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

项目摘要/摘要 这是Trishul的K23指导患者导向研究职业科学家奖的申请书 Siddharthan医学博士作为一名年轻的研究人员，Siddharthan博士表现出了巨大的潜力，而且经验丰富 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，他现在提议接受进行纵向分析和随机化的高级培训 对照试验需要额外的培训和指导才能做到这一点。他的整个职业目标是成为一名 独立调查者和评估慢性呼吸系统药物治疗有效性的专家 这一奖项将为悉达坦博士提供支持和培训，以实现这一目标。他 组建了一支经验丰富的导师团队，包括：William Checkley博士(主要导师，慢性病 罗伯特·怀斯博士(临床试验)，教授(JHU)； James Tonascia(生物统计学)，教授(JHU)；David Dowdy博士(成本评价)，副教授 (JHU)。通过密切的指导、正规的课程和实践经验的结合，Dr。 悉达丹建议完成以下培训目标：1)纵向分析方面的高级培训； 2)随机对照试验的高级培训；3)成本评估的高级培训。 慢性阻塞性肺疾病(COPD)是全球第四大死亡原因，超过90% 在低收入和中等收入国家(LMIC)发生的与COPD相关的死亡人数。家庭空气污染(HAP) -燃烧木头、粪便、农业作物废弃物和煤炭作为能源等固体燃料-是主要风险 在这些设置中COPD的因素。与生物量相关的COPD具有独特的组织病理学、表型和 与烟草介导的慢性阻塞性肺疾病相比较时的炎症情况。尽管全球生物质的负担很重- 与疾病相关，对生物质相关COPD的药物治疗的有效性知之甚少； 到目前为止，还没有临床试验专门集中在生物质相关COPD的治疗上。悉达坦博士 建议评估生物质相关COPD对健康的影响，并测试低剂量的有效性 秘鲁生物质相关慢性阻塞性肺疾病成人患者茶碱与标准治疗的比较。他提议 评估小剂量茶碱是否改善呼吸道症状，减少炎症反应 血清生物标志物和给药是否减弱HAP对肺功能的影响。他还补充道 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- 有效率和支付门槛的意愿范围。这项研究的结果将产生 竞争R01级奖项以在以下方面进行实施-有效性混合试验的初步数据 多个社区评估慢性药物治疗对生物质相关慢性阻塞性肺疾病的影响。

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.