Fractional exhaled nitric oxide (FeNO) added to symptom-guided asthma treatment does not lead to reduced exacerbations in children prone to asthma exacerbation, according to research published in Lancet Respiratory Medicine.
For the multicenter, parallel, randomized, controlled, phase 3 trial, Reducing Asthma Attacks in Children Using Exhaled Nitric Oxide (RAACENO), researchers investigated the efficacy of using FeNO as an add-on to symptom-guided treatment in children with asthma vs symptom-guided treatment alone. Between June 2017 and August 2019, researchers enrolled 509 children in the United Kingdom with asthma, who were prescribed inhaled corticosteroids and, in the 12 months prior to study enrollment, had at least 1 asthma exacerbation for which they received a course of oral corticosteroids. Participants had a mean age of 10.1 years (SD 2.6), and 60.5% were boys. Individuals were randomly assigned to either the standard care cohort of symptom-guided treatment or the FeNO plus symptom-guided treatment intervention cohort.
At baseline, mean predicted forced expiratory volume in the first second (FEV1) was 89.6% (SD 18.0); median FeNO was 21 ppb (IQR, 10-48); median inhaled corticosteroid daily dose was 400 µg budesonide equivalent (IQR, 400-1000); and 256 (50.3%) of participants had asthma fully or partly controlled.
Treatment recommendations based on the Asthma Control Test (ACT) or Childhood ACT (CACT) score, current asthma treatment, adherence to study treatment in the past 3 months, and use of FeNO (in the intervention group) were directed by algorithm. Participants had follow-ups every 3 months for 12 months, and the primary outcome during that span was any asthma exacerbation treated with oral corticosteroids, which occurred in 123 (48.2%) of the 255 participants in the intervention group and in 129 (51.4%) of 251 in the standard care group. The adjusted odds ratio for intention-to-treat was 0.88 (95% CI, 0.61-1.27; P =.49), and the adjusted difference in the percentage of participants with the primary outcome who received intervention compared with standard care was -3.1% (-11.9% to 5.6%). Of the 509 participants, 27 (5.3%) reported adverse events (15 in standard care, 12 in intervention).
Study limitations included using an algorithm that used only 2 categories of control, using a different FeNO level to trigger change in treatment that may have altered results, and the possibility that adherence to medication may have been overreported. Some asthma patients in unidentified subgroups may have also benefitted from FeNO-guided treatment, and many participants were already receiving the highest recommended inhaled corticosteroid dose.
“…[T]he addition of FeNO to symptom-guided asthma treatment did not lead to reduced exacerbations among children prone to asthma exacerbation,” the study authors wrote. “Asthma symptoms remain the only tool for guiding treatment decisions.”
Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Turner S, Cotton S, Wood J, et al. Reducing asthma attacks in children using exhaled nitric oxide (RAACENO) as a biomarker to inform treatment strategy: a multicenter, parallel, randomized, controlled, phase 3 trial. Lancet Respir Med. Published online January 28, 2022. doi:10.1016/S2213-2600(21)00486-0