Exposure to violence and asthma in Puerto Rican youth with high Th2 immunity.

BACKGROUND: Little is known about the determinants of asthma among youth with high T helper 2 (Th2) immunity. We hypothesized that exposure to violence (ETV) and violence-related distress are associated with asthma in children and adolescents with high Th2 immunity. METHODS: We analyzed data from Puerto Ricans with high Th2 immunity aged 9-20 years in the Puerto Rico Genetics of Asthma and Lifestyle (PR-GOAL) and the Epigenetic Variation of Childhood Asthma in Puerto Ricans (EVA-PR) studies, and in a prospective study (PROPRA). High Th2-immunity was defined as ≥1 positive allergen-specific IgE and/or a total IgE ≥ 100 IU/mL and/or an eosinophil count ≥ 150 cells/µL. Asthma was defined as physician-diagnosed asthma and current wheeze. ETV and violence-related distress were assessed with the validated ETV Scale and Checklist of Children's Distress Symptoms (CCDS) questionnaires, respectively. RESULTS: In multivariable analyses, each 1-point increment in ETV score was significantly associated with 1.13-1.17 times increased odds of asthma in PR-GOAL and in EVA-PR (both at p ≤ 0.01), and each 1-point increment in CCDS score was significantly associated with 1.53-1.54 increased odds of asthma in PR-GOAL and in EVA-PR (both at p ≤ 0.03). Further, a persistently high ETV score was significantly associated with asthma in PROPRA (odds ratio [OR] = 2.83, 95% confidence interval [CI] = 1.10-7.29). Similar results were obtained in a sensitivity analysis using an eosinophil count ≥ 300 cells/µL instead of ≥150 cells/µL to define high Th2 immunity. CONCLUSIONS: ETV during childhood is associated with increased risk of persistent or new-onset asthma in youth with high Th2 immunity.

Maternal Depressive Symptoms, Lung Function, and Severe Asthma Exacerbations in Puerto Rican Children.

BACKGROUND: Maternal depression has been linked to health care use for asthma in cross-sectional or short-term follow-up studies of school-aged children. OBJECTIVE: To examine whether increased or persistent maternal depressive symptoms over approximately 5 years are associated with severe asthma exacerbations or worse lung function in youth. METHODS: A prospective study of 386 youth living in Puerto Rico, aged 6 to 14 years at a baseline visit and 9 to 20 years at a second visit, was performed. Our exposure of interest was change in persistence of maternal depressive symptoms, assessed at both visits using the Center for Epidemiologic Studies Depression Scale (CESD). Our outcomes of interest were change in percent predicted forced expiratory volume in 1 second (FEV1) and FEV1/forced vital capacity (FVC) between the first and second visits in all subjects, and ≥1 severe asthma exacerbation in the year before the second visit in subjects with asthma. RESULTS: In a multivariable analysis, each 1-point increment in the CESD score was associated with decrements of 0.15% in percent predicted FEV1 (95% confidence interval [CI] = -0.28% to -0.01%; P = .03) and 0.10% in percent predicted FEV1/FVC (95% CI = -0.20% to 0.001%; P = .05) between visits, as well as with 1.03 times increased odds of ≥1 severe asthma exacerbation at the second visit (95% CI for odds ratio = 0.99 to 1.06, P = .09). In a multivariable analysis, the presence of maternal depressive symptoms (a CESD score ≥21 points) at the second visit or at both visits was significantly associated with 3.17 to 3.52 times increased odds of ≥1 severe asthma exacerbation in the year before the second visit. CONCLUSIONS: Increasing or persistent maternal depressive symptoms over approximately 5 years are associated with worse lung function measures and severe asthma exacerbations among Puerto Rican youth, a high-risk population.

Associations and Heritability of Auditory Encoding, Gray Matter, and Attention in Schizophrenia.

BACKGROUND: Auditory encoding abnormalities, gray-matter loss, and cognitive deficits are all candidate schizophrenia (SZ) endophenotypes. This study evaluated associations between and heritability of auditory network attributes (function and structure) and attention in healthy controls (HC), SZ patients, and unaffected relatives (UR). METHODS: Whole-brain maps of M100 auditory activity from magnetoencephalography recordings, cortical thickness (CT), and a measure of attention were obtained from 70 HC, 69 SZ patients, and 35 UR. Heritability estimates (h2r) were obtained for M100, CT at each group-difference region, and the attention measure. RESULTS: SZ patients had weaker bilateral superior temporal gyrus (STG) M100 responses than HC and a weaker right frontal M100 response than UR. Abnormally large M100 responses in left superior frontal gyrus were observed in UR and SZ patients. SZ patients showed smaller CT in bilateral STG and right frontal regions. Interrelatedness between 3 putative SZ endophenotypes was demonstrated, although in the left STG the M100 and CT function-structure associations observed in HC and UR were absent in SZ patients. Heritability analyses also showed that right frontal M100 and bilateral STG CT measures are significantly heritable. CONCLUSIONS: Present findings indicated that the 3 SZ endophenotypes examined are not isolated markers of pathology but instead are connected. The pattern of auditory encoding group differences and the pattern of brain function-structure associations differ as a function of brain region, indicating the need for regional specificity when studying these endophenotypes, and with the presence of left STG function-structure associations in HC and UR but not in SZ perhaps reflecting disease-associated damage to gray matter that disrupts function-structure relationships in SZ.

Depression, Asthma, and Bronchodilator Response in a Nationwide Study of US Adults.

BACKGROUND: Little is known about the relation between 2 common comorbidities (depression and anxiety) and asthma or bronchodilator response (BDR). OBJECTIVE: To examine the association between depressive symptoms and asthma or BDR in US adults. METHODS: Cross-sectional study of 20,272 adults aged 20 to 79 years from the 2007-2012 National Health and Nutrition Examination Survey. Depressive symptoms were measured using the 9-item Patient Health Questionnaire, and classified as none to minimal, mild, moderate, moderately severe, and severe. Major depression (comprising moderately severe to severe symptoms) was defined as a 9-item Patient Health Questionnaire score of 15 or more. Anxiety was defined as 5 or more days feeling anxious in the previous month. Current asthma was defined as having been diagnosed with asthma by a doctor or health professional and 1 or more asthma attack in the previous year. BDR (as percentage of baseline FEV1) was measured in 1356 participants with FEV1/forced vital capacity of less than 0.70 and/or FEV1 less than 70% of predicted. Logistic or linear regression was used for the multivariable analysis. RESULTS: Depressive symptoms were significantly and linearly associated with asthma, independently of anxiety symptoms. Subjects with major depression had 3.4 times higher odds of asthma than did those with minimal or no depressive symptoms (95% CI, 2.6-4.5; P < .01). Among adults with asthma, major depression was associated with a 4.2% reduction in BDR (95% CI, -7.5% to -0.8%; P = .02). Major depression was not associated with BDR among adults without asthma. Anxiety was not associated with asthma or BDR. CONCLUSIONS: Depressive symptoms are associated with asthma in adults, independently of anxiety symptoms. Major depression is associated with reduced BDR in adults with asthma.

Exposure to gun violence and asthma among children in Puerto Rico.

BACKGROUND AND OBJECTIVES: Although community violence may influence asthma morbidity by increasing stress, no study has assessed exposure to gun violence and childhood asthma. We examined whether exposure to gun violence is associated with asthma in children, particularly in those reporting fear of leaving their home. METHODS: Case-control study of 466 children aged 9-14 years with (n = 234) and without (n = 232) asthma in San Juan, Puerto Rico. Lifetime exposure to gun violence was defined as hearing a gunshot more than once. We also assessed whether the child was afraid to leave his/her home because of violence. Asthma was defined as physician-diagnosed asthma and wheeze in the prior year. We used logistic regression for the statistical analysis. All multivariate models were adjusted for age, gender, household income, parental asthma, environmental tobacco smoke, prematurity and residential distance from a major road. RESULTS: Cases were more likely to have heard a gunshot more than once than control subjects (n = 156 or 67.2% vs. n = 122 or 52.1%, P < 0.01). In a multivariate analysis, hearing a gunshot more than once was associated with asthma (odds ratio [OR] = 1.8, 95% confidence interval [CI] = 1.1-1.7, P = 0.01). Compared with children who had heard a gunshot not more than once and were not afraid to leave their home because of violence, those who had heard a gunshot more than once and were afraid to leave their home due to violence had 3.2 times greater odds of asthma (95% CI for OR = 2.2-4.4, P < 0.01). CONCLUSIONS: Exposure to gun violence is associated with asthma in Puerto Rican children, particularly in those afraid to leave their home. Stress from such violence may contribute to the high burden of asthma in Puerto Ricans.

Stress and asthma: novel insights on genetic, epigenetic, and immunologic mechanisms.

In the United States the economically disadvantaged and some ethnic minorities are often exposed to chronic psychosocial stressors and disproportionately affected by asthma. Current evidence suggests a causal association between chronic psychosocial stress and asthma or asthma morbidity. Recent findings suggest potential mechanisms underlying this association, including changes in the methylation and expression of genes that regulate behavioral, autonomic, neuroendocrine, and immunologic responses to stress. There is also evidence suggesting the existence of susceptibility genes that predispose chronically stressed youth to both post-traumatic stress disorder and asthma. In this review we critically examine published evidence and suggest future directions for research in this field.

Chronic morphine exposure causes pronounced virus replication in cerebral compartment and accelerated onset of AIDS in SIV/SHIV-infected Indian rhesus macaques.

Six morphine-exposed and 3 control male Indian rhesus macaques were intravenously inoculated with mixture of SHIV(KU), SHIV(89.6)P and SIV/17E-Fr. These animals were followed for a period of 56 weeks in order to determine CD4 and CD8 profile, viral loads in plasma and cerebrospinal fluid (CSF), relative distribution of 3 pathogenic viruses in blood and brain, binding as well neutralizing antibody levels and cellular immune responses. Both morphine-exposed and control macaques showed a precipitous loss of CD4+ T cells; control animals, however, showed a greater tendency to recover these cells than did their morphine-exposed counterparts. The plasma and CSF viral loads were significantly higher in morphine-exposed group than those in the control group. Four morphine-exposed animals succumbed to SIV/SHIV-induced AIDS at week 18, 19, 20 and 51; post-infection with neurological disorders was found in 3 of the 4 animals. At the end of the 56-week observation period, 2 morphine-exposed and 3 control animals were still alive. All 3 viruses replicated in the blood of both morphine-exposed and control macaques, but the cerebral compartment showed a selection phenomenon; only SIV/17E-Fr and SHIV(KU) successfully crossed the blood brain barrier (BBB). The morphine-exposed macaques further favored viral migration through the blood brain barrier (BBB). SIV/17E-Fr crossed the BBB within 2 weeks in both morphine-exposed and control macaques, whereas SHIV(KU) crossed the BBB more rapidly in morphine-exposed than in control macaques. Three morphine-exposed macaques (euthanized at weeks 18, 19 and 20) did not develop cellular or humoral immune responses, whereas the other 3 morphine-exposed and 3 control macaques developed both cellular and humoral immune responses.