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Purpose of Review
To assess the role of measuring the fractional concentration of exhaled nitric oxide (FeNO) in the diagnosis, treatment and monitoring of asthma.
- Depending on the FeNO cutoff, the likelihood of having asthma in people ages 5 years and olderincreases by 2.8 to 7.0 times given a positive FeNO test result.
- FeNO is modestly more accurate in diagnosing steroid-naïve asthmatics, children (ages 5-18), andnonsmokers than other patients suspected to have asthma.
- FeNO results can predict which patients will respond to inhaled corticosteroid therapy.
- Using FeNO to manage long-term control medications including dose titration, weaning, andmonitoring of adherence, reduces the frequency of exacerbations.
- There is insufficient evidence supporting the use of FeNO in children (ages 0-4) for predicting afuture diagnosis of asthma.
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.
Wang Z, Pianosi P, Keogh K, et al. The Diagnostic Accuracy of Fractional Exhaled Nitric Oxide Testing in Asthma: A Systematic Review and Meta-analyses. Mayo Clinic Proceedings. ePub ahead of print.
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.