PILOT STUDIES ON THE HEALTH EFFECTS OF DIESEL EXHAUST PARTICULATE EXPOSURES

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。我们建议在柴油废气（DE）暴露系统中进行试点研究，以证明在建议水平上的可行性，物流和初步措施的影响。这些是对照暴露交叉实验，在该实验中，哮喘受试者暴露于稀释的DE或过滤的空气中，然后进行评估，以确定亚临床哮喘控制措施的暴露-效应关系。试点研究将确定实验程序能否按计划进行、暴露的耐受性、症状的发生以及暴露致盲工作的成功。他们还将以探索性的方式评估DE和效应之间的剂量-反应关系，这些关系可用于计划和证明未来暴露剂量和结果的选择，并评估结果差异，以便进行样本量计算。结果包括症状、肺活量测定、呼出一氧化氮以及炎症、氧化应激和早期基因转录的诱导痰测量。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We propose pilot sudies in the diesel exhaust (DE) exposure system to demonstrate feasibility, logistics, and preliminary measures of effect at suggested levels. These are controlled exposure crossover experiments, in which asthmatic subjects are exposed to diluted DE or filtered air, and then are evaluated to determine exposure-effect relations on sub-clinical measures of asthma control. Pilot studies will determine whether experimental procedures can be conducted as planned, tolerability of exposures, occurrence of symptoms, and success of exposure blinding efforts. They will also assess, in an exploratory manner, dose-response relationships between DE and effects that can be used to plan and justify future choices of exposure dose and outcomes, and to assess outcome variance in order to make sample size calculations. Outcomes include symptoms, spirometry, exhaled nitric oxide, and induced sputum measures of inflammation, oxidative stress and early gene transcription.