Indoor air pollution, mucociliary clearance, and mucus properties in COPD

室内空气污染、粘液纤毛清除和慢性阻塞性肺病中的粘液特性

• 批准号: 9315181
• 负责人: LAURA Marie PAULIN
• 金额: $ 5.09万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-30 至 2018-01-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9315181
• 关键词: Affect; Air Pollutants; Air Pollution; Area; Award; Baltimore; Carbon; Cause of Death; Childhood Asthma; Chronic; Chronic Bronchitis; Chronic Obstructive Airway Disease; Clinical; Clinical Investigator; Clinical Research; Clinical assessments; Cohort Studies; Collaborations; Critical Care; DNA; Data; Dedications; Development; Development Plans; Disease; Disease Outcome; Disease Progression; Ensure; Environment; Environmental Exposure; Environmental Health; Environmental Monitoring; Exhibits; Exposure to; Faculty; Foundations; Funding; Future; Gamma Cameras; Goals; Health; Home environment; Host Defense; Impairment; Individual; Indoor Air Pollution; Indoor pollutant; K-Series Research Career Programs; Lead; Lung; Measures; Medicine; Mentors; Mentorship; Methods; Modification; Morbidity - disease rate; Motivation; Mucins; Mucociliary Clearance; Mucous body substance; National Institute of Environmental Health Sciences; Nitrogen Dioxide; Outcome; Outcome Assessment; Parents; Participant; Particulate Matter; Phenotype; Physicians; Play; Pollution; Predisposition; Production; Productivity; Property; Public Health; Quality of life; Randomized Controlled Trials; Recording of previous events; Research; Research Personnel; Research Project Grants; Research Proposals; Resources; Respiratory Signs and Symptoms; Respiratory physiology; Risk; Role; Severity of illness; Smoker; Solid; Sputum; Structure; Subgroup; Symptoms; Technology; Testing; Thick; Time; Training; United States; Universities; air cleaner; base; career; career development; cohort; collaborative environment; design; epidemiology study; experience; follow-up; improved; interest; meetings; member; mortality; parent grant; patient subsets; pollutant; predicting response; public health relevance; response; role model; therapeutic target; therapy design

 DESCRIPTION (provided by applicant) COPD is a disease with high morbidity and mortality. Environmental exposures are often responsible for disease development and worsening of existing disease. Recent evidence shows that exposure to indoor air pollution (particulate matter (PM) and nitrogen dioxide (NO2)) increases COPD severity, but the mechanisms for this worsening remain unknown. Furthermore, preliminary studies suggest that a subgroup of individuals with chronic bronchitis demonstrate worse symptoms and outcomes following exposure to indoor pollutants, suggesting that the alterations in mucus production and clearance common to chronic bronchitics may play a role in this observation. However, the specifics of the why this group may be more susceptible to the health effects of indoor pollution exposure remain to be fully understood. In this application, the investigators plan to investigate the role of mucociliary clearance (MCC) and mucus properties in predicting response to indoor air pollution exposure in individuals with COPD. They also aim to determine whether MCC and mucus properties change over time following PM and NO2 exposure in a subgroup of individuals with chronic bronchitis. To complete their aims the investigators will leverage resources from an ongoing Baltimore-based cohort study of former smokers with COPD that aims to determine whether home interventions designed to reduce PM and NO2 exposure improve health outcomes. In this current application, to determine whether baseline MCC and mucus properties predict response to PM and NO2 exposure, 60 individuals with COPD will undergo baseline assessment of MCC using gamma camera technology and induced sputum will be analyzed for mucin concentration, DNA concentration, and mucus solids concentration; individuals will be followed longitudinally with assessment of clinical outcomes along with comprehensive indoor environmental assessment at baseline, 3 months, and 6 months of follow up. In a group of 20 individuals with chronic bronchitis, we will assess MCC and mucus properties along with indoor environmental monitoring at baseline, 3 months and 6 months of follow up to determine whether changes in NO2 and PM concentration alter these mucus outcomes. Ultimately, the information gained from this application will contribute to understanding the mechanism behind the adverse health effects observed in COPD in relation to pollution exposures, and to determine whether these exposures can alter critical components of host defense. Additionally, these data will have implications for the management of COPD and utilization of environmental modification strategies for at-risk individuals. The candidate, a physician completing her training in Pulmonary and Critical Care Medicine, has demonstrated a dedication to developing a career in clinical research that is tied closely to her strong background in environmental health. Though she is early in her career, she has shown a great deal of initiative, motivation, and productivity in her ongoing research endeavors. This application is structured to allow the candidate to achieve her long-term career goal of becoming an independent clinical investigator exploring the role of environmental exposures in determining COPD outcomes and the mechanisms by which such exposures impact disease. In the immediate timeframe, this application would allow the candidate dedicated time to conduct the outlined research project, as well as pursue didactic training in design and conduct of clinica trials and further quantitative methods relevant to this project and future research plans. Additionally, the data generated from this research proposal will form the basis for an R01 application. The Career Development Plan for this candidate 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 described in this application will assist in Dr. Paulin's successful completion of her career and research goals. The Division of Pulmonary and Critical Care Medicine and Johns Hopkins University have a long history of training successful young clinical researchers in a supportive and collaborative environment. The pre-existing structure of the parent study for this application, set within the strong foundation of the Center for Childhood Asthma in the Urban Environment, as well as the applicant's established and ongoing collaboration with her team of mentors, will ensure that the study goals will be completed within the timeframe of this award. We have assembled a mentoring team 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 candidate's career development into an independent investigator.

 描述（由申请人提供） 慢性阻塞性肺病 (COPD) 是一种发病率和死亡率较高的疾病。最近的证据表明，接触室内空气污染（颗粒物 (PM) 和二氧化氮 (NO2)）会增加慢性阻塞性肺病 (COPD) 的严重程度。但这种恶化的机制仍不清楚。此外，初步研究表明，慢性支气管炎患者在接触室内污染物后表现出更严重的症状和结果，这表明慢性支气管炎常见的粘液产生和清除的变化。可能在这一观察中发挥了作用，但是，为什么这一群体更容易受到室内污染暴露的健康影响的具体原因仍有待充分了解。 在此应用中，研究人员计划研究粘液纤毛清除 (MCC) 和粘液特性在预测慢性阻塞性肺病 (COPD) 患者对室内空气污染暴露的反应中的作用，他们还旨在确定 MCC 和粘液特性是否随着 PM 和 NO2 的时间而变化。为了实现他们的目标，研究人员将利用巴尔的摩正在进行的一项针对患有慢性阻塞性肺病的前吸烟者的队列研究的资源，该研究旨在确定旨在减少 PM 和 NO2 暴露的家庭干预措施是否可以改善健康。在当前的应用中，为了确定基线 MCC 和粘液特性是否可以预测对 PM 和 NO2 暴露的反应，60 名 COPD 患者将使用伽马相机技术接受 MCC 基线评估，并分析诱导痰的粘蛋白浓度、DNA 浓度、和粘液固体浓度；对个体进行纵向随访，评估临床结果以及基线、3 个月和 6 个月随访时的综合室内环境评估。评估 MCC 和粘液特性以及基线、3 个月和 6 个月随访的室内环境监测，以确定 NO2 和 PM 浓度的变化是否会改变这些粘液结果，最终，从该应用中获得的信息将有助于理解背后的机制。此外，这些数据还将对慢性阻塞性肺病的管理和针对高危个体的环境改造策略的利用产生影响。 。 该候选人是一名完成肺科和重症监护医学培训的医生，她表现出了对发展临床研究职业的奉献精神，这与她在环境健康方面的深厚背景密切相关。该应用程序的结构是为了让候选人能够实现她的长期职业目标，即成为一名独立的临床研究者，探索环境暴露在确定慢性阻塞性肺病结果和机制中的作用。此类暴露对疾病的影响。在时间范围内，该应用程序将允许候选人投入时间来进行概述的研究项目，以及在临床试验的设计和进行方面进行教学培训，以及与该项目和未来研究计划相关的进一步定量方法此外，还可以从中生成数据。研究提案将构成 R01 申请的基础。该候选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描述的导师团队将协助 Paulin 博士成功完成她的职业生涯和研究目标。 肺科和重症监护医学部与约翰·霍普金斯大学有着悠久的合作历史。在支持和协作的环境中培训成功的年轻临床研究人员 该应用程序的父级研究的现有结构， 建立在城市环境儿童哮喘中心的坚实基础上，以及申请人与其导师团队建立和持续的合作，将确保研究目标将在我们设定的时间范围内完成。导师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，导师委员会的每位成员都是优秀的榜样。候选人的职业发展成为一名独立调查员。