Effects of Reducing Indoor Particulate Matter on the Asthmatic Response

减少室内颗粒物对哮喘反应的影响

• 批准号: 9068099
• 负责人: Sonali Bose
• 金额: $ 17.05万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-01 至 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9068099
• 关键词: Accounting; Adult; Affect; Air; Air Pollution; Airborne Particulate Matter; Animals; Area; Asthma; Award; Baltimore; Biocompatible Materials; Biological; Biological Markers; Biological Process; Blood; Bronchial Hyperreactivity; Bronchoalveolar Lavage Fluid; Cadherins; Cardiovascular system; Characteristics; Childhood Asthma; Chronic; Clinical; Critical Care; Data; Development Plans; Dose; Ensure; Environment; Environmental Policy; Epidemiology; Epithelial; Epithelial Cells; Etiology; Exhalation; Exposure to; Faculty; Functional disorder; Goals; Grant; Guidelines; Healed; Health; Health Policy; Heat shock proteins; Home environment; Human; In Vitro; Indoor Air Quality; Indoor environment; Inflammation; Inflammatory; Intercellular Junctions; Interdisciplinary Study; Intervention; Life; Link; Lung; Lung diseases; Measurement; Measures; Medicine; Mentors; Mentorship; Modeling; Monitor; Morbidity - disease rate; Neurologic; Outcome; Oxidative Stress; Particulate Matter; Pathology; Pathway interactions; Physicians; Physiological; Policies; Policy Maker; Pollution; Principal Investigator; Procedures; Proteins; Public Policy; Pulmonary Function Test/Forced Expiratory Volume 1; Recommendation; Recording of previous events; Recruitment Activity; Reporting; Research; Research Infrastructure; Research Personnel; Research Priority; Research Proposals; Resources; Respiratory Signs and Symptoms; Respiratory physiology; Sampling; Severities; Spirometry; Structure; Symptoms; Testing; Training; Universities; Urine; Vital capacity; Vulnerable Populations; air cleaner; airway hyperresponsiveness; airway inflammation; airway obstruction; asthmatic; base; career; career development; collaborative environment; cost; cytokine; experience; healing; improved; in vivo; inflammatory marker; meetings; member; methacholine; pollutant; post intervention; reduce symptoms; research study; respiratory; respiratory health; response; role model; stress protein

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.

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，神经系统和呼吸道发病。特别是，已经很好地描述了哮喘受试者中颗粒物（PM）（PM）和肺癌较差的流行病学证据已得到很好的描述。在体外，动物和人类挑战实验也表明了PM暴露与炎症标志和氧化应激之间的机械关联。但是，尚未建立污染物暴露与哮喘发病率之间的因果关系。此外，缺乏有关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准则和公共政策提供信息。幸运的是，我们的研究小组在城市环境（CCAUE）的童年哮喘中心（CCAUE）的研究小组中，可以相对简单地提高房屋室内空气质量，从而改善呼吸道症状。在此应用中，我们计划研究潜在的机制，以减少污染物暴露可能会改善哮喘发病率。目的是研究35个哮喘患者，在长达6个月的干预措施之前和之后，将空气清洁剂放置在家里。炎症，氧化应激和上皮屏障功能障碍等生物学过程将在减轻污染后的改善迹象。具体而言，在暴露于污染后，将测量来自支气管镜样品的生物标志物，呼出的呼吸，血液和尿液会改变。此外，将在干预之前和之后评估改善哮喘发病率的临床测量，例如症状减轻和改善生理措施（即肺功能和支气管高反应性）的临床测量。最终，本应用程序中的信息将有助于理解在室内环境中暴露于清洁空气时哮喘发病率的基本机制。另外，如果是完全或部分逆转 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。 该研究提案产生的数据将构成R01应用程序的基础。该申请人的职业发展计划包括一种结构化的指导方法，教学课程，重点是特定的研究目标，参与本地和国家会议以及对职业里程碑的定期评估以及定期评估。约翰·霍普金斯大学（Johns Hopkins University）提供的研究环境以及本申请中概述的指导团队将有助于成功完成候选人的职业和研究目标。肺和重症监护医学和约翰·霍普金斯大学（Johns Hopkins University）在支持性和协作环境中培训成功的临床研究人员的历史悠久。城市环境中童年哮喘中心（CCAUE）的先前存在的结构是一个合作，多学科研究小组，在巴尔的摩进行哮喘研究已有几年，将提供所需的基础架构和资源，以确保该研究程序将在此奖项的时间范围内完成。一支指导团队由成熟的教职员工组成，拥有多年的生产研究经验和丰富的先前指导经验。在与该提案相关的研究领域中，每个都有明显的互补优势。此外，指导委员会的每个成员都为申请人的职业发展成为独立研究者的出色榜样。