Towards personalized medicine: pathophysiologic contributions to post-stroke sleep apnea

迈向个性化医疗：中风后睡眠呼吸暂停的病理生理学贡献

• 批准号: 10654941
• 负责人: DEVIN L BROWN
• 金额: $ 75.48万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-10 至 2027-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10654941
• 关键词: Adult; American; Anatomy; Ancillary Study; Arousal; Case Study; Categories; Clinical; Clinical Data; Compensation; Complement; Data; Data Collection; Deformity; Development; Disease; Ethnic Origin; Face; Feedback; Functional disorder; General Population; High Prevalence; Individual; Infrastructure; Interruption; Ischemic Stroke; Measures; Methods; Mexican Americans; Modeling; Not Hispanic or Latino; Obstructive Sleep Apnea; Outcome; Parents; Participant; Patients; Pharyngeal structure; Phenotype; Physiological; Polysomnography; Population Study; Predisposition; Prevention; Prospective Studies; Reflex action; Resistance profile; Resolution; Selection for Treatments; Severities; Sleep; Sleep Apnea Syndromes; Stroke; Study Subject; Testing; Time; brain pathway; comparison group; disability; disparity reduction; ethnic difference; follow-up; health disparity; high body mass index; improved; improved outcome; indexing; novel; outcome disparities; personalized care; personalized medicine; pharynx muscle; phenotypic data; population based; portability; post stroke; predictive modeling; stroke outcome; stroke patient; success; treatment response

Abstract Stroke is the leading cause of adult disability in the US, a top killer of Americans, and impacts Mexican Americans (MAs) to a greater extent than non-Hispanic whites (NHWs). One opportunity to improve stroke outcomes and reduce disparities may exist through identification and treatment of obstructive sleep apnea (OSA) in individuals with stroke. OSA in the general population is heterogeneous with respect to pathophysiology, expression of disease, response to therapies, and association with outcomes. Mechanistic causes of airway collapse during sleep can be categorized from polysomnography (PSG) data as OSA endotypes, including an anatomic cause (collapsibility), and 3 non-anatomic causes (pharyngeal muscle compensation, chemoreflex feedback loop/loop gain, and arousal threshold). Unlike traditional PSG data that reflect OSA severity and not underlying cause, these endotypes determine response to treatments, and thus new PSG-based methods to determine endotypes create novel opportunities for personalized care. OSA is overrepresented after stroke (~75%) and manifests differently compared to the general population. Furthermore, OSA is more prevalent and severe among MA stroke patients, who on average have a higher BMI than NHWs, and therefore likely more airway collapsibility. Reasons for the high prevalence and the mechanistic causes of post-stroke OSA are unknown. Due to interruption of brain pathways, non-anatomical causes of OSA may be more likely after stroke than in the general population. In contrast, stroke cases with pre-existing OSA may have endotypes more similar to the general population, with greater contribution from collapsibility. Leveraging the infrastructure of a longstanding population-based study (BASIC) and its ancillary study for subject identification, baseline data collection, and baseline PSG, this prospective study with a stroke- free comparison group, with longitudinal follow-up seeks to: 1) determine specific endotypes and endotypic profiles that contribute to post-stroke OSA, and how these differ by ethnicity and from those without stroke, 2) determine how specific endotypic profiles relate to improvement in OSA severity typically observed early after stroke in order to inform which patients may need longer-term treatment and which may need repeat testing for OSA, and 3) build a model to predict post-stroke OSA endotypic profiles based on clinical information including phenotypic data, to assist in selection of most appropriate treatment options without the need for PSG. Newly proposed facial morphometric measures and other phenotyping will complement the rich demographic and clinical data for consideration as predictors of post-stroke OSA endotypic profiles. This study will expand our understanding of the pathophysiology of post-stroke OSA and open the door to personalized medicine for stroke patients, currently dominated by a one-size-fits-all approach.

抽象的 中风是美国成人残疾的主要原因，是美国人的主要杀手，并影响墨西哥 美国人（MAS）比非西班牙裔白人（NHWS）更大程度。一个改善中风的机会 结局和减少差异可能通过识别和治疗阻塞性睡眠呼吸暂停 （OSA）中风的人。一般人口中的OSA相对于 病理生理学，疾病的表达，对疗法的反应以及与结局的关联。机理 睡眠期间气道崩溃的原因可以从多肌仪（PSG）数据分类为OSA 内型，包括解剖原因（可折叠性）和3个非解剖原因（咽肌肉 补偿，化学反射反馈回路/回路增益和唤醒阈值）。与传统的PSG数据不同 反映OSA的严重程度而不是根本原因，这些内型决定了对治疗的反应，因此 确定内型的新方法为个性化护理创造了新的机会。 OSA是 中风后的代表过多（约75％），与一般人群相比表现出不同的表现。 此外，在MA中风患者中，OSA平均更高 BMI比NHWS，因此可能更多的气道可折叠性。高患病率和 中风后OSA的机械原因尚不清楚。由于大脑通路的中断，非解剖学 中风后OSA的原因可能比普通人群更有可能。相反，中风案件 先前存在的OSA可能具有与一般人群更相似的内型，而贡献更大 可折叠性。利用长期基于人群的研究（基本）及其辅助的基础设施 研究对象识别，基线数据收集和基线PSG的研究，这项前瞻性研究与中风 自由比较组，纵向随访寻求：1）确定特定的内型和内型 造成冲程后OSA的概况，以及这些概况如何因种族和没有中风的人而异，2） 确定特定的内型概况与通常在此后早期观察到的OSA严重程度的改善有何关系 中风以告知哪些患者可能需要长期治疗，哪些可能需要重复测试 OSA和3）建立一个模型，以基于临床信息在内 表型数据，有助于选择最适当的治疗选择，而无需PSG。新 建议的面部形态测量和其他表型将补充丰富的人群和 临床数据以作为冲程后OSA内型轮廓的预测指标。这项研究将扩大我们的 了解后击球后OSA的病理生理学，并为个性化医学打开大门 中风患者，目前以一种适合所有方法为主导。