Obesity-related asthma in children: A role for vitamin D.
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ABSTRACT:
SUBMITTER: O'Sullivan BP
PROVIDER: S-EPMC8341445 | biostudies-literature |
REPOSITORIES: biostudies-literature
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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.
| S-EPMC10582143 | biostudies-literature
Project description:Obesity is an important public health problem. WHO estimates that about 39 million children younger than 5 years of age are overweighted or obese. On the other hand, asthma is the most prevalent chronic disease in childhood, and thus, many children share those two conditions. In the present paper we review the epidemiology of children with asthma and obesity, as well as the consequences of being obese on the respiratory system. On the one hand obesity produces an underlying T-helper 2 (TH2) low inflammation state in which numerous cytokines, which could have an impact in the respiratory system play, a role. On the other hand, some respiratory changes have been described in obese children and, specially, the development of the so called "dysanapsis" (the disproportionate scaling of airway dimensions to lung volume) which seems to be common during the first stages of life, probably related to the early development of this condition. Finally, this review deals with the role of adipokines and insulin resistance in the inception and worsening of asthma in the obese child.
| S-EPMC8624093 | biostudies-literature
Project description: Not available
| S-EPMC8556333 | biostudies-literature
Project description:BackgroundObesity increases asthma risk, and may alter asthma severity. In adults, sex appears to modify the effect of obesity on asthma. Among children, the effect of sex on the relationship between obesity and asthma severity remains less clear, particularly when considering race.ObjectiveTo determine how obesity affects disease characteristics in a diverse cohort of children with poorly controlled asthma, and if obesity effects are altered by sex.DesignWe analyzed 306 children between 6 and 17 years of age with poorly controlled asthma enrolled in a 6-month trial assessing lansoprazole for asthma control. In this secondary analysis, we determined associations between obesity and symptom severity, spirometry, exacerbation risk, airway biomarkers, bronchial reactivity, and airflow perception. We used both a multivariate linear regression and longitudinal mixed-effect model to determine if obesity interacted with sex to affect asthma severity.ResultsRegardless of sex, BMI >95th percentile did not affect asthma control, exacerbation risk or airway biomarkers. Sex changed the effect of obesity on lung function (sex × obesity FEV1%, interaction P-value < 0.01, sex × obesity FEV1/FVC, interaction P-value = 0.03). Obese males had significantly worse airflow obstruction compared to non-obese males, while in females there was no obesity effect on airflow obstruction. In females, obesity was associated with significantly greater FEV1 and FVC, and a trend toward reduced airway reactivity.ConclusionsObesity did not affect asthma control, airway markers or disease stability; however obesity did affect lung function in a sex-dependent manner. In males, obesity associated with reduced FEV1/FVC, and in females, obesity associated with substantially improved lung function.
| S-EPMC3578966 | biostudies-literature
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.
| S-EPMC5795668 | biostudies-literature
Project description:BackgroundLung function impairment in early life often persists into adulthood. Therefore, identifying risk factors for low childhood lung function is crucial.ObjectiveWe examined the effect of 25-hydroxyvitamin D (25[OH]D) level and childhood asthma phenotype on childhood lung function in the Vitamin D Antenatal Asthma Reduction Trial (VDAART).MethodsThe 25(OH)D level was measured at set time points in mothers during pregnancy and in children during early life. On the basis of parental reports, children were categorized into 3 clinical phenotypes: asymptomatic/infrequent wheeze, early transient wheeze, and asthma at age 6 years. Lung function was assessed with impulse oscillometry at ages 4, 5, and 6 years and with spirometry at ages 5 and 6 years.ResultsA total of 570 mother-child pairs were included in this post hoc analysis. Mean gestational 25(OH)D-level quartiles were negatively associated with child respiratory resistance at 5 Hz (R5) from age 4 to 6 years (β, -0.021 kPa/L/s; 95% CI, -0.035 to -0.007; P = .003) and positively associated with FEV1 (β, 0.018 L; 95% CI, 0.005-0.031; P = .008) and forced vital capacity (β, 0.022 L; 95% CI, 0.009-0.036; P = .002) from age 5 to 6 years. Children with asthma at age 6 years had lower lung function from age 4 to 6 years than the asymptomatic/infrequent wheeze group (β, 0.065 kPa/L/s; 95% CI, 0.028 to 0.102; P < .001 for R5 and β, -0.063 L; 95% CI, -0.099 to -0.028; P < .001 for FEV1).ConclusionsLow gestational 25(OH)D level and childhood asthma are important risk factors for decreased lung function in early childhood.
| S-EPMC8315297 | biostudies-literature
Project description:Vitamin D insufficiency (a serum 25(OH)D <30 ng/ml) has been associated with severe asthma exacerbations, but this could be explained by underlying racial ancestry or disease severity. Little is known about vitamin D and asthma in Puerto Ricans.To examine whether vitamin D insufficiency is associated with severe asthma exacerbations in Puerto Rican children, independently of racial ancestry, atopy, and time outdoors.A cross-sectional study was conducted of 560 children ages 6-14 years with (n = 287) and without (n = 273) asthma in San Juan, Puerto Rico. We measured plasma vitamin D and estimated the percentage of African racial ancestry among participants using genome-wide genotypic data. We tested whether vitamin D insufficiency is associated with severe asthma exacerbations, lung function, or atopy (greater than or equal to one positive IgE to allergens) using logistic or linear regression. Multivariate models were adjusted for African ancestry, time outdoors, atopy, and other covariates.Vitamin D insufficiency was common in children with (44%) and without (47%) asthma. In multivariate analyses, vitamin D insufficiency was associated with higher odds of greater than or equal to one severe asthma exacerbation in the prior year (odds ratio [OR], 2.6; 95% confidence interval [CI], 1.5-4.9; P = 0.001) and atopy, and a lower FEV(1)/FVC in cases. After stratification by atopy, the magnitude of the association between vitamin D insufficiency and severe exacerbations was greater in nonatopic (OR, 6.2; 95% CI, 2-21.6; P = 0.002) than in atopic (OR, 2; 95% CI, 1-4.1; P = 0.04) cases.Vitamin D insufficiency is associated with severe asthma exacerbations in Puerto Rican children, independently of racial ancestry, atopy, or markers of disease severity or control.
| S-EPMC3406083 | biostudies-other
Project description:It is estimated that 20% of all cancer cases are caused by obesity. Vitamin D is thought to be one of the mechanisms underlying this association. This review aims to summarise the evidence for the mediating effect of vitamin D on the link between obesity and cancer.Three literature searches using PubMed and Embase were conducted to assess whether vitamin D plays an important role in the pathway between obesity and cancer: (1) obesity and cancer; (2) obesity and vitamin D; and (3) vitamin D and cancer. A systematic review was performed for (1) and (3), whereas a meta-analysis including random effects analyses was performed for (2).(1) 32 meta-analyses on obesity and cancer were identified; the majority reported a positive association between obesity and risk of cancer. (2) Our meta-analysis included 12 original studies showing a pooled relative risk of 1.52 (95% CI: 1.33-1.73) for risk of vitamin D deficiency (<50 nmol/L) in obese people (body mass index>30 kg/m2). (3) 21 meta-analyses on circulating vitamin D levels and cancer risk were identified with different results for different types of cancer.There is consistent evidence for a link between obesity and cancer as well as obesity and low vitamin D. However, it seems like the significance of the mediating role of vitamin D in the biological pathways linking obesity and cancer is low. There is a need for a study including all three components while dealing with bias related to dietary supplements and vitamin D receptor polymorphisms.
| S-EPMC4182855 | biostudies-literature
Project description:Obesity-related asthma is a distinct pediatric asthma phenotype. It is associated with higher disease burden, lower pulmonary function, and suboptimal response to current asthma medications. Recent studies have made inroads into elucidating its pathophysiology. Systemic immune responses in obese children with asthma are skewed to a nonatopic T-helper cell type 1 (Th1) pattern that correlates with pulmonary function deficits. The prevalence of metabolic dysregulation is also higher among obese children with asthma than among normal-weight children with asthma. Insulin resistance and dyslipidemia, particularly low levels of high-density lipoprotein (HDL), are associated with lower airway obstruction and low expiratory reserve volume. These associations are independent of truncal and general adiposity and thereby suggest a direct association between metabolic abnormalities and pulmonary function. Furthermore, insulin resistance is associated with Th1 polarization, whereas low HDL is associated with monocyte activation. Although insulin resistance mediates the association of Th1 polarization with pulmonary function, HDL does not have a similar influence on the association of monocyte activation with pulmonary function. Together, these recent studies have paved the way to the understanding of obesity-related asthma as a distinct asthma phenotype and have begun to identify the complex relationships between metabolic dysregulation, systemic inflammation, and pulmonary function deficits in obese children with asthma. Studies are now needed to elucidate the mechanisms that link metabolic dysregulation and systemic immune responses to pulmonary function.
| S-EPMC5711274 | biostudies-literature
Project description:BACKGROUND:Poor maternal vitamin D intake is a risk factor for subsequent childhood asthma, suggesting that in utero changes related to vitamin D responsive genes might play a crucial role in later disease susceptibility. We hypothesized that vitamin D pathway genes are developmentally active in the fetal lung and that these developmental genes would be associated with asthma susceptibility and regulation in asthma. METHODS:Vitamin D pathway genes were derived from PubMed and Gene Ontology surveys. Principal component analysis was used to identify characteristic lung development genes. RESULTS:Vitamin D regulated genes were markedly over-represented in normal human (odds ratio OR 2.15, 95% confidence interval CI: 1.69-2.74) and mouse (OR 2.68, 95% CI: 2.12-3.39) developing lung transcriptomes. 38 vitamin D pathway genes were in both developing lung transcriptomes with >63% of genes more highly expressed in the later than earlier stages of development. In immortalized B-cells derived from 95 asthmatics and their unaffected siblings, 12 of the 38 (31.6%) vitamin D pathway lung development genes were significantly differentially expressed (OR 3.00, 95% CI: 1.43-6.21), whereas 11 (29%) genes were significantly differentially expressed in 43 control versus vitamin D treated immortalized B-cells from Childhood Asthma Management Program subjects (OR 2.62, 95% CI: 1.22-5.50). 4 genes, LAMP3, PIP5K1B, SCARB2 and TXNIP were identified in both groups; each displays significant biologic plausibility for a role in asthma. CONCLUSIONS:Our findings demonstrate a significant association between early lung development and asthma-related phenotypes for vitamin D pathway genes, supporting a genomic mechanistic basis for the epidemiologic observations relating maternal vitamin D intake and childhood asthma susceptibility.
| S-EPMC4228235 | biostudies-literature