Inflammatory phenotypes in severe asthma are associated with distinct airway microbiology

Publication date: Available online 4 May 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Steven L. Taylor, Lex E.X. Leong, Jocelyn M. Choo, Steve Wesselingh, Ian A. Yang, John W. Upham, Paul N. Reynolds, Sandra Hodge, Alan L. James, Christine Jenkins, Matthew J. Peters, Melissa Baraket, Guy B. Marks, Peter G. Gibson, Jodie L. Simpson, Geraint B. Rogers
BackgroundAsthma pathophysiology and treatment responsiveness are predicted by inflammatory phenotype. However, the relationship between airway microbiology and asthma phenotype is poorly understood. We aimed to characterise airway microbiota in patients with symptomatic stable asthma, and relate composition to airway inflammatory phenotype and other phenotypic characteristics.MethodsThe microbial composition of induced sputum specimens collected from adult patients screened for a multicenter randomized controlled trial was determined by 16S rRNA gene sequencing. Inflammatory phenotypes were defined by sputum neutrophil and eosinophil cell proportions. Microbiota were defined using alpha and beta diversity measures, and inter-phenotype differences identified using SIMPER, network analysis, and taxon fold change. Phenotypic predictors of airway microbiology were identified using multivariate linear regression.ResultsMicrobiota composition was determined in 167 participants, classified as eosinophilic (n=84), neutrophilic (n=14), paucigranulocytic (n=60), or mixed neutrophilic-eosinophilic (n=9) phenotypes of asthma. Airway microbiology was significantly less diverse (p=0.022) and more dissimilar (p=0.005) in neutrophilic compared to eosinophilic participants. Sputum neutrophil proportion, but not eosinophil proportion, correlated significantly with these diversity measures (alpha-diversity: Spearman's r=-0.374, p<0.001; beta-diversity: r=0.238, p=0.002). Inter-phenotype differences were characterised by a greater frequency of pathogenic taxa at high relative abundance, and reduced Streptococcus, Gemella and Porphyromonas relative abundance in neutrophilic asthma. Multivariate regression confirmed sputum neutrophil proportion was the strongest predictor of microbiota composition.ConclusionsNeutrophilic asthma is associated with airway microbiology that is significantly different to that in other inflammatory phenotypes, particularly eosinophilic asthma. Differences in microbiota composition may influence response to antimicrobial and steroid therapies, and risk of lung infection.

Teaser

Utilizing a large, well-defined severe asthma cohort, we show that sputum neutrophilia, but not eosinophilia, was a strong predictor for airway microbiota diversity. These results highlight the divergence in pathophysiology based on asthma inflammatory phenotype.


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