What is the initial workup and treatment for a patient with a persistent cough?

Workup for Persistent Cough

For a patient with persistent cough lasting >8 weeks, begin empiric treatment with a first-generation antihistamine-decongestant combination targeting upper airway cough syndrome (UACS), then sequentially add therapy for asthma and GERD if cough persists, as these three conditions account for approximately 90% of chronic cough cases. 1, 2

Initial Critical Steps

Before beginning the systematic workup, immediately address reversible causes:

• Stop ACE inhibitors if the patient is taking one, as this medication causes cough that resolves within days to 2 weeks (median 26 days) 3, 4
• Counsel smokers on cessation, as chronic bronchitis resolves within 4 weeks in most patients who quit, with 90-94% experiencing resolution within the first year 2, 4
• Obtain a chest radiograph to exclude pneumonia, structural abnormalities, masses, interstitial disease, or congestive heart failure 2, 3

Sequential Empiric Treatment Algorithm

The ACCP guidelines recommend treating the three most common causes in sequential and additive steps, as multiple causes frequently coexist 1:

Step 1: Treat UACS (First 1-2 Weeks)

• Start with an oral first-generation antihistamine-decongestant combination (such as brompheniramine with sustained-release pseudoephedrine) 1, 4
• Clinical pointers suggesting UACS include nasal discharge, throat clearing, postnasal drip sensation, nasal congestion, or rhinorrhea 3, 4
• If prominent upper airway symptoms persist, add a topical nasal corticosteroid 4
• If no response after 1-2 weeks of adequate therapy, proceed to Step 2 while continuing UACS treatment 3

Step 2: Evaluate and Treat Asthma (Response Within 1 Week to 8 Weeks)

• Perform spirometry with bronchodilator response to assess for reversible airflow obstruction 1
• If spirometry is normal but asthma is still suspected, perform bronchoprovocation challenge (BPC) to confirm bronchial hyperresponsiveness 1
• Suspect asthma when cough worsens at night, with cold air exposure, or with exercise 3, 4
• If BPC is unavailable, initiate empiric trial of inhaled bronchodilators and inhaled corticosteroids (ICS) 1, 4
• Response to bronchodilators typically occurs within 1 week, but complete resolution may take up to 8 weeks 3
• If cough persists despite ICS therapy, proceed to Step 3 while continuing asthma treatment 1

Step 3: Treat GERD (Response Takes 2 Weeks to Several Months)

• Initiate high-dose proton pump inhibitor (PPI) therapy along with dietary modifications and lifestyle changes 2, 3
• GERD should be suspected in patients with heartburn, regurgitation, or sour taste 2
• Be patient with GERD therapy, as response may take 2 weeks to several months, with some patients requiring 8-12 weeks before improvement 3
• Treatment for GERD should be instituted even if cough only partially responds to UACS and asthma interventions 1

When to Pursue Advanced Testing

Only proceed to advanced diagnostic testing after completing adequate therapeutic trials (4-6 weeks) of all three common causes 4:

• High-resolution CT (HRCT) chest to evaluate for bronchiectasis, interstitial lung disease, or occult masses 2, 3
• 24-hour esophageal pH monitoring if GERD is suspected but empiric PPI therapy failed 2, 3
• Bronchoscopy to evaluate for endobronchial lesions, sarcoidosis, eosinophilic bronchitis, or occult infection 2, 3
• Induced sputum test for eosinophils to evaluate for non-asthmatic eosinophilic bronchitis (NAEB) if asthma has been ruled out 1

Special Consideration: Post-Infectious Cough

If cough began with an acute respiratory infection 3-8 weeks ago, consider post-infectious cough 1, 3:

• First-line: Trial of inhaled ipratropium 1, 3
• If ipratropium fails: Add inhaled corticosteroids 1, 3
• For severe paroxysms: Short course of oral prednisone (30-40 mg daily) after ruling out other common causes 1, 3

Management of Refractory Chronic Cough

Only diagnose unexplained cough after completing systematic evaluation and adequate therapeutic trials of all common causes 2, 3:

• Consider gabapentin trial starting at 300 mg once daily, escalating as tolerated to maximum 1,800 mg daily in divided doses 2, 3
• Discuss potential side effects and reassess risk-benefit at 6 months before continuing 2
• Multimodality speech pathology therapy is a reasonable alternative approach 2, 3

Critical Pitfalls to Avoid

• Do not use newer generation nonsedating antihistamines, as they are ineffective for cough reduction 1
• Do not stop therapy prematurely—inadequate treatment duration is a common error, as each cause has different expected response times 2
• Do not treat only one cause—multiple factors often contribute simultaneously, requiring additive therapy 1, 4
• Do not prescribe PPIs if objective testing for acid reflux is negative 2
• Do not assume purulent sputum indicates bacterial infection requiring antibiotics 2
• Do not label as idiopathic until thorough assessment excludes uncommon causes 4