Association of elevated fractional exhaled nitric oxide concentration and blood eosinophil count with severe asthma exacerbations

David B. Price; Sinthia Bosnic-Anticevich; Ian D. Pavord; Nicolas Roche; David M. G. Halpin; Leif Bjermer; Omar S. Usmani; Guy Brusselle; Simon Wan Yau Ming; Sarang Rastogi

doi:10.1186/s13601-019-0282-7

Association of elevated fractional exhaled nitric oxide concentration and blood eosinophil count with severe asthma exacerbations

David B. Price^* (Corresponding Author), Sinthia Bosnic-Anticevich, Ian D. Pavord, Nicolas Roche, David M. G. Halpin, Leif Bjermer, Omar S. Usmani, Guy Brusselle, Simon Wan Yau Ming, Sarang Rastogi

^*Corresponding author for this work

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Abstract

Background Blood 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. Methods This 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. Results In 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]). Conclusion The 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.

Original language	English
Article number	41
Number of pages	18
Journal	Clinical and Translational Allergy
Volume	9
Issue number	1
DOIs	https://doi.org/10.1186/s13601-019-0282-7
Publication status	Published - 21 Aug 2019

Bibliographical note

Acknowledgements
The authors thank Gokul Gopalan and Sadia Halim for their contributions to the development of a poster based on the findings of this study, which was presented at the British Thoracic Society (BTS) Winter Meeting, 6–8 December 2017, London, United Kingdom. Editorial support was provided by Michelle Rebello, PhD, of Cactus Communications (Mumbai, India) and Michael A. Nissen, ELS, of AstraZeneca (Gaithersburg, MD, USA) in accordance with Good Publication Practice (GPP3) guidelines (http://www.ismpp.org/gpp3). This support was fully funded by AstraZeneca.

Funding
This study was funded by AstraZeneca.

Availability of data and materials
Data underlying the findings described in this manuscript may be obtained in accordance with AstraZeneca’s data sharing policy described at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Keywords

Asthma
blood eosinophils
exhaled airway markers
nitric oxide
Exhaled airway markers
Blood eosinophils
Nitric oxide
MULTICENTER
MEPOLIZUMAB
GUIDELINES
ADULTS
INHALED CORTICOSTEROIDS
PERSISTENT ASTHMA
CARE

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Association of elevated fractional exhaled nitric oxide concentration and blood eosinophil count with severe asthma exacerbations
© The Author(s) 2019. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/ publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
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Cite this

Price, D. B., Bosnic-Anticevich, S., Pavord, I. D., Roche, N., Halpin, D. M. G., Bjermer, L., Usmani, O. S., Brusselle, G., Ming, S. W. Y., & Rastogi, S. (2019). Association of elevated fractional exhaled nitric oxide concentration and blood eosinophil count with severe asthma exacerbations. Clinical and Translational Allergy, 9(1), Article 41. https://doi.org/10.1186/s13601-019-0282-7

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title = "Association of elevated fractional exhaled nitric oxide concentration and blood eosinophil count with severe asthma exacerbations",

abstract = "Background Blood 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. Methods This 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. Results In 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]). Conclusion The 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.",

keywords = "Asthma, blood eosinophils, exhaled airway markers, nitric oxide, Exhaled airway markers, Blood eosinophils, Nitric oxide, MULTICENTER, MEPOLIZUMAB, GUIDELINES, ADULTS, INHALED CORTICOSTEROIDS, PERSISTENT ASTHMA, CARE",

author = "Price, {David B.} and Sinthia Bosnic-Anticevich and Pavord, {Ian D.} and Nicolas Roche and Halpin, {David M. G.} and Leif Bjermer and Usmani, {Omar S.} and Guy Brusselle and Ming, {Simon Wan Yau} and Sarang Rastogi",

note = "Acknowledgements The authors thank Gokul Gopalan and Sadia Halim for their contributions to the development of a poster based on the findings of this study, which was presented at the British Thoracic Society (BTS) Winter Meeting, 6–8 December 2017, London, United Kingdom. Editorial support was provided by Michelle Rebello, PhD, of Cactus Communications (Mumbai, India) and Michael A. Nissen, ELS, of AstraZeneca (Gaithersburg, MD, USA) in accordance with Good Publication Practice (GPP3) guidelines (http://www.ismpp.org/gpp3). This support was fully funded by AstraZeneca. Funding This study was funded by AstraZeneca. Availability of data and materials Data underlying the findings described in this manuscript may be obtained in accordance with AstraZeneca{\textquoteright}s data sharing policy described at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.",

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doi = "10.1186/s13601-019-0282-7",

language = "English",

volume = "9",

journal = "Clinical and Translational Allergy",

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TY - JOUR

T1 - Association of elevated fractional exhaled nitric oxide concentration and blood eosinophil count with severe asthma exacerbations

AU - Price, David B.

AU - Bosnic-Anticevich, Sinthia

AU - Pavord, Ian D.

AU - Roche, Nicolas

AU - Halpin, David M. G.

AU - Bjermer, Leif

AU - Usmani, Omar S.

AU - Brusselle, Guy

AU - Ming, Simon Wan Yau

AU - Rastogi, Sarang

N1 - Acknowledgements The authors thank Gokul Gopalan and Sadia Halim for their contributions to the development of a poster based on the findings of this study, which was presented at the British Thoracic Society (BTS) Winter Meeting, 6–8 December 2017, London, United Kingdom. Editorial support was provided by Michelle Rebello, PhD, of Cactus Communications (Mumbai, India) and Michael A. Nissen, ELS, of AstraZeneca (Gaithersburg, MD, USA) in accordance with Good Publication Practice (GPP3) guidelines (http://www.ismpp.org/gpp3). This support was fully funded by AstraZeneca. Funding This study was funded by AstraZeneca. Availability of data and materials Data underlying the findings described in this manuscript may be obtained in accordance with AstraZeneca’s data sharing policy described at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

PY - 2019/8/21

Y1 - 2019/8/21

N2 - Background Blood 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. Methods This 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. Results In 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]). Conclusion The 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.

AB - Background Blood 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. Methods This 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. Results In 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]). Conclusion The 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.

KW - Asthma

KW - blood eosinophils

KW - exhaled airway markers

KW - nitric oxide

KW - Exhaled airway markers

KW - Blood eosinophils

KW - Nitric oxide

KW - MULTICENTER

KW - MEPOLIZUMAB

KW - GUIDELINES

KW - ADULTS

KW - INHALED CORTICOSTEROIDS

KW - PERSISTENT ASTHMA

KW - CARE

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UR - http://www.mendeley.com/research/association-elevated-fractional-exhaled-nitric-oxide-concentration-blood-eosinophil-count-severe-ast

U2 - 10.1186/s13601-019-0282-7

DO - 10.1186/s13601-019-0282-7

M3 - Article

C2 - 31452870

SN - 2045-7022

VL - 9

JO - Clinical and Translational Allergy

JF - Clinical and Translational Allergy

IS - 1

M1 - 41

ER -

Association of elevated fractional exhaled nitric oxide concentration and blood eosinophil count with severe asthma exacerbations

Abstract

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Keywords

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