A Comprehensive Analysis of the Stability of Blood Eosinophil Levels

Abstract

Rationale: Blood eosinophil counts are used to inform diagnosis/management of eosinophilic asthma. Objectives: Examine blood eosinophil variability and identify factors affecting eosinophil levels to inform clinical interpretation. Methods:Post hoc analysis to understand eosinophil variability using data from four randomized controlled asthma trials. We examined 1) influence of intrinsic/extrinsic factors (comorbidities, medication, and patient history) using baseline data (n = 2,612); 2) monthly variation using placebo-treated patient data (n = 713); 3) stability of eosinophil classification (<150, 150-299, and ⩾300 cells/μl) in placebo-treated patients with monthly measurements over a 1-year period (n = 751); and 4) impact of technical factors (laboratory-to-laboratory differences and time from collection to analysis). Results: Of intrinsic/extrinsic factors examined, nasal polyps increased eosinophil levels by 38%, whereas current smoking decreased levels by 23%. Substantial seasonal differences in eosinophil counts were observed, with differences of ∼20% between July and January. Eosinophil levels between 150 and 299 cells/μl were least stable, with 44% of patients remaining in the same classification for seven of 10 measurements versus 59% and 66% of patients in the <150 and ⩾300 cells/μl subgroups, respectively. Measurements at different laboratories showed high association (Spearman's correlation coefficient, R = 0.89); however, eosinophil counts were reduced, with longer time from collection to analysis, and variability increased with increasing eosinophil counts. Conclusions: Several intrinsic, extrinsic, and technical factors may influence, and should be considered in, clinical interpretation of eosinophil counts. Additionally, a single measurement may not be sufficient when using eosinophil counts for diagnosis/management of eosinophilic asthma.

Keywords: asthma; diagnosis; eosinophil count; patient management.

Figure 1.

Factors identified as having an influence on eosinophil levels beyond the prespecified threshold of 20% in the univariate (unadjusted) analyses and included in the multivariable (adjusted) analyses of LUTE/VERSE and LAVOLTA I/II. Percentages are relative difference from reference categories. Data are presented as a ratio with the relative reference category. Dotted lines represent nonmeaningful differences (20% plotted as a ratio on a log scale [i.e., 0.8–1.25]). BMI = body mass index.

Figure 2.

Monthly influence on blood eosinophil levels beyond the prespecified threshold of 20% by month in LAVOLTA I/II. Percentages are relative difference from July. Data in the graph are presented as a ratio with July. Dotted lines represent nonmeaningful differences (20% plotted as a ratio on a log scale [i.e., 0.8–1.25]).

Figure 3.

Blood eosinophil (EOS) stability by EOS subgroup. (A) Cumulative distribution plot demonstrating minimal percentage of time remaining in the most commonly observed EOS subgroup. (B) Sankey diagram demonstrating blood EOS subgroup changes by study visit over 1 year. Each of the three black bars aligned vertically represents patients in the three EOS subgroups at a specific visit; the three bars are ordered as <150 cells/μl (top), 150–299 cells/μl (middle), and ⩾300 cells/μl (bottom) for every visit (1 month apart). Gray bars show how many patients flow from one EOS subgroup to another or stay stable from visit to visit, because the width of the gray bars is proportional to the number of patients flowing from one EOS subgroup to another. The table complements the figure by showing the number of patients changing EOS categories from visit to visit. V = visit.

Figure 4.

(A) Absolute eosinophil counts ordered by median values of each patient. Gray shaded area in A indicates patients whose diagnosis of eosinophilic asthma (based on a 300 cells/μl cutoff) is dependent upon the laboratory. (B) Relationship between differences in time from collection to analysis differences and differences in eosinophil counts for the local/regional – central laboratories.