Mixed sputum granulocyte longitudinal impact on lung function in the severe asthma research program

Rationale: Some reports indicate longitudinal variability in sputum differential cell counts, whereas others describe stability. Highly variable sputum eosinophil percentages are associated with greater lung function loss than persistently elevated eosinophil percentages, 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 SARP III (Severe Asthma Research Program III) cohort underwent comprehensive phenotype characterization at baseline and annually over 3 years. Adult subjects with acceptable sputum levels were assigned to one of three longitudinal sputum groups: Eosinophils predominantly,2%, eosinophilspredominantly>2%,orhighly variable eosinophil percentages (.2 SDs determined fromindependent, repeated baseline eosinophil percentages). Subjects were similarly assigned to one of three longitudinal neutrophil groups with a 50% cut point. Measurements and Main Results: The group with predominantly ,2% sputum eosinophils had the highest lung function (prebronchodilator FEV1% predicted, P,0.01; FEV1/FVC ratio, P,0.001) at baseline and throughout 3 years compared with other eosinophil groups. Healthcare use did not differ, although the highly variable eosinophil group reported more asthma exacerbations at Year 3. Longitudinal neutrophil groups showed few differences. However, a combination of predominantly >2% eosinophil and >50% neutrophil groups resulted in the lowest prebronchodilator FEV1% predicted (P = 0.049) compared with the combination with predominantly ,2% eosinophils and,50% neutrophils. Conclusions: Subjects with predominantly >2% sputum eosinophils in combination with predominantly >50% neutrophils showed greater loss of lung function, whereas those with highly variable sputum eosinophils had greater healthcare use.