Original article
High Blood Eosinophil Count Is a Risk Factor for Future Asthma Exacerbations in Adult Persistent Asthma

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Background

Exacerbation-associated uncontrolled asthma represents a major public health problem. The relationship of elevated blood eosinophils to this process needs study.

Objective

To determine whether a high blood eosinophil count is a risk factor for future asthma exacerbations in adult persistent asthma.

Methods

By using electronic pharmacy and health care data from Kaiser Permanente Southern California, 2392 patients, ages 18 to 64 years, were identified who met the Health Effectiveness Data and Information Set 2-year criteria for persistent asthma, did not manifest chronic obstructive pulmonary disease and other major illnesses, and had a blood eosinophil determination in 2010. Exacerbations (primary outcome) were defined as asthma outpatient visits that required systemic corticosteroid dispensing within ±7 days or asthma emergency department visits or hospitalizations. A period of ≥8 days defined a new exacerbation. Multivariate modelling used negative binomial and Poisson regression to examine the association between a blood eosinophil count determined in 2010 and risk of exacerbations, and ≥7 short-acting β2-agonist (SABA) canisters dispensed (secondary outcome) in 2011 by adjusting for demographics, comorbidities, and asthma burden.

Results

The rate of asthma exacerbations in 2011 was 0.41 events per person year (95% CI, 0.37-0.45). Eosinophil count ≥400/mm3 in 2010 was a risk factor for asthma exacerbations in 2011 (adjusted rate ratio 1.31 [95% CI, 1.07-1.60]; P = .009) and ≥7 SABA dispensed (adjusted risk ratio 1.17 [95% CI, 1.03-1.1.33]; P = .015).

Conclusion

A high blood eosinophil count is a risk factor for increased future asthma exacerbations and excessive short-acting β2-agonist use after adjustment of potential confounders in adults with persistent asthma, which suggests a higher disease burden in patients with asthma and with high blood eosinophil counts.

Section snippets

PREDUNA study protocol

The PREDUNA study was a retrospective cohort study that examined the relationship between the blood eosinophil count at baseline (2010) and asthma exacerbations in the following 12 months (2011). The study used the Kaiser Permanente Southern California (KPSC) research data warehouse to capture pharmacy and health care utilization data to identify patients with persistent asthma and to determine asthma-related outcomes (Figure 1, A). The KPSC Institutional Review Board approved the study with a

Identification of patients with persistent asthma

When applying HEDIS criteria for persistent asthma, 71,780 and 70,661 patients of all ages with persistent asthma were identified in 2009 and 2010, respectively, with 55% (n = 39,138) fulfilling the 2-year definition of persistent asthma (Figure 1, B). After exclusion of patients due to noncontinuous membership or pharmacy benefit, age limitation, and specific diseases, 9546 adults 18 to 64 years of age with persistent asthma were identified, with 2392 (25.1%) having had at least 1 blood cell

Discussion

Eosinophilia in blood (tissues also) is a biologic inflammatory marker that links asthma to a specific pathophysiologic phenotype3, 4, 5, 35 and responsiveness to specific medications.15, 16, 17, 18, 36 The PREDUNA study provides evidence that high blood eosinophil counts of adults with persistent asthma are associated with increased risk for future asthma exacerbations and excessive SABA canisters dispensed after adjustments for covariates. High blood eosinophil count was hypothesized as a

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  • Cited by (0)

    MedImmune, Gaithersburg, Md, funded a research grant to the Southern California Permanente Medical Group Research and Evaluation Department to perform the study. The sponsor participated in the study discussions and provided comments to the protocol, data analysis, and manuscript.

    Conflicts of interest: R. Zeiger has received research support from MedImmune, Genentech, GlaxoSmithKline, Aerocrine, Merck, Thermofisher, and AstraZeneca; was on the DBV Technologies research advisory board; has received consultancy fees from GlaxoSmithKline, Genentech, Novartis, the National Heart, Lung, and Blood Institute/Penn State, and Aerocrine; and holds stock/stock options in DBV Technologies. M. Schatz has received research support from MedImmune. Q. Li has received research support from AstraZeneca. W. Chen has received research support from Kaiser Permanente Southern California. D. Khatry is employed by MedImmune/AstraZeneca; has a pending patent with MedImmune; has stock/stock options in MedImmune/AstraZeneca. D. Gossage is employed by Gilead Sciences; has a patent with MedImmune/AstraZeneca; has stock in Gilead Sciences Inc. T. N. Tran is employed by and has stock/stock options in AstraZeneca.

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