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

描述（由申请人提供） 哮喘是一种肺部慢性炎症性疾病，受宿主易感性和环境暴露的影响。 颗粒空气污染是一种促炎剂，与不良健康后果有关。 虽然许多研究都集中在室外暴露，但室内环境至关重要，因为美国人大部分时间都在室内，研究人员的初步数据表明，室内PM浓度大大超过城市家庭的室外PM浓度。 基于初步数据表明，在非过敏性哮喘患者中，粗颗粒物暴露与呼吸道症状之间存在很强的相关性，研究人员假设，暴露于室内粗颗粒物会促进非过敏性哮喘患者的炎症和呼吸道症状和肺功能的恶化。 使用一个研究设计，结合纵向小组研究和暴露挑战模型，研究人员将旨在提供证据的因果关系，室内粗颗粒物暴露和哮喘状态恶化之间的关系。 在具体目标1中，他们将通过进行一项流行病学小组研究来确定室内粗颗粒物暴露对哮喘健康的影响，该研究测量了室内颗粒物浓度以及肺功能、哮喘症状和非过敏性哮喘的内城少数民族儿童炎症生物标志物的相应每日变化。 在具体目标2中，他们将通过给予受控的雾化PM激发并测量气道反应性和炎症生物标志物来研究粗PM暴露对非过敏性哮喘的短期影响。 完成拟议的研究，沿着补充培训和指导，在一个优秀的和支持性的环境，为临床研究，将提供深入接触临床研究设计，实施和分析。 这些经验将使主要研究者成为一个成功的，独立的研究者在学术医学。 在美国，哮喘影响着超过2000万人，其中包括600多万儿童和年轻人。 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。 如果室内暴露于空气中的PM会引发哮喘急性发作并刺激炎症反应，那么这项研究的结果可能会指导新的治疗干预措施，并将代表哮喘治疗的重要进展，具有深远的公共政策意义。

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.