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，流行病学证据表明，颗粒物（PM）与哮喘患者肺部预后恶化有关。体外、动物和人体刺激实验也表明，PM暴露与炎症和氧化应激标志物之间存在机制关联。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，关于故意减少暴露对哮喘健康的影响，缺乏证据，这可能有助于为临床指南和公共政策提供信息。幸运的是，我们在城市环境儿童哮喘中心（CCAUE）的研究小组中有先例，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，我们计划研究减少污染物暴露可能改善哮喘发病率的潜在机制。目的是研究35名室内污染严重的哮喘患者，在家中放置空气净化器6个月的干预前后。生物过程，如炎症、氧化应激和上皮屏障功能障碍，将评估污染减轻后的改善迹象。具体而言，将在暴露于污染后测量支气管镜样本、呼出气体、血液和尿液中的生物标志物，这些生物标志物已知会在哮喘患者中发生改变。此外，将在干预前后评估改善哮喘发病率的临床指标，如症状减轻和生理指标（即肺功能和支气管高反应性）的改善。最终，该应用程序的信息将有助于理解当暴露于室内环境中更清洁的空气时哮喘发病率改善的机制。此外，如果完全或部分逆转

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.