What are the common causes of nocturnal cough in adults and children, and how should it be evaluated and managed?

Nocturnal Cough: Causes, Evaluation, and Management

Primary Causes

The three most common causes of nocturnal cough are asthma, gastroesophageal reflux disease (GERD), and upper airway cough syndrome (UACS), collectively accounting for approximately 90% of chronic cough cases in specialist clinics. 1

Asthma

• Asthma is the leading cause of nocturnal cough that awakens patients from sleep, with 74% of asthmatic patients experiencing nocturnal symptoms at least once weekly 1
• Airway inflammation peaks at 4:00 AM in asthmatic patients, explaining increased coughing upon awakening 1, 2
• Up to 80% of fatal asthma attacks occur overnight or early morning, making nocturnal symptoms a critical marker of disease severity 1
• However, only one-third of children with isolated nocturnal cough actually have asthma-like disease, highlighting the limited diagnostic specificity 1, 3

Gastroesophageal Reflux Disease (GERD)

• GERD commonly causes nocturnal cough through supine positioning, increased vagal tone, and reduced circulating epinephrine during the night 1, 2
• The transition from wakefulness to sleep creates a vulnerable window for reflux before protective sleep mechanisms activate 1
• Absence of dyspepsia does not rule out reflux as the cause of cough 4

Upper Airway Cough Syndrome (UACS)

• UACS accounts for approximately 30% of chronic cough presentations in specialist clinics 1
• Associated with frequent throat clearing and sensation of post-nasal drip 4

Other Important Causes

• Heart failure can cause nocturnal cough that awakens patients 4
• Respiratory infections may present with nocturnal cough 4
• Obstructive sleep apnea (OSA) has emerged as an underrecognized cause of chronic nocturnal cough, particularly in females who also report GERD and rhinitis 5, 6
• Smoking is one of the commonest causes of persistent cough in a dose-related fashion 4
• ACE inhibitors can cause chronic cough; in pediatric patients, discontinuation leads to resolution within 3-7 days 1

Critical Diagnostic Principles

Key Limitations

• The character (wet, dry, paroxysmal) and timing (nocturnal vs. post-prandial) of cough do NOT reliably predict the underlying cause 1, 2
• Nocturnal cough alone has no predictive value for determining etiology 1, 2
• Sleep suppresses the cough reflex; spontaneous cough is almost abolished during sleep stages 3 and 4 4, 5
• Cough is unlikely to occur once patients actually fall asleep, regardless of whether the cause is chronic bronchitis, GERD, or asthma 2, 7

Epidemiologic Patterns

• Nocturnal and non-productive cough is more prevalent in women than men 4
• Chronic cough is more likely to occur in middle-aged women 4

Systematic Evaluation Approach

History Taking

Query for the following specific features:

• Asthma indicators: wheeze, shortness of breath, chest tightness, exercise limitation, symptoms worse with cold air 4, 2
• GERD indicators: heartburn (OR 2.671, specificity 94.9%), belching (OR 2.536, specificity 85.5%), acid regurgitation (OR 2.043, specificity 91.2%), cough after meals (specificity 91.2%) 8
• UACS indicators: postnasal dripping (OR 2.317, specificity 80.8%), history of sinusitis (OR 4.137, specificity 90.2%) 8
• Sleep-disordered breathing: snoring, witnessed apneas, restless sleep 1, 2
• Medication history: ACE inhibitor use 1
• Smoking history: dose-related association with chronic cough 4

Physical Examination

• Clear lung auscultation effectively rules out productive lower-airway diseases such as bronchiectasis, COPD, and chronic bronchitis 1
• Examine external auditory canals for foreign material (Arnold ear-cough reflex present in 2.3-4.2% of individuals) 1

Objective Testing

• Perform spirometry with bronchodilator testing (≥12% and ≥200 mL increase in FEV₁ indicates reversible airway obstruction) 1, 2
• Bronchial provocation testing (methacholine or histamine) has 78-88% positive predictive value for steroid-responsive cough 1
• Consider 24-hour esophageal pH monitoring when GERD is suspected 1, 2
• Reserve sinus imaging (CT or plain radiograph) for patients whose cough persists despite adequate therapeutic trial, not as initial diagnostic tool 1

Treatment Algorithm

First-Line: Empirical Treatment for UACS

Prescribe a first-generation H1-antihistamine (e.g., diphenhydramine or chlorpheniramine) combined with a decongestant for 1-2 weeks 1

• First-generation sedative antihistamines may be particularly suitable for nocturnal cough 4
• Expected response time: 1-2 weeks 1, 2

Second-Line: If No Response After 2 Weeks

Trial inhaled corticosteroids for an additional 2 weeks to address possible cough-variant asthma or eosinophilic bronchitis 1

Third-Line: If Still Unresponsive

Administer oral prednisolone (≈30 mg/day) for 2 weeks; lack of improvement suggests cough is unlikely due to eosinophilic airway inflammation 1

GERD-Specific Treatment (If Suspected)

Initiate standard-dose proton-pump inhibitor (PPI) once daily for 4-8 weeks as first-line therapy 1

Advise lifestyle modifications:

• Avoid meals within 2-3 hours of bedtime 1
• Elevate head of bed 1
• Avoid trigger foods 1
• Achieve weight control if overweight 1
• Cease smoking 1

If cough persists after 4-8 weeks:

• Increase PPI dosing to twice daily 1
• Add prokinetic agent (e.g., metoclopramide) when response to PPI alone is inadequate 1
• Time to clinical response is highly variable: some patients improve within 2 weeks, while others may require several months 1, 2

Alternative Symptomatic Treatments for Nocturnal Cough

• Dextromethorphan at 60 mg provides maximum cough reflex suppression 4
• Menthol by inhalation suppresses cough reflex acutely but is short-lived 4
• Codeine or pholcodine have no greater efficacy than dextromethorphan but have much greater adverse effects and are not recommended 4

Referral Indications

Refer to specialist cough clinic when empirical treatment for the three most common causes (UACS, asthma, GERD) fails 1

Typical reasons for treatment failure include:

• Not empirically treating UACS when clinical findings are absent 1
• Not obtaining sinus imaging for occult sinusitis 1
• Inadequate bronchoprovocation testing 1
• Insufficiently aggressive GERD therapy in the absence of gastrointestinal symptoms 1

Critical Pitfalls to Avoid

• Do not diagnose asthma based on nocturnal cough alone; only 25-33% of children with isolated nocturnal cough have asthma 3, 2
• Do not assume absence of nocturnal cough indicates psychogenic origin 1
• Do not rely on subjective parental reports of nocturnal cough in children; these correlate poorly with objective cough counts (Cohen's κ ≈ 0.3) 1, 2
• Do not attribute primarily nocturnal cough in children to postnasal drip, as this concept lacks scientific validity in pediatric populations 2
• Consider obstructive sleep apnea in unexplained chronic nocturnal cough, especially in females with concomitant GERD and rhinitis symptoms 5, 6