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. 2019 Aug 21:9:41.
doi: 10.1186/s13601-019-0282-7. eCollection 2019.

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

David B Price  1   2 , Sinthia Bosnic-Anticevich  3 , Ian D Pavord  4 , Nicolas Roche  5 , David M G Halpin  6 , Leif Bjermer  7 , Omar S Usmani  8 , Guy Brusselle  9 , Simon Wan Yau Ming  1 , Sarang Rastogi  10
Affiliations

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

David B Price et al. Clin Transl Allergy. .

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.

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Conflict of interest statement

Competing interestsDP reports grants and/or personal fees from Aerocrine, AKL Research and Development Ltd., Almirall, Amgen, AstraZeneca, Boehringer Ingelheim, the British Lung Foundation, Chiesi, Cipla, GlaxoSmithKline, Kyorin, Merck, Mylan, Mundipharma, Napp, Novartis, Pfizer, Regeneron Pharmaceuticals, the Respiratory Effectiveness Group, Sanofi Genzyme, Skyepharma, Teva, Theravance, the UK National Health Service, Zentiva (Sanofi Generics); non-financial support from Efficacy and Mechanism Evaluation Programme and Health Technology Assessment, outside the submitted work; stock/stock options from AKL Research and Development Ltd.; and owns 74% of the social enterprise Optimum Patient Care Ltd. (Australia and UK) and 74% of Observational and Pragmatic Research Institute Pte Ltd. (Singapore). SB reports grants and personal fees from TEVA, personal fees from Boehringer Ingelheim, AstraZeneca, Sanofi, and Mylan, outside the submitted work. IP has received speaker’s honoraria for speaking at sponsored meetings from AstraZeneca, Boehringer Ingelheim, Aerocrine, Almirall, Novartis, Teva, Chiesi, and GlaxoSmithKline, and payments for organising educational events from AstraZeneca and Teva. He has received honoraria for attending advisory panels with Genentech, Regeneron, AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Novartis, Teva, Merck, Sanofi, Circassia, Chiesi, and Knopp. He has received sponsorship to attend international scientific meetings from Boehringer Ingelheim, GlaxoSmithKline, AstraZeneca, Teva, and Chiesi. He has received a grant from Chiesi to support a phase 2 clinical trial in Oxford. NR reports grants and personal fees from Boehringer Ingelheim, Novartis, Pfizer and personal fees from Teva, GlaxoSmithKline, AstraZeneca, Chiesi, Mundipharma, Cipla, Sanofi, Sandoz, 3 M, and Zambon. DH reports personal fees and/or non-financial support from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis, and Pfizer, outside the submitted work. LB has nothing to disclose. OU has received grants and/or personal fees from AstraZeneca, Boehringer Ingelheim, Chiesi, Aerocrine, GlaxoSmithKline, Napp, Mundipharma, Sandoz, Prosonix, Takeda, Zentiva, Edmond Pharma, Cipla, and Pearl Therapeutics. GB reports personal fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis, Sanofi, and Teva, outside the submitted work. SWM reports other from Observational and Pragmatic Research Institute Pte Ltd. (OPRI), outside the submitted work. He was employed by the OPRI at the time the analyses were conducted; OPRI has conducted paid research in respiratory disease on behalf of the following organisations in the past 5 years: Anaxys, AstraZeneca, Boehringer Ingelheim, British Lung Foundation, Chiesi, Circassia (formerly Aerocrine), GlaxoSmithKline, Harvey Walsh, Mapi, Morningside Healthcare, Mundipharma, Mylan (formerly Meda), Napp, Novartis, Orion, Plymouth University, Regeneron, Respiratory Effectiveness Group, Roche, Sanofi, Takeda, Teva, University of East Anglia, and Zentiva (a Sanofi company). SR was an employee of AstraZeneca at the time the analyses were conducted.

Figures

Fig. 1
Fig. 1
Study design. The study period consisted of the year prior to the latest documented FeNO reading. FeNO fractional exhaled nitric oxide
Fig. 2
Fig. 2
Patient selection from OPCRD. COPD chronic obstructive pulmonary disease, FeNO fractional exhaled nitric oxide, ICS inhaled corticosteroid, OCS oral corticosteroid, OPCRD Optimum Patient Care Research Database
Fig. 3
Fig. 3
Comparison of exacerbation rates of cohorts relative to non-high FeNO and non-high blood eosinophil cohorts. CI confidence interval, FeNO fractional exhaled nitric oxide, RR rate ratio
See this image and copyright information in PMC

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