The Impact of Indoor Particulate Matter Exposure on Non-Allergic Asthma

描述(由申请人提供) 哮喘是一种慢性肺部炎症性疾病，受宿主易感性和环境暴露的共同影响。颗粒性空气污染是一种促炎剂，与有害的健康后果有关。虽然许多研究都集中在户外暴露，但室内环境是至关重要的，因为美国人大部分时间都在室内，调查人员的初步数据表明，室内PM浓度远远超过城市家庭的室外PM浓度。根据初步数据显示，在非过敏性哮喘患者中，暴露于粗PM与呼吸道症状之间存在很强的相关性，研究人员假设，暴露于室内粗PM会促进非过敏性哮喘患者的炎症以及呼吸道症状和肺功能的恶化。采用纵向小组研究和暴露挑战模型相结合的研究设计，研究人员将致力于提供室内粗PM暴露和哮喘恶化之间因果关系的证据。 在具体目标1中，他们将通过进行流行病学小组研究来确定室内粗PM暴露对哮喘健康的影响，方法是测量患有非过敏性哮喘的市中心少数民族儿童的室内PM浓度以及相应的肺功能、哮喘症状和炎症生物标志物的日变化。在具体目标2中，他们将通过实施受控的雾化PM挑战，并测量呼吸道反应性和炎症的生物标记物，来调查粗大PM暴露对非过敏性哮喘的短期影响。 拟议研究的完成，以及在出色和支持性的临床研究环境中的补充培训和指导，将提供对临床研究设计、实施和分析的深入接触。这些经验将使首席研究员成为学术医学领域一名成功的、独立的研究员。 在美国，有2000多万人患有哮喘，其中包括600多万儿童和年轻人。这项拟议的研究调查了环境暴露--空气污染--对这种疾病过程的影响。如果室内暴露在空气中的PM会引发哮喘加重并刺激炎症反应，这项研究的发现可能会指导新的治疗干预措施，并将代表着哮喘治疗的重要进展，具有深刻的公共政策意义。

DESCRIPTION (provided by applicant) Asthma is a chronic inflammatory disease of the lungs that is influenced by a combination of host susceptibility and environmental exposures. Particulate air pollution is a pro-inflammatory agent that has been associated with adverse health consequences. While much research has focused on outdoor exposures, the indoor environment is critical as Americans spend most of their time indoors and the investigators' preliminary data have demonstrated that indoor PM concentrations greatly exceed outdoor PM concentrations in urban homes. Based on preliminary data that suggest a strong association between coarse PM exposure and respiratory symptoms among those with non-allergic asthma, the investigators hypothesize that exposure to indoor coarse PM promotes inflammation and worsening of respiratory symptoms and lung function among individuals with non-allergic asthma. Using a study design that combines a longitudinal panel study and an exposure challenge model, the investigators will aim to provide evidence of a causal relationship between indoor coarse PM exposure and exacerbation of asthma status. In specific aim 1, they will determine the effect of indoor coarse PM exposure on asthma health by conducting an epidemiologic panel study measuring in-home PM concentrations and corresponding daily variation in lung function, asthma symptoms, and biomarkers of inflammation among inner-city minority children with non-allergic asthma. In specific aim 2, they will investigate the short-term effects of coarse PM exposure on non-allergic asthma by administering a controlled, nebulized PM challenge and measuring airway reactivity and biomarkers of inflammation. Completion of the proposed research, along with complementary training and mentorship in an outstanding and supportive environment for clinical research, will provide in-depth exposure to clinical research design, conduct, and analysis. These experiences will allow the principal investigator to become a successful, independent investigator in academic medicine. Asthma affects more than 20 million individuals in the U.S, including over 6 million children and young adults. The proposed research investigates the effect of an environmental exposure, air pollution, on this disease process. If indoor exposure to airborne PM triggers asthma exacerbations and stimulates an inflammatory response, the findings from this study may direct new therapeutic interventions and will represent an important advancement in the treatment of asthma with profound public policy implications.