Abstract
Background High exhaled nitric oxide fraction (FENO) levels are associated with greater risk of asthma exacerbation. However, it is not clear how FENO can be used to guide safe reductions in inhaled corticosteroid (ICS) doses in asthma patients. This study assesses the ability of FENO to guide ICS reductions.
Methods Systematic searching of electronic databases identified prospective observational studies and randomised controlled trials which recruited participants with mild-to-moderate asthma aged ≥12 years and measured FENO before reducing ICS. We performed multilevel mixed-effects logistic regression in relation to acute exacerbations and estimated each participant's exacerbation risk using our logistic regression model.
Results We included data from seven out of eight eligible studies, representing 384 participants. ICS doses were halved in four studies and withdrawn in three studies. A baseline FENO measurement of ≥50 ppb was associated with increased risk of exacerbations (crude OR 3.14, 95% CI 1.41–7.00, p=0.005; adjusted OR 3.08, 95% CI 1.36–6.98, p=0.007) and corresponded to an estimated exacerbation risk cut-off of 15%. Reducing ICS when estimated exacerbation risk was <15% versus <10% would result in fewer patients remaining on the same ICS dose (40 (10.4%) out of 384 versus 141 (36.7%) out of 384), but similar proportions of patients avoiding exacerbations (222 (91.4%) out of 243, 95% CI 87.1–94.6% versus 311 (90.4%) out of 344, 95% CI 86.8–93.3%).
Conclusion In patients with mild-to-moderate asthma, gradual ICS reduction when FENO is <50 ppb may help decrease ICS use without increasing exacerbations. Future research should aim to validate these findings in larger populations.
Abstract
In nonsmoking patients with mild-to-moderate well-controlled asthma, stepping down treatment when FENO is <50 ppb reduces prescribing of inhaled corticosteroids without increasing exacerbations http://bit.ly/2SKaxSt
Footnotes
This article has an editorial commentary: https://doi.org/10.1183/13993003.01319-2020
This article has supplementary material available from erj.ersjournals.com
Ethical approval: Overall ethical approval was not required as this study did not require use of patient identifiers. Collaborating groups obtained individual approvals for data sharing from Research Ethics Committees at Juntendo University, Kinki University Hospital, Keio University Hospital, Kagoshima University Medical and Dental Hospital and Shizuoka General Hospital.
Conflict of interest: K. Wang reports grants from National Institute for Health Research, during the conduct of the study.
Conflict of interest: J.Y. Verbakel has nothing to disclose.
Conflict of interest: J. Oke has nothing to disclose.
Conflict of interest: A. Fleming-Nouri has nothing to disclose.
Conflict of interest: J. Brewin has nothing to disclose.
Conflict of interest: N. Roberts has nothing to disclose.
Conflict of interest: N. Harada reports personal fees from AstraZeneca, outside the submitted work. In addition, N. Harada has a patent Japanese Patent Application 2018-097070 pending.
Conflict of interest: R. Atsuta has nothing to disclose.
Conflict of interest: K. Takahashi reports grants and personal fees from Chugai Pharmaceutical Co., Ltd, grants and personal fees from Nippon Boehringer Ingelheim Co., Ltd, grants and personal fees from MSD K.K., grants from GlaxoSmithKline Consumer Healthcare Japan K.K., grants from Nippon Shinyaku Co., Ltd, grants from Tsumura & Co., grants and personal fees from Pfizer Inc., grants and personal fees from AstraZeneca K.K., grants and personal fees from Taiho Pharmaceutical Co., Ltd, grants from Astellas Pharma Inc., grants and personal fees from Kyorin Pharmaceutical Co., Ltd, grants from Kyowa Hakko Kirin Co., Ltd, grants and personal fees from Teijin Pharma Limited, grants from Mochida Pharmaceutical Co., Ltd, grants from Toyama Chemical Co., Ltd, grants from Sanofi K.K., grants and personal fees from Ono Pharmaceutical Co., Ltd, grants and personal fees from Nobelpharma Co., Ltd, grants and personal fees from Novartis Pharma K.K., grants from Shionogi & Co., Ltd, grants and personal fees from Eli Lilly Japan K.K., grants from Nipro Corporation, grants from Torii Pharmaceutical Co., Ltd, grants from MiZ Company Limited, personal fees from Sumitomo Dainippon Pharma Co., Ltd, personal fees from Bristol-Myers K.K., personal fees from Meiji Seika Pharma Co., Ltd, personal fees from Otsuka Pharmaceutical Co., Ltd, personal fees from Parexel International Corporation, personal fees from Eisai Co., Ltd, personal fees from Mitsubishi Tanabe Pharma, outside the submitted work.
Conflict of interest: K. Mori has nothing to disclose.
Conflict of interest: T. Fujisawa has nothing to disclose.
Conflict of interest: T. Shirai has nothing to disclose.
Conflict of interest: T. Kawayama has nothing to disclose.
Conflict of interest: H. Inoue reports grants from Astellas, AstraZeneca, Boehringer-Ingelheim, Chugai Pharm, GlaxoSmithKline, Pfizer, Merck Sharp & Dohme, Novartis, Teijin-Pharma, personal fees from Astellas, AstraZeneca, Boehringer-Ingelheim, Chugai Pharm, GlaxoSmithKline, Kyorin, Merck Sharp & Dohme, Meiji Seika Pharma, Novartis, Otsuka, Pfizer, Taiho, outside the submitted work.
Conflict of interest: S. Lazarus reports grants from NIH/NHLBI, during the conduct of the study; grants from NIH/NHLBI, grants from American Lung Association – Airway Clinical Research Centers Network (ALA-ACRC), outside the submitted work.
Conflict of interest: S. Szefler reports other from Boehringer-Ingelheim, other from Genentech, other from GlaxoSmithKline, other from AstraZeneca, other from Daiichi Sankyo, grants from GlaxoSmithKline, other from Propeller Health, other from Sanofi, other from Regeneron, outside the submitted work.
Conflict of interest: F. Martinez reports grants from NIH/NHLBI, grants from NIH/NIEHS, grants from NIH/NIAID, grants from NIH/Office of Director, grants from Johnson & Johnson, personal fees from Copeval, personal fees from Commense Inc, outside the submitted work.
Conflict of interest: D. Shaw reports personal fees from AstraZeneca, GSK, TEVA and Novartis, outside the submitted work.
Conflict of interest: I.D. Pavord reports personal fees from AstraZeneca, personal fees from Boehringer Ingelheim, personal fees from Aerocrine, personal fees from Almirall, personal fees from Novartis, personal fees from GlaxoSmithKline, personal fees from Genentech, personal fees from Regeneron, speakers’ fees from Teva, speakers’ fees from Chiesi, advisory board fees from Sanofi, advisory board fees from Circassia, advisory board fees from Knopp, grants from NIHR, outside the submitted work.
Conflict of interest: M. Thomas reports personal fees from GSK, personal fees from Novartis, personal fees from Boehringer Ingelheim, outside the submitted work; and recent membership of the BTS SIGN Asthma guideline steering group and the NICE Asthma Diagnosis and Monitoring guideline development group.
Support statement: This paper presents independent research funded by the National Institute for Health Research under its Postdoctoral Fellowship Programme (grant reference number PDF-2016-09-007). Funding information for this article has been deposited with the Crossref Funder Registry.
- Received November 5, 2019.
- Accepted February 13, 2020.
- Copyright ©ERS 2020
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