Abstract

BackgroundBlood eosinophil count (BEC) and fractional exhaled nitric oxide (FeNO) concentration are established biomarkers in asthma, associated particularly with the risk of exacerbations. We evaluated the relationship of BEC and FeNO as complementary and independent biomarkers of severe asthma exacerbations.MethodsThis observational study included data from the Optimum Patient Care Research Database. Asthma patients (18–80 years) with valid continuous data for 1 year before FeNO reading, ≥ 1 inhaled corticosteroid prescription, and BEC recorded ≤ 5 years before FeNO reading were separated into cohorts. Categorisation 1 was based on the American Thoracic Society criteria for elevated FeNO concentration (high: ≥ 50 ppb; non-high: < 25 ppb) and BEC (high: ≥ 0.300 × 109 cells/L; non-high: < 0.300 × 109 cells/L). Categorisation 2 (FeNO concentration, high: ≥ 35 ppb; non-high: < 35 ppb) was based on prior research. Reference groups included patients with neither biomarker raised.ResultsIn categorisation 1, patients with either high FeNO or high BEC (n = 200) had a numerically greater exacerbation rate (unadjusted rate ratio, 1.31 [95% confidence interval: 0.97, 1.76]) compared with patients in the reference group. Combination of high FeNO and high BEC (n = 27) resulted in a significantly greater exacerbation rate (3.67 [1.49, 9.04]). Similarly, for categorisation 2, when both biomarkers were raised (n = 53), a significantly greater exacerbation rate was observed (1.72 [1.00, 2.93]).ConclusionThe combination of high FeNO and high BEC was associated with significantly increased severe exacerbation rates in the year preceding FeNO reading, suggesting that combining FeNO and BEC measurements in primary care may identify asthma patients at risk of exacerbations.

Highlights

  • Blood eosinophil count (BEC) and fractional exhaled nitric oxide (FeNO) concentration are established biomarkers in asthma, associated with the risk of exacerbations

  • A significant reduction in severe exacerbations has been observed for severe asthma patients with elevated blood eosinophils treated with biologics targeting type 2 cytokines involved in eosinophilic inflammation [15,16,17,18]

  • Two sets of thresholds were used for FeNO: (1) based on the American Thoracic Society (ATS) [19] criteria defining high FeNO (≥ 50 ppb), medium FeNO (25 to < 50 ppb), and low FeNO (< 25 ppb) concentrations; and (2) based on previous research [31, 32] suggesting poor asthma control with FeNO concentrations ≥ 35 ppb, high FeNO was defined as ≥ 35 ppb and non-high FeNO, < 35 ppb

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Summary

Introduction

Blood eosinophil count (BEC) and fractional exhaled nitric oxide (FeNO) concentration are established biomarkers in asthma, associated with the risk of exacerbations. Blood eosinophil counts and fractional exhaled nitric oxide (FeNO) concentrations are established biomarkers in asthma. A high blood eosinophil count, used as a marker for eosinophilic airway inflammation, correlates well with poor asthma control, an increased risk of severe exacerbations, and re-hospitalisations [11,12,13,14]. A significant reduction in severe exacerbations has been observed for severe asthma patients with elevated blood eosinophils treated with biologics targeting type 2 cytokines involved in eosinophilic inflammation [15,16,17,18]. Measurement of FeNO may provide additional predictive value to blood eosinophil counts for severe exacerbations in asthma patients

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