Linden Dermot, Dorrian Delia, Tandel Shikha, McKelvey Michael, Bailey Melanie, Conlon John, Moore David, Carr Sharon, Taggart Clifford C, Bradley Judy M, Kidney Joseph, OKane Cecilia M, McAuley Daniel Francis
Wellcome-Wolfson Institute for Experimental Medicine, School of Medicine, Dentistry & Biomedical Sciences, Queen's University Belfast, Belfast, UK
Mater Infirmorum Hospital Health and Social Services Trust, Belfast, UK.
BMJ Open Respir Res. 2025 Feb 12;12(1):e002393. doi: 10.1136/bmjresp-2024-002393.
Liberal administration of supplemental oxygen (O) is ubiquitous across numerous healthcare settings. However, appropriate O titration targets remain controversial and despite numerous large-scale randomised trials, there is an ongoing lack of consensus regarding optimal oxygenation strategies and the absence of high-quality mechanistic data pertaining to the potential proinflammatory effects of hyperoxia.
We hypothesise that (1) short-term exposure to hyperoxia will induce mild pulmonary inflammation and cellular injury and that (2) hyperoxia will accentuate pulmonary inflammation and cellular injury in the setting of inhaled lipopolysaccharide challenge. To test our hypotheses, we will conduct a randomised, double-blind, placebo-controlled study of hyperoxia administered via a high-flow nasal O delivery system (fractional inspired oxygen 1.0, 60 L/min flow rate) compared with synthetic medical air. Blocked randomisation will be undertaken by an independent clinical trials statistician. Healthy non-smoking adult volunteers (<45 years of age), taking no regular medications will be recruited. Bronchoalveolar lavage (BAL) will be performed at 6 hours. The study outcome measures will include BAL markers of inflammation and injury (including but not limited to interleukin (IL)-8, IL-6, tumour necrosis factor alpha), BAL differential cell counts, BAL markers of oxidative stress (superoxide dismutase and glutathione), alveolar epithelial cell injury (SP-D, vWF, RAGE) and markers of systemic inflammation (neutrophils and plasma C-reactive protein).
Dissemination of the research findings will be achieved in the following ways: (1) Our findings will be presented at national and international meetings with open-access abstracts online and (2) in accordance with the open-access policies proposed by the leading research funding bodies we aim to publish the findings in high quality peer-reviewed open-access journals.
NCT05414370.
在众多医疗环境中，补充氧气（O）的大量使用很普遍。然而，合适的氧滴定目标仍存在争议，尽管有众多大规模随机试验，但对于最佳氧合策略仍缺乏共识，并且缺乏关于高氧潜在促炎作用的高质量机制数据。
我们假设：（1）短期暴露于高氧会诱发轻度肺部炎症和细胞损伤；（2）在吸入脂多糖激发的情况下，高氧会加重肺部炎症和细胞损伤。为了验证我们的假设，我们将进行一项随机、双盲、安慰剂对照研究，将通过高流量鼻氧输送系统给予高氧（吸入氧分数为1.0，流速60升/分钟）与合成医用空气进行比较。由独立的临床试验统计学家进行区组随机化。将招募健康的不吸烟成年志愿者（年龄<45岁），且他们不服用常规药物。将在6小时时进行支气管肺泡灌洗（BAL）。研究结果测量指标将包括BAL炎症和损伤标志物（包括但不限于白细胞介素（IL）-8、IL-6、肿瘤坏死因子α）、BAL细胞分类计数、BAL氧化应激标志物（超氧化物歧化酶和谷胱甘肽）肺泡上皮细胞损伤（SP-D、vWF、RAGE）以及全身炎症标志物（中性粒细胞和血浆C反应蛋白）。
研究结果将通过以下方式传播：（1）我们的研究结果将在国内和国际会议上以在线开放获取摘要的形式展示；（2）根据主要研究资助机构提出的开放获取政策，我们旨在将研究结果发表在高质量的同行评审开放获取期刊上。
NCT0⁵4¹4³70。
