Dataset Information

Obesity-related asthma in children: A role for vitamin D.

ABSTRACT: Excess adipose tissue predisposes to an enhanced inflammatory state and can contribute to the pathogenesis and severity of asthma. Vitamin D has anti-inflammatory properties and low-serum levels are seen in children with asthma and in children with obesity. Here we review the intersection of asthma, obesity, and hypovitaminosis D in children. Supplementation with vitamin D has been proposed as a simple, safe, and inexpensive adjunctive therapy in a number of disease states. However, little research has examined the pharmacokinetics of vitamin D and its therapeutic potential in children who suffer from obesity-related asthma.

SUBMITTER: O'Sullivan BP

PROVIDER: S-EPMC8341445 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Obesity-related asthma in children: A role for vitamin D.

O'Sullivan Brian P BP James Laura L Majure Joseph M JM Bickel Scott S Phan Ly-Thao LT Serrano Gonzalez Monica M Staples Heather H Tam-Williams Jade J Lang Jason J Snowden Jessica J

Pediatric pulmonology 20201208 2

Excess adipose tissue predisposes to an enhanced inflammatory state and can contribute to the pathogenesis and severity of asthma. Vitamin D has anti-inflammatory properties and low-serum levels are seen in children with asthma and in children with obesity. Here we review the intersection of asthma, obesity, and hypovitaminosis D in children. Supplementation with vitamin D has been proposed as a simple, safe, and inexpensive adjunctive therapy in a number of disease states. However, little resea ...[more]

PMID: 32930511

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Project description:Background and objectiveVitamin D insufficiency is common in several pediatric diseases including obesity and asthma. Little data exist describing the pharmacokinetics of oral vitamin D in children or the optimal dosing to achieve therapeutic 25(OH)D targets. Describe the pharmacokinetics of oral Vitamin D in children with asthma.MethodsThis was a multi-center, randomized, open-label, oral supplementation study to describe the pharmacokinetics of vitamin D in children aged 6-17 years who have asthma and were overweight/obese. Participants had a serum 25(OH)D concentration between 10 and < 30 ng/mL at baseline. In Part 1 of the study, we assessed four 16-week dosing regimens for their ability to achieve 25(OH)D concentrations ≥ 40 ng/mL. Using serial serum 25(OH)D sampling over 28 weeks, we created a population pharmacokinetic model and performed dosing simulations to achieve 25(OH)D concentrations ≥ 40 ng/mL. In Part 2, the optimal regimen chosen from Part 1 was compared (2:1) to a standard-of-care control dose (600 international units [IU] daily) over 16 weeks. A final population pharmacokinetic model using both parts was developed to perform dosing simulations and determine important co-variates in the pharmacokinetics of vitamin D.ResultsBased on empiric and simulation data, the daily dose of 8000 IU and a loading dose of 50,000 IU were chosen; this regimen raised 25(OH)D concentrations above 40 ng/mL in the majority of participants while avoiding concentrations > 100 ng/mL. A 50,000-IU loading dose led to faster achievement of 25(OH)D therapeutic concentrations (≥ 40 ng/mL). The estimated median (5th-95th percentiles) apparent clearance of vitamin D from the final population pharmacokinetic model was 0.181 (0.155-0.206) L/h. The body mass index z-score was a significant covariate on apparent clearance and was associated with a significantly decreased median half-life in 25(OH)D (body mass index z-score 1.00-1.99: 97.7 days, body mass index z-score 2.00-2.99: 65.9 days, body mass index z-score ≥ 3.00: 39.1 days, p < 0.001).ConclusionsObesity impacts vitamin D clearance and the half-life, but serum concentrations > 40 ng/mL can be reached in most children using a loading dose of 50,000 IU followed by a daily dose of 8000 IU.Clinical trial registrationClinicalTrials.gov identifier number NCT03686150.

Project description:This study was designed to investigate the correlation of vitamin D receptor (VDR) gene polymorphism with bronchial asthma in children. Seventy patients admitted to Daqing Longnan Hospital and diagnosed as bronchial asthma for the first time from April 2015 to May 2017 were selected as observation group. Patients received routine treatment and intervention. Seventy healthy subjects admitted to hospital during the same period were enrolled as the control group. Vitamin D gene polymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism assay; the levels of total serum immunoglobulin E (IgE) in the two groups were determined by electrochemiluminescence immunoassay; lung function levels in patients were measured using PowerCube (Germany) pulmonary function instrument before and after treatment, and the relationship between VDR gene polymorphism and lung function in children with bronchial asthma was analyzed. The difference in comparison of base frequency of rs1544410 locus of VDR gene had no statistical significance between the two groups (P>0.05). The locus CC frequency of rs7975232 of VDR gene in observation group was lower in the observation group than that in the control group (P<0.05); the locus AC and AA frequencies of rs7975232 of VDR gene were higher in the observation group than those in the control group (P<0.05). The level of vitamin D was lower in the observation group than that in the control group (P<0.05); the level of total serum IgE was higher in the observation group than that in the control group (P<0.05). The forced expiratory volume in 1 sec (FEV1), peak expiratory flow (PEF) and the ratio of FEV1 to forced vital capacity (FVC) in children with bronchial asthma in the observation group were higher after treatment than those before treatment (P<0.05). The correlation research displayed that VDR gene polymorphism was negatively correlated with lung function levels in children with bronchial asthma (P<0.05). The results showed that children with bronchial asthma are often accompanied by different degrees of changes in VDR gene polymorphism, which is negatively correlated with the severity of asthma, so vitamin D should be strengthened to ameliorate the prognosis of children.

Dataset Information

Obesity-related asthma in children: A role for vitamin D.

Publications

Obesity-related asthma in children: A role for vitamin D.

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