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Relationship between inflammatory status and microbial composition in severe asthma and during exacerbation
Author(s) -
Diver Sarah,
Haldar Koirobi,
McDowell Pamela Jane,
Busby John,
Mistry Vijay,
Micieli Claudia,
Brown Vanessa,
Cox Ciara,
Yang Freda,
Borg Catherine,
Shrimanker Rahul,
Ramsheh Mohammadali Yavari,
Hardman Tim,
Arron Joseph,
Bradding Peter,
Cowan Douglas,
Mansur Adel Hasan,
Fowler Stephen J.,
Lordan Jim,
MenziesGow Andrew,
Robinson Douglas,
Matthews John,
Pavord Ian D.,
Chaudhuri Rekha,
Heaney Liam G.,
Barer Michael R.,
Brightling Christopher
Publication year - 2022
Publication title -
allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.363
H-Index - 173
eISSN - 1398-9995
pISSN - 0105-4538
DOI - 10.1111/all.15425
Subject(s) - sputum , medicine , mepolizumab , exacerbation , immunology , asthma , eosinophil , tuberculosis , pathology
Background In T2‐mediated severe asthma, biologic therapies, such as mepolizumab, are increasingly used to control disease. Current biomarkers can indicate adequate suppression of T2 inflammation, but it is unclear whether they provide information about airway microbial composition. We investigated the relationships between current T2 biomarkers and microbial profiles, characteristics associated with a Proteobacteria HIGH microbial profile and the effects of mepolizumab on airway ecology. Methods Microbiota sequencing was performed on sputum samples obtained at stable and exacerbation state from 140 subjects with severe asthma participating in two clinical trials. Inflammatory subgroups were compared on the basis of biomarkers, including FeNO and sputum and blood eosinophils. Proteobacteria HIGH subjects were identified by Proteobacteria to Firmicutes ratio ≥0.485. Where paired sputum from stable visits was available, we compared microbial composition at baseline and following ≥12 weeks of mepolizumab. Results Microbial composition was not related to inflammatory subgroup based on sputum or blood eosinophils. FeNO ≥50 ppb when stable and at exacerbation indicated a group with less dispersed microbial profiles characterised by high alpha‐diversity and low Proteobacteria. Proteobacteria HIGH subjects were neutrophilic and had a longer time from asthma diagnosis than Proteobacteria LOW subjects. In those studied, mepolizumab did not alter airway bacterial load or lead to increased Proteobacteria. Conclusion High FeNO could indicate a subgroup of severe asthma less likely to benefit from antimicrobial strategies at exacerbation or in the context of poor control. Where FeNO is <50 ppb, biomarkers of microbial composition are required to identify those likely to respond to microbiome‐directed strategies. We found no evidence that mepolizumab alters airway microbial composition.