Sputum microbiome profiles identify severe asthma phenotypes of relative stability at 12 to 18 months - 09/01/21
on behalf of the
U-BIOPRED Study Group∗
Abstract |
Background |
Asthma is a heterogeneous disease characterized by distinct phenotypes with associated microbial dysbiosis.
Objectives |
Our aim was to identify severe asthma phenotypes based on sputum microbiome profiles and assess their stability after 12 to 18 months. A further aim was to evaluate clusters’ robustness after inclusion of an independent cohort of patients with mild-to-moderate asthma.
Methods |
In this longitudinal multicenter cohort study, sputum samples were collected for microbiome profiling from a subset of the Unbiased Biomarkers in Prediction of Respiratory Disease Outcomes adult patient cohort at baseline and after 12 to 18 months of follow-up. Unsupervised hierarchical clustering was performed by using the Bray-Curtis β-diversity measure of microbial profiles. For internal validation, partitioning around medoids, consensus cluster distribution, bootstrapping, and topological data analysis were applied. Follow-up samples were studied to evaluate within-patient clustering stability in patients with severe asthma. Cluster robustness was evaluated by using an independent cohort of patients with mild-to-moderate asthma.
Results |
Data were available for 100 subjects with severe asthma (median age 55 years; 42% males). Two microbiome-driven clusters were identified; they were characterized by differences in asthma onset, smoking status, residential locations, percentage of blood and/or sputum neutrophils and macrophages, lung spirometry results, and concurrent asthma medications (all P values < .05). The cluster 2 patients displayed a commensal-deficient bacterial profile that was associated with worse asthma outcomes than those of the cluster 1 patients. Longitudinal clusters revealed high relative stability after 12 to 18 months in those with severe asthma. Further inclusion of an independent cohort of 24 patients with mild-to-moderate asthma was consistent with the clustering assignments.
Conclusion |
Unbiased microbiome-driven clustering revealed 2 distinct robust phenotypes of severe asthma that exhibited relative overtime stability. This suggests that the sputum microbiome may serve as a biomarker for better characterizing asthma phenotypes.
Le texte complet de cet article est disponible en PDF.Graphical abstract |
Key words : Sputum microbiome, metagenomics, asthma phenotypes, unbiased clusters, follow-up, neutrophils, macrophages, lung function
Abbreviations used : FDR, PAM, RI, rRNA, TDA, U-BIOPRED
Plan
| U-BIOPRED has received funding from the Innovative Medicines Initiative Joint Undertaking (under grant agreement No. 115010), the resources of which comprise financial contributions from the European Union’s Seventh Framework Programme (FP7/2007–2013) and European Federation of Pharmaceutical Industries and Associations companies’ in-kind contributions (www.imi.europa.eu). M.I.A.'s salary was sponsored by the Egyptian Government PhD Research Scholarships. |
|
| Disclosure of potential conflict of interest: J. H. Riley, S. Bates, and P. H. Howarth are employees and shareholders of GlaxoSmithKline. R. Djukanovic has received fees for lectures at symposia organized by Novartis, AstraZeneca, and TEVA, as well as consultation fees for serving as a member of advisory boards TEVA and Novartis and participating in a scientific discussion about asthma organized by GlaxoSmithKline. R. Djukanovic is a cofounder and current consultant of and has shares in Synairgen, a University of Southampton spinout company. S-E. Dahlén reports personal fees from AstraZeneca, GlaxoSmithKline, Merck & Company, Novartis, Regeneron, Sanofi, and Teva outside the submitted work. I. M. Adcock, K. F. Chung, and P. J. Sterk received grants from Innovative Medicines Initiative during the conduct of the study. A. H. Maitland-van der Zee has been reimbursed for visiting the American Thoracic Society (ATS) by Chiesi; received a fee for participating in advisory boards for Boehringer lngelheim and AstraZeneca; and received unrestricted research grants from GlaxoSmithKline, Chiesi, and Boehringer Ingelheim. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 147 - N° 1
P. 123-134 - janvier 2021 Retour au numéro
Article précédent
- Association between early antibiotic treatment and clinical outcomes in children hospitalized for asthma exacerbation
- Yusuke Okubo, Kenta Horimukai, Nobuaki Michihata, Kojiro Morita, Hiroki Matsui, Kiyohide Fushimi, Hideo Yasunaga
- Incidence of cancer after asthma development: 2 independent population-based cohort studies
- Ala Woo, Seung Won Lee, Hyun Yong Koh, Mi Ae Kim, Man Yong Han, Dong Keon Yon
Bienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.
Déjà abonné à cette revue ?