What is the recommended management for a patient with cough variant asthma?

Management of Cough Variant Asthma

Initiate inhaled corticosteroids (ICS) immediately as first-line therapy for cough variant asthma, starting at low to medium doses (equivalent to beclomethasone 200-800 μg daily) combined with an inhaled bronchodilator. 1, 2

Initial Treatment Strategy

• Start combination therapy with ICS plus inhaled beta-agonist bronchodilator as soon as the diagnosis is established, rather than using either agent alone 1, 2
• Use twice-daily dosing with proper inhaler technique, employing large volume spacers with metered-dose inhalers to optimize drug delivery 2
• Continue treatment for 4-8 weeks while monitoring cough symptoms to assess initial response 2
• Ensure medication compliance and proper inhaler technique before considering treatment failure, as apparent non-response is often due to poor adherence or incorrect use 2

Diagnostic Confirmation

• Perform bronchial challenge testing (methacholine inhalation test) to confirm airway hyperresponsiveness when physical examination and spirometry are non-diagnostic 1
• Consider measuring non-invasive inflammatory markers (sputum eosinophil counts or fractional exhaled nitric oxide) to assess eosinophilic inflammation and predict corticosteroid responsiveness 1, 2
• A definitive diagnosis of cough variant asthma requires resolution of cough with specific antiasthmatic therapy 1

Stepwise Escalation for Incomplete Response

Step 1: Increase ICS Dose

• If cough persists after 4-8 weeks of initial therapy, increase the ICS dose up to a daily equivalent of 2000 μg beclomethasone before adding other agents 1, 2
• Reassess for alternative causes of cough, particularly gastroesophageal reflux disease, ACE inhibitor use, and upper airway cough syndrome 1, 2

Step 2: Add Leukotriene Receptor Antagonist

• Add montelukast or another leukotriene receptor antagonist (LTRA) to the existing ICS and bronchodilator regimen if cough remains refractory after dose escalation 1, 2
• Montelukast has demonstrated specific efficacy in suppressing cough previously resistant to bronchodilators and inhaled steroids, with a 75.7% reduction in cough frequency versus 20.7% with placebo 3
• LTRAs should be used in addition to inhaled steroids rather than as monotherapy, as the question of whether these agents are sufficient alone remains unresolved 1

Step 3: Short Course of Oral Corticosteroids

• For severe or refractory cough that fails to respond to maximized inhaled therapy plus LTRA, prescribe oral prednisolone 30 mg daily (or equivalent) for 1-2 weeks 1, 2
• Follow the oral steroid course with transition back to inhaled corticosteroids for long-term maintenance 1, 4
• Cough control should occur within 1-2 weeks if due to eosinophilic airway inflammation 2, 4

Evidence Quality and Strength

The 2020 CHEST guideline provides Grade 1B recommendations for ICS as first-line treatment, reflecting very strong evidence for stepwise asthma treatment in general, though cough-specific studies are limited 1. The combination of ICS with beta-agonists is more effective than beta-agonist monotherapy, with one study showing 90% complete cough relief with ICS versus 80% persistent cough with beta-agonists alone 5. Combination therapy with salmeterol/fluticasone propionate provides superior improvements in cough symptoms, pulmonary function, and airway inflammation compared to salmeterol alone 6.

Critical Pitfalls to Avoid

• Never use long-acting beta-agonists as monotherapy without concurrent ICS, as this increases the risk of serious asthma-related events 7
• Do not jump directly to systemic steroids without trying inhaled therapy first, as this exposes patients to unnecessary systemic side effects when inhaled medications are highly effective 7
• Do not discontinue anti-inflammatory therapy prematurely, as stopping treatment causes worsening of cough symptoms, pulmonary function, and eosinophilic airway inflammation back to baseline levels 6
• Exclude ACE inhibitor use before escalating therapy, as these drugs commonly cause persistent dry cough that mimics cough variant asthma 2

Long-Term Management Considerations

• Chronic anti-inflammatory therapy is appropriate for cough variant asthma given the presence of subepithelial layer thickening and airway remodeling, though to a lesser extent than typical asthma 1, 2
• Monitor for progression to classic asthma, as inadequate treatment may lead to development of wheezing and dyspnea over time 2
• Maintain long-term control with inhaled corticosteroids after any oral steroid course, and avoid repeated courses of oral steroids 2

Differential Diagnosis: Non-Asthmatic Eosinophilic Bronchitis

• Consider non-asthmatic eosinophilic bronchitis (NAEB) in patients with chronic cough who have eosinophilic inflammation but lack airway hyperresponsiveness on bronchial challenge testing 1, 2
• NAEB also responds to ICS as first-line treatment with similar stepwise escalation if response is incomplete (Grade 2B recommendation) 1
• A negative bronchial hyperresponsiveness test excludes asthma but does not rule out steroid-responsive cough 2