Exposure to violence during childhood and Th2-high asthma in young Puerto Rican adults

波多黎各年轻人童年时期遭受暴力和 Th2 高哮喘的情况

• 批准号: 10649746
• 负责人: Juan Carlos Celedon
• 金额: $ 69.59万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2028-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10649746
• 关键词: Abbreviations; Adolescent; Adult; Affect; Asthma; British; Bronchodilator Agents; Child; Child Abuse and Neglect; Childhood; Childhood Asthma; Cross-Sectional Studies; Data; Distress; Elderly; Environment; Ethnic Population; Generalized Anxiety Disorder; Genetic; Goals; Interdisciplinary Study; Knowledge; Life Style; Literature; Major Depressive Disorder; Mediating; Mediation; Mediator; Mental disorders; Methods; Minority; Minority Groups; Outcome; Pathogenesis; Pathway interactions; Prevention; Prevention approach; Prospective Studies; Publishing; Puerto Rican; Puerto Rico; Quality of life; Regulatory Pathway; Risk; Role; Severities; Symptoms; Testing; Therapeutic Intervention; Time; Underserved Population; Violence; Youth; associated symptom; asthma prevention; cohort; economic disparity; emerging adult; epigenetic variation; health disparity; inner city; member; novel; novel strategies; pharmacologic; prevent; preventive intervention; psychosocial stressors; pulmonary function; response; stress reduction; underserved minority; violence exposure; young adult

Puerto Ricans (PRs) are disproportionately affected with asthma. We have shown that psychosocial stressors such as child maltreatment and exposure to violence (ETV) are associated with major depressive disorder (MDD) and generalized anxiety disorder (GAD), asthma, and worse asthma outcomes in PR children and adolescents. We have also demonstrated that violence-related distress is associated with reduced response to short-acting bronchodilators, and that increased violence-related distress over time is associated with worse lung function and asthma-related quality of life in PR and non-PR children and adolescents. More recently, we found that high ETV and high violence-related distress are associated with a Th2-high asthma endotype in two cohorts of PR youth. In a separate study, we also recently demonstrated that ~38% of the estimated effects of child maltreatment on asthma in British adults older than 40 years are mediated by MDD and/or GAD. However, it is not known whether ETV and violence-related distress cause persistence of Th2-high asthma into early adulthood or whether MDD and GAD (independently of or because of prior ETV) are associated with Th2-high asthma in young PR adults. Indeed, we have very limited knowledge of the mechanisms underlying persistence of Th2- high asthma, including a violence-related Th2-high asthma endotype, in young adults. Lack of such knowledge is an important problem, because, without it, gaining the ability to prevent or treat violence-related asthma in underserved populations is highly unlikely. Based on our novel preliminary results, we hypothesize that ETV and violence-related distress leads to persistence of Th2-high asthma in young PR adults, and that these effects are mediated or modified by MDD or GAD. To test this hypothesis, we will first determine examine whether high ETV or high violence-related distress during childhood are associated with persistence of a Th2-high asthma endotype and worse asthma severity or control in young PR adults (Specific [Sp.] Aim 1). We will then test for association between high ETV or violence-related distress during childhood and MDD or GAD in young PR adults (Sp. Aim 2). Next, we will examine whether MDD or GAD is associated with the presence of a Th2-high asthma endotype and worse asthma severity or control in young PR adults (Sp. Aim 3a). Finally, we will assess whether MDD or GAD modifies or mediates any estimated effects of high ETV and violence-related distress on Th2-high asthma and asthma severity or control in young PR adults. This proposal should determine whether and how ETV and violence-related distress forecast persistence of a Th2-high asthma endotype and worse asthma severity or control among young adults in an ethnic group heavily burdened by asthma (PRs), while also identifying novel pathways and mediators of distress-induced asthma. To achieve this goal, we have assembled an outstanding multidisciplinary research team.

波多黎各人 (PR) 受哮喘影响的比例不成比例。我们已经表明，社会心理压力源 例如虐待儿童和接触暴力 (ETV) 与重度抑郁症 (MDD) 相关 以及广泛性焦虑症 (GAD)、哮喘以及 PR 儿童和青少年的哮喘结局恶化。我们 还表明，与暴力相关的痛苦与对短效药物的反应减弱有关 支气管扩张剂，随着时间的推移，与暴力相关的痛苦增加与肺功能恶化有关 PR 和非 PR 儿童和青少年的哮喘相关生活质量。最近，我们发现高 在两组 PR 中，ETV 和高度暴力相关的痛苦与 Th2 高哮喘内型相关 青年。在另一项研究中，我们最近还证明，儿童的估计影响约占 38% 40 岁以上英国成年人的哮喘虐待是由 MDD 和/或 GAD 介导的。然而，它是 尚不清楚 ETV 和暴力相关的痛苦是否会导致 Th2 高哮喘持续到成年早期 或者 MDD 和 GAD（独立于或由于之前的 ETV）是否与 Th2 高哮喘有关 年轻的公关成年人。事实上，我们对 Th2- 持续存在的机制了解非常有限。 年轻人的高哮喘，包括与暴力相关的 Th2 高哮喘内型。缺乏这样的知识 是一个重要的问题，因为如果没有它，就无法获得预防或治疗与暴力相关的哮喘的能力 服务不足的人群的可能性极小。根据我们新颖的初步结果，我们假设 ETV 和 与暴力相关的痛苦会导致年轻 PR 成年人持续患有 Th2 高哮喘，而这些影响是 由 MDD 或 GAD 介导或修改。为了检验这个假设，我们首先确定检查是否高 ETV 或童年时期与暴力相关的高度痛苦与 Th2 高哮喘的持续存在相关 年轻 PR 成年人的内型和哮喘严重程度或控制情况较差（具体 [Sp.] 目标 1）。然后我们将测试 儿童期高 ETV 或与暴力相关的痛苦与年轻 PR 成年人的 MDD 或 GAD 之间的关联 （具体目标 2）。接下来，我们将检查 MDD 或 GAD 是否与 Th2 高哮喘的存在相关 年轻 PR 成年人的内型和哮喘严重程度或控制情况较差（Sp. Aim 3a）。最后，我们将评估是否 MDD 或 GAD 修改或调节高 ETV 和暴力相关痛苦对 Th2-high 的任何估计影响 年轻 PR 成年人的哮喘和哮喘严重程度或控制情况。该提案应确定是否以及如何 ETV 和暴力相关的痛苦预测 Th2 高哮喘内型的持续存在和更严重的哮喘 患有哮喘 (PR) 的族群中的年轻人的严重程度或控制情况，同时也 确定应激性哮喘的新途径和介质。为了实现这一目标，我们聚集了 优秀的多学科研究团队。