What is the initial approach to treating a patient with a chronic cough, defined as a cough lasting more than eight weeks, with no identified underlying cause such as pneumonia, asthma, or gastroesophageal reflux disease (GERD)?

Initial Approach to Chronic Cough Without Identified Underlying Cause

Begin with systematic empiric treatment for upper airway cough syndrome (UACS) using a first-generation antihistamine-decongestant combination, as UACS is the single most common cause of chronic cough (33-44% of cases), and proceed sequentially through asthma and GERD if initial treatment fails. 1

Mandatory Initial Workup

Before starting empiric treatment, complete these essential steps:

• Obtain chest radiograph to exclude structural lung disease, malignancy, pneumonia, or other serious thoracic conditions 1
• Perform spirometry to assess for airflow obstruction and bronchodilator response 2
• Review all medications immediately and discontinue ACE inhibitors or sitagliptin if present, as these are common iatrogenic causes that must be eliminated before pursuing extensive workup 3, 4
• Assess cough severity using validated cough visual analogue scores or quality-of-life questionnaires to objectively measure treatment response 2

Sequential Empiric Treatment Algorithm

Step 1: Treat UACS First (Weeks 1-4)

• Start first-generation antihistamine-decongestant combination as UACS accounts for 33-44% of chronic cough cases 1
• Target rhinosinus conditions including postnasal drip, allergic rhinitis, and chronic sinusitis 3
• Reassess at 4-6 weeks to determine response before proceeding 1

Step 2: Add or Switch to Asthma Treatment (Weeks 4-12)

If UACS treatment provides no or partial relief:

• Initiate inhaled corticosteroids even with normal spirometry, as cough-variant asthma may not show airflow obstruction 1
• Consider bronchial provocation testing in patients without clinically obvious etiology and normal spirometry 2
• Allow up to 8 weeks for complete resolution of cough-variant asthma with inhaled corticosteroids 5
• Look for cough worsening at night, with cold air exposure, or with exercise as clues to asthma 3

Step 3: Address GERD (Weeks 8-16)

If cough persists after adequate UACS and asthma trials:

• Implement comprehensive GERD management including lifestyle modifications and potentially prokinetic agents 1
• Do not use acid suppression alone, as proton pump inhibitors as monotherapy are no longer recommended for GERD-related cough 3, 5

Critical Management Principles

Expect Multiple Simultaneous Causes

• Up to 40% of patients have two or more contributing factors requiring combination therapy 3, 1
• Sequential and additive therapy is essential rather than assuming a single etiology 1
• Continue effective treatments while adding new ones for partial responders 1

Red Flags Requiring Immediate Specialist Referral

Stop the algorithmic approach and refer urgently if:

• Hemoptysis is present, mandating evaluation for life-threatening conditions 3
• Smoker >45 years with new cough, change in cough, or coexisting voice disturbance 3
• Prominent dyspnea at rest or at night 3
• Systemic symptoms including fever, weight loss, or night sweats 3
• Significant sputum production, which usually indicates primary lung pathology 2

When to Pursue Additional Testing

Proceed to advanced investigations only after:

• 4-6 weeks of failed empiric treatment for each of the top three diagnoses 1
• Medication review confirms no ACE inhibitor or sitagliptin use 3
• Red flag symptoms are present 1

Additional testing may include:

• High-resolution CT in patients with normal chest radiograph and failed empiric trials 2
• Bronchoscopy if foreign body aspiration is suspected 2
• Assessment of airway inflammation (induced sputum or BAL) to identify nonasthmatic eosinophilic bronchitis 5

Common Pitfalls to Avoid

• Assuming single etiology when multiple causes frequently coexist 3, 1
• Using acid suppression alone for GERD-related cough instead of comprehensive management 3, 5
• Failing to discontinue ACE inhibitors before extensive workup 3
• Not using validated cough severity tools to objectively assess treatment response 2, 3
• Abandoning inhaled corticosteroids after one formulation fails rather than trying alternative formulations 5
• Insufficient treatment duration for asthma, which may require up to 8 weeks for complete resolution 5

Refractory Cough Management (After 8+ Weeks)

If cough persists despite adequate sequential trials:

• Verify all three top diagnoses (UACS, asthma, GERD) were properly treated with adequate duration 5
• Consider nonasthmatic eosinophilic bronchitis as an important but less common cause requiring specific identification 3, 5
• Trial gabapentin starting at 300mg once daily, escalating to maximum 1,800mg daily in divided doses 3, 5
• Consider multimodality speech pathology therapy as an alternative approach 3
• Recognize cough hypersensitivity syndrome as an underlying mechanism in truly refractory cases 3