How should I evaluate and manage an adult with a chronic cough lasting more than eight weeks, considering causes such as post‑nasal drip (upper‑airway cough syndrome), cough‑variant asthma, gastro‑oesophageal reflux disease, smoking, and ACE‑inhibitor use?

Evaluation and Management of Chronic Cough in Adults

For an adult with chronic cough lasting more than 8 weeks, begin with a chest radiograph and spirometry, then initiate empiric treatment with a first-generation antihistamine/decongestant combination for upper airway cough syndrome (UACS), followed by sequential trials targeting asthma and gastroesophageal reflux disease if the cough persists after 2 weeks. 1, 2

Initial Assessment and Red-Flag Identification

Mandatory Baseline Investigations

• Obtain a chest radiograph in every patient to exclude infectious, inflammatory, or malignant thoracic disease 2, 3
• Perform spirometry in all patients to detect obstructive airway pathology 2, 3
• Quantify cough severity using visual analog scales or validated quality-of-life questionnaires 2

Critical Red Flags Requiring Urgent Evaluation

• Hemoptysis mandates immediate investigation for life-threatening conditions 2, 3
• New cough in smokers >45 years or those with 30 pack-year history requires urgent evaluation for lung cancer 2, 3
• Systemic symptoms including fever, unintentional weight loss, or night sweats 2
• Prominent dyspnea at rest or at night 2
• History of cancer, tuberculosis, or immunosuppression 2

Essential History Elements

• Discontinue ACE inhibitors immediately if present; cough typically resolves within a median of 26 days after cessation 2, 3
• Advise smoking cessation; smoking-related cough usually resolves within 4 weeks of quitting 2, 3
• Review all medications including sitagliptin, which can cause chronic cough 3
• Assess occupational and environmental exposures systematically 2, 3

Sequential Empiric Treatment Algorithm

The Three Major Causes (Account for >90% of Cases)

Upper Airway Cough Syndrome (UACS) accounts for 18.6%–81.8% of cases 1, 2, 3, asthma for 14.6%–41.3% 2, 3, and GERD for 4.6%–85.4% 2, 3. Up to 67% of patients have multiple simultaneous causes, requiring additive treatment strategies rather than abandoning partially effective therapies 2, 3.

Step 1: Treat Upper Airway Cough Syndrome (First 2 Weeks)

Initiate a first-generation antihistamine/decongestant combination immediately as the most effective evidence-based first-line treatment 1. Specific effective combinations include dexbrompheniramine maleate plus sustained-release pseudoephedrine sulfate, or azatadine maleate plus sustained-release pseudoephedrine sulfate 1.

Dosing Strategy to Minimize Side Effects

• Start with once-daily dosing at bedtime for a few days before increasing to twice-daily therapy to minimize sedation 1
• Most patients improve within days to 2 weeks of initiating therapy 1
• Common side effects include dry mouth and transient dizziness 1
• Monitor for serious side effects including insomnia, urinary retention, jitteriness, tachycardia, worsening hypertension, and increased intraocular pressure in glaucoma patients 1

Add Intranasal Corticosteroids if No Response After 1–2 Weeks

• Add fluticasone 100–200 mcg daily for a 1-month trial if the antihistamine-decongestant combination alone is insufficient 1
• Intranasal corticosteroids are effective for both allergic and non-allergic rhinitis-related UACS 1

Alternative for Patients with Contraindications to Decongestants

• Use ipratropium bromide nasal spray (42 mcg per spray, 2 sprays per nostril 4 times daily) for patients with hypertension, cardiovascular disease, or glaucoma 1
• Ipratropium provides anticholinergic drying effects without systemic cardiovascular side effects 1

Adjunctive Therapy

• Add high-volume saline nasal irrigation (150 mL) to mechanically remove secretions and improve mucociliary function 1
• Nasal irrigation is more effective than saline spray because it better expels secretions 1

Critical Pitfall: "Silent" UACS

• Approximately 20% of patients have "silent" postnasal drip with no obvious symptoms yet still respond to treatment 1, 2
• The absence of visible posterior pharyngeal drainage or cobblestoning does not exclude UACS; diagnosis is confirmed by response to therapy 1, 2

Step 2: Evaluate and Treat Asthma (If Cough Persists After 2 Weeks)

If symptoms persist despite adequate upper airway treatment for 2 weeks, proceed with sequential evaluation for asthma 1, 2.

Diagnostic Approach

• Normal spirometry does NOT exclude asthma; cough may be the sole manifestation 2
• Perform methacholine bronchial provocation testing when spirometry is normal and no obvious etiology is identified 2
• No pulmonary function test can reliably exclude cough that would respond to corticosteroids 4, 2

Treatment Trial for Asthma/Eosinophilic Airway Inflammation

• Initiate inhaled corticosteroids following national asthma guidelines 4
• A 2-week trial of oral prednisolone 30 mg/day helps differentiate eosinophilic airway inflammation; lack of improvement suggests the cough is unlikely due to this mechanism 4, 2
• At step 3 of asthma management, use leukotriene receptor antagonists rather than long-acting β-agonists for cough-variant asthma 4

Non-Asthmatic Eosinophilic Bronchitis (NAEB)

• NAEB accounts for 6.4%–17.2% of chronic cough cases and presents with eosinophilic airway inflammation in the absence of airway hyperresponsiveness or variable airflow obstruction 4, 2, 3
• NAEB responds to inhaled corticosteroids 4, 2

Step 3: Treat Gastroesophageal Reflux Disease (If Cough Persists)

GERD can cause cough without any gastrointestinal symptoms 2. Failure to consider GERD is a frequent cause of therapeutic failure 2.

Intensive Acid Suppression Protocol

• Initiate omeprazole 20–40 mg twice daily before meals for at least 8 weeks 4, 1
• Add dietary and lifestyle modifications including elimination of medications potentially worsening reflux (bisphosphonates, nitrates, calcium channel blockers, theophylline, progesterones) 4
• Consider adding prokinetic agents such as metoclopramide 10 mg three times daily in a proportion of patients 4
• Full acid suppression may require a combination of twice-daily PPIs and nocturnal H2 antagonists 4

Critical Timing Consideration

• Clinical response may require 2 weeks to 12 weeks; improvement in cough from GERD treatment may take up to 3 months 1, 2
• A minimum of 3 months of intensive acid suppression with PPIs plus alginates is advised 2

When to Consider Antireflux Surgery

• Antireflux surgery may be effective in carefully selected cases 4
• Prior to surgery, perform comprehensive evaluation including exclusion of other causes of cough, esophageal ambulatory 24-hour pH measurement, esophageal manometry, barium meal, gastric emptying studies, Bernstein acid infusion tests, trial of PPI treatment, and elimination of medications potentially worsening reflux 4

Follow-Up and Reassessment

• Schedule a follow-up visit 4–6 weeks after initial evaluation to reassess cough severity with validated scales and verify treatment adherence 1, 2
• Maintain all partially effective treatments rather than discontinuing them prematurely, as multiple etiologies often coexist 1, 2
• Formally quantify treatment effects using validated cough severity measures 2

Advanced Evaluation for Refractory Cough

When to Pursue Additional Testing

• If cough persists beyond 8 weeks despite systematic treatment of UACS, asthma, and GERD, consider referral to a specialized cough clinic 1, 2
• Obtain high-resolution computed tomography when targeted work-up is normal and empirical treatments have failed 2
• Bronchoscopy is reserved for suspected foreign-body aspiration 2

Management of Refractory Chronic Cough

• Consider cough hypersensitivity syndrome as an underlying mechanism in refractory cases 3
• Gabapentin trial starting at 300 mg once daily, escalating to maximum 1,800 mg daily in divided doses, may be effective 3
• Multimodality speech pathology therapy is an alternative approach for refractory chronic cough 2, 3
• Low-dose morphine is preferred over other neuromodulators in some guidelines 5

Common Pitfalls to Avoid

• Do not assume a single etiology; up to 67% of patients have multiple simultaneous causes requiring combination therapy 2, 3
• Do not rely solely on physical examination to diagnose UACS; lack of visible postnasal drainage or cobblestoning does not rule it out 1, 2
• Do not use newer-generation antihistamines (cetirizine, fexofenadine, loratadine) for non-allergic UACS, as they are ineffective 1, 2
• Do not confuse GERD with UACS; both can cause pharyngeal inflammation and throat symptoms and may coexist 1
• Do not use topical nasal decongestants (oxymetazoline, xylometazoline) for more than 3–5 consecutive days due to the risk of rhinitis medicamentosa 1
• Do not abandon partially effective therapies when adding new treatments for additional etiologies 1, 2