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Relationship between inflammatory status and microbial composition in severe asthma and during exacerbation
Sarah Diver1, Koirobi Haldar1, Pamela Jane McDowell2,3
1Department of Respiratory Sciences, Leicester NIHR BRC, Institute for Lung Health, University of Leicester, Leicester, UK.
Allergy
|July 1, 2022
Summary
Severe asthma patients with high FeNO (fraction of exhaled nitric oxide) may not benefit from antimicrobial strategies. Mepolizumab treatment did not alter airway microbial composition in this study.
Area of Science:
- Pulmonology
- Microbiology
- Immunology
Background:
- Severe asthma management increasingly utilizes biologic therapies like mepolizumab to control T2 inflammation.
- Current biomarkers effectively assess T2 inflammation but their correlation with airway microbial composition remains unclear.
- Investigating the interplay between T2 biomarkers, microbial profiles, and mepolizumab's effects is crucial for personalized asthma care.
Purpose of the Study:
- To explore the relationship between established T2 biomarkers and airway microbial composition in severe asthma.
- To characterize subjects with a high Proteobacteria to Firmicutes ratio (ProteobacteriaHIGH).
- To evaluate the impact of mepolizumab on airway microbial ecology.
Main Methods:
- Sputum microbiota sequencing was conducted on 140 severe asthma patients during stable and exacerbation states.
- Subjects were categorized into inflammatory subgroups based on FeNO, sputum, and blood eosinophils.
- ProteobacteriaHIGH status was defined by a Proteobacteria to Firmicutes ratio ≥0.485; microbial changes post-mepolizumab were assessed.
Main Results:
- Microbial composition did not correlate with sputum or blood eosinophil levels.
- High FeNO (≥50 ppb) identified patients with less dispersed microbial profiles, characterized by high alpha-diversity and low Proteobacteria.
- ProteobacteriaHIGH subjects exhibited neutrophilia and a longer duration since asthma diagnosis; mepolizumab did not affect bacterial load or Proteobacteria levels.
Conclusions:
- Elevated FeNO may suggest a severe asthma subgroup less responsive to antimicrobial interventions during exacerbations or poor control.
- For patients with FeNO <50 ppb, microbial biomarkers are needed to guide microbiome-directed therapeutic strategies.
- Mepolizumab treatment demonstrated no significant alteration of airway microbial composition in the studied cohort.
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