Novel physiologiC prEdictors of Positive Airway Pressure effectiveness: NICE-PAP study.

气道正压有效性的新型生理预测因素：NICE-PAP 研究。

• 批准号: 10473795
• 负责人: ANDREY ZINCHUK
• 金额: $ 17.23万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10473795
• 关键词: Accounting; Acetazolamide; Address; Adherence; Adult; Affect; Age; American; Anatomy; Apnea; Arousal; Atrial Fibrillation; Automobile Driving; Biological; Biometry; Breathing; Catheters; Clinical Pathways; Clinical Research; Clinical Trials Design; Complement; Continuous Positive Airway Pressure; Critical Care; Data; Data Set; Development Plans; Diabetes Mellitus; Diagnosis; Drowsiness; Effectiveness; Engineering; Environment; Epidemiology; Equipment; Exhibits; Expectancy; Financial compensation; Future; Goals; Gold; Growth; Heart failure; Hour; Hypertension; Impairment; Individual; Infrastructure; Institution; Internal Medicine; Knowledge; Laboratories; Lead; Link; Lung; Measurement; Measures; Medicine; Mentored Patient-Oriented Research Career Development Award; Mentors; Methodology; Modification; Morbidity - disease rate; Myocardial Infarction; Obstructive Sleep Apnea; Outcome; Oxygen; Pathogenesis; Patient Care; Patient-Focused Outcomes; Patients; Physicians; Physiological; Physiology; Polysomnography; Predisposition; Prospective cohort; Psychological Factors; Psychosocial Factor; Pulmonology; Quality of life; Randomized Clinical Trials; Research; Research Methodology; Research Personnel; Research Project Grants; Research Training; Residual state; Resources; Risk; Role; Science; Scientist; Self Efficacy; Sleep; Sleep Apnea Syndromes; Sleeplessness; Social support; Stroke; Symptoms; Techniques; Training; Training Activity; Training Programs; Translating; Work; base; career development; clinical application; clinical epidemiology; cohort; common treatment; design; efficacy outcomes; epidemiology study; experience; externship; hypnotic; improved; ineffective therapies; mortality; novel; novel strategies; patient oriented; patient oriented research; personalized care; personalized medicine; pharynx muscle; poor sleep; positive airway pressure; pressure; prevent; programs; prospective; psychologic; randomized trial; remote monitoring; response; sex; skills; sleep position; sleep quality; social; social factors; success; symptomatic improvement; tool; trait; treatment adherence; vehicular accident

Candidate. My goal is to become an independent physician-scientist who merges physiology and patient-ori- ented research methods to personalize care for patients with obstructive sleep apnea (OSA). My training as an engineer and a doctor in Pulmonary, Critical Care and Sleep Medicine (PCCSM), complemented by research training in epidemiology, have given me the background necessary to pursue this goal. I propose training activ- ities that will allow me to personalize treatments for one of the most pressing problems for OSA patients- effec- tiveness of continuous positive airway pressure (CPAP). Through coursework, externships and mentored expe- rience in physiologic and patient-oriented research, this training program will build skills and knowledge in 1) physiologic characterization of OSA, 2) treatment adherence, efficacy and patient-oriented outcomes, 3) conduct of clinical studies, 4) advanced biostatistics and 5) leading a research program. Executing this program will bridge current knowledge gaps related to the role of physiologic traits in CPAP effectiveness and set me up for success as an independent investigator. Mentors and Environment. I have engaged an exceptional team of mentors with expertise tailored for this proposal. My primary mentor, Dr. Yaggi, is a national expert in OSA epidemiology and clinical study conduct. My co-mentors are Dr. Wellman, a pioneer in translational OSA physiology, and Dr. Redeker, a leader in patient- centered outcomes sleep research. This proposal leverages a wealth of resources across institutions, including Yale’s Center for Precision Pulmonary Medicine and Clinical Epidemiology Research Center, Centers for Sleep Medicine, PCCSM Section and Internal Medicine Department. The Sleep Disordered Breathing laboratory led by Dr. Wellman at Harvard is a renowned OSA physiology center. This environment provides methodologic expertise, research tools and a venue to conduct cutting-edge patient-oriented research in sleep. Mentored Research Project. Most patients with OSA who are prescribed the gold-standard therapy, CPAP, are ineffectively treated. This is due to 1) poor CPAP adherence, 2) high residual apnea in 20% of users (low efficacy) and 3) inconsistent symptom improvement. To improve CPAP effectiveness, we propose to address novel phys- iologic targets that cause OSA in each individual: arousability, ventilatory control sensitivity and pharyngeal mus- cle compensation. Our overall objective is to determine the contribution of these traits to CPAP effectiveness independently of established biological, psychological and social predictors. This work leverages state-of-the art sleep study analysis tools and validated measures of the determinants of CPAP effectiveness to create a prag- matic, prospective cohort (n=267) of OSA patients. This unique dataset will help determine whether physiologic causes of OSA influence CPAP adherence, efficacy, sleep quality, symptoms, function and quality of life. The results will inform design and conduct of a randomized clinical trial designed to modify physiologic traits such as easy arousability to improve CPAP effectiveness and other patient-centered outcomes in OSA patients.

候选人我的目标是成为一个独立的医生，科学家谁融合生理学和病人的起源， 阻塞性睡眠呼吸暂停综合征（OSA）患者的治疗方法我作为一个 工程师和医生在肺，重症监护和睡眠医学（PCCSM），辅以研究 流行病学的培训，给了我追求这一目标所必需的背景。我建议积极训练- 这将使我能够个性化治疗OSA患者最紧迫的问题之一-效果- 持续气道正压通气（CPAP）通过课程作业、校外实习和辅导经验- 在生理学和以病人为导向的研究方面，这项培训计划将在1） OSA的生理特征，2）治疗依从性、疗效和患者导向结局，3）行为 临床研究，4）先进的生物统计学和5）领导一个研究计划。执行该计划将 弥合当前与生理特征在CPAP有效性中的作用相关的知识差距，并为我建立 作为一名独立的调查员。 导师与环境我已经聘请了一个特殊的导师团队，他们拥有专门为此定制的专业知识。 提议我的主要导师Yaggi博士是OSA流行病学和临床研究开展方面的国家专家。我 共同导师是韦尔曼博士，在翻译OSA生理学的先驱，和博士Redeker，在病人的领导者， 以睡眠为中心的研究成果。该提案利用了各机构的丰富资源，包括 耶鲁大学精准肺医学和临床流行病学研究中心，睡眠中心 医学、PCCSM科和内科。睡眠呼吸障碍实验室 是一个著名的阻塞性睡眠呼吸暂停生理学中心。这种环境提供了方法论 专业知识，研究工具和场地进行尖端的以病人为导向的研究睡眠。 指导研究项目。大多数接受金标准治疗CPAP的OSA患者， 无效治疗。这是由于1）CPAP依从性差，2）20%的使用者存在高残留呼吸暂停（疗效低） （3）症状改善不一致。为了提高CPAP的有效性，我们建议解决新的物理- 导致每个个体OSA的生物学指标：唤醒能力、解释控制敏感性和咽肌- 清洁补偿。我们的总体目标是确定这些特征对CPAP有效性的贡献 独立于已建立的生物学、心理学和社会学预测因素。这项工作利用了最先进的 睡眠研究分析工具和经验证的CPAP有效性决定因素的测量，以创建一个prag- matic，前瞻性队列（n=267）的OSA患者。这一独特的数据集将有助于确定生理 阻塞性睡眠呼吸暂停的病因影响CPAP的依从性、疗效、睡眠质量、症状、功能和生活质量。的 结果将为设计和进行随机临床试验提供信息，该临床试验旨在改变生理特征， 易于唤醒，以提高CPAP的有效性和其他以患者为中心的结果在OSA患者。