What is the appropriate evaluation and treatment approach for a patient presenting with a persistent cough, considering potential underlying respiratory conditions and their medical history?

Persistent Cough: Evaluation and Management

Duration Classification and Initial Approach

For persistent cough, immediately classify duration as acute (<3 weeks), subacute (3-8 weeks), or chronic (>8 weeks), as this fundamentally determines your diagnostic and treatment pathway. 1, 2, 3

• Obtain a chest radiograph in all patients with chronic cough (>8 weeks) to exclude malignancy, structural abnormalities, infiltrates, masses, or cardiac enlargement. 1, 3, 4
• Perform spirometry in all patients with chronic cough to identify obstructive patterns, assess bronchodilator response, and diagnose asthma or COPD. 1, 3, 4
• Note that normal spirometry does not exclude asthma, as many patients with cough-variant asthma have normal pulmonary function tests. 1

Critical Medication and Exposure History

Immediately discontinue ACE inhibitors if present—they are a common reversible cause of cough, with resolution typically occurring within 26 days (though may take up to 40 weeks in some patients). 5, 3, 4

• Most patients with ACE inhibitor-associated cough can tolerate angiotensin II receptor blockers. 5
• Counsel on smoking cessation, as 90-94% of smokers experience cough resolution within the first year of quitting. 3
• Obtain a thorough occupational history, as workplace sensitizers and dust/chemical exposure can lead to chronic cough. 5

Most Common Causes (Account for ~90% of Cases)

The four conditions that account for most chronic cough cases are: 6, 7

1. Upper Airway Cough Syndrome (UACS)

• Treat empirically with first-generation antihistamine/decongestant combination (not newer non-sedating antihistamines, which are ineffective for cough). 2, 3
• Add topical corticosteroid if prominent upper airway symptoms are present. 3
• Note that physical examination and sinus radiographs may be normal despite chronic rhinosinusitis being the cause. 8

2. Asthma (Including Cough-Variant Asthma)

• Asthma is the most common cause of persistent cough with wheezing, particularly when accompanied by a prolonged expiratory phase on auscultation. 1
• If spirometry shows reversible airflow obstruction, initiate inhaled bronchodilators and inhaled corticosteroids. 3
• For suspected asthma with normal spirometry, consider bronchoprovocation challenge or empiric trial of inhaled corticosteroids and bronchodilators. 3, 8
• Cough-variant asthma typically presents with persistent cough worsening at night or after exposure to cold or exercise. 5

3. Gastroesophageal Reflux Disease (GERD)

• Initiate empiric treatment with intensive acid suppression using proton pump inhibitors for a minimum of 2 months before performing esophageal testing. 3
• GERD is one of the three most common causes of chronic cough in secondary care and specialist clinics. 1

4. Non-Asthmatic Eosinophilic Bronchitis (NAEB)

• First-line treatment is inhaled corticosteroids. 2
• Perform induced sputum test for eosinophils; use empiric treatment with inhaled corticosteroids if testing is unavailable. 3
• NAEB presents with persistent cough and eosinophilic airway inflammation but lacks the bronchial hyperresponsiveness and variable airflow obstruction seen in asthma. 1

Sequential and Additive Treatment Approach

Use a sequential and additive treatment approach, as multiple causes frequently coexist and require simultaneous treatment. 2, 3, 6

• Treat each potential cause for 4-6 weeks before concluding it is not contributing. 3
• Do not treat only one cause, as multiple factors often contribute simultaneously. 3
• Formally quantify treatment effects using validated instruments such as visual analogue scores or cough-specific quality of life questionnaires. 3

Important Diagnoses Not to Miss

Cough is the fourth most common presenting feature of lung cancer, and chest radiograph is mandatory to exclude malignancy. 1

• Consider lung cancer especially in smokers with persistent symptoms and examine for finger clubbing, pleural effusion, or lobar collapse. 5, 1
• Pertussis infection can cause persistent cough; consider diagnostic testing if suspected. 5
• COPD should be considered in smokers with persistent cough, usually accompanied by phlegm production and breathlessness. 5, 1
• Bronchiectasis can cause persistent cough (even "dry" bronchiectasis), with coarse crackles more prominent than wheezes on examination. 5, 1

When to Pursue Advanced Testing or Referral

If cough persists after 4-6 weeks of empiric treatment for the top diagnoses, consider high-resolution CT scan or bronchoscopic evaluation for uncommon causes. 3

• Bronchoscopy should be undertaken in all patients in whom inhalation of a foreign body is suspected. 3
• Consider referral to a pulmonologist or specialist cough clinic when diagnosis remains unclear despite thorough evaluation. 3, 4

Refractory Chronic Cough Management

For refractory chronic cough with uncertain etiology and negative evaluation for life-threatening causes, consider cough hypersensitivity syndrome and treat with gabapentin or pregabalin plus speech therapy. 7, 9

• Low-dose opioids may also be considered for neuromodulatory treatment. 9
• Patient satisfaction with care depends most on physician-patient communication rather than on specific treatments. 5

Critical Pitfalls to Avoid

• Do not rely on cough characteristics alone for diagnosis, as they have limited diagnostic value. 2, 3
• Do not use single peak expiratory flow (PEF) measurements for assessing bronchodilator response, as they are not as accurate as FEV1. 3
• Do not label as idiopathic until thorough assessment excludes uncommon causes. 3
• Do not use newer generation non-sedating antihistamines for cough, as they are ineffective. 2