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Sputum microbiome profiles identify severe asthma phenotypes of relative stability at 12-18 months

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Title: Sputum microbiome profiles identify severe asthma phenotypes of relative stability at 12-18 months
Authors: Abdel-Aziz, MI
Brinkman, P
Vijverberg, SJH
Neerincx, AH
Riley, JH
Bates, S
Hashimoto, S
Kermani, NZ
Chung, KF
Djukanovic, R
Dahlén, S-E
Adcock, IM
Howarth, PH
Sterk, PJ
Kraneveld, AD
Maitland-van der Zee, AH
U-BIOPRED Study Group
Item Type: Journal Article
Abstract: BACKGROUND: Asthma is a heterogeneous disease characterized by distinct phenotypes with associated microbial dysbiosis. OBJECTIVES: To identify severe asthma phenotypes based on sputum microbiome profiles and assess their stability after 12-18 months. Furthermore, to evaluate clusters' robustness after inclusion of an independent mild-to-moderate asthmatics. METHODS: In this longitudinal multicenter cohort study, sputum samples were collected for microbiome profiling from a subset of the U-BIOPRED adult patient cohort at baseline and after 12-18 months of follow-up. Unsupervised hierarchical clustering was performed 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 severe asthmatics. Cluster robustness was evaluated by an independent mild-moderate asthma cohort. RESULTS: Data were available for 100 severe asthma subjects (median age: 55 yrs, 42% males). Two microbiome-driven clusters were identified, characterized by differences in asthma onset, smoking status, residential locations, percentage of blood and/or sputum neutrophils and macrophages, lung spirometry, and concurrent asthma medications (all p-values <.05). Cluster 2 patients displayed a commensal-deficient bacterial profile which was associated with worse asthma outcomes compared to cluster 1. Longitudinal clusters revealed high relative stability after 12-18 months in the severe asthmatics. Further inclusion of 24 independent mild-to-moderate asthmatics was consistent with the clustering assignments. CONCLUSION: Unbiased microbiome-driven clustering revealed two distinct robust severe asthma phenotypes, which exhibited relative overtime stability. This suggests that the sputum microbiome may serve as a biomarker for better characterizing asthma phenotypes.
Date of Acceptance: 9-Apr-2020
URI: http://hdl.handle.net/10044/1/79185
DOI: 10.1016/j.jaci.2020.04.018
ISSN: 0091-6749
Publisher: Elsevier
Journal / Book Title: Journal of Allergy and Clinical Immunology
Copyright Statement: © 2020 Elsevier Ltd. All rights reserved. This manuscript is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International Licence http://creativecommons.org/licenses/by-nc-nd/4.0/.
Sponsor/Funder: Commission of the European Communities
Funder's Grant Number: 115010
Keywords: Asthma Phenotypes
Follow-up
Lung Function
Macrophages
Metagenomics
Neutrophils
Sputum Microbiome
Unbiased Clusters
U-BIOPRED Study Group
Asthma Phenotypes
Follow-up
Lung Function
Macrophages
Metagenomics
Neutrophils
Sputum Microbiome
Unbiased Clusters
1107 Immunology
Allergy
Publication Status: Published online
Conference Place: United States
Embargo Date: 2021-04-09
Online Publication Date: 2020-04-09
Appears in Collections:Computing
National Heart and Lung Institute
National Heart and Lung Institute
Faculty of Medicine