1/2 Multi-Center CLEAN AIR 2 Randomized Control Trial in COPD

项目总结。慢性阻塞性肺病是世界范围内导致死亡和发病的主要原因，可归因于 个人一生中吸入的有毒气体和颗粒物的总负担。在美国，这种曝光率 主要是香烟烟雾；然而，即使在戒烟后，慢性阻塞性肺病患者仍在遭受 呼吸道疾病。2022年国际慢性阻塞性肺病指南(GOLD)强调非药理学 旨在改善健康的干预措施很少，但基于证据的干预措施却很少。室内环境是 尤其令人担忧的是，患有慢性阻塞性肺病的成年人90%的时间都待在家里。颗粒物(PM)和 二氧化氮(NO2)是室内环境中常见的污染物，会导致呼吸道疾病的加重。 我们自己的研究发现，患有慢性阻塞性肺病的前吸烟者暴露在室内污染物中的情况更糟 呼吸系统特有的生活质量、症状和更高的呼吸恶化风险。我们的小组最近 在马里兰州巴尔的摩完成了一项针对116名患有COPD的前吸烟者的随机对照试验(Pi Hansel)， 论证了放置两个具有高效颗粒空气和碳的便携式空气净化器 过滤器可以显著降低室内PM和NO2浓度。在意向治疗分析中，有一项 由圣乔治呼吸问卷测量的更好的呼吸特有生活质量的趋势 (SGRQ)和统计上显著较低的中度恶化风险，但不是严重恶化，在 那些接受了主动空气净化器的人与假的人相比。此外，每种方案的分析表明- 在至少80%的时间使用空气净化器的人中，有统计学意义的 SGRQ的改进。尽管结果令人鼓舞，但这项研究没有达到其主要终点，也没有 有权确定空气净化器干预措施是否可以减少中度/重度恶化，包括 急性卫生保健利用情况。此外，试验不包括提高遵从性的战略；和结果 仅限于较小的地理区域，限制了普适性。拟议的研究是第三阶段多中心研究 随机假对照环境试验以测试空气净化器干预靶向的有效性 室内污染物(PM和NO2)对既往吸烟者生活质量和恶化风险的影响 慢性阻塞性肺疾病(COPD)(n~770)分布在多个临床实践地点。我们会进行成本效益分析，以确保 该研究结果解决了支持政策决策的临床和经济效果。我们假设 放置两个带有高效颗粒空气和碳过滤器的便携式空气净化器可导致 提高生活质量，降低COPD恶化风险，减少抢救用药需求。最后， 我们假设使用手提式空气净化器是符合成本效益的。该试验将提供一种新的方法来 改善这些发病率较高的患者的生活质量；为了防止COPD恶化， 这导致了这种慢性致残性疾病的发病率和死亡率。除了解决临床疗效问题外， 研究结果将提供经济评估，以支持有关补偿的政策决定。

PROJECT SUMMARY. COPD is a leading cause of death and morbidity worldwide and is attributable to the aggregate burden of toxic gases and particles that individuals inhale during their lifetime. In the US, this exposure is primarily cigarette smoke; however, even after smoking cessation, patients with COPD continue to suffer respiratory morbidity. International 2022 COPD guidelines (GOLD) emphasize non-pharmacological interventions to improve health, but few evidence-based interventions exist. The indoor environment is of particular concern, as adults with COPD spend >90% of their time in the home. Particulate matter (PM) and nitrogen dioxide (NO2) are common pollutants in indoor environments and lead to worse respiratory morbidity. Our own study found that former smokers with COPD who have higher exposure to indoor pollutants have worse respiratory-specific quality of life, symptoms, and a higher risk of respiratory exacerbations. Our group recently completed a randomized controlled trial of 116 former smokers with COPD in Baltimore, MD (PI Hansel), demonstrating that the placement of two portable air cleaners with high efficiency particulate air and carbon filters can significantly reduce in-home PM and NO2 concentrations. In intention-to-treat analysis, there was a trend toward better respiratory-specific quality of life, as measured by the St. George's Respiratory Questionnaire (SGRQ) and statistically significant lower risk for moderate exacerbation, but not severe exacerbations, among those who received the active air cleaner compared to sham. Further, per-protocol analysis suggested a dose- response; among those who used the air cleaner at least 80% of the time, with a statistically significant improvement in SGRQ. Despite encouraging results, the study did not meet its primary endpoint and was not powered to determine whether air cleaner interventions can reduce moderate/severe exacerbations, including acute health care utilization. Furthermore, the trial did not include strategies to increase adherence; and results are limited to a small geographic area, limiting generalizability. The proposed study is a Phase III multi-center randomized sham-controlled environmental trial to test the effectiveness of an air cleaner intervention targeting indoor pollutants (PM and NO2) on quality of life and exacerbation risk reduction among former smokers with COPD (n~770) across multiple clinical practice locations. We will conduct cost-effectiveness analysis to ensure that study results address both clinical and economic efficacy to support policy decisions. We hypothesize that the placement of two portable air cleaners with high efficiency particulate air and carbon filters can lead to improved quality of life, reduced COPD exacerbation risk and reduced need for rescue medication use. Lastly, we hypothesize that the use of portable air cleaners is cost-effective. The trial will provide a novel approach to improve quality of life in these patients with significant morbidity; and for the prevention of COPD exacerbations, which drive the morbidity and mortality of this chronic disabling disease. In addition to addressing clinical efficacy, the study results will provide an economic evaluation to support policy decisions regarding reimbursement.