Rosalind J. Wright

The impact of stress on the development and expression of atopy

Purpose of reviewBiological hypersensitivity to environmental stimuli is a fundamental feature of atopy predisposing to a number of clinically expressed disorders including allergic rhinitis, atopic dermatitis or eczema, and allergic asthma. There is provocative evidence that psychological stress constitutes an increased risk for atopy. This risk is thought to be mediated by the effects of stress on neuroimmunoregulation which in turn modulates the hypersensitivity response. The primary objective is to review recent evidence updating our understanding of the role for psychological stress in atopy. Recent findingsThe Th1–Th2 paradigm has been central to interpreting quantitative differences in cytokine expression in response to environmental stimuli like stress. Here we argue that examination of other mechanisms (e.g. oxidative stress pathways, glucocorticoid resistance, nerve–mast cell interactions, intestinal dysbiosis) and a broader range of cytokines and neuropeptides produced by cells both within and outside the immune system may better delineate the true complexity of the underlying mechanisms linking stress to allergic sensitization and asthma. The role of genetics and gene by environment interactions – based on evolving knowledge of candidate genes that may be relevant to both the stress response in general and pathways linked specifically to atopy – is also discussed. SummaryPsychological stress may be conceptualized as a social pollutant that, when ‘breathed’ into the body, may disrupt biological systems related to inflammation through mechanisms potentially overlapping with those altered by physical pollutants and toxicants. Abbreviations HPA: hypothalamic–pituitary–adrenocortical; SAM: sympathetic and adrenomedullary; TNF: tumor necrosis factor.

Effects of early-life exposure to allergens and bacteria on recurrent wheeze and atopy in urban children

BACKGROUND Wheezing illnesses cause major morbidity in infants and are frequent precursors to asthma. OBJECTIVE We sought to examine environmental factors associated with recurrent wheezing in inner-city environments. METHODS The Urban Environment and Childhood Asthma study examined a birth cohort at high risk for asthma (n = 560) in Baltimore, Boston, New York, and St Louis. Environmental assessments included allergen exposure and, in a nested case-control study of 104 children, the bacterial content of house dust collected in the first year of life. Associations were determined among environmental factors, aeroallergen sensitization, and recurrent wheezing at age 3 years. RESULTS Cumulative allergen exposure over the first 3 years was associated with allergic sensitization, and sensitization at age 3 years was related to recurrent wheeze. In contrast, first-year exposure to cockroach, mouse, and cat allergens was negatively associated with recurrent wheeze (odds ratio, 0.60, 0.65, and 0.75, respectively; P ≤ .01). Differences in house dust bacterial content in the first year, especially reduced exposure to specific Firmicutes and Bacteriodetes, was associated with atopy and atopic wheeze. Exposure to high levels of both allergens and this subset of bacteria in the first year of life was most common among children without atopy or wheeze. CONCLUSIONS In inner-city environments children with the highest exposure to specific allergens and bacteria during their first year were least likely to have recurrent wheeze and allergic sensitization. These findings suggest that concomitant exposure to high levels of certain allergens and bacteria in early life might be beneficial and suggest new preventive strategies for wheezing and allergic diseases.

Elevated Midpregnancy Corticotropin-Releasing Hormone Is Associated with Prenatal, But Not Postpartum, Maternal Depression

CONTEXT Elevated hypothalamic CRH has been implicated in melancholic major depression in nonpregnant individuals, but the role of placental CRH in maternal prenatal and postpartum depression is largely unexplored. OBJECTIVE The objective of the study was to examine the association of maternal midpregnancy plasma CRH levels with prenatal and postpartum depression. PARTICIPANTS The study included 800 participants in Project Viva, a pregnancy and childhood cohort. METHODS CRH levels were analyzed from blood samples obtained at mean 27.9 wk gestation (+/- 1.3 sd; range 24.6-37.4 wk) and were normalized on the logarithmic scale. Depression was assessed with the Edinburgh Postpartum Depression Scale (range 0-30 points) in midpregnancy and at 6 months postpartum. We used logistic regression to estimate the odds of scoring 13 or more points on the Edinburgh Postpartum Depression Scale as indicative of major or minor depression. RESULTS Seventy (8.8%) and 46 (7.5%) women had prenatal and postpartum depression symptoms, respectively. Mean log CRH was 4.93 (+/- 0.62 sd). After adjusting for confounders, an sd increase in log CRH was associated with nearly 50% higher odds of prenatal depression symptoms (odds ratio 1.48, 95% confidence interval 1.14-1.93). Higher CRH levels during pregnancy were unassociated with greater risk of postpartum depressive symptoms. In fact, there was a suggestion that prenatal CRH levels might be inversely associated with risk of postpartum depressive symptoms (odds ratio 0.82, 95% confidence interval 0.58-1.15). CONCLUSIONS Elevated placental CRH levels in midpregnancy are positively associated with risk of prenatal depression symptoms but not postpartum depression symptoms.

Breathing easy: A prospective study of optimism and pulmonary function in the normative aging study

Although there is good evidence that emotions are associated with chronic airways obstruction, evidence for the influence of psychological factors on the level and decline of pulmonary function is sparse. Optimism has been linked to enhanced well-being, whereas pessimism has been identified as a risk factor for poor physical health. This investigation examines prospectively the effects of optimism versus pessimism on pulmonary function. Data are from the Veterans Administration Normative Aging Study, an ongoing cohort of older men. In 1986, 670 men completed the revised Minnesota Multiphasic Personality Inventory from which we derived the bipolar Revised Optimism-Pessimism Scale. During an average of 8 years of follow-up, an average of 3 pulmonary function exams were obtained. Men with a more optimistic explanatory style had significantly higher levels of forced expiratory volume in 1 sec (FEV1) and forced vital capacity (both p > .01). Interactions between time and optimism suggested that rate of decline in FEV1 over time was slower in men with a more optimistic explanatory style relative to men who were more pessimistic. These data are the first to link optimism with higher levels of pulmonary function and slower rate of pulmonary function decline in older men, a protective effect that is independent of smoking.

Parental Characteristics, Somatic Fetal Growth, and Season of Birth Influence Innate and Adaptive Cord Blood Cytokine Responses

BACKGROUND Immunologic responses at birth likely relate to subsequent risks for allergic diseases and wheezing in infancy; however, the influences of parental characteristics and prenatal factors on neonatal immune responses are incompletely understood. OBJECTIVE This study investigates potential correlations between urban parental, prenatal, and perinatal factors on innate and adaptive stimuli-induced cytokine responses. METHODS Five hundred sixty and 49 children of parents with and without allergic disease or asthma, respectively, were enrolled into a prospective birth cohort study (Urban Environment and Childhood Asthma). Cord blood mononuclear cells were incubated with innate and adaptive immune stimuli, and cytokine responses (ELISA) were compared with season of birth, parental characteristics, in utero stressors, and fetal growth. RESULTS Many cytokine responses varied by season of birth, including 2-fold to 3-fold fluctuations with specific IFN-alpha and IFN-gamma responses. Birth weight was inversely associated with IFN-gamma responses to respiratory syncytial virus (R = -0.16), but positively associated with IL-8 responses to a variety of innate stimuli (R = 0.08-0.12). Respiratory syncytial virus-induced cytokine responses were 21% to 54% lower in children of mothers with asthma. Cytokine responses were generally lower in babies born to parents with allergy/asthma. CONCLUSIONS Innate cytokine responses are associated with parental allergic or airway disease, somatic fetal growth, ethnicity, and season of birth. Collectively, these findings suggest that urban prenatal exposures and familial factors affect the development of the fetal immune system.

The Urban Environment and Childhood Asthma (URECA) birth cohort study: design, methods, and study population

BackgroundThe incidence and morbidity of wheezing illnesses and childhood asthma is especially high in poor urban areas. This paper describes the study design, methods, and population of the Urban Environment and Childhood Asthma (URECA) study, which was established to investigate the immunologic causes of asthma among inner-city children.Methods and ResultsURECA is an observational prospective study that enrolled pregnant women in central urban areas of Baltimore, Boston, New York City, and St. Louis and is following their offspring from birth through age 7 years. The birth cohort consists of 560 inner-city children who have at least one parent with an allergic disease or asthma, and all families live in areas in which at least 20% of the population has incomes below the poverty line. In addition, 49 inner-city children with no parental history of allergies or asthma were enrolled. The primary hypothesis is that specific urban exposures in early life promote a unique pattern of immune development (impaired antiviral and increased Th2 responses) that increases the risk of recurrent wheezing and allergic sensitization in early childhood, and of asthma by age 7 years. To track immune development, cytokine responses of blood mononuclear cells stimulated ex vivo are measured at birth and then annually. Environmental assessments include allergen and endotoxin levels in house dust, pre- and postnatal maternal stress, and indoor air nicotine and nitrogen dioxide. Nasal mucous samples are collected from the children during respiratory illnesses and analyzed for respiratory viruses. The complex interactions between environmental exposures and immune development will be assessed with respect to recurrent wheeze at age 3 years and asthma at age 7 years.ConclusionThe overall goal of the URECA study is to develop a better understanding of how specific urban exposures affect immune development to promote wheezing illnesses and asthma.

Lifetime maternal experiences of abuse and risk of pre-natal depression in two demographically distinct populations in Boston

BACKGROUND To investigate lifetime history of interpersonal abuse and risk of pre-natal depression in socio-economically distinct populations in the same city. METHODS We examined associations of physical and sexual abuse with the risk of pre-natal depression in two cohorts in the Boston area, including 2128 participants recruited from a large urban- and suburban-managed care organization (Project Viva) and 1509 participants recruited primarily from urban community health centres (Project ACCESS). Protocols for the studies were designed in parallel to allow us to merge data to enhance ethnic and socio-economic diversity in the combined sample. In mid-pregnancy, the Personal Safety Questionnaire and Edinburgh Postnatal Depression Scale (EPDS) were administered in both cohorts. An EPDS score ≥ 13 indicated probable pre-natal depression. Logistic regression was used to estimate the odds ratio (OR) of pre-natal depression associated with lifetime abuse history. RESULTS Project ACCESS participants were twice as likely as Project Viva participants to report symptoms consistent with pre-natal depression: 22% of Project ACCESS participants had EPDS scores ≥ 13, compared with 11% of Project Viva participants. Fifty-seven percent of women in ACCESS and 46% in Viva reported lifetime physical and/or sexual abuse. In merged analysis, women reporting lifetime physical or sexual abuse had an OR for mid-pregnancy depression of 1.63 [95% confidence interval (95% CI): 1.29-2.07], adjusted for age and race/ethnicity. Lifetime histories of physical abuse [OR 1.48 (95% CI 1.15-1.90)] and sexual abuse [OR 1.68 (95% CI 1.24-2.28)] were independently associated with pre-natal depression. When child/teen, pre-pregnancy adult and pregnancy life periods were considered simultaneously, abuse in childhood was independently associated with an OR of 1.23 (95% CI 1.00-1.59), pre-pregnancy adult abuse with an OR of 1.70 (95% CI 1.31-2.21) and abuse during pregnancy with an OR of 1.77 (95% CI 1.14-2.74). Further adjustment for childhood socio-economic position made no material difference, and there were no clear interactions between abuse and adult socio-economic position. CONCLUSIONS Physical and sexual abuse histories were positively associated with pre-natal depression in two economically and ethnically distinct populations. Stronger associations with recent abuse may indicate that the association of abuse with depression wanes with time or may result from less accurate recall of remote events.

Gender and asthma

The preponderance of epidemiologic evidence demonstrates disparities in asthma burden when comparing females and males. Males develop asthma at a younger age than do females [1], and the incidence of asthma generally is reported to be higher in boys throughout preadolescence, resulting in a 2:1 male predominance in childhood [2,3]. The increased risk for asthma and wheeze among boys reverses at puberty, however, after which the incidence rate of asthma in girls increases, resulting in a 2:1 female predominance among adults [4–6]. These findings are demonstrated by De Marco and colleagues in a retrospective analysis of data from the European Respiratory Health Survey (Fig. 1). In infancy, girls have a lower risk for developing asthma than do boys, with a rate ratio (RR) for girls compared with boys ranging from 0.74 to 0.56 among children 10 years old or younger. At the time of puberty, the risk equalizes in both sexes (RR, 0.84; 95% confidence interval [CI], 0.66–1.12), and after puberty the risk is significantly higher in women than in men, ranging from 1.38 to 5.91 [7]. Among adults aged 25 to 74, being female has been shown to be the strongest predictor of incident cases of asthma [8]. There is evidence for a disparate increase in the prevalence of asthma between men and women. Between 1982 and 1992, the prevalence among US women increased 82% (from 2.9% to 5.4%) compared with an increase of 29% among men (4.0% to 5.1%) [9]. Other investigators suggest that the reversal in the prevalence rates of asthma among young adults is caused by a higher remission rate among boys and a higher incidence rate among girls [10–14].