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: 8948493
• 负责人: LAURA Marie PAULIN
• 金额: $ 16.65万
• 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 2020-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8948493
• 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; Epidemiologic Studies; Exhibits; Exposure to; Faculty; Foundations; Funding; Future; Gamma Cameras; Goals; Health; Home environment; Host Defense; 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; Parents; Participant; Particulate Matter; Patients; 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 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; experience; follow-up; improved; interest; meetings; member; mortality; parent grant; pollutant; public health relevance; respiratory; 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) COPD是一种发病率和死亡率都很高的疾病。环境暴露往往是疾病发展和现有疾病恶化的原因。最近的证据表明，暴露于室内空气污染(颗粒物(PM)和二氧化氮(NO2))会增加COPD的严重程度，但这种恶化的机制尚不清楚。此外，初步研究表明，慢性支气管炎患者在暴露于室内污染物后表现出更糟糕的症状和结局，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作用。然而，为什么这一群体可能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。 在这项应用中，研究人员计划调查粘液纤毛清除(MCC)和粘液特性在预测COPD患者对室内空气污染暴露的反应中的作用。他们还旨在确定在PM和NO2暴露后，慢性支气管炎患者的MCC和粘液属性是否随着时间的推移而变化。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COPD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会改善健康结果。在目前的应用中，为了确定基线MCC和粘液特性是否可以预测PM和NO2暴露的反应，60名COPD患者将接受使用伽马相机技术的MCC基线评估，诱导痰将被分析粘蛋白浓度、DNA浓度和粘液固体浓度；在基线、3个月和6个月的随访中，将对个人进行纵向跟踪，评估临床结果以及全面的室内环境评估。在一组20名慢性支气管炎患者中，我们将在基线、3个月和6个月的随访中评估MCC和粘液特性，并进行室内环境监测，以确定NO2和PM浓度的变化是否会改变这些粘液结果。最终，从这项应用中获得的信息将有助于理解COPD中观察到的与污染暴露相关的不良健康影响背后的机制，并确定这些暴露是否会改变宿主防御的关键组成部分。此外，这些数据将对慢性阻塞性肺疾病的管理和针对高危个体的环境修改策略的使用产生影响。 这位候选人是一名完成了肺部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生涯的奉献精神，这与她在环境健康方面的强大背景密切相关。虽然她还处于职业生涯的早期，但在她正在进行的研究工作中，她表现出了极大的主动性、动力和生产力。这项申请旨在使应聘者实现她的长期职业目标，即成为一名独立的临床调查员，探索环境暴露在决定COPD结果中的作用以及这种暴露影响疾病的机制。在当前的时间框架内，这项申请将使候选人有专门的时间进行概述的研究项目，以及在设计和实施临床试验以及与该项目和未来研究计划相关的进一步量化方法方面进行教学培训。此外，从这项研究提案中产生的数据将构成R01应用的基础。该候选人的职业发展计划包括一种结构化的指导方法、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表中描述的导师团队将有助于Paulin博士成功完成她的职业生涯和研究目标。肺部和重症监护医学部和约翰霍普金斯大学在支持和合作的环境中培养成功的年轻临床研究人员有着悠久的历史。本申请的母体研究的预先存在的结构， 在城市环境儿童哮喘研究中心的坚实基础上，以及申请者与她的导师团队建立和持续的合作，将确保在本奖项的时间框架内完成研究目标。我们组建了一支由资深教师组成的指导团队，他们拥有多年的富有成效的研究经验和丰富的先前指导经验。在与这一提议相关的研究领域，每个国家都有不同的、互补的优势。此外，指导委员会的每一名成员都是候选人职业发展为独立调查员的优秀榜样。