Peripheral blood eosinophil and neutrophil counts independently predict asthma exacerbations

Abstract

Background: Type 2 and 17 cytokines are potential targets in severe asthma and are associated with eosinophilic and neutrophilic inflammation, respectively. Blood eosinophils predict benefit from Type 2 cytokine inhibition and are prognostic for risk of future asthma exacerbations. In light of counter-regulatory mechanisms driving eosinophilic and neutrophilic inflammation, we hypothesized that blood eosinophil and neutrophil counts could independently predict asthma exacerbations. Methods: Meta-analysis of placebo arms of 7 severe asthma studies. Baseline blood eosinophil (eos) and neutrophil (PMN) counts classified patients as biomarker low ( > median). Exacerbation rate estimated by Poisson regression with adjustment for overdispersion, accounting for time on study. Results: 1,455 patients had complete exacerbation and blood count data totaling 905 exacerbations over 1,179 patient-years (0.77/year). Median (IQR) blood eos and PMN counts were 220 (260) and 4010 (1890) per microliter, respectively, and were not correlated. Individually, blood eos or PMN status significantly predicted future exacerbations: the increase (95% CI) in exacerbation rates comparing biomarker high versus low were +60(32, 94)% and +39(15, 68)%. An additive model considering blood eos and PMN status together further differentiated exacerbation rate: exacerbation rate increase comparing biomarker high/high versus low/low was +121(68,192)%. Conclusion: Blood eos and PMN counts identify severe asthma patients at increased risk for exacerbations and may be useful biomarkers for therapies targeting Type 2 and 17 pathways.