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（由适用提供）：虽然将产前压力与儿童过敏和喘息的证据持续增长，但潜在的机制仍然很少了解。动物研究的数据很大程度上表明，压力通过破坏关键的监管系统的破坏，尤其侧重于改变皮质醇产生索引指数索引的母乳和婴儿下丘脑 - 下丘脑 - 垂体 - 肾上腺（HPA）轴。人们认为，应压力引起的母亲HPA轴的变化被认为会影响后代风险，部分原因是遗传激素（例如皮质醇）的临时通过，这可能会对儿童的HPA轴从子宫开始并持续出生后持续。 HPA功能中断，要么 母亲产前或婴儿，可能会导致儿童患过敏或哮喘的免疫变化。这是结合产前和产后早期HPA轴测量的研究，可以洞悉与早期呼吸系统疾病产前应激所吸引的编程有关的机制。由于在评估孕妇和婴儿的皮质醇生产方面的独特挑战上，证明动物中记录在动物中的编程机制是否更加困难。为了响应慢性应激，HPA轴可能比正常体内平衡的水平更高或更低。但是，评估流行病学研究中HPA轴的最佳方法尚不清楚。研究很大程度上取决于唾液皮质醇节奏的指标必要的重复措施，例如皮质醇觉醒反应，昼夜皮质醇坡度和日常输出（曲线下的面积； AUC）。单个唾液样品反映了在几分钟到几个小时内皮质醇的产生；唾液AUC和坡度代表几天内的暴露。唾液皮质醇测量也应遵守由于情绪状态，采样日的压力和其他因素（例如睡眠，体育锻炼）所致的情况差异。已经提出了对数周至数月的水平的皮质醇水平进行的整合测量，以捕获HPA轴的长期（特征样）功能。早期证据表明，皮质醇可能是对HPA轴功能的有效测量。虽然一次性头发样品具有优势，但主要限制是反复的唾液抽样提供的动态信息丢失。我们建议，由于这些方法涉及与HPA轴类性状功能相关的不同方面，因此，一种复合指数既结合了综合的头发测量值和重复的唾液抽样中获得的信息，可以更好地指示影响胎儿免疫和肺部发育的荷尔蒙环境。这些分析将采用先进的统计方法来探索新颖的计算方法，以表征孕妇和婴儿的慢性皮质醇产生，并评估它们在建模HPA功能的压力引起的变化以及考虑衍生的皮质溶质生物标志物的预测呼吸呼吸/过敏性的预测因素时，它们是否具有优于更常规的摘要措施。这将是第一项将头发和唾液皮质醇视为产前应激效应的复合生物标志物测量的研究。