Neither baseline blood nor sputum eosinophils predict future exacerbations in the SPIROMICS cohort

<b>Introduction:</b> Multiple reports propose using eosinophils (EOS) in blood to identify patients with chronic obstructive pulmonary disease (COPD) at increased risk for exacerbations. Others, including biologic therapy trials, report dissimilar results, possibly due to enrichment for those with a history of exacerbations. In a previous cross-sectional analysis (Lancet Res Med, PMID:29146301) of the SPIROMICS (SubPopulations and InteRmediate Outcome Measures In COPD Study) cohort, we found significant associations of greater retrospective exacerbation frequency with high sputum EOS, but not high blood EOS. Here, we examined whether elevated baseline blood or sputum EOS predicted future exacerbations. <b>Methods:</b> We stratified SPIROMICS participants having COPD by GOLD criteria (N=740) based on baseline high blood (≥300/microL) or sputum (≥2%) EOS. We evaluated EOS associations with prospective exacerbations (up to 10.54 years for visit 5) using zero-inflated negative binomial models with age, sex, race, smoking pack years, current smoker, asthma diagnosis, prior total exacerbations, and raw slope of post-bronchodilator FEV1 as covariates. <b>Results:</b> Neither blood nor sputum EOS were significantly associated with greater longitudinal exacerbations rates, nor was either associated with exacerbation counts in adjusted multivariate models. <b>Conclusions:</b> Neither higher blood or sputum EOS are predictive of increased future exacerbations in the SPIROMICS cohort. Although not population-based, SPIROMICS is a multi-center cohort of heavy smokers without enrichment for previous exacerbations; hence, it may more closely represent general populations, in which this question should be further studied.