What is the appropriate evaluation and management for a patient with a chronic cough lasting more than eight weeks?

Chronic Cough Evaluation and Management

Initial Definition and Red Flag Assessment

For adult patients with chronic cough lasting more than 8 weeks, immediately assess for red flag symptoms requiring urgent evaluation before proceeding with the standard diagnostic algorithm. 1

Critical Red Flags Requiring Immediate Investigation:

• Hemoptysis - mandates urgent workup for life-threatening conditions 1, 2
• Smoker >45 years with new cough, change in cough pattern, or coexisting voice disturbance 2
• Adults aged 55-80 years with ≥30 pack-year smoking history who currently smoke or quit within past 15 years (lung cancer screening criteria) 2
• Prominent dyspnea at rest or at night 2
• Systemic symptoms including fever, weight loss, or night sweats 2, 3

Step 1: Medication Review and Risk Factor Elimination

Before any diagnostic workup, discontinue ACE inhibitors and sitagliptin, as these are common iatrogenic causes that must be eliminated first. 2, 4

• ACE inhibitors should be switched to an alternative antihypertensive class 5
• Allow 4 weeks after discontinuation before proceeding with further evaluation 2
• Eliminate environmental and occupational exposures 1, 2
• Smoking cessation is mandatory - chronic bronchitis resolves within 4 weeks in most patients 2

Step 2: Initial Diagnostic Evaluation

Required Initial Testing:

• Chest radiography - perform in all patients unless contraindicated 1, 5
• Spirometry with bronchodilator reversibility - essential for asthma diagnosis 6, 7
• Validated cough severity assessment tool (Leicester Cough Questionnaire or Cough-Specific Quality of Life Questionnaire) - required to objectively measure treatment response 1, 2

Additional Testing Based on Clinical Suspicion:

• Exhaled nitric oxide and blood eosinophil count - helps identify eosinophilic airway inflammation 6
• Methacholine challenge - if asthma suspected but spirometry normal 1, 7
• Induced sputum analysis - to identify nonasthmatic eosinophilic bronchitis 1, 4

Chest CT should NOT be performed routinely in the initial workup - reserve for patients with abnormal chest radiograph, red flag symptoms, or failed empiric treatment after 4-6 weeks. 1

Step 3: The "Big Four" Causes - Systematic Empiric Treatment

The top four diagnoses account for >90% of chronic cough cases, either alone or in combination: Upper Airway Cough Syndrome (UACS), asthma, GERD, and nonasthmatic eosinophilic bronchitis. 1, 2, 5

Critical Pitfall to Avoid:

Up to 40% of patients have multiple simultaneous causes - do NOT stop one treatment when starting another. Continue effective therapies and add sequential treatments until cough resolves. 2, 4

Treatment Algorithm (Sequential, Not Exclusive):

First: Upper Airway Cough Syndrome (UACS)

• First-generation antihistamine-decongestant combination (e.g., brompheniramine/pseudoephedrine or chlorpheniramine/phenylephrine) 8
• Plus intranasal corticosteroid spray (fluticasone or mometasone) 8
• Expected response time: Days to 1-2 weeks 8
• Continue if partial improvement and add next treatment 8

Second: Asthma/Cough-Variant Asthma

• Inhaled corticosteroids (fluticasone 220 mcg or budesonide 360 mcg twice daily) plus bronchodilators 1, 8
• Expected response time: Up to 8 weeks for complete resolution 1, 4
• Consider bronchoprovocation challenge if diagnosis uncertain 1
• Do NOT abandon ICS therapy prematurely - switching formulations may be needed before declaring failure 4

Third: Gastroesophageal Reflux Disease (GERD)

• High-dose PPI therapy (omeprazole 40 mg twice daily) with dietary modifications 8
• Expected response time: 2 weeks to several months 8
• Critical: Acid suppression alone is NO LONGER recommended - comprehensive GERD management required including lifestyle modifications 1, 2, 4
• GERD can cause cough even without typical GI symptoms ("silent GERD") 8

Fourth: Nonasthmatic Eosinophilic Bronchitis (NAEB)

• Requires identification via induced sputum or BAL showing eosinophilia without airflow obstruction 1, 2
• Treatment: Inhaled corticosteroids 2, 4

Step 4: Follow-Up and Reassessment

Schedule follow-up within 4-6 weeks after initiating treatment to objectively assess response using validated cough severity tools. 1, 2

• If partial improvement, continue current therapy and add next treatment in algorithm 8
• If no improvement after adequate treatment duration, reassess for:
  • Medication adherence 4
  • Correct diagnosis 4
  • Multiple simultaneous causes 2, 4
  • Less common causes 1

Step 5: Refractory Chronic Cough Management

If cough persists despite 4-6 weeks of appropriate empiric treatment for the top four causes, the patient has refractory chronic cough. 1, 4

Before Declaring Cough "Refractory":

• Confirm adequate treatment duration - asthma may require up to 8 weeks 1, 4
• Verify all contributing causes addressed - remember 40% have multiple etiologies 2, 4
• Reassess medication list - confirm ACE inhibitors and sitagliptin discontinued 2, 4

Advanced Evaluation for Refractory Cases:

• High-resolution CT chest - if not already performed 1, 8
• Assessment of airway inflammation via induced sputum or BAL 4
• Consider bronchoscopy if imaging and empiric treatments fail 8
• Evaluate for uncommon causes: bronchiectasis, interstitial lung disease, malignancy, connective tissue diseases 1

Pharmacologic Treatment for Confirmed Refractory Chronic Cough:

Gabapentin is the preferred first-line neuromodulator for refractory chronic cough. 1, 2, 4, 3

• Dosing: Start 300 mg once daily, escalate to maximum 1,800 mg daily in divided doses 2, 4
• Alternative: Pregabalin 6, 3
• Second alternative: Low-dose morphine (though gabapentin preferred) 1, 9
• Amitriptyline showed benefit in one trial 1

Non-Pharmacologic Treatment:

• Multimodality speech pathology therapy - evidence-based alternative for refractory cough 1, 2, 3

Less Common But Important Causes to Consider

• Atopic cough - more commonly reported in Asian countries 2
• Postinfectious cough - typically resolves within 3-8 weeks but can persist 1, 8
• Medication-induced - beyond ACE inhibitors, consider sitagliptin 1, 2
• Occupational/environmental exposures - systematically evaluate in all patients 1, 2
• Uncommon pulmonary and systemic diseases - bronchiectasis, interstitial lung disease, connective tissue diseases, vasculitis 1

Key Pitfalls to Avoid

• Assuming single etiology - up to 40% have multiple causes requiring combination therapy 2, 4
• Stopping effective treatments when adding new ones - continue all partially effective therapies 8
• Using acid suppression alone for GERD - comprehensive management required 1, 2, 4
• Premature CT imaging - not indicated in initial workup with normal chest X-ray 1
• Inadequate treatment duration - asthma may require 8 weeks, GERD up to several months 1, 8
• Failing to use validated cough assessment tools - objective measurement essential 1, 2, 4
• Prescribing antibiotics for postinfectious cough - explicitly contraindicated unless bacterial sinusitis or pertussis suspected 8