Hair cortisol as a novel biomarker of HPA suppression by inhaled corticosteroids in children

Background: Asthma is the most common chronic condition in childhood, and the recommended pharmacotherapy for long-term control includes the use of inhaled corticosteroids (ICS). ICS were designed to act at the site of inflammation in the lung, thus decreasing systemic absorption and reducing the risk of adverse effects associated with corticosteroid use (e.g., HPA suppression and its consequent effects). Available data show that measurement of hair cortisol successfully reflects endogenous cortisol levels. We sought to examine whether hair cortisol measurements can be used to identify HPA suppression surrounding ICS therapy in children with asthma.Methods:Hair samples were collected from the vertex posterior region of the head of 18 asthmatic children. We compared their hair cortisol concentration during ICS use with the concentration prior to ICS use.Results:During ICS therapy, median hair cortisol levels were twofold lower compared with the period of no ICS use (median 89.8 ng/g vs. 198.2 ng/g, P = 0.0015).Conclusion:Hair cortisol is an effective biomarker of the HPA suppression associated with ICS therapy and can be a sensitive tool for determining systemic effects of ICS use and monitoring adherence. Future research is needed to characterize the effect of untreated asthma on hair cortisol concentrations, if any

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure

SN1987A and the properties of neutrino burst

We reanalyze the neutrino events from SN1987A in IMB and Kamiokande-II (KII) detectors, and compare them with the expectations from simple theoretical models of the neutrino emission. In both detectors the angular distributions are peaked in the forward direction, and the average cosines are 2 sigma above the expected values. Furthermore, the average energy in KII is low if compared with the expectations; but, as we show, the assumption that a few (probably one) events at KII have been caused by elastic scattering is not in contrast with the 'standard' picture of the collapse and yields a more satisfactory distributions in angle and (marginally) in energy. The observations give useful information on the astrophysical parameters of the collapse: in our evaluations, the mean energy of electron antineutrinos is =12-16 MeV, the total energy radiated around (2-3)*1.E53 erg, and there is a hint for a relatively large radiation of non-electronic neutrino species. These properties of the neutrino burst are not in disagreement with those suggested by the current theoretical paradigm, but the data leave wide space to non-standard pictures, especially when neutrino oscillations are included.Comment: 14 pages, 5 figure

Measurement of Hair Cortisol Concentration in Pregnant Women and Children with Asthma to Assess Its Potential as a Biomarker of the Hypothalamic-pituitary-adrenal Axis

The recommended long-term treatment for asthma is inhaled corticosteroid (ICS) therapy, but research has shown that ICS use is associated with adrenal suppression. Cortisol is important physiologically and involved in fetal maturation and epigenetic programming. Hair cortisol has been used as a biomarker of the long-term effects on the hypothalamic-pituitary- adrenal (HPA) axis for a variety of psychiatric and medical conditions. This research hypothesizes that hair cortisol may be able to detect lower cortisol concentrations in pregnant women and children on ICS therapy and, therefore, have potential as a useful biomarker for possible adrenal suppression due to ICS use. This retrospective cohort study collected hair samples from children and pregnant women with asthma, treated and not treated with ICS, and those without asthma. Hair samples were segmented, based on an average growth of 1 cm/month, and analyzed using a validated ELISA method. A children's pilot study analyzed the hair prior to and during ICS therapy for the same children. The proximal 3 cm hair segment was analyzed for the large cohort of children. Hair segments for preconception, trimesters 1-3, and postpartum were analyzed for the pregnant women. The results were compared within and among the groups, as appropriate. The children's pilot study showed hair cortisol concentrations were twofold lower during ICS therapy (median 89.8 ng/g vs. 198.2 ng/g, p=0.0015, n=18). For pregnant women (n=118), asthma was a significant factor associated with lower hair cortisol. Women with asthma and consistent ICS use had significantly lower third trimester hair cortisol (47%, p=0.029) compared to Controls. The comparison of median hair cortisol concentrations among the three groups in the large cohort of children (n=460) was not significant. However, 5.3% of children on ICS therapy had hair cortisol below 2 ng/g compared to none in the control groups, which may indicate children with or at risk of adrenal suppression. The significant factors associated with hair cortisol in children were age, female sex, intranasal corticosteroid use, and BMI. Hair cortisol analysis successfully detected significantly lower hair cortisol concentrations suggesting it is a useful biomarker of the HPA axis in pregnant women and children. The correlation of hair cortisol concentrations with a diagnosis of adrenal suppression or insufficiency and the potential impact of decreased maternal cortisol in women with asthma on perinatal outcomes remain to be determined.Ph.D

Hair cortisol as a hypothalamic-pituitary-adrenal axis biomarker in pregnant women with asthma: a retrospective observational study

Abstract Background Cortisol is a hormone involved in many physiological functions including fetal maturation and epigenetic programming during pregnancy. This study aimed to use hair cortisol as a biomarker of chronic inhaled corticosteroid (ICS) exposure and assess the potential effects of asthma on the hypothalamic-pituitary-adrenal (HPA) axis in pregnant women. We hypothesized that pregnant women with asthma treated with ICS would exhibit lower hair cortisol concentrations, indicative of adrenal suppression, compared to women with asthma not using ICS and women who do not have asthma. Methods We performed an observational retrospective cohort study. Hair samples were analyzed from pregnant women with asthma, with (n = 56) and without (n = 31) ICS treatment, and pregnant women without asthma (n = 31). Hair samples were segmented based on the growth rate of 1 cm/month and analyzed by enzyme immunoassay to provide cortisol concentrations corresponding to preconception, trimesters 1–3, and postpartum. Hair cortisol concentrations were compared within and among the groups using non-parametric statistical tests. Results Hair cortisol concentrations increased across trimesters for all three groups, but this increase was dampened in women with asthma (P = 0.03 for Controls vs. ICS Treated and Controls vs. No ICS). ICS Treated women taking more than five doses per week had hair cortisol concentrations 47 % lower in third trimester than Controls. Linear regression of the third trimester hair cortisol results identified asthma as a significant factor when comparing consistent ICS use or asthma as the predictor (F(1, 25) = 9.7, P = 0.005, R2 adj = 0.257). Conclusions Hair cortisol successfully showed the expected change in cortisol over the course of pregnancy and may be a useful biomarker of HPA axis function in pregnant women with asthma. The potential impact of decreased maternal cortisol in women with asthma on perinatal outcomes remains to be determined

Hair cortisol as a hypothalamic-pituitary-adrenal axis biomarker in pregnant women with asthma: a retrospective observational study

Background: Cortisol is a hormone involved in many physiological functions including fetal maturation and epigenetic programming during pregnancy. This study aimed to use hair cortisol as a biomarker of chronic inhaled corticosteroid (ICS) exposure and assess the potential effects of asthma on the hypothalamic-pituitary-adrenal (HPA) axis in pregnant women. We hypothesized that pregnant women with asthma treated with ICS would exhibit lower hair cortisol concentrations, indicative of adrenal suppression, compared to women with asthma not using ICS and women who do not have asthma. Methods: We performed an observational retrospective cohort study. Hair samples were analyzed from pregnant women with asthma, with (n = 56) and without (n = 31) ICS treatment, and pregnant women without asthma (n = 31). Hair samples were segmented based on the growth rate of 1 cm/month and analyzed by enzyme immunoassay to provide cortisol concentrations corresponding to preconception, trimesters 1–3, and postpartum. Hair cortisol concentrations were compared within and among the groups using non-parametric statistical tests. Results: Hair cortisol concentrations increased across trimesters for all three groups, but this increase was dampened in women with asthma (P = 0.03 for Controls vs. ICS Treated and Controls vs. No ICS). ICS Treated women taking more than five doses per week had hair cortisol concentrations 47 % lower in third trimester than Controls. Linear regression of the third trimester hair cortisol results identified asthma as a significant factor when comparing consistent ICS use or asthma as the predictor (F(1, 25) = 9.7, P = 0.005, R2 adj = 0.257). Conclusions: Hair cortisol successfully showed the expected change in cortisol over the course of pregnancy and may be a useful biomarker of HPA axis function in pregnant women with asthma. The potential impact of decreased maternal cortisol in women with asthma on perinatal outcomes remains to be determined.Medicine, Faculty ofOther UBCNon UBCPediatrics, Department ofReviewedFacult

Assessment of hair cortisol as a potential biomarker for possible adrenal suppression due to inhaled corticosteroid use in children with asthma: A retrospective observational study.

BACKGROUND Inhaled corticosteroids (ICS) are the recommended long-term control therapy for asthma in children. However, concern exists regarding potential adrenal suppression with chronic ICS use. Our pilot study reported that hair cortisol in children was 50% lower during ICS therapy than prior to therapy, suggestive of adrenal suppression. OBJECTIVE To evaluate hair cortisol concentration (HCC) as a potential biomarker for possible adrenal suppression from ICS use in children with asthma. METHODS A retrospective observational study was performed at asthma clinics in Vancouver, Winnipeg, and Toronto, Canada. Children (n = 586) were recruited from July 2012 to December 2014 inclusive of those without asthma, with asthma not using ICS, and with asthma using ICS. The most recent three-month HCC was measured by enzyme immunoassay and compared among the groups. Quantile regression analysis was performed to identify factors potentially affecting HCC. RESULTS The median HCC was not significantly different among the children: No ICS (n = 47, 6.7 ng/g, interquartile range (IQR) 3.7-9.8 ng/g), ICS Treated (n = 360, 6.5 ng/g, IQR 3.8-14.3 ng/g), and Controls (n = 53, 5.8 ng/g, IQR 4.6-16.7 ng/g). 5.6% of the children using ICS had hair cortisol <2.0 ng/g compared to none in the control groups (P < .05, comparing ICS Treated (20/360) to all Controls combined (0/100)) and only half had been exposed to systemic corticosteroids. Age, sex, BMI, and intranasal corticosteroid use were significantly associated with HCC. CONCLUSIONS Results suggest HCC may be a potential biomarker for adrenal suppression as a population of children using ICS with HCC < 2.0 ng/g was identified compared to none in the control groups. Further research is needed to determine if those children have or are at risk of adrenal suppression or insufficiency

Hair cortisol as a novel biomarker of HPA suppression by inhaled corticosteroids in children

Background: Asthma is the most common chronic condition in childhood, and the recommended pharmacotherapy for long-term control includes the use of inhaled corticosteroids (ICS). ICS were designed to act at the site of inflammation in the lung, thus decreasing systemic absorption and reducing the risk of adverse effects associated with corticosteroid use (e.g., HPA suppression and its consequent effects). Available data show that measurement of hair cortisol successfully reflects endogenous cortisol levels. We sought to examine whether hair cortisol measurements can be used to identify HPA suppression surrounding ICS therapy in children with asthma.Methods:Hair samples were collected from the vertex posterior region of the head of 18 asthmatic children. We compared their hair cortisol concentration during ICS use with the concentration prior to ICS use.Results:During ICS therapy, median hair cortisol levels were twofold lower compared with the period of no ICS use (median 89.8 ng/g vs. 198.2 ng/g, P = 0.0015).Conclusion:Hair cortisol is an effective biomarker of the HPA suppression associated with ICS therapy and can be a sensitive tool for determining systemic effects of ICS use and monitoring adherence. Future research is needed to characterize the effect of untreated asthma on hair cortisol concentrations, if any

Low energy radioactivity BG model in Super-Kamiokande detector from SK-IV data

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