Inflammation and alcohol-related racial/ethnic health disparities

摘要 与酒精有关的健康问题包括非常普遍和严重的疾病，如高血压， 糖尿病和抑郁症。大量证据支持饮酒和饮酒之间的J型关系 糖尿病1，而饮酒和高血压之间的线性关系有很好的记录2，而且 关于饮酒和抑郁之间的关系的形式，证据是混合的3，4。常见的 酒精对这些疾病的作用的生物学机制可能是炎症。炎症是一种普遍现象 免疫系统对伤害的反应，如身体伤害或接触刺激物(如酒精)5. 慢性炎症，可能会持续数年，与增加健康风险有关 问题6，包括高血压、糖尿病和抑郁症。因此，对炎症的干预提供了新的 预防和治疗的机会。然而，在酒精背景下的炎症机制 使用和健康需要进一步研究。在这方面，种族/民族健康差距尤其重要。 因为种族/少数族裔分担了不成比例的很大一部分负担 混乱8.此外，最近的研究表明，种族/少数民族一直有更高的水平 发炎，这些差异在整个生命周期中都被观察到了。 K01职业发展奖的总体目标是为首席研究员Dr。 马丁内斯，拥有进行酒精研究所需的技能，将社会、行为和 生理领域。本奖项下建议的研究活动将有助于更好地了解 酒精使用和炎症是造成与酒精有关的种族/族裔健康差异的机制。在……里面 反过来，调查结果将为后续R01资助的纵向项目的开发和实施提供信息 可能解释不同饮酒模式的免疫学机制及其相关因素的研究 以及相关的种族/族裔少数群体的身心健康结果。完成学业后 作为一名独立的、由美国国立卫生研究院资助的科学家，马丁内斯博士将成为一名富有成效的职业生涯。 马丁内斯博士是一名酒精研究人员，在生物科学和 在酒精流行病学方面的专业知识，特别是酒精使用和抑郁之间的共病。Dr。 马丁内斯的长期目标是成为一名成功的NIH资助的科学家，拥有人际关系方面的专业知识 生物机制和与酒精有关的种族/民族健康差异之间的关系。她正在提议一项 教学和应用研究活动相结合，在她领导的该领域专家的指导下 主要导师Sarah Zemore博士，为她提供完成这一目标所需的以下技能：(1) 关于炎症对身心健康的作用的专门知识；(2)关于#年种族/族裔差异的专门知识 酒精对身心健康的影响，(3)纵向统计建模技术，(4) 流行病学和生物标志物数据收集的现场方法。 拟议的研究活动包括两项研究(A和B)，每项研究都有两个目标。研究A是一项 全国青少年至成人健康纵向研究I-V波资料的二次分析 (AddHealth)。研究B需要通过自给血点(SaDBS)收集初步试点数据 这是2020年全国酒精调查(NAS)的一个子样本。研究A，目标一：描述纵向 饮酒、炎症和健康结局(高血压、糖尿病和 抑郁)。马丁内斯博士将通过以下方式实现这一目标：(A)检查 酒精使用、炎症和健康与AddHealth的前瞻性数据，以及(B)测试炎症作为 酒精使用与每种健康结果之间的关系的调解人。研究A，目标二：描述 种族/民族如何通过炎症和环境应激源的作用影响酒精对健康的影响 和不健康的行为。马丁内斯博士将通过以下方式实现这一目标：(A)测试饮酒的影响 与白人相比，少数族裔对炎症和健康的影响更强，以及(B)检测 环境因素和健康行为是否在种族/民族对人际关系的影响中起中介作用 酒精使用与炎症和健康之间的关系。研究B，目标一：对一种新的生物样本的使用进行中试 采集法(自采干血斑(SADBS))。马丁内斯博士将通过以下方式实现这一目标： 评估SADBS在国家行动计划参与者样本中的可接受性和可行性，以及(B)评估 学员完成SADBS样本的经验。研究B，目标二：探索额外的免疫 与饮酒、炎症和健康之间跨种族/民族群体关系的相关标记物 在一个具有全国代表性的成人样本中。马丁内斯博士将通过以下方式实现这一目标：(A)探索免疫 使用NAS的研究A中包括的标记之外的标记，以及(B)探索这些标记之间的关联 免疫标记物和酒精使用以及各种族/民族群体的健康。 这些研究活动将最终提交R01作为NIAAA健康计划的一部分 差异倡议前瞻性研究免疫机制对酒精相关健康的影响 各种族/族裔群体的结果。K01中建议的职业发展和研究活动 申请将为马丁内斯博士作为一名成功的、独立的、由NIH资助的科学家的职业生涯奠定基础。

ABSTRACT Alcohol-related health problems include highly prevalent and serious disorders such as hypertension, diabetes, and depression. Substantial evidence supports a J-shaped relationship between alcohol use and diabetes1, whereas a linear relationship is well-documented between alcohol use and hypertension2, and there is mixed evidence regarding the shape of the relationship between alcohol use and depression3,4. A common biologic mechanism for alcohol's effects on these disorders may be inflammation. Inflammation is a general response by the immune system to harm, such as bodily injury or exposure to irritants (e.g. alcohol)5. Inflammation that becomes chronic, potentially lasting for years, is associated with an increased risk of health problems6, including hypertension, diabetes, and depression7. Thus, intervening on inflammation offers new opportunities for prevention and treatment. However, the mechanisms of inflammation in the context of alcohol use and health require further study. Racial/ethnic health disparities are especially relevant in this context because racial/ethnic minorities share a disproportionately large portion of the burden caused by these disorders8. Moreover, recent studies show racial/ethnic minorities have consistently higher levels of inflammation9, and these differences have been observed across the lifespan10,11. The overall objective of this K01 Career Development Award is to provide the principal investigator, Dr. Martinez, with the skills necessary to conduct alcohol research that bridges social, behavioral, and physiological domains. The research activities proposed under this award will lead to a better understanding of alcohol use and inflammation as mechanisms contributing to alcohol-related racial/ethnic health disparities. In turn, findings will inform the development and implementation of a subsequent R01-funded longitudinal investigation of immunologic mechanisms and associated factors that may explain differential drinking patterns and related physical and mental health outcomes among racial/ethnic minorities. Upon completion of study activities, Dr. Martinez will be poised for a productive career as an independent, NIH-funded scientist. Dr. Martinez is trained as an alcohol researcher with a strong background in the biological sciences and expertise in alcohol epidemiology, particularly the comorbidity between alcohol use and depression. Dr. Martinez's long-term goal is to become a successful NIH-funded scientist with expertise in the relationships between biologic mechanisms and alcohol-related racial/ethnic health disparities. She is proposing a combination of didactic and applied research activities, under the mentorship of experts in the field led by her primary mentor Dr. Sarah Zemore, to provide her with the following skills necessary to accomplish this goal: (1) expertise in the role of inflammation in mental and physical health, (2) expertise in racial/ethnic disparities in the effects of alcohol on mental and physical health, (3) longitudinal statistical modeling techniques, and (4) field methods in epidemiologic and biomarker data collection. The proposed research activities consist of two studies (A & B) with two aims each. Study A is a secondary analysis of data from Waves I-V of the National Longitudinal Study of Adolescent to Adult Health (AddHealth). Study B entails primary pilot data collection via self-administered dried blood spots (saDBS) from a subsample of the 2020 National Alcohol Survey (NAS). Study A, Aim I: To describe the longitudinal relationships between alcohol use, inflammation, and health outcomes (hypertension, diabetes, and depression). Dr. Martinez will accomplish this aim by: (a) examining the individual associations between alcohol use and inflammation and health with prospective data from AddHealth, and (b) testing inflammation as a mediator of the relationships between alcohol use and each health outcome. Study A, Aim II: To describe how race/ethnicity impacts alcohol's effects on health via inflammation and the roles of environmental stressors and unhealthy behaviors. Dr. Martinez will accomplish this aim by: (a) testing whether the effects of alcohol use on inflammation and health are stronger among racial/ethnic minorities compared to Whites, and (b) testing whether environmental factors and health behaviors mediate the effect of race/ethnicity on the relationships between alcohol use and inflammation and health. Study B, Aim I: To pilot test the use of a novel biosample collection method (self-administered dried blood spots (saDBS)). Dr. Martinez will accomplish this aim by: (a) assessing the acceptability and feasibility of saDBS among a sample of NAS participants, and (b) assessing the participant's experience of completing a saDBS sample. Study B, Aim II: To explore additional immune markers relevant to the relationships between alcohol use, inflammation and health across racial/ethnic groups in a nationally representative adult sample. Dr. Martinez will accomplish this aim by: (a) exploring immune markers beyond those included in Study A using the NAS, and (b) exploring associations between these immune markers and alcohol use and health across racial/ethnic groups. These research activities will culminate in the submission of an R01 as part of NIAAA's Health Disparities Initiative to study prospectively the effect of immunological mechanisms on alcohol-related health outcomes across racial/ethnic groups. The career development and research activities proposed in this K01 application will lay the foundation for Dr. Martinez's career as a successful, independent, NIH-funded scientist.