How should I manage a patient with chronic cough, sputum eosinophils >3%, and a negative methacholine challenge consistent with non‑asthmatic eosinophilic bronchitis?

Management of Non-Asthmatic Eosinophilic Bronchitis

Start inhaled corticosteroids immediately as first-line therapy—specifically budesonide 400 μg twice daily—which will improve cough symptoms and reduce sputum eosinophils within 4 weeks. 1, 2

Confirm the Diagnosis First

Before initiating treatment, verify you have the correct diagnosis by ensuring all three criteria are met:

• Sputum eosinophils >3% (gold standard diagnostic test) 1, 3
• Normal methacholine challenge (PC20 >8 mg/ml, confirming absence of airway hyperresponsiveness) 1, 4, 3
• Normal spirometry and peak flow variability (excluding asthma) 4, 3

The presence of elevated fractional exhaled nitric oxide (FeNO) can provide additional supportive evidence for eosinophilic inflammation and predict corticosteroid responsiveness. 1

Initial Treatment Strategy

First-Line: Inhaled Corticosteroids

Budesonide 400 μg inhaled twice daily is the evidence-based starting regimen, demonstrating normalization of capsaicin cough sensitivity after 4 weeks and significant reduction in sputum eosinophil counts from 40% to 4%. 1, 2, 4, 3

• Expect clinical improvement in cough within 4 weeks of starting therapy 1, 2
• The treatment-induced change in cough sensitivity correlates positively with reduction in sputum eosinophil count 2
• Response to inhaled corticosteroids is associated with the presence of airway eosinophilia and serves as both therapeutic and diagnostic confirmation 1, 5

Alternative First-Line: Allergen/Occupational Avoidance

If you identify a causal allergen or occupational sensitizer, avoidance takes priority over pharmacotherapy and is the best treatment. 1, 2

• Always inquire about occupational exposures to known sensitizers (isocyanates, flour, laboratory animals, etc.) 1, 2
• Common inhalant allergens should also be investigated 6, 7
• When a trigger is identified and removed, pharmacotherapy may become unnecessary 1

Escalation for Incomplete Response

If symptoms persist despite 4 weeks of budesonide 400 μg twice daily:

1. Step up the inhaled corticosteroid dose to high-dose therapy 1, 2
2. Reconsider alternative causes of cough before escalating further (gastroesophageal reflux, rhinitis, post-viral) 1
3. Add a leukotriene receptor antagonist as adjunctive therapy 1, 7
4. Reserve oral corticosteroids for patients with persistently troublesome symptoms despite high-dose inhaled corticosteroids or when eosinophilic inflammation progresses despite maximal inhaled therapy 1, 2

The evidence for leukotriene receptor antagonists and oral corticosteroids in non-asthmatic eosinophilic bronchitis is limited to expert opinion and small case series, but these agents are recommended when first-line therapy fails. 1, 6

Monitoring Treatment Response

• Reassess cough symptoms and sputum eosinophil counts after 4 weeks of therapy 2, 3
• Improvement in both clinical symptoms and reduction in sputum eosinophils confirms appropriate treatment 2, 4
• Treatment duration is inversely correlated with relapse rate—longer treatment courses reduce recurrence 6

Critical Pitfalls to Avoid

Do not confuse non-asthmatic eosinophilic bronchitis with eosinophilic pneumonitis—the latter has 100% treatment failure with inhaled corticosteroids alone and requires systemic therapy. 2, 8

Do not expect improvement in patients with chronic cough without sputum eosinophilia—they will not respond to inhaled corticosteroids, making sputum analysis essential before starting therapy. 2, 3

Do not use beta-agonists as monotherapy—unlike asthma, beta-agonists have no established role in non-asthmatic eosinophilic bronchitis since there is no bronchospasm or airway hyperresponsiveness. 1, 7

Natural History and Long-Term Management

The natural history is generally benign but rarely self-limiting:

• 66% of patients have persistent symptoms and/or ongoing airway inflammation requiring continued treatment 1
• 9% may progress to asthma with development of airway hyperresponsiveness 1
• Only a minority achieve complete resolution without ongoing corticosteroid therapy 1

Whether to discontinue therapy when symptoms resolve remains unclear, given evidence of basement membrane thickening and airway remodeling even in treated patients. 1, 2, 6 The optimal duration of treatment beyond symptom resolution is unknown, but longer treatment courses appear to reduce relapse rates. 6

Unanswered Questions in Current Evidence

The optimal dose of inhaled corticosteroids beyond budesonide 400 μg twice daily has not been systematically studied. 2 The role of antihistamines requires further exploration, though they are not currently recommended. 1, 2 Emerging data suggest anti-IL-5 biologics could be promising for refractory cases, but evidence is insufficient for routine recommendation. 6