A Severe Asthma Disease Signature from Gene Expression Profiling of Peripheral Blood from U-BIOPRED Cohorts

Am J Respir Crit Care Med. 2017 May 15;195(10):1311-1320. doi: 10.1164/rccm.201604-0866OC.


Rationale: Stratification of asthma at the molecular level, especially using accessible biospecimens, could greatly enable patient selection for targeted therapy.

Objectives: To determine the value of blood analysis to identify transcriptional differences between clinically defined asthma and nonasthma groups, identify potential patient subgroups based on gene expression, and explore biological pathways associated with identified differences.

Methods: Transcriptomic profiles were generated by microarray analysis of blood from 610 patients with asthma and control participants in the U-BIOPRED (Unbiased Biomarkers in Prediction of Respiratory Disease Outcomes) study. Differentially expressed genes (DEGs) were identified by analysis of variance, including covariates for RNA quality, sex, and clinical site, and Ingenuity Pathway Analysis was applied. Patient subgroups based on DEGs were created by hierarchical clustering and topological data analysis.

Measurements and main results: A total of 1,693 genes were differentially expressed between patients with severe asthma and participants without asthma. The differences from participants without asthma in the nonsmoking severe asthma and mild/moderate asthma subgroups were significantly related (r = 0.76), with a larger effect size in the severe asthma group. The majority of, but not all, differences were explained by differences in circulating immune cell populations. Pathway analysis showed an increase in chemotaxis, migration, and myeloid cell trafficking in patients with severe asthma, decreased B-lymphocyte development and hematopoietic progenitor cells, and lymphoid organ hypoplasia. Cluster analysis of DEGs led to the creation of subgroups among the patients with severe asthma who differed in molecular responses to oral corticosteroids.

Conclusions: Blood gene expression differences between clinically defined subgroups of patients with asthma and individuals without asthma, as well as subgroups of patients with severe asthma defined by transcript profiles, show the value of blood analysis in stratifying patients with asthma and identifying molecular pathways for further study. Clinical trial registered with www.clinicaltrials.gov (NCT01982162).

Keywords: biomarker; immune cell; microarray.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Cortex Hormones / blood
  • Adrenal Cortex Hormones / therapeutic use*
  • Adult
  • Asthma / blood*
  • Asthma / drug therapy*
  • Cluster Analysis
  • Cohort Studies
  • Europe
  • Female
  • Gene Expression Profiling / methods*
  • Humans
  • Male
  • Microarray Analysis / statistics & numerical data
  • Middle Aged
  • Prospective Studies
  • Severity of Illness Index
  • Transcriptome / drug effects


  • Adrenal Cortex Hormones

Associated data

  • ClinicalTrials.gov/NCT01982162