Variability of Eosinophil Levels Over Time in Chronic Obstructive Pulmonary Disease Patients Within an Integrated Healthcare Delivery System

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Abstract Rationale: Chronic obstructive pulmonary disease (COPD) has high morbidity and mortality, but novel therapies for those with type 2 inflammation offer significant benefits. Current GOLD guidelines state that present blood eosinophil counts (EOS) ≥300 cells/microliter (µl) may be used to identify COPD patients at higher risk of exacerbations and suggest beneficial therapies in this population. However, variability of EOS levels may occur, and we sought to better understand the longitudinal changes of EOS levels within COPD patients specifically in those patients with a most recent EOS level of <300/µl. Methods: Using a retrospective longitudinal analysis of linked electronic medical records (EMR) data for the inpatient and outpatient settings in a large group-model, integrated healthcare system, we identified COPD patients over the age of 40 who had ≥1 eosinophil (EOS) measurement between 2005 and 2020. Distributions of longitudinal eosinophil levels were assessed for patients in 3 standard risk categories (<150 cells/microliter (µl), 150-299/µl, ≥300/µl). We then assessed the variability of EOS levels over 15 years for patients with most recent EOS levels that were <150/µl and 150-299/µl. Results: We identified 9017 COPD patients of whom 8709 had 127,208 EOS measures in their EMR. 3633 (47.1%) unique patients had most recent EOS <150/µl with a mean (SD) of 78/µl (43.5), 3142 (36.1%) in 150-299/µl range had a mean (SD) of 210/µl, (41.3) and 1934 (22.2%) ≥300/µl group had a mean (SD) of 485/µl (276). Frequent changes in EOS level were observed over the 15-year observation period in subjects with current EOS levels <300/µl. 31% of these individuals had ≥1 EOS level ≥300/µl [mean (SD) of 485/µl (306)] and 52.8% of those with current EOS level 150-299/µl had ≥1 EOS ≥300/µl [mean (SD) of 451/µl (232)]. The patient profile plot shows the EOS levels in 20 randomly selected patients with most recent EOS between 150-299/µl with at least 5 levels longitudinally; this plot shows EOS levels occurring >300/µl at various times over the 10-year period despite the most EOS level being <300/µl (Figure). Conclusions: We identified significant temporal variability in EOS levels in those patients with EOS levels <300/µl. Variability of EOS levels over time may be related to exacerbations, viral infections, or treatment with corticosteroids. Further assessment of EOS levels, taking these factors into account, is needed to better understand the natural variability of EOS in COPD.

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