What is the treatment approach for a persistent cough lasting over 1 month with a normal chest x-ray?

Treatment of Chronic Cough (>1 Month) with Normal Chest X-ray

For a cough persisting over 1 month with a normal chest radiograph, initiate sequential empiric treatment targeting the three most common causes in descending order: upper airway cough syndrome (UACS) first, followed by asthma, then gastroesophageal reflux disease (GERD). 1, 2

Initial Medication Review and Smoking Assessment

Before proceeding with diagnostic workup, address two critical reversible causes:

• Discontinue ACE inhibitors immediately if the patient is taking one, regardless of temporal relationship to cough onset. The original cause may have resolved while ACE inhibitor-induced cough persists. Resolution typically occurs within days to 2 weeks, though median time is 26 days. 1

• If the patient is a current smoker, smoking cessation is the priority intervention. Most patients achieve cough resolution within 4 weeks of cessation, though some may take longer. 1

Sequential Empiric Treatment Algorithm

The evidence strongly supports treating empirically rather than extensive upfront testing, as this approach is more cost-effective when UACS prevalence is approximately 44%. 1, 2

First-Line: Treat for UACS (Most Common - 56% of cases)

• Initiate antihistamine-decongestant combination therapy for several weeks. 2, 3
• Look for clinical indicators: postnasal drip sensation, throat clearing, nasal discharge, or rhinosinusitis symptoms. 2
• UACS accounts for the majority of chronic cough cases in immunocompetent nonsmokers. 1

Second-Line: Treat for Asthma (14-30% of cases)

If cough persists after adequate UACS treatment trial:

• Initiate inhaled corticosteroids with or without bronchodilators, even without spirometric evidence of obstruction. Many patients with cough-variant asthma lack sufficient reversibility to meet traditional asthma criteria. 1, 3
• Consider a therapeutic trial of oral prednisolone if asthma or eosinophilic bronchitis is suspected. 1
• Clinical clues include nocturnal cough, post-exercise cough, or cough after allergen exposure. 1
• Note that spirometry does not exclude asthma as a cause—patients with cough-variant asthma may not exhibit airflow obstruction. 1

Third-Line: Treat for GERD (5-6% as sole cause)

If cough persists after adequate trials of UACS and asthma treatment:

• Initiate intensive acid suppression therapy for at least 3 months, as GERD requires prolonged treatment duration. 2
• GERD is frequently overlooked as an extrapulmonary cause in general respiratory clinics. 1

Additional Diagnostic Considerations

Nonasthmatic Eosinophilic Bronchitis (NAEB)

• Consider NAEB early in the evaluation, as it is frequent enough to warrant consideration alongside the "big three" causes. 1
• NAEB presents with eosinophilic inflammation but without bronchial hyperresponsiveness or airflow obstruction. 1

When to Obtain Spirometry

• Perform spirometry with bronchodilator response to identify chronic airways obstruction. 1
• Measure FEV1 before and after short-acting β2 agonist (salbutamol 400 mcg by MDI with spacer or 2.5 mg by nebulizer). 1
• Avoid using single PEF measurements for diagnosis, as they are less accurate than FEV1. 1

Advanced Imaging Indications

When to Order High-Resolution CT (HRCT)

Proceed to HRCT only after:

• Sequential empiric treatment for all three common causes has failed. 1, 2
• Adequate treatment duration has been allowed (several weeks for UACS/asthma, ≥3 months for GERD). 2

HRCT is the reference standard for detecting bronchiectasis, which accounts for up to 8% of chronic cough cases and may be missed on chest radiography. 1

HRCT Diagnostic Yield

• HRCT identifies abnormalities in up to 42% of patients with presumed normal chest radiographs. 1
• Studies show HRCT was diagnostic in 24% of patients with chronic cough who had normal radiographs and failed initial protocols. 1

Bronchoscopy Considerations

• Reserve bronchoscopy for suspected foreign body aspiration or when other targeted investigations are normal. 1
• Diagnostic yield is low (1-6%) in unselected chronic cough patients, though it may be higher in carefully selected cases. 1
• In 15,420 patients undergoing bronchoscopy without foreign body history, only 0.3% had foreign bodies identified. 1

Red Flags Requiring Immediate Investigation

Pursue direct investigation if any of the following are present:

• Hemoptysis 4, 5
• Significant dyspnea 4, 5
• Fever or systemic symptoms 1
• Weight loss 1, 4
• History of cancer, tuberculosis, or AIDS 1
• Chest radiograph findings suggestive of mass or malignancy 1

Treatment Success Rates

When following this systematic anatomic protocol, success rates of 91% have been achieved in resolving chronic cough. 3 The key is adequate treatment duration for each condition before moving to the next step in the algorithm.

Common Pitfalls to Avoid

• Do not order extensive testing upfront—sequential empiric treatment is more cost-effective than comprehensive initial investigation. 1, 2
• Do not use guaifenesin for chronic cough—it is FDA-approved only for productive cough and should be stopped if cough lasts more than 7 days. 6
• Do not rely on chest radiography alone to exclude bronchiectasis—up to 34% of CT-proven bronchiectasis cases have normal chest radiographs. 5
• Do not assume normal spirometry excludes asthma—cough-variant asthma frequently presents without demonstrable airflow obstruction. 1