What is the best approach to diagnose and treat a non-smoking patient with a chronic cough lasting several years, without accompanying symptoms of illness, and potential underlying conditions such as Gastroesophageal Reflux Disease (GERD), asthma, or environmental allergies?

Chronic Cough in a Non-Smoker Without Illness

In a non-smoking patient with chronic cough lasting several years without other symptoms, systematically treat the three most common causes sequentially and additively: upper airway cough syndrome (UACS), asthma, and gastroesophageal reflux disease (GERD), as each can present silently with cough as the only manifestation. 1

Initial Assessment

Obtain a chest radiograph and spirometry with bronchodilator response immediately to exclude serious pathology and characterize any airflow obstruction. 2, 3 The chest X-ray rules out malignancy, tuberculosis, bronchiectasis, and other structural lung diseases that require different management. 3, 4

Critical point: The character, timing, or presence of sputum production has no diagnostic value and should not guide your clinical approach. 1 Even patients with significant sputum production typically have UACS, asthma, or GERD as the underlying cause. 1

Sequential Empiric Treatment Algorithm

Step 1: Upper Airway Cough Syndrome (First-Line)

Start with a first-generation antihistamine plus decongestant combination as UACS accounts for approximately 44% of chronic cough cases. 2, 3 This should be tried for 2-4 weeks before moving to the next step. 1

• UACS frequently presents with no nasal symptoms, throat clearing, or postnasal drip sensation—hence the term "silent UACS." 1
• If no response after 2-4 weeks of antihistamine/decongestant therapy, obtain sinus imaging (CT sinuses) to evaluate for chronic sinusitis. 1

Step 2: Asthma (Second-Line)

If cough persists after treating UACS, evaluate for asthma even with normal spirometry. 1, 2

• Normal spirometry does not exclude cough-variant asthma. 2, 3 Many patients with cough-variant asthma lack sufficient reversibility to meet traditional diagnostic criteria. 3
• Ideally perform bronchoprovocation challenge testing if spirometry is normal. 1, 4
• If bronchoprovocation testing is unavailable, initiate an empiric trial of inhaled corticosteroids with or without bronchodilators for 4-6 weeks. 3, 5
• Consider checking exhaled nitric oxide and blood eosinophil count to support the diagnosis. 5

Step 3: Gastroesophageal Reflux Disease (Third-Line)

GERD commonly presents without heartburn or regurgitation—termed "silent GERD." 1, 3

• Initiate intensive acid suppression therapy (proton pump inhibitor twice daily) for at least 3 months, as GERD-related cough requires prolonged treatment to respond. 3, 5
• Do not rely on the presence or absence of GI symptoms to rule in or out GERD as a cause. 1

Step 4: Non-Asthmatic Eosinophilic Bronchitis

If the above treatments fail, obtain induced sputum for eosinophil count to evaluate for non-asthmatic eosinophilic bronchitis (NAEB). 1

• NAEB accounts for 13-33% of chronic cough cases in some series and responds predictably to inhaled corticosteroids. 1
• This diagnosis is characterized by eosinophilic airway inflammation, normal spirometry, and absence of bronchial hyperresponsiveness. 1

When to Pursue Advanced Testing

Proceed to high-resolution CT chest only after sequential empiric treatment for all three common causes has failed and adequate treatment duration has been allowed (several weeks for UACS/asthma, ≥3 months for GERD). 3

• HRCT identifies abnormalities in up to 42% of patients with normal chest radiographs and is diagnostic in 24% of chronic cough patients who failed initial protocols. 3
• HRCT is the reference standard for detecting bronchiectasis, which accounts for up to 8% of chronic cough cases and may be missed on chest radiography. 3

Critical Pitfalls to Avoid

Multiple causes are present simultaneously in 25% of patients. 6 Treatment must be sequential AND additive—do not stop one therapy when starting another. 1, 2 Partial treatment of multifactorial cough will not resolve symptoms. 2

Do not order extensive testing upfront. Sequential empiric treatment is more cost-effective than comprehensive initial investigation when UACS prevalence is approximately 44%. 3

Do not rely solely on spirometry to diagnose or exclude asthma. Normal spirometry does not rule out cough-variant asthma. 2, 3

Red Flags Requiring Direct Investigation

Pursue immediate diagnostic workup rather than empiric treatment if any of the following are present: 3

• Hemoptysis
• Significant dyspnea or respiratory distress
• Fever or systemic symptoms
• Unintentional weight loss
• History of cancer, tuberculosis, or AIDS
• Chest radiograph findings suggestive of mass or malignancy

Refractory Chronic Cough

If cough persists despite optimal treatment of all identified causes for 4-6 weeks (or 3+ months for GERD), consider neuromodulatory therapy: 7, 5

• Low-dose morphine (preferred agent)
• Gabapentin or pregabalin
• Speech and language therapy (cough control therapy)

These agents target the hypersensitive cough reflex that characterizes refractory chronic cough. 7, 5