How should cough‑variant asthma be treated?

Treatment of Cough Variant Asthma

Start with inhaled corticosteroids (ICS) combined with an inhaled bronchodilator as first-line therapy immediately upon diagnosis, as this regimen provides the most effective initial control of cough and airway inflammation. 1, 2

Initial Treatment Strategy

• Begin with low to medium dose ICS (equivalent to beclomethasone 200-800 μg daily) combined with an inhaled bronchodilator (beta-2 agonist) 1, 2
• Use twice-daily dosing with proper inhaler technique, employing large volume spacers with metered-dose inhalers to optimize drug delivery 2
• Expect partial improvement within 1 week, but complete cough resolution may require up to 8 weeks of continuous ICS therapy 1
• Ensure medication compliance and proper inhaler technique before considering treatment failure, as this is the most common reason for apparent non-response 2

Diagnostic Confirmation During Treatment

• The diagnosis of cough variant asthma is only definitively established after documented resolution of cough with specific antiasthmatic therapy 1
• Methacholine inhalation challenge (MIC) testing should be performed when available to confirm airway hyperresponsiveness, though a positive test is consistent with but not diagnostic of cough variant asthma 1
• Non-invasive markers of eosinophilic inflammation (sputum eosinophils or fractional exhaled nitric oxide) predict corticosteroid responsiveness and should be measured when available 1, 2

Stepwise Escalation for Inadequate Response

Step 1: Optimize ICS Delivery

• Before escalating therapy, exclude contributing conditions: gastroesophageal reflux disease, ACE inhibitor use, upper airway cough syndrome, and poor compliance 1, 2
• Consider adding a spacer device or switching to a different ICS formulation, as the aerosol dispersant itself may induce cough (particularly with beclomethasone dipropionate) 1

Step 2: Increase ICS Dose

• Increase ICS dose up to 2000 μg beclomethasone daily equivalent if cough persists after 4-8 weeks of standard-dose therapy 2
• Continue the inhaled bronchodilator throughout dose escalation 2

Step 3: Add Leukotriene Receptor Antagonist

• Add montelukast (or another LTRA) to the existing ICS and bronchodilator regimen if cough remains refractory after ICS dose escalation 1, 2, 3
• This combination has specific evidence supporting efficacy in cough variant asthma, with zafirlukast showing 88% response rates and ability to suppress cough even when refractory to ICS alone 1
• The mechanism appears to involve more effective modulation of inflammatory mediators affecting sensory cough receptors in the airway epithelium 1

Step 4: Assess Airway Inflammation

• In patients with persistent cough despite maximized inhaled therapy plus LTRA, measure sputum eosinophils or induced sputum to assess ongoing airway inflammation 1
• Demonstration of persistent airway eosinophilia identifies patients who will benefit from more aggressive anti-inflammatory therapy 1
• Patients without sputum eosinophilia do not respond to corticosteroids and require reconsideration of alternative diagnoses 2

Step 5: Short-Course Oral Corticosteroids

• For severe and/or refractory cough, prescribe oral prednisone 30-40 mg daily (or equivalent) for 1-2 weeks, followed by transition to inhaled corticosteroids 1, 2, 4, 5
• This approach is reserved for cases that fail maximized inhaled therapy plus LTRA, after excluding poor compliance and contributing conditions 1
• Cough control should occur within 1-2 weeks if due to eosinophilic airway inflammation; lack of response suggests an alternative diagnosis 2, 5
• 80% of patients require long-term ICS therapy for sustained cough suppression after the oral steroid course 1

Critical Pitfalls to Avoid

• Never use long-acting beta-agonists (LABA) as monotherapy; they must always be combined with ICS to avoid increased asthma-related mortality risk 2
• Do not escalate to oral steroids without first attempting ICS dose escalation and LTRA addition, as this violates guideline-based stepwise therapy 2
• Recognize that inhaled steroids themselves may induce cough due to aerosol dispersants; switch formulations rather than abandoning ICS therapy 1
• Do not assume treatment failure without verifying proper inhaler technique and medication adherence 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 with wheezing and dyspnea, which occurs in a significant proportion of inadequately treated patients 2
• Maintain long-term control with inhaled corticosteroids after any oral steroid course; repeated courses of oral steroids should be avoided 2
• In 90% of patients treated appropriately with ICS, cough is completely relieved, compared to 80% of patients treated with bronchodilators alone who experience no improvement 6

Alternative Agents (Limited Role)

• Other agents with evidence of efficacy include theophylline, nedocromil sodium, azelastine hydrochloride, and suplatast tosilate, but there are no data suggesting these offer added benefit to the standard regimen of ICS, bronchodilator, and LTRA 1