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

项目概要/摘要 这是Trishul的K23指导以患者为导向的研究职业科学家奖的申请 Siddharthan医学博士Siddharthan博士作为一名年轻的调查员表现出了很大的潜力， 在低收入和中等收入国家开展流行病学和慢性病研究。 然而，他现在建议在进行纵向分析和随机化方面获得高级培训。 对照试验需要额外的培训和指导。他的职业目标是成为一名 独立研究者和专家，评估慢性呼吸道疾病药物治疗的有效性 该奖项将为Siddharthan博士提供支持和培训，以实现这一目标。他 已经组建了一支经验丰富的导师团队，包括：William Checkley博士（初级导师，慢性 呼吸系统疾病），副教授（JHU）;博士罗伯特·怀斯（临床试验），教授（JHU）;博士。 James Tonascia（生物统计学），教授（JHU）;和大卫道迪博士（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相结合，博士。 Siddharthan建议完成以下培训目标：1）纵向分析的高级培训; 2)随机对照试验高级培训; 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， 低收入和中等收入国家（LMIC）中发生的COPD相关死亡。家庭空气污染（HAP） - 从燃烧固体燃料，如木材，粪便，农作物废料，煤炭能源-是主要的风险 在这些环境中的COPD因素。生物量相关的COPD具有不同的组织病理学、表型和 与烟草介导的COPD相比，尽管全球生物质负担很高- 与生物质相关的疾病，对生物质相关的COPD药物治疗的有效性知之甚少; 迄今为止，没有临床试验专门关注生物质相关COPD的治疗。Siddharthan博士 建议评估生物量相关的COPD对健康的影响，并测试低剂量 在秘鲁，茶碱与标准治疗在患有生物质相关COPD的成人中的比较。他拟 评估低剂量茶碱是否能改善呼吸道症状，降低 血清生物标志物和给药是否减弱HAP对肺功能的影响。他还 旨在评估低剂量茶碱是否是一种基于增量成本的成本效益干预措施- 有效性比率和一系列支付意愿阈值。这项研究的结果将产生 初步数据，以竞争R 01级奖项，在 多个社区评估慢性药物治疗对生物质相关COPD的影响。

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.