What is the next step in diagnosing and treating an 18-year-old female with a chronic cough (x3 months) who has completed a course of Azithromycin (Azithromycin) with mild improvement but no resolution of cough, has no history of asthma, and is currently using allergy medication and nasal spray?

Next Step: Evaluate for Asthma as Primary Diagnosis

Given the 3-month duration of cough with only mild improvement after azithromycin and ongoing allergy treatment, you should now proceed with bronchoprovocation challenge testing (if available) or empiric asthma therapy with inhaled corticosteroids plus bronchodilators. 1

Rationale for This Approach

The ACCP guidelines specify a sequential diagnostic algorithm for chronic cough (>8 weeks). Since this patient has already received treatment for upper airway cough syndrome (UACS) with allergy medications and nasal spray—which represents first-generation antihistamine/decongestant therapy—and the cough persists, asthma must be evaluated next. 1

Why Asthma Should Be Considered Now

• Asthma is the second most common cause of chronic cough after UACS and must always be considered even without typical asthmatic symptoms. 1
• Cough-variant asthma (CVA) can present as isolated cough with no wheezing, dyspnea, or other classic asthma symptoms—this is called "silent asthma." 1
• The patient's age (18 years) and gender (female) fit the demographic for CVA. 1
• Partial response to azithromycin suggests possible airway inflammation that may respond to anti-inflammatory therapy. 1

Specific Diagnostic Steps

Option 1: If Spirometry and Bronchoprovocation Available

• Perform baseline spirometry to assess for reversible airflow obstruction. 1
• If spirometry is normal, proceed with methacholine inhalation challenge (MIC) testing to confirm bronchial hyperresponsiveness. 1
• A positive MIC test supports asthma diagnosis, but definitive diagnosis requires cough resolution with asthma treatment. 1
• A negative MIC test essentially excludes asthma from consideration. 1

Option 2: If Testing Unavailable (Most Practical)

• Initiate empiric asthma therapy immediately with inhaled corticosteroids (ICS) plus inhaled bronchodilators. 1
• Recommended regimen: Fluticasone/salmeterol (ICS/LABA combination) twice daily. 2
• Expected response timeline: Some improvement within 1 week, but complete resolution may require up to 8 weeks of ICS therapy. 1

Critical Treatment Considerations

If Inadequate Response to Inhaled Therapy

• Consider a short course of oral corticosteroids (prednisone 40 mg daily for 5-10 days) before concluding asthma is not the cause. 1
• Before escalating to oral steroids, consider adding a leukotriene receptor antagonist (e.g., montelukast) to the regimen. 1

Common Pitfalls to Avoid

• Do not assume asthma is ruled out if inhaled steroids alone fail—some patients require oral corticosteroids for diagnosis. 1
• Inhaled corticosteroids themselves can cause cough due to dispersant components; if this occurs, switch to a different ICS formulation. 1
• Ensure proper inhaler technique before concluding treatment failure. 1

Sequential Algorithm If Asthma Treatment Fails

Step 1: Add UACS Treatment (if not already optimized)

If the patient's current "allergy medication and nasal spray" is not a first-generation antihistamine/decongestant:

• Switch to or add a first-generation antihistamine/decongestant (e.g., brompheniramine with sustained-release pseudoephedrine). 1
• Newer non-sedating antihistamines are ineffective for cough and should not be used. 1

Step 2: Consider Sinus Imaging

• If UACS symptoms persist despite first-generation antihistamine/decongestant therapy, obtain sinus CT or plain films to evaluate for chronic sinusitis. 1
• Chronic sinusitis can be "clinically silent" with no typical sinusitis symptoms. 1
• If mucosal thickening or air-fluid levels are present, treat with antibiotics effective against H. influenzae, S. pneumoniae, and mouth anaerobes for minimum 3 weeks. 1

Step 3: Evaluate for Non-Asthmatic Eosinophilic Bronchitis (NAEB)

• If asthma and UACS have been adequately treated without resolution, consider NAEB. 1
• Perform induced sputum testing for eosinophils if available. 1, 2
• If testing unavailable, empiric trial of oral corticosteroids (prednisone 40 mg daily for 1-2 weeks) is appropriate. 1

Step 4: Treat for GERD

• If cough persists after addressing UACS, asthma, and NAEB, initiate empiric GERD therapy. 1
• Start with proton pump inhibitor (PPI) therapy plus lifestyle modifications. 1
• GERD can be "silent" with no GI symptoms in up to 75% of cases. 3
• Response may take 2 weeks to several months. 1

When to Refer

Refer to a pulmonologist or cough specialist if:

• Cough remains undiagnosed after sequential trials of therapy for UACS, asthma, NAEB, and GERD. 1
• Red flags are present (hemoptysis, significant weight loss, abnormal chest X-ray). 4

Important Note on Multifactorial Cough

Chronic cough is often caused by multiple conditions simultaneously (e.g., both asthma and GERD). 1

• Continue previous treatments when adding new ones—do not discontinue UACS therapy when starting asthma treatment. 1, 2
• Cough will not resolve until all contributing conditions are adequately treated. 1