Biological exacerbation clusters demonstrate asthma and COPD overlap with distinct mediator and microbiome profiles.

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Title: Biological exacerbation clusters demonstrate asthma and COPD overlap with distinct mediator and microbiome profiles.
Authors: Ghebre, MA
Pang, PH
Diver, S
Desai, D
Bafadhel, M
Haldar, K
Kebadze, T
Cohen, S
Newbold, P
Rapley, L
Woods, J
Rugman, P
Pavord, ID
Johnston, SL
Barer, M
May, RD
Brightling, CE
Item Type: Journal Article
Abstract: BACKGROUND: Exacerbations of asthma and chronic obstructive pulmonary disease (COPD) are heterogeneous. OBJECTIVE: We sought to investigate the sputum cellular, mediator, and microbiome profiles of both asthma and COPD exacerbations. METHODS: Patients with severe asthma or moderate-to-severe COPD were prospectively recruited to a single centre. Sputum mediators were available in 32 asthma and 73 COPD patients assessed at exacerbation. Biologic clusters were determined using factor and cluster analyses on a panel of sputum mediators. Patterns of clinical parameters, sputum mediators, and microbiome communities were assessed across the identified clusters. RESULTS: The asthma and COPD patients had different clinical characteristics and inflammatory profiles, but similar microbial ecology. Three exacerbation biologic clusters were identified. Cluster 1 was COPD predominant, with 27 COPD and 7 asthma patients exhibiting elevated blood and sputum neutrophil counts, proinflammatory mediators (IL-1β, IL-6, IL-6R, TNFα, TNF-R1, TNF-R2, and VEGF), and proportion of the bacterial phylum Proteobacteria. Cluster 2 had 10 asthma and 17 COPD patients with elevated blood and sputum eosinophil counts, Type 2 (T2) mediators (IL-5, IL-13, CCL13, CCL17, and CCL26), and proportion of the bacterial phylum Bacteroidetes. Cluster 3 had 15 asthma and 29 COPD subjects with elevated Type 1 (T1) mediators (CXCL10, CXCL11, and IFN-ϒ) and proportions of phyla Actinobacteria and Firmicutes. CONCLUSIONS: A biologic clustering approach revealed three subgroups of asthma and COPD exacerbations each with different percentages of overlapping asthma and COPD patients. The sputum mediator and microbiome profiles were distinct between clusters. CLINICAL IMPLICATIONS: Sputum mediator and microbiome profiling can determine the distinct and overlapping asthma and COPD biologic exacerbation clusters, highlighting the heterogeneity of these exacerbations.
Issue Date: 28-Apr-2018
Date of Acceptance: 24-Apr-2018
URI: http://hdl.handle.net/10044/1/59280
DOI: https://doi.org/10.1016/j.jaci.2018.04.013
ISSN: 0091-6749
Publisher: Elsevier
Start Page: 2027
End Page: 2036.e12
Journal / Book Title: Journal of Allergy and Clinical Immunology
Volume: 141
Issue: 6
Copyright Statement: © 2018 The Authors. Published by Elsevier Inc. on behalf of the American Academy ofAllergy, Asthma & Immunology. This is an open access article under the CC BY li-cense (http://creativecommons.org/licenses/by/4.0/).
Sponsor/Funder: Medical Research Council (MRC)
Asthma UK
Medical Research Council (MRC)
Funder's Grant Number: G1000758
Asthma UK Centre
G1000758
Keywords: Science & Technology
Life Sciences & Biomedicine
Allergy
Immunology
Asthma
chronic obstructive pulmonary disease
asthma and chronic obstructive pulmonary disease heterogeneity
inflammatory profiles
microbiome abundances
phylum and genus levels
factor and cluster analyses
PLACEBO-CONTROLLED TRIAL
RANDOMIZED CONTROLLED-TRIAL
SEVERE EOSINOPHILIC ASTHMA
CONTROLLED PHASE-3 TRIAL
DOUBLE-BLIND
RHINOVIRUS INFECTION
SPUTUM EOSINOPHILIA
COPD
AZITHROMYCIN
MEPOLIZUMAB
Asthma
asthma and chronic obstructive pulmonary disease heterogeneity
chronic obstructive pulmonary disease
factor and cluster analyses
inflammatory profiles
microbiome abundances
phylum and genus levels
Asthma
asthma and COPD heterogeneity
chronic obstructive pulmonary disease
factor and cluster analyses
inflammatory profiles
microbiome abundances
phylum and genus levels
Allergy
1107 Immunology
Publication Status: Published
Conference Place: United States
Online Publication Date: 2018-04-28
Appears in Collections:National Heart and Lung Institute
Faculty of Medicine



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