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

基本信息

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
项目类别：
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

项目摘要

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高的疾病。环境暴露通常是导致疾病发展和担心现有疾病的原因。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的严重性，但是这种担忧的机制仍然未知。此外，初步研究表明，暴露于室内污染物后的慢性支气管炎个体的亚组表现出更严重的症状和结果，这表明慢性支气管症常见的粘液产生和清除率的改变可能在这一观察中起作用。但是，为什么该群体可能更容易受到室内污染暴露的健康影响的细节尚待充分理解。在此应用中，研究人员计划研究粘膜钙清除率（MCC）和粘液特性在预测COPD患者室内空气污染暴露的反应中的作用。他们还旨在确定在PM和慢性支气管炎个体的亚组中PM和NO2暴露后的MCC和粘液特性是否随着时间的流逝而变化。为了完成他们的目标，研究人员将利用正在进行的巴尔的摩的同类群体研究中，对COPD的前吸烟者进行研究，旨在确定旨在减少PM和NO2暴露的家庭干预措施是否改善了健康结果。在当前的应用中，为了确定基线MCC和粘液特性是否预测对PM和NO2暴露的反应，将使用伽马摄像头技术和诱导的痰液对MCC进行基线评估，以分析粘蛋白浓度，DNA浓度和粘液固体浓度；在基线，3个月和6个月的随访时，将纵向遵循纵向评估临床结果以及全面的室内环境评估。在20个患有慢性支气管炎的人群中，我们将评估MCC和粘液特性，以及基线时室内环境监测，3个月零6个月的随访，以确定NO2和PM浓度的变化是否会改变这些粘液结果。最终，从本应用中获得的信息将有助于理解COPD在污染暴露中观察到的不良健康影响背后的机制，并确定这些暴露是否可以改变宿主防御的关键组成部分。此外，这些数据将对COPD的管理和高危个人的环境修改策略的利用有影响。这位候选人是她在肺和重症监护医学方面的身体培训，这表明奉献于发展临床研究的职业，这与她在环境健康方面的强大背景紧密相关。尽管她是职业生涯的早期，但她在正在进行的研究工作中表现出了很多主动，动力和生产力。该应用的结构是使候选人实现她的长期职业目标，即成为一名独立的临床研究者，探讨环境暴露在确定COPD结果和这种暴露影响疾病的机制中的作用。在直接的时间范围内，此应用程序将允许候选人专门的时间进行概述的研究项目，并在设计和进行临床试验的设计和进行临床试验中进行教学培训以及与该项目和未来研究计划有关的进一步定量方法。此外，该研究建议产生的数据将构成R01应用程序的基础。该候选人的职业发展计划包括一种结构化的心理，教学课程，重点是特定的研究目标，参与本地和国家会议以及对职业里程碑的定期评估以及定期评估。约翰·霍普金斯大学（Johns Hopkins University）提供的研究环境以及本申请中描述的精通团队将有助于鲍林（Paulin）博士成功完成其职业和研究目标。肺和重症监护医学和约翰·霍普金斯大学（Johns Hopkins University）在支持和协作环境中培训成功的年轻临床研究人员的历史悠久。该应用程序的父母研究的先前结构，设定在城市环境中童年哮喘中心的强大基础上，以及该申请与她的导师团队的建立和持续合作，将确保在该奖项的时间范围内完成学习目标。我们已经组建了一支拥有多年产品研究经验和大量先前指导经验的既定教师的心理团队。在与该提案相关的研究领域中，每个人都具有明显的完整优势。此外，指导委员会的每个成员都为候选人的职业发展成为一个独立研究者的杰出榜样。