Imperial College London
Alternate

ProfessorWisiaWedzicha

Faculty of Medicine, National Heart & Lung Institute

Consul (clinical) for the Faculty of Medicine
 
 
 
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Contact

 

j.wedzicha

 
 
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Location

 

B142Guy Scadding BuildingRoyal Brompton Campus

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Summary

 

Publications

Citation

BibTex format

@article{Wang:2020:10.1164/rccm.202009-3448OC,
author = {Wang, Z and Locantore, N and Haldar, K and Ramsheh, MY and Beech, AS and Ma, W and Brown, JR and Tal-Singer, R and Barer, MR and Bafadhel, M and Donaldson, GC and Wedzicha, JA and Singh, D and Wilkinson, TMA and Miller, BE and Brightling, CE},
doi = {10.1164/rccm.202009-3448OC},
journal = {Am J Respir Crit Care Med},
title = {Inflammatory Endotype Associated Airway Microbiome in COPD Clinical Stability and Exacerbations - A Multi-Cohort Longitudinal Analysis.},
url = {http://dx.doi.org/10.1164/rccm.202009-3448OC},
year = {2020}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - RATIONALE: Understanding the role of airway microbiome in chronic obstructive pulmonary disease (COPD) inflammatory endotypes may help to develop microbiome-based diagnostic and therapeutic approaches. OBJECTIVES: To understand the association of airway microbiome with neutrophilic and eosinophilic COPD at stability and exacerbations. METHODS: An integrative analysis was performed on 1,706 sputum samples collected longitudinally from 510 COPD patients recruited at four UK sites in BEAT-COPD, COPDMAP and AERIS cohorts. The microbiome was analyzed using COPDMAP and AERIS as discovery dataset and BEAT-COPD as validation dataset. RESULTS: The airway microbiome in neutrophilic COPD was heterogeneous with two primary community types differentiated by the predominance of Haemophilus. The Haemophilus-predominant subgroup had elevated sputum IL-1b and TNFa and was relatively stable over time. The other neutrophilic subgroup with a balanced microbiome profile had elevated sputum and serum IL-17A and was temporally dynamic. Patients in this state at stability were susceptible to greatest microbiome shifts during exacerbations. This subgroup can temporally switch to both neutrophilic-Haemophilus-predominant and eosinophilic states which were otherwise mutually exclusive. Time-series analysis on the microbiome showed the temporal trajectories of Campylobacter and Granulicatella were indicative of intra-patient switches from neutrophilic to eosinophilic inflammation, and in track with patient sputum eosinophilia over time. Network analysis revealed distinct host-microbiome interaction patterns between neutrophilic-Haemophilus-predominant, neutrophilic-balanced-microbiome and eosinophilic subgroups. CONCLUSIONS: The airway microbiome can stratify neutrophilic COPD into subgroups that justify different therapies. Neutrophilic and eosinophilic COPD are inter-changeable in some patients. Monitoring temporal variability of the airway microbiome may track patient inflammatory status ov
AU  - Wang,Z
AU  - Locantore,N
AU  - Haldar,K
AU  - Ramsheh,MY
AU  - Beech,AS
AU  - Ma,W
AU  - Brown,JR
AU  - Tal-Singer,R
AU  - Barer,MR
AU  - Bafadhel,M
AU  - Donaldson,GC
AU  - Wedzicha,JA
AU  - Singh,D
AU  - Wilkinson,TMA
AU  - Miller,BE
AU  - Brightling,CE
DO  - 10.1164/rccm.202009-3448OC
PY  - 2020///
TI  - Inflammatory Endotype Associated Airway Microbiome in COPD Clinical Stability and Exacerbations - A Multi-Cohort Longitudinal Analysis.
T2  - Am J Respir Crit Care Med
UR  - http://dx.doi.org/10.1164/rccm.202009-3448OC
UR  - https://www.ncbi.nlm.nih.gov/pubmed/33332995
ER  -
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