Phenotypes favoring fractional exhaled nitric oxide discordance vs guideline-based uncontrolled asthma

Background Despite potential value of identification of allergic inflammation with fractional exhaled nitric oxide (FeNO) in managing asthma, randomized clinical trials have not consistently shown better outcomes compared with guideline management alone. Objective To assess the effectiveness of FeNO vs non–FeNO-based therapeutic algorithms in managing asthma, and the phenotypic profile associated with FeNO >35 ppb yet well controlled by guidelines, as a potential model to predict better FeNO-based algorithm outcomes. Methods This is a randomized controlled study (RCT) in 88 high-risk children with asthma 7 to 18 years of age across 352 visits over a 1-year period. Generalized estimating equations analysis assessed algorithm group differences in outcomes and characteristics associated with higher odds uncontrolled by FeNO alone in the treatment decision algorithm. Results The FeNO treatment algorithm did not show superiority in reducing exacerbations and morbidity (P > .05). Phenotypes that more than doubled the odds FeNO alone identified uncontrolled asthma included adolescence, non-adherence, high atopy (>6+), and baseline FeNO >35 ppb, whereas obesity, FEF25-75% 10% decreased the odds. Uncontrolled asthma by FeNO alone (F) vs guidelines alone (G) showed overall F/G > 1.0 in adolescents, but 20 ppb. Conclusion Our study suggests that age and phenotypes play a key role in FeNO discordance compared with the conventional guideline-based uncontrolled asthma. The FeNO-based therapeutic algorithm, if confirmed further, could provide the clinician with an effective asthma management tool. The clinical implication could improve future FeNO-based RCTs and treatment decision algorithms in managing asthma by considering phenotypes and age-dependent FeNO thresholds.