Relationship between inflammatory status and microbial composition in severe asthma and during exacerbation.
Diver, Sarah Haldar, Koirobi McDowell, Pamela Jane Busby, John Mistry, Vijay Micieli, Claudia Brown, Vanessa Cox, Ciara Yang, Freda Borg, Catherine
Diver, Sarah
Haldar, Koirobi
McDowell, Pamela Jane
Busby, John
Mistry, Vijay
Micieli, Claudia
Brown, Vanessa
Cox, Ciara
Yang, Freda
Borg, Catherine
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2022-07-15
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Abstract
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 ProteobacteriaHIGH 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. ProteobacteriaHIGH 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. ProteobacteriaHIGH subjects were neutrophilic and had a longer time from asthma diagnosis than ProteobacteriaLOW 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.
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Diver S, Haldar K, McDowell PJ, Busby J, Mistry V, Micieli C, Brown V, Cox C, Yang F, Borg C, Shrimanker R, Ramsheh MY, Hardman T, Arron J, Bradding P, Cowan D, Mansur AH, Fowler SJ, Lordan J, Menzies-Gow A, Robinson D, Matthews J, Pavord ID, Chaudhuri R, Heaney LG, Barer MR, Brightling C; Medical Research Council: Refractory Asthma Stratification Programme (RASP-UK Consortium). Relationship between inflammatory status and microbial composition in severe asthma and during exacerbation. Allergy. 2022 Nov;77(11):3362-3376. doi: 10.1111/all.15425. Epub 2022 Jul 15
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Article