputum
• Routine esophagoscopy (normal findings do not rule out GERD as cause of cough)
• Skin prick testing (unless specific allergic triggers are suspected)
• Mantoux testing (unless tuberculosis is clinically suspected)

Critical Clinical Pitfalls to Avoid

• Do not overlook medication-induced cough: All patients on ACE inhibitors must discontinue these medications before extensive workup, as they are a common reversible cause 1, 4

• Do not assume GERD is ruled out by normal esophagoscopy or history of antireflux surgery—these do not exclude GERD as the cause of chronic cough 3

• Do not rely solely on spirometry to diagnose or exclude asthma—bronchial provocation testing is needed when clinical suspicion is high but spirometry is normal 1

• Do not order extensive testing before empiric treatment trials—for patients fitting the clinical profile of common causes (upper airway cough syndrome, asthma, GERD), empiric treatment should be initiated first 3, 1, 2

• Allow adequate treatment duration before declaring failure: GERD treatment requires at least 3 months of intensive acid suppression for proper evaluation, and some patients may take 2-3 months to respond 3, 1

Pediatric Considerations

For children with chronic cough (>4 weeks duration): 3

• Chest radiograph is mandatory
• Spirometry with bronchodilator response when age-appropriate (typically >6 years)
• Pertussis testing when clinically indicated
• Additional tests (skin prick, Mantoux, bronchoscopy, CT) should be individualized based on specific clinical features, not routinely performed