Mixed Sputum Granulocyte Longitudinal Impact on Lung Function in the Severe Asthma Research Program

Abstract

Rationale: Reports indicate longitudinal variability in sputum differential cell counts while others describe stability. Highly variable sputum eosinophil percents are associated with greater lung function loss than persistently elevated eosinophil percents, but elevated neutrophils are linked to more severe asthma. Objectives: To examine sputum granulocyte stability or variability longitudinally and associations with important clinical characteristics. Methods: The Severe Asthma Research Program (SARP 3) cohort underwent comprehensive phenotype characterization at baseline and annually over three years. Adult subjects with acceptable sputum were assigned to one of 3 longitudinal sputum groups: Eosinophils predominantly 2%, or highly variable (>2SD determined from independent, repeated baseline eosinophil %s). Subjects were similarly assigned to 1 of 3 longitudinal neutrophil groups with a 50% cut-point. Measurements and Main Results: The group with predominantly 50% neutrophil groups resulted in the lowest prebronchodilator FEV1%predicted (p=0.049) compared to predominantly 50% neutrophils showed greater loss of lung function, whereas those with highly variable sputum eosinophils had greater healthcare utilization.