What is the likely cause and appropriate management of a patient with an isolated dry nocturnal cough, clear lung auscultation and no evidence of gastro‑esophageal reflux?

Isolated Nocturnal Dry Cough with Clear Lung Sounds and No Reflux

The most likely cause is upper airway cough syndrome (UACS), and first-line treatment should be a first-generation H1-antihistamine combined with a decongestant for 1-2 weeks. 1, 2

Diagnostic Reasoning

Why UACS is Most Likely

• UACS (formerly postnasal drip syndrome) accounts for approximately 30% of chronic cough cases presenting to specialist clinics and is one of the three most common causes alongside asthma and GERD. 1, 2

• The absence of typical reflux symptoms does NOT rule out GERD (up to 75% of GERD-related cough presents without heartburn), but you explicitly state no reflux is present, making UACS the leading diagnosis. 3, 4

• Clear breath sounds effectively exclude productive lower airway diseases like bronchiectasis, COPD, and chronic bronchitis. 1

• The nocturnal timing alone is NOT diagnostically specific—cough character and timing do not reliably predict the underlying cause. 1, 5, 6

Key Diagnostic Pitfalls to Avoid

• Do not assume nocturnal cough automatically means asthma. In children with isolated nocturnal cough, only one-third actually have asthma-like disease. 5

• Do not use the absence of nocturnal cough to suggest psychogenic cough or to exclude GERD. Established sleep suppresses the cough reflex regardless of the underlying disease. 1, 5

• UACS is a clinical diagnosis of exclusion with no pathognomonic findings or objective testing. Diagnosis is inferential, based on clinical presentation and response to specific therapy. 4, 2

Systematic Evaluation Approach

Initial Clinical Assessment

• Look for rhinitis/sinusitis symptoms: postnasal dripping sensation (specificity 80.8%), history of sinusitis (specificity 90.2%), nasal congestion, or throat clearing. 6, 2

• Examine the ears: The Arnold (ear-cough) reflex is present in 2.3-4.2% of individuals and can be triggered by external auditory canal debris or hair. 5

• Review medications: ACE inhibitors cause chronic cough in ~10% of patients and should be discontinued if present—resolution occurs within 3-7 days in pediatric patients. 5, 7

When to Consider Alternative Diagnoses

• If nocturnal cough is the ONLY symptom (no other upper airway symptoms), consider cough-variant asthma. Nocturnal cough alone has high specificity (97.6%) but very low sensitivity (8.1%) for asthma. 6

• Perform bronchial provocation testing (methacholine or histamine) if asthma is suspected. A positive test has 78-88% positive predictive value for steroid-responsive cough. However, a negative test does NOT rule out steroid-responsive cough, as eosinophilic bronchitis can present without airway hyperresponsiveness. 1

• Consider occult GERD even without typical symptoms. The transition from wakefulness to sleep creates a vulnerable window for reflux before protective mechanisms engage. 3, 5

Treatment Algorithm

First-Line Therapy for UACS

• Prescribe a FIRST-GENERATION H1-antihistamine (e.g., diphenhydramine, chlorpheniramine) combined with a decongestant. Second-generation non-sedating antihistamines are LESS effective for non-histamine-mediated UACS. 4

• Expected response time: 1-2 weeks for UACS-related cough. 5

• Diagnosis is confirmed when therapeutic intervention results in symptom resolution. 2

If No Response After 2 Weeks

• Consider empiric trial of inhaled corticosteroids (ICS) for 2 weeks. This addresses both cough-variant asthma and eosinophilic bronchitis, which together account for ~30% of chronic cough cases. 1

• If still no response, consider oral prednisolone 30 mg/day for 2 weeks. Expert opinion suggests cough is unlikely due to eosinophilic airway inflammation if there is no response to this trial. 1

If Cough Persists Despite Above Measures

• Initiate empiric GERD therapy with a standard-dose proton pump inhibitor (PPI) once daily for 4-8 weeks, EVEN WITHOUT typical reflux symptoms. 3

• Implement lifestyle modifications: avoid eating within 2-3 hours of bedtime, elevate head of bed, avoid trigger foods, pursue weight management if overweight, and smoking cessation if applicable. 3

• If inadequate response after 4-8 weeks, increase to twice-daily PPI dosing. 3

• Response to GERD therapy may take SEVERAL MONTHS in some patients—adequate treatment duration is essential. 3

Specialist Referral Indications

• Refer to a specialist cough clinic when empirical treatment for the three most common causes (UACS, asthma, GERD) has failed. 1

• Common reasons for treatment failure include: failure to empirically treat UACS when findings are absent, failure to obtain sinus imaging for occult sinusitis, inadequate bronchoprovocation testing, and failure to aggressively treat GERD when GI symptoms are lacking. 1

Critical Clinical Pearls

• Women, particularly middle-aged women, have higher prevalence of chronic cough and more sensitive cough reflex. 3

• Rhinitis/sinusitis-related symptoms show moderate sensitivity (72.9%) but mild specificity (46.1%) for UACS, meaning their presence supports the diagnosis but their absence does not exclude it. 6

• The mechanism of UACS-related cough likely involves hypersensitivity of upper airway sensory nerves, lower airway sensory nerves, or both, with inflammatory mediators from nasal mucosa sensitizing the cough reflex. 7, 8

• Sinus imaging (CT or plain radiograph) should be reserved for patients with persistent cough despite adequate treatment trial, not as initial diagnostic testing. 1