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

波多黎各人（PR）不成比例地受到哮喘的影响。我们已经证明，心理社会压力 如虐待儿童和暴力（ETV）与重度抑郁症（MDD）有关 和广泛性焦虑症（GAD），哮喘，以及PR儿童和青少年中更严重的哮喘结局。我们 还表明，与暴力有关的痛苦与对短效 支气管扩张剂，随着时间的推移，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， 在两组PR患者中，ETV和高暴力相关的痛苦与Th 2高哮喘内型相关 青年在一项单独的研究中，我们最近还证明，儿童的估计影响约有38%， 英国40岁以上成人哮喘的虐待是由MDD和/或GAD介导的。但据 尚不清楚ETV和暴力相关的痛苦是否会导致Th 2高哮喘持续到成年早期 或MDD和GAD（独立于或由于既往ETV）是否与Th 2-高哮喘相关， 年轻的成年人。事实上，我们对Th 2持续存在的机制了解非常有限， 高哮喘，包括暴力相关的Th 2高哮喘内型，在年轻人。缺乏这种知识 是一个重要的问题，因为，没有它，获得预防或治疗暴力相关哮喘的能力， 得不到充分服务的人口是极不可能的。基于我们新的初步结果，我们假设ETV和 与暴力相关的痛苦导致年轻PR成人持续Th 2高哮喘，这些影响是 由MDD或GAD介导或修饰。为了验证这一假设，我们将首先确定检查是否高ETV 儿童时期与暴力有关的痛苦与Th 2高哮喘的持续存在有关 在年轻PR成人中，内型和更差的哮喘严重程度或控制（特异性[Sp.]目标1）。然后我们将测试 在年轻的PR成人中，儿童期高ETV或暴力相关的痛苦与MDD或GAD之间的关联 (Sp.目标2）。接下来，我们将研究MDD或GAD是否与Th 2高哮喘的存在相关 在年轻PR成人中，内源型和更差的哮喘严重程度或控制（Sp. Aim 3a）。最后，我们将评估 MDD或GAD修改或介导高ETV和暴力相关的痛苦对Th 2-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。这一建议应确定是否以及如何 ETV和暴力相关的痛苦预测Th 2高哮喘内源性和更严重哮喘的持续性 严重哮喘（PR）的种族群体中年轻成人的严重程度或控制，同时还 确定新的途径和介质的痛苦引起的哮喘。为了实现这一目标，我们聚集了 优秀的多学科研究团队。

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.