What are the likely causes, work‑up, and treatment for a patient with a cough that is worse in the early morning?

Early‑Morning Cough: Causes, Evaluation, and Management

Most Likely Etiologies

A cough that worsens in the early morning is most commonly caused by asthma, gastroesophageal reflux disease (GERD), or upper airway cough syndrome (UACS), with asthma being particularly characteristic due to peak airway inflammation around 04:00 h. 1

Asthma and Cough‑Variant Asthma

• Approximately 74% of asthmatic patients report nocturnal symptoms that awaken them at least once per week, making early‑morning cough a hallmark feature. 1
• Airway inflammation in asthmatic patients peaks around 04:00 h, which directly explains increased coughing upon awakening in the early morning. 1
• Up to 80% of fatal asthma attacks occur during the night or early morning, making nocturnal and early‑morning symptoms critical markers of disease severity. 1
• Cough may be the sole manifestation of asthma (cough‑variant asthma), occurring without wheeze or dyspnea, and accounts for approximately 14.6%–41.3% of chronic cough cases. 2, 3
• Normal spirometry does not exclude asthma‑related cough; bronchial hyperresponsiveness may still be present despite unremarkable baseline lung function. 2

Gastroesophageal Reflux Disease (GERD)

• GERD is implicated in approximately 4.6%–85.4% of chronic cough cases and frequently occurs without typical gastrointestinal symptoms such as heartburn or regurgitation. 2
• The transition from wakefulness to sleep creates a vulnerable window during which gastroesophageal reflux can occur, and supine positioning, increased vagal tone, and reduced circulating epinephrine during the night exacerbate reflux‑related cough. 1
• Cough after meals or when lying down supports a reflux‑related etiology, though early‑morning timing alone is not diagnostically specific. 1, 4

Upper Airway Cough Syndrome (UACS)

• UACS accounts for approximately 18.6%–81.8% of chronic cough cases and may present without prominent nasal symptoms such as postnasal drip. 2
• Postnasal dripping and history of sinusitis are indicators for UACS with high specificity (80.8% and 90.2%, respectively). 4
• UACS can present as "silent post‑nasal drip syndrome," where cough is the only symptom despite the absence of overt nasal complaints. 5

Other Important Considerations

• Established sleep suppresses the cough reflex, so cough is generally uncommon during deep sleep; early‑morning cough typically occurs during the transition from sleep to wakefulness. 1
• Non‑asthmatic eosinophilic bronchitis (NAEB) accounts for 6.4%–17.2% of chronic cough cases and is characterized by eosinophilic airway inflammation without airway hyperresponsiveness. 2
• Nocturnal cough alone was a predictor of cough‑variant asthma with high specificity (97.6%) but low sensitivity (8.1%). 4

Systematic Work‑Up

Mandatory Baseline Investigations

• Obtain a chest radiograph for all adults with chronic cough (>8 weeks) to exclude infectious, inflammatory, or malignant thoracic disease. 2
• Perform spirometry with bronchodilator testing to detect obstructive airway pathology; a ≥12% and ≥200 mL increase in FEV₁ indicates reversible airway obstruction. 2, 1
• Quantify cough severity using visual‑analog scales or validated quality‑of‑life questionnaires to objectively monitor treatment response. 2

Targeted History

• Verify smoking status and assess occupational or environmental irritant exposures, as tobacco exposure is a dominant cause of chronic cough. 5
• Review all medications and discontinue any ACE‑inhibitor, as drug‑induced cough typically resolves within a median of 26 days after cessation. 2
• Query for upper‑airway symptoms (frequent throat clearing, postnasal drip sensation, nasal congestion, sinus pressure) that may indicate UACS. 5
• Inquire about gastroesophageal symptoms (heartburn, regurgitation, sour taste, throat burning, hoarseness), though silent GERD frequently presents with cough as the sole manifestation. 5
• Ask about asthma features: wheeze, dyspnea, chest tightness, exercise limitation, and worsening with cold air. 1

Physical Examination

• Nasal inspection: pale, boggy turbinates suggest allergic rhinitis; erythematous turbinates suggest infectious rhinitis; nasal polyps may support chronic rhinosinusitis. 5
• Oropharyngeal inspection: cobblestoning of the posterior pharynx is classic for postnasal drip/UACS. 5
• Auscultate during forced expiration and immediately after coughing; wheezes that appear only with these maneuvers are characteristic of cough‑variant asthma. 5

Advanced Testing When Initial Work‑Up Is Normal

• Methacholine bronchial provocation testing is advised for patients with chronic cough, normal spirometry, and no obvious etiology after referral to a pulmonologist. 2
• Bronchoprovocation testing has a positive predictive value of 78–88% for steroid‑responsive cough, though a negative test does not exclude eosinophilic bronchitis. 1
• Query for gastrointestinal symptoms and consider 24‑hour esophageal pH monitoring when reflux is suspected. 1

Treatment Algorithm

First‑Line Empiric Therapy

Because up to 67% of patients have multiple simultaneous etiologies, retain partially effective therapies and employ additive treatment strategies rather than sequential monotherapy. 2

For Suspected UACS

• Prescribe a first‑generation H1‑antihistamine (e.g., diphenhydramine or chlorpheniramine) combined with a decongestant for 1–2 weeks as the recommended initial treatment. 1
• When prominent upper‑airway symptoms are present, add a topical intranasal corticosteroid (e.g., fluticasone or mometasone). 2, 5
• Clinical response typically appears within days to 1–2 weeks. 1

For Suspected Asthma or Cough‑Variant Asthma

• Initiate inhaled corticosteroids according to national asthma guidelines for patients whose cough persists after adequate treatment of upper‑airway causes. 2
• A 2‑week trial of oral prednisone (30–40 mg daily) can differentiate eosinophilic airway inflammation; lack of improvement makes an eosinophilic mechanism unlikely. 2
• Complete resolution of asthmatic cough may require up to 8 weeks of inhaled corticosteroids. 5
• For cough‑variant asthma refractory to inhaled steroids, step 3 therapy recommends leukotriene‑receptor antagonists rather than long‑acting β‑agonists. 2

For Suspected GERD

• Initiate intensive acid suppression with omeprazole 20–40 mg twice daily before meals for ≥8 weeks, combined with dietary and lifestyle modifications. 2
• Advise lifestyle modifications: avoid meals within 2–3 hours of bedtime, elevate the head of the bed, avoid trigger foods, achieve weight control if overweight, and cease smoking. 1
• Clinical response may require 2 weeks to 12 weeks, so maintain therapy for an adequate duration. 2
• Add a prokinetic agent (e.g., metoclopramide 10 mg three times daily) if response to PPI alone is inadequate. 2

Second‑Line and Refractory Management

• If all empiric therapies fail after 8 weeks, obtain high‑resolution CT of the chest to evaluate for bronchiectasis, interstitial lung disease, or occult masses. 2
• Consider bronchoscopy to assess for endobronchial lesions, sarcoidosis, eosinophilic bronchitis, or occult infection when the comprehensive work‑up remains inconclusive. 2
• Refer to a specialist cough clinic when the condition remains undiagnosed after systematic evaluation of UACS, asthma, and GERD. 2

Common Pitfalls

• Assuming a single etiology: Up to 67% of chronic cough patients have multiple concurrent causes; combination therapy is often required. 2
• Neglecting medication review: Failure to discontinue ACE inhibitors before extensive work‑up can lead to unnecessary investigations. 2
• Relying solely on acid suppression for GERD‑related cough: Comprehensive management (lifestyle modification, dietary changes, possible prokinetics) is necessary. 2
• Inadequate trial duration: Empiric therapeutic trials should be maintained for 4–6 weeks before deeming them ineffective. 2
• Not quantifying cough severity: Use validated instruments to objectively assess treatment response. 2
• The character and timing of cough do not reliably predict the underlying cause, so systematic empiric treatment is essential. 1