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，是美国人的头号杀手，并影响墨西哥 美国人 (MA) 的比例高于非西班牙裔白人 (NHW)。改善中风的一次机会 通过识别和治疗阻塞性睡眠呼吸暂停可能存在结果并减少差异 (OSA) 发生在中风患者中。一般人群中的 OSA 在以下方面存在差异： 病理生理学、疾病的表现、对治疗的反应以及与结果的关联。机械论 睡眠期间气道塌陷的原因可根据多导睡眠图 (PSG) 数据分类为 OSA 内型，包括解剖原因（塌陷性）和 3 个非解剖原因（咽肌 补偿、chemoreflex 反馈环路/环路增益和唤醒阈值）。与传统 PSG 数据不同的是 反映 OSA 严重程度而非根本原因，这些内型决定对治疗的反应，因此 基于 PSG 的确定内型的新方法为个性化护理创造了新的机会。阻塞性睡眠呼吸暂停是 中风后比例过高（~75%），并且与一般人群相比表现不同。 此外，OSA 在 MA 中风患者中更为普遍和严重，他们的平均死亡率更高 BMI 高于 NHW，因此气道塌陷的可能性更大。发病率高的原因及 中风后 OSA 的机制原因尚不清楚。由于大脑通路的中断，非解剖学 与一般人群相比，中风后导致 OSA 的可能性更大。相比之下，中风病例 先前存在的 OSA 可能具有与普通人群更相似的内型，其中贡献更大 塌陷性。利用长期基于人群的研究 (BASIC) 的基础设施及其辅助 受试者识别、基线数据收集和基线 PSG 的研究，这项针对中风的前瞻性研究 自由对照组，纵向随访旨在：1）确定特定的内型和内型 导致中风后 OSA 的因素，以及这些因素在种族和非中风人群中的差异，2) 确定特定的内型特征与通常在术后早期观察到的 OSA 严重程度的改善有何关系 中风，以便告知哪些患者可能需要长期治疗以及哪些患者可能需要重复检测 OSA，以及 3) 建立一个模型，根据临床信息预测中风后 OSA 内型特征，包括 表型数据，帮助选择最合适的治疗方案，无需 PSG。新 拟议的面部形态测量和其他表型分析将补充丰富的人口和 考虑作为中风后 OSA 内型特征预测因子的临床数据。这项研究将扩大我们的 了解中风后 OSA 的病理生理学并为个体化医疗打开大门 中风患者目前主要采用一刀切的方法。