Inflammatory phenotypes in patients with severe asthma are associated with distinct airway microbiology

dc.contributor.author Taylor, Steven L
dc.contributor.author Leong, Lex E X
dc.contributor.author Choo, Jocelyn M
dc.contributor.author Wesselingh, Steven L
dc.contributor.author Yang, Ian A
dc.contributor.author Upham, John W
dc.contributor.author Reynolds, Paul N
dc.contributor.author Hodge, Sandra
dc.contributor.author James, Alan L
dc.contributor.author Jenkins, Christine
dc.contributor.author Peters, Matthew J
dc.contributor.author Baraket, Melissa
dc.contributor.author Marks, Guy B
dc.contributor.author Gibson, Peter G
dc.contributor.author Simpson, Jodie L
dc.contributor.author Rogers, Geraint B
dc.date.accessioned 2018-03-26T23:11:24Z
dc.date.available 2018-03-26T23:11:24Z
dc.date.issued 2017-05-04
dc.description This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). en_US
dc.description.abstract Background Asthma pathophysiology and treatment responsiveness are predicted by inflammatory phenotype. However, the relationship between airway microbiology and asthma phenotype is poorly understood. Objective We aimed to characterize the airway microbiota in patients with symptomatic stable asthma and relate composition to airway inflammatory phenotype and other phenotypic characteristics. Methods The microbial composition of induced sputum specimens collected from adult patients screened for a multicenter randomized controlled trial was determined by using 16S rRNA gene sequencing. Inflammatory phenotypes were defined by sputum neutrophil and eosinophil cell proportions. Microbiota were defined by using α- and β-diversity measures, and interphenotype differences were identified by using similarity of percentages, network analysis, and taxon fold change. Phenotypic predictors of airway microbiology were identified by using multivariate linear regression. Results Microbiota composition was determined in 167 participants and classified as eosinophilic (n = 84), neutrophilic (n = 14), paucigranulocytic (n = 60), or mixed neutrophilic-eosinophilic (n = 9) asthma phenotypes. Airway microbiology was significantly less diverse (P = .022) and more dissimilar (P = .005) in neutrophilic compared with eosinophilic participants. Sputum neutrophil proportions, but not eosinophil proportions, correlated significantly with these diversity measures (α-diversity: Spearman r = −0.374, P < .001; β-diversity: r = 0.238, P = .002). Interphenotype differences were characterized by a greater frequency of pathogenic taxa at high relative abundance and reduced Streptococcus, Gemella, and Porphyromonas taxa relative abundance in patients with neutrophilic asthma. Multivariate regression confirmed that sputum neutrophil proportion was the strongest predictor of microbiota composition. Conclusions Neutrophilic asthma is associated with airway microbiology that is significantly different from that seen in patients with other inflammatory phenotypes, particularly eosinophilic asthma. Differences in microbiota composition might influence the response to antimicrobial and steroid therapies and the risk of lung infection. en_US
dc.identifier.citation Taylor, S. L., Leong, L. E. X., Choo, J. M., Wesselingh, S., Yang, I. A., Upham, J. W., … Rogers, G. B. (2018). Inflammatory phenotypes in patients with severe asthma are associated with distinct airway microbiology. Journal of Allergy and Clinical Immunology, 141(1), 94–103.e15. https://doi.org/10.1016/j.jaci.2017.03.044 en
dc.identifier.doi https://doi.org/10.1016/j.jaci.2017.03.044 en
dc.identifier.issn 0091-6749
dc.identifier.uri http://hdl.handle.net/2328/37819
dc.language.iso en
dc.publisher Elsevier en
dc.relation http://purl.org/au-research/grants/nhmrc/569246 en
dc.relation.grantnumber NHMRC/569246 en
dc.rights Copyright 2017 The Authors. Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma & Immunology en
dc.rights.holder The Authors. en
dc.rights.license CC-BY-NC-ND
dc.subject Asthma, en
dc.subject microbiome, en
dc.subject neutrophil, en
dc.subject eosinophil en
dc.title Inflammatory phenotypes in patients with severe asthma are associated with distinct airway microbiology en
dc.type Article en
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