Asthma and lower airway disease
Inflammatory phenotypes in patients with severe asthma are associated with distinct airway microbiology

https://doi.org/10.1016/j.jaci.2017.03.044Get rights and content
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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.

Key words

Asthma
microbiome
neutrophil
eosinophil

Abbreviations used

ICS
Inhaled corticosteroid
OTU
Operational taxonomic unit
PERMANOVA
Permutational multiple ANOVA
qPCR
Quantitative PCR
SIMPER
Similarity of percentages

Cited by (0)

Supported by the Australian National Health and Medical Research Council (NHMRC); grant no. 569246) and a grant from the John Hunter Hospital Charitable Trust.

Disclosure of potential conflict of interest: I. A. Yang's, J. W. Upham's, and C. Jenkins' institution received a grant from National Health & Medical Research Council (NHMRC), Australia, for this work. P. N. Reynolds' and J. L. Simpson's institution received a grant from John Hunter Charitable Trust and the NHMRC CRE Severe Asthma for this work. S. Hodge is employed by the University of Adelaide; her institution has grants with NHMRC; and she received royalties from the book Lung Macrophages in Health and Disease. G. B. Marks' institution received grants from AstraZeneca and GlaxoSmithKline for other works. P. G. Gibson's institution received a grant from NHMRC for this work and has grants from the NHMRC, AstraZeneca, and GlaxoSmithKline for other works; he has personally received payment for lectures from AstraZeneca, GlaxoSmithKline, and Novartis. The rest of the other authors declare that they have no relevant conflicts of interest.

These authors contributed equally to this work.

These authors contributed equally to this work.