Royal Aberdeen Children's Hospital, University of Aberdeen, Aberdeen, UK.
Health Services Research Unit, University of Aberdeen, Aberdeen, UK.
Lancet Respir Med. 2022 Jun;10(6):584-592. doi: 10.1016/S2213-2600(21)00486-0. Epub 2022 Jan 31.
The benefit of fractional exhaled nitric oxide (FeNO) in guiding asthma treatment is uncertain. We evaluated the efficacy of adding FeNO to symptom-guided treatment in children with asthma versus only symptom-guided treatment.
RAACENO was a multicentre, parallel, randomised, controlled, phase 3 trial done in 35 secondary care centres and 17 primary care recruitment sites (only seven primary care sites managed to recruit patients) in the UK. Patients with a confirmed asthma diagnosis, aged 6-15 years, prescribed inhaled corticosteroids, and who received a course of oral corticosteroids for at least one asthma exacerbation during the 12 months before recruitment were included. Participants were randomly assigned to either FeNO plus symptom-guided treatment (intervention) or symptom-guided treatment alone (standard care) using a 24 h in-house, web-based randomisation system. Participants and the clinical and research teams were not masked to the group allocation. A web-based algorithm gave 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). Follow-up occurred at 3-month intervals for 12 months. The primary outcome was any asthma exacerbation treated with oral corticosteroids in the 12 months after randomisation, assessed in the intention-to-treat population. This study is registered with the International Standard Randomised Controlled Trial Registry, ISRCTN67875351.
Between June 22, 2017, and Aug 8, 2019, 535 children were assessed for eligibility, 20 were ineligible and six were excluded post-randomisation. 509 children were recruited and at baseline, the mean age of participants was 10·1 years (SD 2·6), and 308 (60·5%) were male. The median FeNO was 21 ppb (IQR 10-48), mean predicted FEV was 89·6% (SD 18·0), and median daily dose of inhaled corticosteroids was 400 μg budesonide equivalent (IQR 400-1000). Asthma was partly or fully controlled in 256 (50·3%) of 509 participants. The primary outcome, which was available for 506 (99%) of 509 participants, occurred in 123 (48·2%) of 255 participants in the intervention group and 129 (51·4%) of 251 in the standard care group, the intention-to-treat adjusted odds ratio (OR) was 0·88 (95% CI 0·61 to 1·27; p=0·49). The adjusted difference in the percentage of participants who received the intervention in whom the primary outcome occurred compared with those who received standard care was -3·1% (-11·9% to 5·6%). In 377 (21·3%) of 1771 assessments, the algorithm recommendation was not followed. Adverse events were reported by 27 (5·3%) of 509 participants (15 in the standard care group and 12 in the intervention group). The most common adverse event was itch after skin prick testing (reported by eight participants in each group).
We found that the addition of FeNO to symptom-guided asthma treatment did not lead to reduced exacerbations among children prone to asthma exacerbation. Asthma symptoms remain the only tool for guiding treatment decisions.
National Institute for Health Research.
Fractional exhaled nitric oxide (FeNO) 在指导哮喘治疗方面的益处尚不确定。我们评估了在哮喘儿童中，将 FeNO 添加到症状指导治疗中与仅进行症状指导治疗相比的疗效。
RAACENO 是一项多中心、平行、随机、对照、3 期临床试验，在英国的 35 个二级护理中心和 17 个初级保健招募点（只有 7 个初级保健点设法招募了患者）进行。纳入了确诊哮喘、年龄 6-15 岁、使用吸入性皮质类固醇且在招募前 12 个月内因哮喘加重至少接受过一次口服皮质类固醇治疗的患者。参与者使用内部 24 小时网络随机化系统被随机分配到 FeNO 加症状指导治疗（干预组）或仅症状指导治疗（标准护理组）。参与者和临床及研究团队对分组分配不知情。一个基于网络的算法根据哮喘控制测试（ACT）或儿童 ACT（CACT）评分、当前哮喘治疗、过去 3 个月对研究治疗的依从性以及 FeNO 的使用情况（在干预组）给出治疗建议。在 12 个月的时间里，每隔 3 个月进行一次随访。主要结局是在随机分组后 12 个月内用口服皮质类固醇治疗的任何哮喘加重，在意向治疗人群中进行评估。本研究在国际标准随机对照试验注册库（ISRCTN67875351）注册。
2017 年 6 月 22 日至 2019 年 8 月 8 日期间，535 名儿童接受了资格评估，20 名不合格，6 名随机分组后被排除。509 名儿童被招募，基线时，参与者的平均年龄为 10.1 岁（标准差 2.6），308 名（60.5%）为男性。中位 FeNO 为 21 ppb（IQR 10-48），平均预测 FEV 为 89.6%（标准差 18.0），中位吸入皮质类固醇日剂量为 400 μg 布地奈德当量（IQR 400-1000）。509 名参与者中有 256 名（50.3%）哮喘部分或完全控制。主要结局是 509 名参与者中的 506 名（99%）可获得，255 名参与者中的 123 名（48.2%）和 251 名标准护理组中的 129 名（51.4%）发生，意向治疗调整后的优势比（OR）为 0.88（95%CI 0.61-1.27；p=0.49）。与接受标准护理的参与者相比，接受干预的参与者中主要结局发生的比例差异为 -3.1%（-11.9%至 5.6%）。在 1771 次评估中的 377 次（21.3%），算法建议未得到遵循。509 名参与者中有 27 名（5.3%）报告了不良事件（标准护理组 15 名，干预组 12 名）。最常见的不良事件是皮肤点刺试验后的瘙痒（每组 8 名参与者报告）。
我们发现，将 FeNO 添加到哮喘症状指导治疗中并不能减少易发生哮喘加重的儿童的哮喘加重。哮喘症状仍然是指导治疗决策的唯一工具。
英国国家卫生研究院。
