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

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.