Respiratory Therapy Department, College of Medical Rehabilitation Sciences, Taibah University, Madinah, Saudi Arabia.
Faculty of Biology, Medicine and Health, School of Biological Sciences, Division of Infection, Immunity & Respiratory Medicine, The University of Manchester, and Manchester Academic Health Science Centre and NIHR Manchester Biomedical Research Unit and Manchester University NHS Foundation Trust, Manchester M23 9LT, United Kingdom.
J Breath Res. 2022 Jul 5;16(4). doi: 10.1088/1752-7163/ac7a57.
Inhaled corticosteroids (ICS) are the mainstay of therapy in asthma, but benefits vary due to disease heterogeneity. Steroid insensitivity is a particular problem in severe asthma, where patients may require systemic corticosteroids and/or biologics. Biomarkers sensitive to ICS over a short period of time could inform earlier and more personalised treatment choices. To investigate how exhaled breath biomarkers change over two-hours and one-week following monitored ICS dosing in severe asthma patients with evidence of uncontrolled airway inflammation. Patients with severe asthma and elevated fractional exhaled nitric oxide (FeNO) (⩾45 ppb, indicative of active airway inflammation) were recruited. Exhaled breath biomarkers were evaluated using (FeNO), exhaled breath temperature (EBT), particles in exhaled air (PExA) and volatile organic compounds (VOCs). Samples were collected over 2 h following observed inhalation of 1000 mcg fluticasone propionate, and at a second visit 1 week after taking the same dose daily via an inhaler monitoring device that recorded correct actuation and inhalation. Changes in parameters over 2 h were analysed by the Friedman test and 1 week by Wilcoxon's test (-value for significance set at 0.05; for VOCs false discovery rateof 0.1 by Benjamini-Hochberg method applied). 17 participants (9 male) were recruited, but three could not complete PExA and two FeNO testing, as they were unable to comply with the necessary technique; complete datasets were available from 12 (9 male) with median (interquartile range) age 45 (36-59) yrs. EBT (< 0.05) and levels of six VOCs (< 0.1) fell over the 2 h after high dose ICS; there were no changes in FeNO or PExA. After one week of using high dose ICS, there were falls in FeNO, EBT and two VOCs (< 0.05), but no changes in PExA. Reduction in EBT over the short and medium term after high dose ICS may reflect airway vascular changes, and this, together with the observed changes in exhaled VOCs, merits further investigation as potential markers of ICS use and effectiveness.
吸入性皮质类固醇（ICS）是哮喘治疗的主要药物，但由于疾病的异质性，其疗效存在差异。在严重哮喘中，类固醇不敏感是一个特殊的问题，患者可能需要全身皮质类固醇和/或生物制剂。在短时间内对 ICS 敏感的生物标志物可以为更早和更个性化的治疗选择提供信息。为了研究在有证据表明气道炎症未得到控制的严重哮喘患者中，监测 ICS 给药后 2 小时和 1 周内呼出的呼吸生物标志物如何变化。招募了严重哮喘且呼出气一氧化氮分数（FeNO）升高（≥45 ppb，提示气道炎症活跃）的患者。使用（FeNO）、呼气温度（EBT）、呼出空气中的颗粒（PExA）和挥发性有机化合物（VOCs）评估呼出呼吸生物标志物。在观察到吸入 1000 mcg 丙酸氟替卡松后 2 小时内收集样本，并在使用吸入器监测装置每天服用相同剂量 1 周后再次收集样本，该装置记录了正确的启动和吸入。通过 Friedman 检验分析 2 小时内参数的变化，通过 Wilcoxon 检验分析 1 周内的参数变化（显著性水平设为 0.05；通过 Benjamini-Hochberg 方法应用错误发现率（false discovery rate）为 0.1 对 VOCs 进行调整）。共招募了 17 名参与者（9 名男性），但有 3 名参与者无法完成 PExA 和 2 名参与者无法完成 FeNO 测试，因为他们无法遵守必要的技术要求；有 12 名（9 名男性）参与者的完整数据集可用，中位（四分位间距）年龄为 45（36-59）岁。在高剂量 ICS 后 2 小时内，EBT（<0.05）和 6 种 VOC 水平（<0.1）下降；FeNO 或 PExA 无变化。使用高剂量 ICS 一周后，FeNO、EBT 和两种 VOC 下降（<0.05），但 PExA 无变化。高剂量 ICS 后短期和中期 EBT 的下降可能反映了气道血管的变化，这一点，加上呼出 VOCs 的观察到的变化，值得进一步研究，作为 ICS 使用和有效性的潜在标志物。
