Background: Eosinophilic airway inflammation in patients with chronic obstructive pulmonary disease (COPD) is associated with exacerbations and responsivity to steroids, suggesting potential shared mechanisms with eosinophilic asthma. However, there is no consistent blood eosinophil count that has been used to define the increased exacerbation risk. Objective: We sought to investigate blood eosinophil counts associated with exacerbation risk in patients with COPD. Methods: Blood eosinophil counts and exacerbation risk were analyzed in patients with moderate-to-severe COPD by using 2 independent studies of former and current smokers with longitudinal data. The Genetic Epidemiology of COPD (COPDGene) study was analyzed for discovery (n = 1,553), and the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study was analyzed for validation (n = 1,895). A subset of the ECLIPSE study subjects were used to assess the stability of blood eosinophil counts over time. Results: COPD exacerbation risk increased with higher eosinophil counts. An eosinophil count threshold of 300 cells/μL or greater showed adjusted incidence rate ratios for exacerbations of 1.32 in the COPDGene study (95% CI, 1.10-1.63). The cutoff of 300 cells/μL or greater was validated for prospective risk of exacerbation in the ECLIPSE study, with adjusted incidence rate ratios of 1.22 (95% CI, 1.06-1.41) using 3-year follow-up data. Stratified analysis confirmed that the increased exacerbation risk associated with an eosinophil count of 300 cells/μL or greater was driven by subjects with a history of frequent exacerbations in both the COPDGene and ECLIPSE studies. Conclusions: Patients with moderate-to-severe COPD and blood eosinophil counts of 300 cells/μL or greater had an increased risk exacerbations in the COPDGene study, which was prospectively validated in the ECLIPSE study.
Bibliographical noteFunding Information:
Supported by National Institute of Health grants R01HL125583, R01HL130512, R01HL124233, R01HL126596, U01HL089897, U01HL089856, T32HL007427, P01HL105339, and P01HL132825. J.V. was supported by the National Institute of Health Research Manchester Biomedical Research Centre. The COPDGene project is also supported by the COPD foundation through contributions made to an industry advisory board comprised of AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Novartis, Pfizer, Siemens, and Sunovion. ECLIPSE was funded by GlaxoSmithKline.
Disclosure of potential conflict of interest: D. Singh has received grants from AstraZeneca, Boehringer Ingelheim, Chiesi Pharmaceuticals, GlaxoSmithKline, Glenmark, Menarini, Merck, Mundipharma, Novartis, Pfizer, Pulmatrix, Teva, Therevance, and Verona and has served as a consultant for Apellis, AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, Genentech, GlaxoSmithKline, Glenmark, Menarini, Merck, Mundipharam, Novartis, Peptinnovate, Pfizer, Pulmatrix, Skyepharma, Teva, Therevance, and Verona. J. Vestbo has served a as consultant for GlaxoSmithKline, Chiesi Pharmaceuticals, Boehringer Ingelheim, Novartis, and AstraZeneca. R. Tal-Singer is an employee and shareholder of GlaxoSmithKline. P. J. Castaldi has received personal fees and grant support from GlaxoSmithKline. E. K. Silverman has received grants and travel expenses from the COPD Foundation and GlaxoSmithKline. C. P. Hersh has served as a consultant for AstraZeneca, Concert Pharmaceuticals, Mylan, and 23andMe and has received grants from Boehringer Ingelheim and Novartis. The rest of the authors declare that they have no relevant conflicts of interest.
© 2018 American Academy of Allergy, Asthma & Immunology
- Chronic obstructive pulmonary disease