Advancing use of hair and salivary cortisol in stress-asthma research

推进头发和唾液皮质醇在应激性哮喘研究中的应用

• 批准号: 8986805
• 负责人: Rosalind J Wright
• 金额: $ 21.29万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8986805
• 关键词: Address; Adrenal Glands; Adult; Age; Allergic; Animal Model; Animals; Area Under Curve; Asthma; Biological Assay; Biological Markers; Birth; Child; Child Development; Child health care; Childhood; Chronic; Chronic stress; Circadian Rhythms; Computing Methodologies; Data; Development; Environment; Epidemiologic Studies; Epidemiology; Fetal Development; Hair; Health; Homeostasis; Hormonal; Hormones; Hour; Human; Human Development; Hydrocortisone; Hypersensitivity; Hypothalamic structure; Immune; Individual; Infant; Joints; Life; Life Cycle Stages; Link; Lung diseases; Measures; Methods; Modeling; Moods; Mothers; Outcome; Output; Phenotype; Physical activity; Pituitary Gland; Pregnancy; Pregnant Women; Production; Reporting; Research; Research Personnel; Risk; Rodent; Saliva; Salivary; Sampling; Sleep; Statistical Methods; Stress; System; Time; Validation; Wheezing; care giving burden; disorder risk; fetal; fetal programming; human data; hypothalamic-pituitary-adrenal axis; in utero; indexing; insight; intergenerational; lung development; maternal stress; nonhuman primate; novel; offspring; postnatal; pregnant; prenatal; prenatal health; prenatal stress; programs; psychological outcomes; respiratory; respiratory health; response; stressor; trait

 DESCRIPTION (provided by applicant): While evidence linking prenatal stress to childhood allergy and wheeze continues to grow, underlying mechanisms remain poorly understood. Data largely from animal studies suggest that stress influences fetal development through disruption of key regulatory systems with particular focus on altered maternal and infant hypothalamic-pituitary-adrenal (HPA) axis functioning indexed by cortisol production. Stress-induced changes to the mother's HPA axis are thought to influence offspring risk in part through trans-placental passage of maternal hormones (e.g., cortisol) which may have programming effects on the child's HPA axis starting in utero and persisting after birth. Disrupted HPA functioning, either in mothers prenatally or in infants, may result in immune changes that predispose children to allergy or asthma. Thus, studies incorporating HPA axis measures in the prenatal and early postnatal period may provide insight into mechanisms involved in prenatal stress-elicited programming of early respiratory disease. Demonstrating whether the programming mechanism documented in animals is operating in humans has been more difficult due to unique challenges to assessing cortisol production in pregnant women and infants. In response to chronic stress, the HPA axis may operate at higher or lower levels than in normal homeostasis. Best methods for assessing the HPA axis in epidemiological studies remain unclear however. Research has relied largely on indices of salivary cortisol rhythms necessitating repeated measures, e.g., cortisol awakening response, diurnal cortisol slope, and daily output (area under the curve; AUC). Individual saliva samples reflect cortisol production over minutes to hours; salivary AUC and slope represent exposure over days. Salivary cortisol measures are also subject to situational variance due to mood states, stressors on sampling days, and other factors (e.g., sleep, physical activity). An integrated measure of cortisol levels from hair, which reflects level over weeks to months, has been proposed to capture more long term (trait-like) functioning of the HPA axis. Early evidence suggests that hair cortisol may be a valid measure of HPA axis functioning. While a one-time hair sample offers advantages, a major limitation is the loss of dynamic information provided with repeated saliva sampling. We propose that since these approaches tap into different aspects relevant to trait-like functioning of the HPA axis, a composite index incorporating both the integrated hair measure and information available from repeated saliva sampling may provide a better indicator of the hormonal milieu influencing fetal immune and lung development. These analyses will apply advanced statistical approaches to explore novel computational methods for characterizing chronic cortisol production in pregnant women and infants and assess whether they offer advantages over more conventional summary measures when modeling stress-elicited changes in HPA functioning as well as considering the derived cortisol biomarkers as predictors of child respiratory/allergic outcomes. This will be the first study to consider hair and salivary cortisol as a composite biomarker measure of prenatal stress effects.

 描述（由申请人提供）：虽然将产前压力与儿童过敏和喘息联系起来的证据不断增加，但主要来自动物研究的数据表明，压力通过破坏关键的调节系统（特别是母亲和儿童）来影响胎儿发育。婴儿下丘脑-垂体-肾上腺 (HPA) 轴功能以皮质醇的产生为指标，压力引起的母亲 HPA 轴的变化被认为部分通过胎盘通道影响后代的风险。母体激素（例如皮质醇）可能对孩子的 HPA 轴产生编程影响，这种影响从子宫内开始并在出生后持续存在。 因此，在产前和产后早期纳入 HPA 轴测量的研究可能会深入了解产前应激引发的早期呼吸道疾病的机制。由于评估孕妇和婴儿皮质醇产生的独特挑战，证明动物记录的编程机制是否在人类身上发挥作用变得更加困难。为了应对慢性压力，HPA 轴的运作水平可能高于或低于人类。然而，流行病学研究中评估 HPA 轴的最佳方法仍不清楚，研究很大程度上依赖于需要重复测量的唾液皮质醇节律指标，例如皮质醇觉醒反应、昼间皮质醇斜率和每日输出量（曲线下面积； AUC）。唾液 AUC 反映了皮质醇的产生情况；唾液 AUC 和斜率代表了数天内的暴露情况。已提出对头发皮质醇水平的综合测量，反映了数周至数月的水平，以捕获更长期的（类似特征的）情绪状态、采样日的压力源和其他因素。早期证据表明，头发皮质醇可能是衡量 HPA 轴功能的有效指标，虽然一次性头发样本具有一定的优势，但我们认为，重复唾液采样所提供的动态信息会丢失。由于这些方法利用了不同的与 HPA 轴的性状功能相关的方面，结合综合毛发测量和重复唾液采样获得的信息的综合指数可以提供影响胎儿免疫和肺部发育的激素环境的更好指标。这些分析将应用先进的统计。探索新的计算方法来表征孕妇和婴儿的慢性皮质醇产生，并评估在对压力引起的 HPA 功能变化进行建模以及考虑衍生的皮质醇生物标志物作为儿童的预测因子时，它们是否比更传统的汇总测量具有优势这将是第一项将头发和唾液皮质醇视为产前应激影响的复合生物标志物的研究。