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

Autor: Abdel-Aziz MI; Department of Respiratory Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands; Department of Clinical Pharmacy, Faculty of Pharmacy, Assiut University, Assiut, Egypt., Brinkman P; Department of Respiratory Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands., Vijverberg SJH; Department of Respiratory Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands., Neerincx AH; Department of Respiratory Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands., Riley JH; Respiratory Therapeutic Unit, GlaxoSmithKline, Stockley Park, United Kingdom., Bates S; Respiratory Therapeutic Unit, GlaxoSmithKline, Stockley Park, United Kingdom., Hashimoto S; Department of Respiratory Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands; Department of Pediatric Respiratory Medicine, Emma Children's Hospital, Amsterdam UMC, Amsterdam, The Netherlands., Kermani NZ; Data Science Institute, Imperial College London London, United Kingdom., Chung KF; National Heart and Lung Institute, Imperial College London, and Royal Brompton and Harefield NHS Trust, London, United Kingdom., Djukanovic R; NIHR Southampton Respiratory Biomedical Research Unit, Clinical and Experimental Sciences and Human Development and Health, University of Southampton, Southampton, United Kingdom., Dahlén SE; Centre for Allergy Research, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden., Adcock IM; National Heart and Lung Institute, Imperial College London, and Royal Brompton and Harefield NHS Trust, London, United Kingdom., Howarth PH; NIHR Southampton Respiratory Biomedical Research Unit, Clinical and Experimental Sciences and Human Development and Health, University of Southampton, Southampton, United Kingdom., Sterk PJ; Department of Respiratory Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands., Kraneveld AD; Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands; Institute for Risk Assessment Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands., Maitland-van der Zee AH; Department of Respiratory Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands; Department of Pediatric Respiratory Medicine, Emma Children's Hospital, Amsterdam UMC, Amsterdam, The Netherlands. Electronic address: a.h.maitland@amsterdamumc.nl.
Jazyk: angličtina
Zdroj: The Journal of allergy and clinical immunology [J Allergy Clin Immunol] 2021 Jan; Vol. 147 (1), pp. 123-134. Date of Electronic Publication: 2020 Apr 28.
DOI: 10.1016/j.jaci.2020.04.018
Abstrakt: 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.
(Copyright © 2020 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: