How should I manage an asthma patient with a persistent cough despite optimized inhaled corticosteroid and long‑acting β2‑agonist therapy?

Management of Refractory Cough in Asthma Patients

For asthma patients with persistent cough despite optimized ICS/LABA therapy, first verify medication adherence and inhaler technique, then add a leukotriene receptor antagonist (montelukast) as the next step before considering oral corticosteroids. 1

Initial Assessment Before Escalating Therapy

Before assuming treatment failure, systematically address these common pitfalls:

• Verify inhaler technique and medication adherence – apparent treatment failure is most often due to poor inhaler technique or non-adherence rather than true refractory disease 1, 2

• Exclude contributing conditions that commonly coexist with or mimic asthma-related cough:

  • Gastroesophageal reflux disease (GERD) – requires intensive acid suppression with proton pump inhibitors for 3 months 1
  • Upper airway cough syndrome (post-nasal drip) 3, 1
  • ACE inhibitor use – a common cause of persistent dry cough that must be discontinued 1
  • Pertussis infection in patients with paroxysmal cough, post-tussive vomiting, or inspiratory whooping 3

• Consider adding a spacer device or changing the inhaled corticosteroid medication or delivery system – this can often overcome asthma-related cough without escalating therapy 3

Stepwise Treatment Algorithm for Refractory Cough

Step 1: Optimize Current ICS Dose

• Increase ICS dose up to 2000 μg beclomethasone daily equivalent (or high-dose equivalent of your chosen ICS) before adding additional agents 1
• Continue LABA therapy – never discontinue LABA when escalating ICS, as the combination provides synergistic benefit 3, 4

Step 2: Add Leukotriene Receptor Antagonist

• Add montelukast to existing ICS/LABA therapy – this is the preferred add-on therapy for refractory cough variant asthma with specific evidence supporting this combination 1
• This step should be taken before considering oral corticosteroids 1

Step 3: Consider Long-Acting Muscarinic Antagonist

• Add a LAMA (such as umeclidinium 62.5 μg once daily) to ICS/LABA for patients with FEV1 <80% predicted and ongoing symptoms despite optimized controller therapy 2
• This represents triple therapy and should be considered before oral corticosteroids 2

Step 4: Short-Course Oral Corticosteroids

• Prescribe oral prednisolone 30 mg daily for 1-2 weeks only after maximizing inhaled therapy plus leukotriene receptor antagonist 1
• This serves both diagnostic and therapeutic purposes – cough should improve within 1-2 weeks if due to eosinophilic airway inflammation 1, 5
• Immediately transition back to high-dose inhaled corticosteroids after the oral steroid course; do not maintain patients on oral steroids long-term 1

Assessment of Airway Inflammation in Truly Refractory Cases

If cough persists despite the above stepwise approach:

• Measure sputum eosinophil counts or fractional exhaled nitric oxide (FeNO) to assess ongoing eosinophilic inflammation 1
• Patients without sputum eosinophilia do not respond to corticosteroids and require reconsideration of the diagnosis 1
• Perform bronchial challenge testing (methacholine) to confirm airway hyperresponsiveness and distinguish cough variant asthma from non-asthmatic eosinophilic bronchitis 1

Alternative Diagnosis: Non-Asthmatic Eosinophilic Bronchitis

• This condition presents with isolated chronic cough and eosinophilic inflammation without airway hyperresponsiveness (negative methacholine test) 1
• It responds to the same stepwise ICS escalation as cough variant asthma 1
• A negative bronchial hyperresponsiveness test excludes asthma but does not rule out steroid-responsive cough 1

When to Refer to Specialist

• Consult an asthma specialist if the patient requires Step 5-6 therapy (high-dose ICS/LABA plus additional controller), has uncontrolled asthma despite optimizing therapy, or may be a candidate for biologic therapies such as omalizumab 2, 6
• Patients with apparent corticosteroid resistance require specialist evaluation for alternative diagnoses 1

Critical Pitfalls to Avoid

• Never use LABA as monotherapy – this increases risk of asthma-related deaths and must always be combined with ICS 3, 7, 2
• Do not prescribe oral steroids without first optimizing inhaled therapy – this violates guideline-based stepwise therapy 1
• Do not add long-acting beta-agonists at step 3 in cough variant asthma – there is no evidence supporting their use at this stage; leukotriene receptor antagonists are preferred 1
• Avoid repeated courses of oral steroids – maintain long-term control with inhaled corticosteroids after an oral steroid course 1