Basal or stress-induced cortisol--论文代写范文精选

唾液皮质醇评估一天三次，收到了他们的唾液样本。压力测试包括两个部分。在第一部分中,青少年被要求准备一个6分钟的演讲关于自己和生活,在摄像机前进行演讲。紧随其后的是一个三分钟的插曲，青少年不被允许说话。

Abstract
We examined the association between: 1) cortisol levels and asthma or asthma development; 2) cortisol levels upon stress and asthma. In addition, we performed a post hoc meta-analysis on results from the literature.Cortisol, cortisol upon stress, asthma (doctor diagnosis of asthma and/or symptoms and/or treatment in the past 12 months) and asthma development (asthma at a specific survey while not having asthma at the previous survey(s)) were assessed in the TRAILS study (n=2230, mean age at survey 1 11 years, survey 2 14 years and survey 3 16 years). Logistic regression models were used to study associations between: 1) cortisol (cortisol awakening response, area under the curve (AUC) with respect to the ground (AUCg) or with respect to the increase (AUCi), and evening cortisol) and asthma or asthma development; 2) cortisol upon stress (AUCg or AUCi) and asthma. The meta-analyses included nine case–control articles on basal cortisol in asthma.

No significant association was found between: 1) cortisol and asthma (age 11 years) or asthma development (age 14 or 16 years); 2) cortisol upon stress and asthma (age 16 years). The meta-analysis found lower morning and evening cortisol levels in asthmatics compared to non-asthmatics; however, the summary estimates were not significant.

Itroduction
Asthma is a chronic inflammatory airway disorder, with many pathways involved in its aetiology. Psychosocial stress can trigger asthma exacerbations [1] and it is suggested that psychosocial stress is also involved in asthma development [2–6]. Psychosocial stress activates the hypothalamic–pituitary–adrenal (HPA) axis leading to an increase in cortisol secretion on top of the circadian rhythm of cortisol secretion [7]. Cortisol influences the activity of many systems in the human body, including the immune system [8]. Since cortisol induces a shift in the T-helper cell 1 (Th1)/Th2 balance of peripheral blood mononuclear cells towards a predominantly Th2 response [7], an alteration in HPA axis function is suggested to be one of the potential mechanisms via which psychosocial stress leads to asthma development.

Several cross-sectional studies have investigated cortisol levels in asthmatics and non-asthmatics, with diverse results. Not only have lower [9–11] or normal cortisol levels [12–16] been reported in asthmatics compared to non-asthmatics, but also higher [17, 18] cortisol levels have been reported. Since all these studies investigated different aspects of the circadian pattern of cortisol secretion in relation to asthma, their results are incomparable.

Because psychosocial stress triggers asthma exacerbations [1], it could be argued that dysfunctions of the HPA axis become more evident under stressful conditions. One previous study investigated both basal cortisol levels and cortisol responses to a laboratory stress task (Trier Social Stress Test) in asthmatics and non-asthmatics [12]. Although this study found no differences in basal cortisol levels between asthmatics and non-asthmatics, cortisol levels in response to a laboratory stress task were lower in asthmatics compared to non-asthmatics, indicating hyporesponsiveness of the HPA axis which only became evident under exposure to stress. Because of the small sample size of this study (asthmatics n=17, non-asthmatics n=18) these findings need to be replicated in a larger sample size.

In conclusion, results from previous cross-sectional studies have suggested that asthmatics have an altered HPA axis function. However, it is unclear whether this alteration in HPA axis function precedes the development of asthma or is the result of asthma. To our knowledge, no previous longitudinal study has been performed to investigate alterations in HPA axis function as an aetiologic mechanism contributing to the development of asthma. We hypothesised that: 1) there is a cross-sectional association between low cortisol and asthma; 2) low cortisol levels precede the development of asthma; and 3) adolescents with asthma have a blunted cortisol response upon exposure to stress.

Study participants
The Tracking Adolescents' Individual Lives Survey (TRAILS) is a prospective cohort study among Dutch adolescents. A detailed description of the sampling procedure and methods has been published previously [19]. Briefly, the TRAILS target sample involved 10–12-year-olds (born between October 1, 1989 and September 30, 1990 for the first two municipalities or between October 1, 1990 and September 30, 1991 for the last three municipalities) living in five municipalities in the north of the Netherlands, including both urban and rural areas. A total of 135 primary schools were invited to participate, encompassing 3483 eligible children. Of the 135 schools 13 refused to participate, resulting in the exclusion of 338 children. Of the 3145 remaining eligible children, 210 were excluded because they were either unable to participate or incapable of participating due to severe mental retardation or due to a serious physical illness or handicap, or if no Dutch-speaking parent or parent surrogate was available (Turkish and Moroccan parents who were unable to speak Dutch were interviewed in their own language). After intensive recruitment efforts (including telephone calls, reminder letters and home visits), a total of 2230 children (76.0%) were included in the study at baseline. So far, three assessment surveys have been completed (n=2230, mean±SD age 11±0.6 years; n=2149, 14±0.5 years; n=1816, 16±0.7 years).

Cortisol collection at age 11 years
Cortisol was assessed from saliva taken at three times during one day: shortly after waking up (Cort07.00); 30 minutes after waking up (Cort07.30); and at 20.00 h (Cort20.00) at age 11 years. Saliva samples were received from 1768 adolescents (details on collection and assays have been published previously [20]). Non-responders did not differ from responders in terms of sex; non-responders were slightly older (mean age 11.2 versus 11.1 years) [20].

Stress test and cortisol collection at age 16 years
At age 16 years, 715 adolescents performed a stress test, based on (but not identical to) the Trier Social Stress Task [21]. The stress test consisted of two parts. In the first part, the adolescents were instructed to prepare a 6-min speech about themselves and their lives and deliver this speech in front of a video camera. The speech was followed by a 3-min interlude in which the adolescents were not allowed to speak. In the second part, adolescents were asked to perform a 6-min mental arithmetic task. The adolescents were instructed to repeatedly subtract the number 17 from a larger sum, starting with 13 287. The mental arithmetic task was followed by a 3-min period of silence, after which the adolescents were debriefed about the experiment. Adolescents with a high risk of mental health problems were over-represented in this population (details in the online supplementary material).

Cortisol was assessed from saliva collected prior to the stress test (Cort1), directly after (Cort2), and 20 minutes (Cort3) and 40 minutes (Cort4) after the stress test (details on collection and assays have been published previously [22]). Non-responders did not differ from responders in terms of sex; non-responders were slightly older (mean age 16.4 versus 16.1 year) [23].

Asthma
Data on asthma were collected via questionnaires at age 11, 14 and 16 years [24]. Asthma was defined as having a doctor diagnosis (Did a physician give your child a diagnosis of asthma?) (assessed at age 11 years) and/or symptoms and/or treatment for asthma in the past 12 months (assessed at all surveys). Asthma development was defined as having asthma at a specific survey, while not having asthma at all previous surveys.

Statistical analysis
Area under the curve with respect to the ground (AUCg) (11 years), AUCg (stress-induced), area under the curve with respect to the increase (AUCi) (11 years) and AUCi (stress-induced) were calculated (formulae are in the online supplementary material) [20, 25, 26]. To correct for skewed distributions, cortisol values above or below 3×SD of the mean were regarded as outliers and excluded, after which all cortisol values were transformed to z-scores to normalise the data in order to be able to compare results on different cortisol measures. Including adolescents with cortisol values below or above 3×SD of the mean in the analysis did not change the results.

Logistic regression analyses were used to study associations between basal cortisol and asthma at age 11 years and between basal cortisol and asthma development at age 14 and 16 years. All analyses were adjusted for sex and quadratic effect of sampling month, since these are known to be associated with cortisol values [20] and/or asthma [24] in this cohort.

Furthermore, logistic regression analyses were used to study associations between cortisol response to stress test and asthma at age 16 years, adjusted for sex and sampling weights to correct for the oversampling of adolescents with a high risk of mental health problems, and in case of AUCi (stress-induced) also for baseline cortisol level (Cort1) (online supplementary material).

All analyses were repeated adjusting for depression (affective problems scale of the Youth Self-Report [27]), physical activity and smoking in case of basal cortisol, and additionally adjusting for age, body mass index (BMI) and oral contraceptive use in case of stress-induced cortisol. A previous study in this cohort showed that age and BMI were not related to basal cortisol [20].To examine the impact of (inhaled and oral) steroid treatment on the above studied associations, sensitivity analyses were performed by excluding adolescents who used corticosteroid medication at age 11 years, in case of basal cortisol, or at age 16 years, in case of stress-induced cortisol.Statistical analyses were performed using SPSS Version 18.0 (SPSS Inc., Chicago, IL, USA). p-values <0.05 (tested two-sided) were considered to be significant.

This study is the first one investigating the research question of whether alterations in HPA-axis function precede asthma development. Neither asthma development at age 14 years, nor asthma development at age 16 years was significantly associated with basal cortisol levels upon awakening or evening cortisol level measured at age 11 years. Therefore, we did not find evidence that an alteration in HPA axis function precedes asthma development between ages 14 and 16 years. However, this study cannot rule out that alterations in HPA axis function precede adult-onset asthma.

Contrary to a previous study that showed a blunted cortisol response to stress in asthmatics [12], our study did not find such an association. Differences in study population and sample sizes could explain these inconsistent findings. The previous study included children (n=35, age 7–13 years), whereas our study included adolescents (n=715, age 15–17 years). Other explanations could involve differences in the time points at which cortisol was measured, and differences in the way the associations between cortisol levels to a stress task and asthma were studied. The previous study measured cortisol 35, 25, 15 and 1 min before, and 10, 20, 30 and 40 min after the stress test and compared individual time points between asthmatic and healthy children. Our study measured cortisol at the start, directly after, and 20 and 40 min after the end of the stress test and investigated whether AUC was associated with asthma. When investigating individual cortisol levels measured at 20 and 40 min after the stress test in our study, we found no differences in cortisol levels between asthmatics and non-asthmatics (U=12 731.0, p=0.98 and U=11 453.0, p=0.39, respectively). Therefore, our data suggest that cortisol responses upon exposure to stress are not associated with asthma.(论文代写)

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