What is the best treatment for cough variant asthma?

Treatment of Cough Variant Asthma

Inhaled corticosteroids (ICS) should be considered first-line treatment for cough variant asthma, with a step-up to combination low-dose ICS-formoterol as both maintenance and reliever therapy if response is incomplete. 1

First-Line Treatment Approach

Cough variant asthma (CVA) is characterized by persistent cough as the predominant or sole symptom, with minimal or no wheezing or dyspnea, but with underlying airway hyperresponsiveness and inflammation.

Initial Treatment:

• Start with inhaled corticosteroids (ICS) as first-line therapy 1
  • This addresses the underlying eosinophilic airway inflammation that is present in CVA
  • Studies show ICS can relieve cough in up to 90% of patients with CVA 2
  • ICS therapy not only relieves cough but also decreases bronchial hyperresponsiveness, reducing the risk of progression to classic asthma 2

Step-Up Treatment Algorithm

If response to initial ICS therapy is incomplete, follow this evidence-based approach:

1. Step-up to low-dose ICS-formoterol as both maintenance and reliever therapy

   • This combination provides both anti-inflammatory effects and bronchodilation
   • The CHEST guidelines recommend beta-agonists in combination with ICS when initial ICS therapy is insufficient 1

2. Consider increasing the ICS dose

   • If cough persists despite combination therapy, stepping up the ICS dose may be beneficial 1
   • This approach targets the persistent eosinophilic inflammation that may require higher doses for control

3. Add a leukotriene receptor antagonist (LTRA) such as montelukast

   • Evidence supports the use of LTRAs as an add-on therapy for CVA 1
   • A randomized controlled trial showed montelukast reduced cough frequency by 75.7% after 4 weeks of treatment compared to 20.7% with placebo 3

Treatment Considerations and Monitoring

Biomarkers:

• Consider measuring airway inflammation (e.g., fractional exhaled nitric oxide, sputum eosinophils) to guide therapy 1
• Presence of eosinophilic airway inflammation is associated with a more favorable response to corticosteroids 1

Duration of Treatment:

• Long-term management with ICS is recommended as approximately 30% of patients with CVA develop typical bronchial asthma within several years 4
• Regular follow-up to assess cough control and medication requirements is essential

Common Pitfalls to Avoid:

1. Misdiagnosis: Ensure proper diagnosis of CVA through bronchial challenge testing when spirometry is normal 1
2. Inadequate treatment duration: A trial of at least 2-4 weeks is needed to properly assess response to therapy 1, 5
3. Overlooking alternative causes: If cough persists despite optimal therapy, reconsider the diagnosis and evaluate for other causes 1
4. Using only bronchodilators: Treating with beta-agonists alone without addressing underlying inflammation is insufficient 2

Why ICS-Formoterol Combination is Superior

The combination of ICS and formoterol provides several advantages:

1. Synergistic effects: Formoterol enhances glucocorticoid action at the transcriptome level, while budesonide (an ICS) represses formoterol-induced proinflammatory gene expression 6

2. Dual action: Addresses both inflammation (with ICS) and bronchoconstriction (with formoterol)

3. Flexible dosing: Can be used both as maintenance and as-needed therapy for symptom relief

4. Rapid onset: Formoterol provides quick relief while ICS addresses the underlying inflammation

In conclusion, while montelukast may be beneficial as an add-on therapy, and intermittent ICS-formoterol could be considered for milder cases, the evidence most strongly supports using low-dose ICS-formoterol as both maintenance and reliever therapy for optimal control of cough variant asthma when initial ICS therapy is insufficient.