Blood eosinophil counts in the general population and airways disease: a comprehensive review and meta-analysis

Abstract

Background: The clinical context for using blood eosinophil (EOS) counts as treatment-response biomarkers in asthma and COPD requires better understanding of EOS distributions and ranges. We describe EOS distributions and ranges published in asthma, COPD, control (non-asthma/COPD) and general populations.

Methods: We conducted a comprehensive literature review and meta-analysis of observational studies (January 2008 to November 2018) that included EOS counts in asthma, severe asthma, COPD, control and general populations. Excluded studies had total sample sizes <200, EOS as inclusion criterion, hospitalised population only and exclusively paediatric participants.

Results: Overall, 91 eligible studies were identified, most had total-population-level data available: asthma (39 studies), severe asthma (12 studies), COPD (23 studies), control (seven studies) and general populations (14 studies); some articles reported data for multiple populations. Reported EOS distributions were right-skewed (seven studies). Reported median EOS counts ranged from 157-280 cells·µL^-1 (asthma, 22 studies); 200-400 cells·µL^-1 (severe asthma, eight studies); 150-183 cells·µL^-1 (COPD, six studies); and 100-160 cells·µL^-1 (controls, three studies); and 100-200 cells·µL^-1 (general populations, six studies). The meta-analysis showed that observed variability was mostly between studies rather than within studies. Factors reportedly associated with higher blood EOS counts included current smoking, positive skin-prick test, elevated total IgE, comorbid allergic rhinitis, age ≤18 years, male sex, spirometric asthma/COPD diagnosis, metabolic syndrome and adiposity.

Conclusion: EOS distribution and range varied by study population, and were affected by clinical factors including age, smoking history and comorbidities, which, regardless of severity, should be considered during treatment decision-making.

FIGURE 1

Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) diagram of articles for inclusion, overall and by population type. EOS: eosinophil​​​​​​​. ^#: the sum across the five categories (n=106) is greater than n=91 because some articles reported data for multiple relevant populations; ^¶: studies where total population-level data were available; data for the studies presenting subgroup-level-only data are presented in supplementary results B.

FIGURE 2

Blood eosinophil distributions in a) asthma, b) COPD and c) control and d) general populations. IQR: interquartile range. a, c) Reproduced from [47] with permission. b, d) Reproduced and modified from [54] with permission.

FIGURE 3

Forest plots of median (interquartile range (IQR) or range) and geometric mean (gmean) (95% CI) blood eosinophil (EOS) counts for each of the five population types: a) asthma, b) severe asthma, c) COPD and d) controls and general populations. Symbols are presented according to study size, in ascending order: n<500; n≥500–<1000; n=≥1000–<10 000; n≥10 000–<100 000; n>100 000. Horizontal dotted lines represent the division between studies presenting median and geometric mean data. Vertical solid lines indicate a blood EOS count of 150 cells·μL⁻¹, while dashed lines represent the upper limit of normal blood EOS levels, generally considered to be ∼500 cells·μL⁻¹ [–121]. Unless otherwise indicated, all studies measured the blood EOS values at baseline. GEIRD: Gene Environment Interactions in Respiratory Diseases; CGPS: Copenhagen General Population Study; CPRD: Clinical Practice Research Datalink; OPCRD: Optimum Patient Care Research Database; SARP: Severe Asthma Research Program; COBRA: Cohort of Bronchial Obstruction and Asthma; SAAS: Seinäjoki Adult Asthma Study; NHANES: National Health and Nutrition Examination Surveys; EGEA: Epidemiological Study on the Genetics and Environment of Asthma; RItA: the Italian severe/uncontrolled asthma registry; TENOR: The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens; BTS: British Thoracic Society; SA: severe asthma; BSAR: Belgian Severe Asthma Registry; KOLD: Korean Obstructive Lung Disease; KOCOSS: Korean COPD Subtype Study; ELISABET: Enquête Littoral Souffle Air Biologie Environnement survey. ^#: blood EOS values not measured at baseline, but during the observation period (January 2003–August 2013); ^¶: data from a separate patient cohort (as indicated); ⁺: maximum count in 2 years prior to index date; ^§: control population reported in the respective published study of asthma; ^ƒ: general population study; ^##: control population reported in the respective published study of COPD; ^¶¶: median (5–95th percentile); ⁺⁺: median (range); ^§§: where IQR was reported as one value, the range could not be plotted due to unknown skew.

FIGURE 4

Blood eosinophil (EOS) levels and risk factors of interest for the general population reported in a) the Copenhagen General Population Study; b, c) the Lung, Heart, Social, Body (LEAD) study; and d, e) the non-asthmatic population reported in the Program for Control of Asthma in Bahia (ProAR) study. a) Clinical attributes associated with increased blood eosinophil count (≥300 cells·μL⁻¹). Reversibility was defined as forced expiratory volume in 1 s (FEV₁) reversibility of ≥12% and ≥200 mL. Logistic regression models were used. Estimates are unadjusted. p-values were from Wald's test. Reproduced with permission from [41]. b, c) Reproduced with permission [23]. c, d) Reproduced with permission from [26]. BMI: body mass index; LLN: lower limit of normal; FVC: forced vital capacity; SPT: skin-prick test; AR: allergic rhinitis.

FIGURE 4

Blood eosinophil (EOS) levels and risk factors of interest for the general population reported in a) the Copenhagen General Population Study; b, c) the Lung, Heart, Social, Body (LEAD) study; and d, e) the non-asthmatic population reported in the Program for Control of Asthma in Bahia (ProAR) study. a) Clinical attributes associated with increased blood eosinophil count (≥300 cells·μL⁻¹). Reversibility was defined as forced expiratory volume in 1 s (FEV₁) reversibility of ≥12% and ≥200 mL. Logistic regression models were used. Estimates are unadjusted. p-values were from Wald's test. Reproduced with permission from [41]. b, c) Reproduced with permission [23]. c, d) Reproduced with permission from [26]. BMI: body mass index; LLN: lower limit of normal; FVC: forced vital capacity; SPT: skin-prick test; AR: allergic rhinitis.