RATIONALE Poor adherence is common in difficult-to-control asthma. Distinguishing patients with difficult-to-control asthma who respond to inhaled corticosteroids (ICS) from refractory asthma is an important clinical challenge. OBJECTIVES Suppression of fractional exhaled nitric oxide (FeNO) with directly observed ICS therapy over 7 days can identify nonadherence to ICS treatment in difficult-to-control asthma. We examined the feasibility and utility of FeNO suppression testing in routine clinical care within UK severe asthma centers using remote monitoring technologies. METHODS A web-based interface with integrated remote monitoring technology was developed to deliver FeNO suppression testing. We examined the utility of FeNO suppression testing to demonstrate ICS responsiveness and clinical benefit on electronically monitored treatment with standard high-dose ICS and long-acting β2-agonist treatment. MEASUREMENTS AND MAIN RESULTS Clinical response was assessed using the Asthma Control Questionnaire-5, spirometry, and biomarker measurements (FeNO and peripheral blood eosinophil count). Of 250 subjects, 201 completed the test with 130 positive suppression tests. Compared with a negative suppression test, a positive test identified a FeNO-low population when adherent with ICS/long-acting β2-agonist (median, 26 ppb [interquartile range, 16-36 ppb] vs. 43 ppb [interquartile range, 38-73 ppb]) with significantly greater FEV1% (mean, 88.2 ± 16.4 vs. 74.1 ± 20.9; P < 0.01). Asthma Control Questionnaire-5 improved significantly in both groups (positive test: mean difference, -1.2; 95% confidence interval, -0.9 to -1.5; negative test: mean difference, -0.9; 95% confidence interval, -0.4 to -1.3). CONCLUSIONS Remote FeNO suppression testing is an effective means of identifying nonadherence to ICS in subjects with difficult-to-control asthma and the substantial population of subjects who derive important clinical benefits from optimized ICS/long-acting β2-agonist treatment.

中文翻译：

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远程监测治疗和一氧化氮抑制可识别严重哮喘患者的不依从性。

基本原理 依从性差在难以控制的哮喘中很常见。区分对吸入皮质类固醇 (ICS) 有反应的难治性哮喘患者与难治性哮喘是一项重要的临床挑战。目的 直接观察 ICS 治疗 7 天内抑制呼出气一氧化氮（FeNO）分数可以识别难以控制的哮喘患者对 ICS 治疗的不依从性。我们使用远程监测技术在英国严重哮喘中心的常规临床护理中检查了 FeNO 抑制测试的可行性和实用性。方法 开发了具有集成远程监控技术的基于 Web 的界面来提供 FeNO 抑制测试。我们检查了 FeNO 抑制测试的效用，以证明 ICS 对采用标准大剂量 ICS 和长效 β2 受体激动剂治疗的电子监测治疗的反应性和临床益处。测量和主要结果 使用哮喘控制问卷 5、肺活量测定和生物标志物测量（FeNO 和外周血嗜酸性粒细胞计数）评估临床反应。在 250 名受试者中，201 名完成了 130 次阳性抑制测试的测试。与阴性抑制试验相比，阳性试验确定了在使用 ICS/长效 β2 激动剂时 FeNO 低的人群（中位数，26 ppb [四分位距，16-36 ppb] vs. 43 ppb [四分位距，38 -73 ppb]），FEV1% 显着增加（平均值，88.2 ± 16.4 vs. 74.1 ± 20.9；P < 0.01）。两组哮喘控制问卷 5 显着改善（阳性检验：平均差 -1.2；95% 置信区间，-0.9 到 -1.5；阴性检验：平均差，-0.9；95% 置信区间，-0.4 到 -1.3 ）。结论 远程 FeNO 抑制测试是识别难以控制哮喘患者和大量从优化 ICS/长效 β2 受体激动剂治疗中获得重要临床益处的受试者对 ICS 不依从性的有效方法。