Sodium in the Skin and Atopic Dermatitis: The SIS-AD Study

皮肤中的钠与特应性皮炎：SIS-AD 研究

• 批准号: 10712714
• 负责人: Katrina Elaine Abuabara
• 金额: $ 70.56万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-22 至 2028-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10712714
• 关键词: Address; Affect; African American population; Age; Area; Atopic Dermatitis; Biological Markers; Biopsy; Black Populations; Blood; Cardiovascular Diseases; Cells; Chronic; Chronic Disease; Clinical Research; Clinical Trials; Cohort Studies; Consumption; Cytometry; Development; Diet; Dietary Factors; Dietary Sodium; Disease; Eczema; Elderly; Enrollment; Environmental Risk Factor; Epidemiological trend; Epidemiology; Food; Frequencies; Future; Goals; Heterogeneity; Hydration status; Hypertension; Image; Imaging Techniques; Immune; Immune System Diseases; Immunologic Stimulation; Immunology; Immunosuppression; Industrialization; Inflammation; Inflammatory; Intake; Intervention; Laboratories; Link; Longitudinal cohort study; Magnetic Resonance Imaging; Measures; Modeling; Organ; Participant; Pathway interactions; Patient-Focused Outcomes; Patients; Persons; Phenotype; Physiological; Physiology; Population; Process; Proteins; Proteomics; Pruritus; Quality of life; Questionnaires; Research; Research Personnel; Research Project Grants; Role; Severities; Skin; Sodium; Sodium Chloride; Subgroup; Techniques; Testing; Th2 Cells; Time; Tissues; Translational Research; Urine; Variant; Visit; Water; Waxes; Woman; Work; aged; aptamer; burden of illness; cardiovascular disorder epidemiology; clinical phenotype; cohort; design; dietary; dietary excess; dietary salt; economic impact; environmental change; epidemiology study; experience; immune function; immunomodulatory therapies; improved; innovation; lifestyle factors; men; multidisciplinary; normal aging; novel; novel strategies; nutritional epidemiology; preservation; prevent; recruit; response; salt intake; salt sensitive; skin barrier; skin disorder; skin lesion; systemic inflammatory response; treatment response

ABSTRACT Atopic dermatitis (AD) rates have tripled since the 1950s, and are highest in urban and industrialized areas, likely due to changing environmental and dietary factors. Atopic dermatitis is now the most burdensome skin disease globally, and disease course and response to new immunomodulatory treatments remain highly variable. There is a critical need to identify modifiable factors that could improve patient outcomes. The central hypothesis of this proposal is that excess dietary sodium (consumed primarily as salt) is concentrated in the skin as a physiologic response to poor barrier function and water loss, and that high levels of skin sodium exacerbate the clinical phenotype of atopic dermatitis. The rationale for this project is that the skin serves as an osmoregulatory organ, storing large amounts of sodium; and that high sodium concentrations trigger inflammation, including TH2 pathways specific to atopic dermatitis. Our long-term goals are to understand how skin sodium influences inflammation and to test whether reducing salt intake or storage improves atopic dermatitis. The first specific aim will focus on reasons for sodium storage in the skin and will evaluate the impact of dietary sodium intake and skin barrier function on skin sodium concentration. The second specific aim will focus on the implications of skin sodium and will examine the extent to which skin sodium is associated with atopic dermatitis severity and persistence. It will also define functional immune profiles associated with high skin sodium both in skin and in the blood. To achieve these aims, we will perform a longitudinal cohort study of 90 men and women age > 50 at enrollment. Enrollment will be stratified by sodium intake and atopic dermatitis status and severity at baseline. Diet will be evaluated using food frequency questionnaires and urine biomarkers prior to each study visit, and skin sodium concentration will be measured using a novel, non- invasive sodium MRI technique. Participants will be followed for two years after enrollment. Our multidisciplinary team combines expertise in clinical and translational research, nutritional and cardiovascular epidemiology, immunology, and advanced imaging. This proposal is innovative in its application of cutting-edge techniques to image sodium in the skin and to define immune cell subsets in the skin and blood. It also tests a new conceptual model that links developments in the understanding of sodium physiology and immune stimulation with epidemiologic trends in atopic dermatitis. It is significant because the results will be used to design a clinical trial that would represent a fundamentally new approach to AD management that addresses disease triggers rather than focusing only on immunosuppression. Moreover, it will improve our understanding of sodium physiology in ways that could ultimately impact the management of patients with hypertension and cardiovascular disease.

抽象的 自 20 世纪 50 年代以来，特应性皮炎 (AD) 发病率增加了两倍，并且在城市和工业化地区最高， 可能是由于环境和饮食因素的变化。特应性皮炎是现在最困扰皮肤的问题 全球范围内的疾病，疾病过程和对新免疫调节治疗的反应仍然高度 多变的。迫切需要确定可以改善患者治疗结果的可改变因素。中央 该提案的假设是，膳食中过量的钠（主要以盐的形式消耗）集中在 皮肤对屏障功能差和水分流失的生理反应，以及皮肤钠含量高 加剧特应性皮炎的临床表型。这个项目的基本原理是皮肤作为 渗透调节器官，储存大量钠；高钠浓度会引发 炎症，包括特应性皮炎特有的 TH2 通路。我们的长期目标是了解如何 皮肤钠会影响炎症，并测试减少盐摄入或储存是否可以改善特应性 皮炎。第一个具体目标将重点关注皮肤中钠储存的原因，并评估 膳食钠摄入量和皮肤屏障功能对皮肤钠浓度的影响。第二具体 目标将重点关注皮肤钠的影响，并将检查皮肤钠的相关程度 与特应性皮炎的严重程度和持续性有关。它还将定义与相关的功能性免疫特征 皮肤和血液中的皮肤钠含量都很高。为了实现这些目标，我们将进行纵向队列研究 对 90 名入学时年龄 > 50 岁的男性和女性进行的研究。入学将根据钠摄入量和特应性进行分层 基线时的皮炎状态和严重程度。将使用食物频率调查问卷和尿液来评估饮食 每次研究访问之前的生物标志物，以及皮肤钠浓度将使用一种新型的、非 侵入性钠 MRI 技术。参与者将在注册后进行两年的跟踪。我们的 多学科团队结合了临床和转化研究、营养和心血管方面的专业知识 流行病学、免疫学和高级成像。该方案在前沿技术的应用上具有创新性 对皮肤中的钠进行成像并定义皮肤和血液中的免疫细胞子集的技术。它还测试了一个 将钠生理学和免疫学理解的发展联系起来的新概念模型 刺激特应性皮炎的流行病学趋势。这很重要，因为结果将用于 设计一项临床试验，代表一种全新的 AD 管理方法，解决 疾病的触发因素而不是仅仅关注免疫抑制。而且，它会增进我们的理解 钠生理学的改变可能最终影响高血压患者的治疗 心血管疾病。