Exacerbation risk in severe asthma is stratified by inflammatory phenotype using longitudinal measures of sputum eosinophils

Abstract

Background

Airway inflammatory phenotyping is increasingly applied to subjects with asthma. However its relationship to clinical outcomes in difficult asthma is incompletely elucidated.

Objective

The goal of our study was to determine the relationship between exacerbation rates and phenotypes of difficult asthma based on longitudinal measures of sputum eosinophils and neutrophils.

Methods

Subjects in the longitudinal observational study from 2 tertiary care centers that completed 1 year of observation and provided at least 3 sputum samples were classified by inflammatory phenotypes using previously established thresholds. Kaplan-Meier curves, univariable and multivariable Cox Proportional Hazards models were used to determine the association between inflammatory phenotypes and exacerbation rate.

Results

During the study, 115 exacerbations occurred in 73 severe asthmatic subjects. Subjects with the persistently eosinophilic phenotype had a significantly shorter time to first exacerbation and greater risk for exacerbation over a 1-year period than those with the non-eosinophilic phenotype based on univariable and multivariable Cox Proportional Hazards model (Hazard Ratio [HR], 3.24; 95% confidence interval [CI], 1.35-7.72; adjusted HR 3.90; 95% CI 1.34-11.36). No significant differences in time to first exacerbation or exacerbation risk over a 1-year period were found among the neutrophilic phenotypes.

Conclusions

The persistent eosinophilic phenotype is associated with increased exacerbation risk compared to the non-eosinophilic phenotype in severe asthma. No differences in time to first exacerbation or exacerbation risk over a 1-year period were detected among neutrophilic phenotypes.

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