Effectiveness of Low-dose Theophylline for the Management of biomass-associated COPD

低剂量茶碱治疗生物质相关慢性阻塞性肺病的有效性

基本信息

批准号：
10415226
负责人：
Trishul Siddharthan
金额：
$ 19.63万
依托单位：
UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-07-15 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10415226
关键词：
Adrenal Cortex Hormones Adult Age Agricultural Crops Albuterol Altitude Anti-Inflammatory Agents Attenuated Award Benchmarking Biological Markers Biomass Biometry Body mass index Bronchodilator Agents Cardiovascular Diseases Cause of Death Cessation of life Chronic Chronic Disease Chronic Obstructive Pulmonary Disease Clinical Trials Clinical effectiveness Coal Communities Comparative Effectiveness Research Data Diabetes Mellitus Disease Doctor of Medicine Dose Down-Regulation Effectiveness Epidemiology Evaluation Fibrinogen Forced expiratory volume function Frequencies Funding Genes Genetic Transcription Goals Health Health Status Heating Histopathology Hour Household Air Pollution Income Individual Inflammation Inflammatory Inhalation Intervention K-Series Research Career Programs Lung diseases Measurement Measures Mediating Medical Mentors Mentorship Modeling Outcome Outcome Study Pathogenesis Persons Peru Peruvian Pharmacotherapy Phenotype Placebos Population Study Prognosis Quality-Adjusted Life Years Questionnaires Randomized Randomized Controlled Trials Regimen Research Research Personnel Respiratory Signs and Symptoms Risk Factors Scientist Serum Theophylline Tobacco Training United States National Institutes of Health Urbanization Wood material arm base biomass fuel career chronic respiratory disease cohort cooking cost cost effective cost effective intervention cost effectiveness cost estimate cost-effectiveness ratio economic evaluation effective therapy effectiveness evaluation effectiveness implementation study effectiveness testing experience follow-up functional disability group intervention health care service utilization health related quality of life improved incremental cost-effectiveness instrument longitudinal analysis low and middle-income countries markov model mid-career faculty multidisciplinary patient oriented research pilot trial primary outcome professor pulmonary function pulmonary function decline respiratory sex side effect skills socioeconomics solid fuel standard care treatment response wasting willingness to pay

项目摘要

PROJECT SUMMARY/ABSTRACT This is an application for the K23 Mentored Patient-Oriented Research Career Scientist Award for Trishul Siddharthan M.D. Dr. Siddharthan has shown great promise as a young investigator, and has experience conducting research in epidemiology and chronic disease in low- and middle-income countries (LMICs). However, he is now proposing to gain advanced training in conducting longitudinal analysis and randomized controlled trials requires additional training and mentorship to do so. His overall career goal is to become an independent investigator and expert in evaluating the effectiveness medical therapies for chronic respiratory diseases, and this award will provide Dr. Siddharthan with the support and training to accomplish this goal. He has assembled an experienced mentorship team including: Dr. William Checkley (Primary Mentor, Chronic Respiratory Diseases), Associate Professor (JHU); Dr. Robert Wise (Clinical Trials), Professor (JHU); Dr. James Tonascia (Biostatistics), Professor (JHU); and Dr. David Dowdy (Cost-evaluation), Associate Professor (JHU). Through a combination of close mentorship, formal coursework, and practical experience, Dr. Siddharthan proposes to accomplish the following training goals: 1) Advanced training in longitudinal analysis; 2) Advanced training in randomized controlled trials; and 3) Advanced training in cost-evaluation. Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death worldwide, and over 90% of COPD-related deaths occurring in low- and middle-income countries (LMICs). Household air pollution (HAP) – from burning solid fuels such as wood, dung, agricultural crop waste, and coal for energy – is the primary risk factor for COPD in these settings. Biomass-related COPD has a distinct histopathology, phenotype and inflammatory profile when compared to tobacco mediated COPD. Despite the high global burden of biomass- related disease, little is known about the effectiveness of pharmacotherapies for biomass-related COPD; to date, no clinical trials have focused specifically on treatment of biomass-related COPD. Dr. Siddharthan proposes to assess the health impact of biomass-related COPD and test the effectiveness of low dose theophylline compared to standard therapy among adults with biomass-related COPD in Peru. He proposes to assess whether low-dose theophylline improves respiratory symptoms, decreases the inflammatory profile of serum biomarkers and whether administration attenuates the effect of HAP on lung function. He additionally aims to assess whether low-dose theophylline is a cost-effective intervention based on the incremental cost- effectiveness ratio and a range of willingness to pay thresholds. Results from this study will generate preliminary data to compete for an R01-level award to conduct an implementation-effectiveness hybrid trial in multiple communities to assess the impact of chronic pharmacotherapy for biomass-related COPD.

项目概要/摘要这是 Trishul 的 K23 指导的以患者为导向的研究职业科学家奖的申请 Siddharthan M.D. 作为一名年轻的研究者，Siddharthan 博士表现出了巨大的潜力，并且拥有丰富的经验在低收入和中等收入国家（LMIC）开展流行病学和慢性病研究。然而，他现在提议获得进行纵向分析和随机分析的高级培训。受控试验需要额外的培训和指导才能做到这一点，他的总体职业目标是成为一名。评估慢性呼吸道疾病药物治疗有效性的独立研究者和专家该奖项将为 Siddharthan 博士提供实现这一目标的支持和培训。组建了一支经验丰富的指导团队，其中包括： William Checkley 博士（主要导师，慢性病呼吸系统疾病），副教授（JHU）；Robert Wise 博士（临床试验），教授（JHU）； James Tonascia（生物统计学）教授（JHU）；David Dowdy 博士（成本评估）副教授（JHU），通过密切的指导、正式的课程和实践经验的结合，博士。 Siddharthan提出要完成以下培训目标： 1）纵向分析高级培训； 2) 随机对照试验高级培训；以及 3) 成本评估高级培训。慢性阻塞性肺疾病 (COPD) 是全球第四大死亡原因，超过 90% 低收入和中等收入国家 (LMIC) 发生的慢性阻塞性肺病 (COPD) 相关死亡人数家庭空气污染 (HAP)。 – 燃烧木材、粪便、农作物废料和煤炭等固体燃料来获取能源 – 是主要风险生物质相关的 COPD 具有独特的组织病理学、表型和特征。与烟草介导的慢性阻塞性肺病相比，尽管生物量的全球负担很高，但炎症特征仍然存在。相关疾病，但对于生物量相关 COPD 的药物疗法的有效性知之甚少； Siddharthan 博士表示，迄今为止，还没有专门针对生物质相关 COPD 治疗的临床试验。建议评估生物量相关慢性阻塞性肺病的健康影响并测试低剂量的有效性他建议将茶碱与秘鲁生物量相关慢性阻塞性肺病成人患者的标准治疗进行比较。评估低剂量茶碱是否可以改善呼吸道症状、降低炎症特征血清生物标志物以及给药是否会减弱 HAP 对肺功能的影响。旨在根据增量成本评估低剂量茶碱是否是一种具有成本效益的干预措施这项研究将产生有效性比率和一系列支付意愿阈值。竞争 R01 级奖项的初步数据，以在多个社区评估慢性药物治疗对生物质相关慢性阻塞性肺病的影响。