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、神经和呼吸系统疾病。特别是，关于颗粒物 (PM) 与哮喘患者肺部结局恶化之间的联系的流行病学证据已得到充分描述。体外、动物和人类挑战实验也表明 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之间的因果关系尚未确定。此外，缺乏证据表明故意减少暴露对哮喘健康的影响，这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) 的研究小组率先提出，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。在此应用中，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。其目的是对 35 名室内污染严重的哮喘患者进行为期 6 个月的在家中放置空气净化器干预前后的研究。污染消除后，将评估炎症、氧化应激和上皮屏障功能障碍等生物过程的改善迹象。具体来说，将测量哮喘患者暴露于污染后发生变化的支气管镜样本、呼出气、血液和尿液中的生物标志物。此外，将在干预前后评估哮喘发病率改善的临床指标，例如症状减轻和生理指标改善（即肺功能和支气管高反应性）。最终，来自该应用的信息将有助于理解暴露在室内环境中清洁空气时哮喘发病率改善的机制。此外，如果全部或部分逆转 病理学可以通过减少室内 PM 来证明，它将加强 PM 与哮喘发病率之间的因果关系，从而支持旨在改善呼吸系统健康的公共政策行动。 本研究提案生成的数据将构成 R01 应用的基础。该申请人的职业发展计划包括结构化的指导方法、专注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中概述的导师团队将有助于候选人成功完成职业和研究目标。肺科和重症监护医学部和约翰·霍普金斯大学在支持和协作环境中培训成功的临床研究人员方面有着悠久的历史。城市环境儿童哮喘中心 (CCAUE) 是一个协作性多学科研究小组，多年来一直在巴尔的摩进行哮喘研究，其现有结构将提供所需的基础设施和资源，以确保研究程序能够并在本奖项授予的期限内完成。指导团队由具有多年富有成效的研究经验和丰富的指导经验的资深教师组成。每个人在与本提案相关的研究领域都有独特的、互补的优势。此外，指导委员会的每位成员都为申请人的职业发展成为独立研究者提供了优秀的榜样。