Reducing Asthma Attacks in Children using Exhaled Nitric Oxide as a biomarker to inform treatment strategy: a randomised trial (RAACENO)

Abstract

Introduction: The role of FeNO in guiding asthma treatment is uncertain. We tested the hypothesis that FeNO guided care reduces exacerbations in children with asthma.

Methods: A multicentre RCT recruited children (6-16 years) with asthma on regular inhaled corticosteroids (ICS) with an exacerbation in the previous year. They were randomised to asthma treatment guided by FeNO plus symptoms (FeNO group) or by symptoms only (standard care). A web-based algorithm using symptom control, ICS adherence, current treatment and (within the FeNO group) changes in FeNO gave treatment recommendations. Participants attended 3, 6, 9 and 12 month follow-up. The primary outcome was exacerbation requiring oral steroid. Secondary outcomes included time to first exacerbation, asthma control and quality of life.

Results: 509 children were recruited. The mean (SD) age was 10.1 (2.6) years (61% male), median (IQR) FeNO 21 ppb (10, 48), mean (SD) %FEV1 90% (18), 56% were treated with ≤400 microg budesonide equivalent and 33% >800 microg. The primary outcome occurred in 123/255 (48%) in the FeNO group and 129/251 (51%) in the standard care group. In adjusted intention to treat analysis the odds ratio (OR) for primary outcome was 0.88 [95%CI 0.61, 1.27]. This OR was consistent across pre-defined subgroups. On 377 of 1771 assessments, the algorithm’s recommendation was not followed. In complier average causal effect analysis, adjusting for algorithm adherence, the OR for primary outcome was 0.82 [95%CI 0.48, 1.41].There were no differences in secondary outcomes between groups.

Conclusion: In this population, adding FeNO to standard care did not reduced exacerbations.