Imperial College London


Faculty of MedicineNational Heart & Lung Institute

Asthma UK Clinical Chair



+44 (0)20 7594 3764s.johnston




Mr Christophe Tytgat +44 (0)20 7594 3849




343Norfolk PlaceSt Mary's Campus






BibTex format

author = {Ghebre, MA and Pang, PH and Diver, S and Desai, D and Bafadhel, M and Haldar, K and Kebadze, T and Cohen, S and Newbold, P and Rapley, L and Woods, J and Rugman, P and Pavord, ID and Johnston, SL and Barer, M and May, RD and Brightling, CE},
doi = {10.1016/j.jaci.2018.04.013},
journal = {Journal of Allergy and Clinical Immunology},
pages = {2027--2036.e12},
title = {Biological exacerbation clusters demonstrate asthma and COPD overlap with distinct mediator and microbiome profiles.},
url = {},
volume = {141},
year = {2018}

RIS format (EndNote, RefMan)

AB - 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.
AU - Ghebre,MA
AU - Pang,PH
AU - Diver,S
AU - Desai,D
AU - Bafadhel,M
AU - Haldar,K
AU - Kebadze,T
AU - Cohen,S
AU - Newbold,P
AU - Rapley,L
AU - Woods,J
AU - Rugman,P
AU - Pavord,ID
AU - Johnston,SL
AU - Barer,M
AU - May,RD
AU - Brightling,CE
DO - 10.1016/j.jaci.2018.04.013
EP - 2036
PY - 2018///
SN - 0091-6749
SP - 2027
TI - Biological exacerbation clusters demonstrate asthma and COPD overlap with distinct mediator and microbiome profiles.
T2 - Journal of Allergy and Clinical Immunology
UR -
UR -
UR -
UR -
VL - 141
ER -