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Clinical Trial
. 2021 Jan;147(1):123-134.
doi: 10.1016/j.jaci.2020.04.018. Epub 2020 Apr 28.

Sputum microbiome profiles identify severe asthma phenotypes of relative stability at 12 to 18 months

Mahmoud I Abdel-Aziz  1 , Paul Brinkman  2 , Susanne J H Vijverberg  2 , Anne H Neerincx  2 , John H Riley  3 , Stewart Bates  3 , Simone Hashimoto  4 , Nazanin Zounemat Kermani  5 , Kian Fan Chung  6 , Ratko Djukanovic  7 , Sven-Erik Dahlén  8 , Ian M Adcock  6 , Peter H Howarth  7 , Peter J Sterk  2 , Aletta D Kraneveld  9 , Anke H Maitland-van der Zee  10 ; U-BIOPRED Study Group
Affiliations
Clinical Trial

Sputum microbiome profiles identify severe asthma phenotypes of relative stability at 12 to 18 months

Mahmoud I Abdel-Aziz et al. J Allergy Clin Immunol. 2021 Jan.

Abstract

Background: Asthma is a heterogeneous disease characterized by distinct phenotypes with associated microbial dysbiosis.

Objectives: Our aim was to identify severe asthma phenotypes based on sputum microbiome profiles and assess their stability after 12 to 18 months. A further aim was to evaluate clusters' robustness after inclusion of an independent cohort of patients with mild-to-moderate asthma.

Methods: In this longitudinal multicenter cohort study, sputum samples were collected for microbiome profiling from a subset of the Unbiased Biomarkers in Prediction of Respiratory Disease Outcomes adult patient cohort at baseline and after 12 to 18 months of follow-up. Unsupervised hierarchical clustering was performed by using the Bray-Curtis β-diversity measure of microbial profiles. For internal validation, partitioning around medoids, consensus cluster distribution, bootstrapping, and topological data analysis were applied. Follow-up samples were studied to evaluate within-patient clustering stability in patients with severe asthma. Cluster robustness was evaluated by using an independent cohort of patients with mild-to-moderate asthma.

Results: Data were available for 100 subjects with severe asthma (median age 55 years; 42% males). Two microbiome-driven clusters were identified; they were characterized by differences in asthma onset, smoking status, residential locations, percentage of blood and/or sputum neutrophils and macrophages, lung spirometry results, and concurrent asthma medications (all P values < .05). The cluster 2 patients displayed a commensal-deficient bacterial profile that was associated with worse asthma outcomes than those of the cluster 1 patients. Longitudinal clusters revealed high relative stability after 12 to 18 months in those with severe asthma. Further inclusion of an independent cohort of 24 patients with mild-to-moderate asthma was consistent with the clustering assignments.

Conclusion: Unbiased microbiome-driven clustering revealed 2 distinct robust phenotypes of severe asthma that exhibited relative overtime stability. This suggests that the sputum microbiome may serve as a biomarker for better characterizing asthma phenotypes.

Keywords: Sputum microbiome; asthma phenotypes; follow-up; lung function; macrophages; metagenomics; neutrophils; unbiased clusters.

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