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

波多黎各人(PR)患哮喘的比例更高。我们已经证明，心理社会压力源 例如虐待儿童和接触暴力(ETV)与严重抑郁障碍(MDD)有关 以及公关儿童和青少年中的广泛性焦虑症(GAD)、哮喘和更糟糕的哮喘结局。我们 也证明了与暴力相关的痛苦与对短时行为的反应减少有关 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 和哮喘相关的生活质量在PR和非PR儿童和青少年中。最近，我们发现这个数字很高 在两个PR队列中，ETV和高度暴力相关的痛苦与Th2高哮喘内型相关 青春年华。在另一项单独的研究中，我们最近还证明了~38%的估计儿童影响 40岁以上的英国成年人对哮喘的虐待是由MDD和/或GAD介导的。然而，它是 尚不清楚ETV和与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(独立于或因为先前的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。 高哮喘，包括与暴力相关的Th2高哮喘内型，在年轻人中。缺乏这样的知识 是一个重要的问题，因为如果没有它，就有能力预防或治疗与暴力有关的哮喘 服务不足的人群是极不可能的。根据我们新的初步结果，我们假设ETV和 与暴力相关的痛苦会导致年轻的公关成年人持续存在Th2高哮喘，这些影响是 由MDD或GAD调解或修改。为了验证这一假设，我们将首先确定高ETV 儿童时期高暴力相关的痛苦与持续的Th2高哮喘有关 年轻PR成人的内型和更严重的哮喘严重程度或控制(特定[Sp.]目标1)。然后我们将测试 年轻公关成年人儿童期高ETV或暴力相关痛苦与MDD或GAD的关系 (sp.目标2)。接下来，我们将检查MDD或GAD是否与Th2高哮喘的存在有关 在年轻的PR成人中，内型和更严重的哮喘严重程度或控制(Sp。目标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 哮喘和哮喘严重程度或控制在年轻的公关成人。这项提议应该决定是否以及如何 ETV和暴力相关的痛苦预测Th2高哮喘内型的持续性和更严重的哮喘 在患有严重哮喘(PR)的民族中的年轻人中，严重程度或控制，同时也 确定窘迫诱发哮喘的新途径和媒介。为了实现这一目标，我们聚集在一起 一支杰出的多学科研究团队。

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.