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The Clinical Utility of Fractional Exhaled Nitric Oxide (FeNO) in Asthma Management
Comparative Effectiveness Reviews, No. 197
Investigators: Zhen Wang, PhD, Paolo Pianosi, MD, Karina Keogh, MD, Feras Zaiem, MD, Mouaz Alsawas, MD, MSc, Fares Alahdab, MD, Jehad Almasri, MD, Khaled Mohammed, MBCH, Laura Larrea-Mantilla, MD, Wigdan Farah, MBBS, Lubna Daraz, PhD, Patricia Barrionuevo, MD, Shalak Gunjal, MS, Larry J Prokop, MLS, and M Hassan Murad, MD, MPH.
Author Information and AffiliationsStructured Abstract
Objectives:
To evaluate the clinical utility and diagnostic accuracy of fractional exhaled nitric oxide (FeNO) in people age 5 years and older with asthma; and the ability of FeNO measured at age 4 years or younger to predict a future diagnosis of asthma.
Data sources:
MEDLINE, EMBASE, Cochrane Central Databases, and SciVerse Scopus, references lists, trials registries, and grey literature sources.
Review methods:
We searched from databases’ inception to April 2017 for studies enrolling patients with or suspected to have asthma that evaluated the diagnosis or clinical utility of FeNO. We included randomized and nonrandomized comparative studies.
Results:
We included 175 studies. In adults (>18) and children (ages 5–18), 43 studies showed that FeNO results increased the odds of correctly diagnosing asthma between 5.85 and16.95 fold. Using FeNO cutoffs of <20, 20–30, 30–40, ≥40 part per billion (ppb); respectively, FeNO testing had sensitivities of 0.79, 0.64, 0.53 and 0.41; and specificities of 0.72, 0.81, 0.84, 0.94 (Strength of Evidence (SOE): Moderate). Depending on the FeNO cutoff, the posttest odds of having asthma given a positive FeNO test result increased by 2.80 to 7.00 fold. Diagnostic accuracy was modestly better in steroid-naïve asthmatics, children and nonsmokers than the overall population. Data from 58 studies showed that in adults and children (age 5–18), FeNO levels had a weak association with asthma control and the risk of subsequent and prior exacerbations (SOE: Low). Elevated FeNO levels were likely more predictive of exacerbation risk in those with atopy. In adults and children with acute asthma exacerbations, FeNO levels did not correlate with exacerbation severity and were poorly reproducible. In children and adolescents (ages 5–18), FeNO levels were inversely associated with adherence to inhaled corticosteroids (SOE: Low). Data from 14 randomized controlled trials showed that asthma management following algorithms that included FeNO monitoring, compared to no FeNO, reduced the risk of exacerbations (SOE: High) but did not affect other outcomes such as hospitalization, or quality of life. FeNO testing may identify patients who were more likely to respond to inhaled corticosteroids (SOE: Low). FeNO testing predicted exacerbations in patients undergoing ICS reduction or withdrawal. Data from 9 studies showed that althoughFeNO levels in children at age 0–4 years correlated with the Asthma Predictive Index and wheezing (SOE: Low), there was insufficient evidence to determine if FeNO results at age 0–4 years can reliably predict a future asthma diagnosis.
Conclusions:
This systematic review provides the diagnostic accuracy measures of FeNO in people ages 5 years and older. Test performance is modestly better in steroid-naïve asthmatics, children, and nonsmokers than the general population with suspected asthma. Algorithms that include FeNO measurements can help in monitoring response to anti-inflammatory, or long-term control medications, including dose titration, weaning, and treatment adherence. At this time, evidence is insufficient to support the measurement of FeNO in children under the age of 5 as a means for predicting a future diagnosis of asthma.
Contents
- Preface
- Technical Expert Panel
- Peer Reviewers
- Evidence Summary
- Introduction
- Methods
- Criteria for Inclusion/Exclusion of Studies in the Review
- Literature Search Strategies
- Data Abstraction and Data Management
- Assessment of Methodological Risk of Bias of Individual Studies
- Data Synthesis
- Grading the Strength of Evidence for Major Comparisons and Outcomes
- Assessing Applicability
- Peer Review and Public Commentary
- Results
- Discussion
- Conclusion
- References
- Abbreviations
- Appendix A. Search Strategy
- Appendix B. Excluded Studies
- Appendix C. Description of Included Studies
- Appendix D. Figures
- Appendix E. Subgroup Analyses
- Appendix F. Sensitivity Analysis
- Appendix G. Risk of Bias
- Appendix H. Assessment of the Strength of Evidence
- Appendix I. Additional Tables
- Appendix J. References
Suggested citation:
Wang Z, Pianosi P, Keogh K, Zaiem F, Alsawas M, Alahdab F, Almasri JM, Mohammed K, Larrea-Mantilla L, Farah W, Daraz L, Barrionuevo P, Gunjal S, Prokop LJ, Murad MH. The Clinical Utility of Fractional Exhaled Nitric Oxide (FeNO) in Asthma Management. Comparative Effectiveness Review No. 197 (Prepared by the Mayo Clinic Evidence-based Practice Center under Contract No. 290-2015-00013-I). AHRQ Publication No.17(18)-EHC030-EF. Rockville, MD: Agency for Healthcare Research and Quality. December 2017. www.effectivehealthcare.ahrq.gov/reports/final.cfm.
This report is based on research conducted by Mayo Clinic Evidence-based Practice Center (EPC) under contract to the Agency for Healthcare Research and Quality (AHRQ), Rockville, MD (Contract No. 290-2015-00013-I). The National Institutes of Health (NIH) National Heart, Lung, and Blood Institute (NHLBI) sponsor the report. The findings and conclusions in this document are those of the authors, who are responsible for its contents; the findings and conclusions do not necessarily represent the views of AHRQ or NIH/NHLBI. Therefore, no statement in this report should be construed as an official position of AHRQ, NIH/NHLBI or of the U.S. Department of Health and Human Services.
None of the investigators have any affiliations or financial involvement that conflicts with the material presented in this report.
The information in this report is intended to help health care decision makers—patients and clinicians, health system leaders, and policymakers, among others—make well-informed decisions and thereby improve the quality of health care services. This report is not intended to be a substitute for the application of clinical judgment. Anyone who makes decisions concerning the provision of clinical care should consider this report in the same way as any medical reference and in conjunction with all other pertinent information, i.e., in the context of available resources and circumstances presented by individual patients.
AHRQ or U.S. Department of Health and Human Services endorsement of any derivative products that may be developed from this report, such as clinical practice guidelines, other quality enhancement tools, or reimbursement or coverage policies, may not be stated or implied.
This report may periodically be assessed for the currency of conclusions. If an assessment is done, the resulting surveillance report describing the methodology and findings will be found on the Effective Health Care Program Web site at www.effectivehealthcare.ahrq.gov. Search on the title of the report.
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