What is the recommended treatment for cough variant asthma?

Management of Cough Variant Asthma

Inhaled corticosteroids (ICS) are the first-line treatment for cough variant asthma and should be initiated immediately upon diagnosis. 1

Initial Treatment Approach

Start with inhaled corticosteroids as monotherapy for all patients with cough variant asthma, as this represents the cornerstone of management with strong evidence supporting its efficacy. 1, 2

• Begin with low to medium doses of ICS (equivalent to beclomethasone 200-800 μg daily), as higher starting doses have not demonstrated additional clinical benefits. 2
• Use twice-daily dosing with proper inhaler technique, employing large volume spacers with metered-dose inhalers to optimize drug delivery. 2
• Consider dry powder inhalers as first-line options for many patients due to ease of use and lower environmental impact. 2

Diagnostic Confirmation

Before initiating treatment, confirm the diagnosis through:

• Bronchial challenge testing (methacholine inhalation test) to demonstrate airway hyperresponsiveness, which distinguishes cough variant asthma from non-asthmatic eosinophilic bronchitis. 1
• Non-invasive inflammatory markers such as sputum eosinophil counts or fractional exhaled nitric oxide (FENO) to assess eosinophilic inflammation and predict corticosteroid responsiveness. 1, 2
• A negative bronchial hyperresponsiveness test excludes asthma but does not rule out steroid-responsive cough. 1

Stepwise Treatment Algorithm

Step 1: ICS Monotherapy

• Initiate ICS at standard doses for 4-8 weeks. 1
• Monitor cough symptoms and assess response. 1

Step 2: Incomplete Response

If cough persists after initial ICS therapy:

• Increase ICS dose up to a daily equivalent of 2000 μg beclomethasone. 1, 2
• Add a leukotriene receptor antagonist (such as montelukast) as there is specific evidence supporting this combination at step 3. 1
• Consider adding beta-agonists in combination with ICS, as bronchodilators can be effective in cough variant asthma. 1, 3
• Reconsider alternative causes of cough before escalating therapy further. 1

Step 3: Combination Therapy

For patients requiring further escalation:

• Add a long-acting beta2-agonist (LABA) to low-medium dose ICS rather than continuing to increase ICS dose alone, as combination therapy provides superior outcomes. 2, 4
• Combination therapy with salmeterol/fluticasone has been shown to provide more pronounced improvements in cough symptoms, pulmonary function, and airway inflammation compared to beta-agonist alone. 4
• Note: At step 3, there is no evidence for using LABA in cough variant asthma according to older guidelines, though newer evidence supports combination therapy. 1, 4

Step 4: Refractory Cases

For patients with persistent cough despite optimized inhaled therapy:

• Short-burst oral corticosteroids (prednisolone 30 mg daily for 1-3 weeks) can establish diagnosis and provide rapid symptom control. 1, 3, 5, 6
• If no response to prednisolone 30 mg/day for 2 weeks, cough is unlikely due to eosinophilic airway inflammation and alternative diagnoses should be considered. 1
• Refer to cough specialists if symptoms persist despite appropriate therapy. 3

Long-Term Management

Continue inhaled corticosteroids for extended periods as maintenance therapy, as discontinuation leads to recurrence of symptoms and worsening of airway inflammation. 4, 7

• 30% of patients with cough variant asthma develop typical bronchial asthma within several years, making long-term anti-inflammatory therapy essential. 3, 7
• Allow 1-3 months of stability before attempting stepwise reduction in ICS dose. 2
• When reducing therapy, decrease by 25-50% at each step. 2
• Monitor for symptom control; patients requiring short-acting beta2-agonists more than 2-3 times daily should remain on or be started on ICS. 2

Critical Pitfalls to Avoid

Do not discontinue or interrupt anti-inflammatory therapy prematurely, as this causes rapid return of cough symptoms, deterioration of pulmonary function, and aggravation of eosinophilic airway inflammation to baseline levels. 4

• Verify proper inhaler technique and medication adherence before escalating therapy. 2
• Be aware that spontaneous relief of cough can lead to false-positive therapeutic diagnosis. 3
• Consider checking for gastroesophageal reflux disease as a contributing factor, as it commonly coexists with cough variant asthma. 1
• Monitor for adverse effects with high-dose ICS, including adrenal suppression and local side effects. 2

Special Considerations

Non-asthmatic eosinophilic bronchitis (characterized by eosinophilic inflammation without airway hyperresponsiveness) also responds to ICS as first-line treatment, with similar stepwise escalation if response is incomplete. 1, 2

The distinction between cough variant asthma and non-asthmatic eosinophilic bronchitis lies in the presence of airway hyperresponsiveness and response to bronchodilators in the former. 7