Effects of Reducing Indoor Particulate Matter on the Asthmatic Response

描述(由申请人提供)：空气污染与一系列不良健康影响有关，包括心血管、神经和呼吸系统疾病。特别是，在哮喘患者中，将颗粒物(PM)与更糟糕的肺部结局联系起来的流行病学证据已经得到了很好的描述。在体外、动物和人类的挑战实验中，也表明PM暴露与炎症和氧化应激的标志物之间存在机械联系。然而，污染物暴露与哮喘发病率之间的因果关系尚未确定。此外，缺乏关于故意减少暴露对哮喘健康的影响的证据，这可能有助于为临床指南和公共政策提供信息。幸运的是，我们城市环境儿童哮喘中心(CCAUE)的研究小组有一个先例，即改善家庭室内空气质量可以相对简单地实现，从而改善呼吸道症状。在这项应用中，我们计划调查减少污染物暴露可能改善哮喘发病率的潜在机制。这项研究的目的是对35名室内污染水平较高的哮喘患者进行为期6个月的室内空气净化器干预前后的研究。将对炎症、氧化应激和上皮屏障功能障碍等生物过程进行评估，以寻找污染减轻后改善的迹象。具体地说，哮喘患者的支气管镜样本、呼气、血液和尿液中已知发生变化的生物标记物将在暴露于污染后进行测量。此外，将在干预前后评估改善哮喘发病率的临床措施，如减少症状和改善生理指标(即肺功能和支气管高反应性)。最终，这项应用的信息将有助于理解暴露在室内环境中更清洁的空气中时哮喘发病率改善的潜在机制。此外，如果完全或部分逆转 可以通过减少室内PM来证明病理学，它将加强PM和哮喘发病率之间的因果关系，这将支持旨在改善呼吸健康的公共政策行动。从这项研究提案中产生的数据将构成R01应用的基础。该申请者的职业发展计划包括一种结构化的指导方法、侧重于特定研究目标的教学课程、参加地方和国家会议以及确定和定期评估职业里程碑。约翰霍普金斯大学提供的研究环境以及本申请表中概述的导师团队将有助于成功完成候选人的职业生涯和研究目标。肺和重症监护医学部和约翰霍普金斯大学在支持和合作环境中培训成功的临床研究人员方面有着悠久的历史。城市环境中的儿童哮喘研究中心(CCAUE)是一个合作的多学科研究小组，多年来一直在巴尔的摩进行哮喘研究，该中心原有的结构将提供必要的基础设施和资源，以确保在本奖项的时间框架内完成研究程序。一支由拥有多年富有成效的研究经验和丰富的先前指导经验的资深教师组成的指导团队已经组成。在与这一提议相关的研究领域，每个国家都有不同的、互补的优势。此外，指导委员会的每一名成员都是申请者职业发展成为独立调查员的优秀榜样。

DESCRIPTION (provided by applicant): Air pollution has been linked to a range of ill health effects, including cardiovascular, neurological, and respiratory morbidity. In particular, epidemiologic evidence linking particulate matter (PM) and worse pulmonary outcomes in subjects with asthma has been well described. In vitro, animal, and human challenge experiments have also suggested mechanistic associations between PM exposure and markers of inflammation and oxidative stress. However, a causal relationship between pollutant exposure and asthma morbidity has not yet been established. Moreover, there is a lack of evidence regarding the impact of deliberately decreasing exposures on asthma health that could help inform clinical guidelines and public policies. Fortunately, there is precedence in our research group at the Center for Childhood Asthma in the Urban Environment (CCAUE) that improving indoor air quality in homes can be achieved relatively simply, resulting in improved respiratory symptoms. In this application, we plan to investigate the potential mechanisms whereby reducing pollutant exposure may improve asthma morbidity. The aim is to study 35 asthmatics with high levels of indoor pollution before and after a 6 month-long intervention that places air cleaners in the home. Biological processes such as inflammation, oxidative stress, and epithelial barrier dysfunction will be assessed for signs of amelioration after pollution abatement. Specifically, biomarkers from bronchoscopic samples, exhaled breath, blood and urine known to be altered in people with asthma will be measured after exposure to pollution. In addition, clinical measures of improved asthma morbidity such as decreased symptoms and improved physiologic measures (i.e. lung function and bronchial hyperreactivity) will be assessed before and after the intervention. Ultimately, the information from this application will contribute to the understanding of mechanisms underlying improvement of asthma morbidity when exposed to cleaner air in the indoor environment. Additionally, if full or partial reversal of pathology can be demonstrated by reducing indoor PM, it will strengthen a causal relationship between PM and asthma morbidity that would support public policy actions aimed at improving respiratory health. The data generated from this research proposal will form the basis for an R01 application. The career development plan for this applicant includes a structured approach to mentoring, didactic coursework focused on a specific research goal, participation in local and national meetings and identification and regular assessment of career milestones. The research environment provided by Johns Hopkins University as well as the mentorship team outlined in this application will assist in a successful completion of the candidate's career and research goals. The Division of Pulmonary and Critical Care Medicine and Johns Hopkins University have a long history of training successful clinical researchers in a supportive and collaborative environment. The pre-existing structure of the Center for Childhood Asthma in the Urban Environment (CCAUE), a collaborative, multidisciplinary research group that has been conducting asthma research in Baltimore for several years, will provide the infrastructure and resources needed to ensure that study procedures will be completed within the timeframe of this award. A mentoring team has been assembled of established faculty with many years of productive research experience and substantial prior mentoring experience. Each has distinct, complementary strengths in areas of research relevant to this proposal. In addition, each member of the mentoring committee serves as an excellent role model for the applicant's career development into an independent investigator.