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Decreased Serum Vitamin D Levels in Children with Asthma are Associated with Increased Corticosteroid Usage
Abstract
There is little knowledge about clinical variables associated with vitamin D (VitD) insufficiency in asthmatic children.
We sought to investigate disease variables associated with VitD insufficiency in patients with childhood asthma and interaction of VitD with corticosteroid-mediated anti-inflammatory responses.
We analyzed 25-hydroxyvitamin D serum levels in 100 asthmatic children to investigate relationships between 25-hydroxyvitamin D levels and patients' characteristics. We determined VitD's effects on dexamethasone (DEX) induction of mitogen-activated protein kinase phosphatase 1 and IL-10 in PBMCs.
The median 25-hydroxyvitamin D serum level was 31 ng/mL. Forty-seven percent of subjects had VitD levels in the insufficient range (<30 ng/mL), whereas 17% were VitD deficient (<20 ng/mL). Log(10) IgE (P = .01, rho = -0.25) and the number of positive aeroallergen skin prick test responses (P = .02, rho = -0.23) showed a significant inverse correlation with VitD levels, whereas FEV(1) percent predicted (P = .004, rho = 0.34) and FEV(1)/forced vital capacity ratio (P = .01, rho = 0.30) showed a significant positive correlation with VitD levels. The use of inhaled steroids (P = .0475), use of oral steroids (P = .02), and total steroid dose (P = .001) all showed significant inverse correlations with VitD levels. The amount of mitogen-activated protein kinase phosphatase 1 and IL10 mRNA induced by VitD plus DEX was significantly greater than that induced by DEX alone (P < .01). In an experimental model of steroid resistance in which DEX alone did not inhibit T-cell proliferation, addition of VitD to DEX resulted in significant dose-dependent suppression of cell proliferation.
Corticosteroid use and worsening airflow limitation are associated with lower VitD serum levels in asthmatic patients. VitD enhances glucocorticoid action in PBMCs from asthmatic patients and enhances the immunosuppressive function of DEX in vitro.
... Lower vitamin D levels are associated with chronic lung diseases [10] and an increased susceptibility to infections [208]. In this context, asthmatic patients show lower levels of vitamin D than healthy subjects, independent of age [12,208,292,293,[296][297][298][299][299][300][301][302][303], and a more serious vitamin D deficiency correlates with asthma severity [208,302,304,305], lower asthma control, and ICS responsiveness [14,61,302,304,[306][307][308][309][310]. Lower vitamin D levels increase the number of exacerbations of the disease [14,306,311,312], the risk of developing asthma and atopy [104,105], and the progression of the disease [313]. ...
... Lower vitamin D levels increase the number of exacerbations of the disease [14,306,311,312], the risk of developing asthma and atopy [104,105], and the progression of the disease [313]. At the same time, asthmatic vitamin-D-deficient patients have higher ICS needs [58,308,310,314]. Vitamin D supplementation in subjects deficient in vitamin D decreases the numbers of asthma exacerbations and general asthma symptoms [315,316]. ...
Vitamins play a crucial role in the proper functioning of organisms. Disturbances of their levels, seen as deficiency or excess, enhance the development of various diseases, including those of the cardiovascular, immune, or respiratory systems. The present paper aims to summarize the role of vitamins in one of the most common diseases of the respiratory system, asthma. This narrative review describes the influence of vitamins on asthma and its main symptoms such as bronchial hyperreactivity, airway inflammation, oxidative stress, and airway remodeling, as well as the correlation between vitamin intake and levels and the risk of asthma in both pre- and postnatal life.
... Highly sensitive CRP (HSCRP) and vitD had estimated by "CALBIOTECH ® ELISA kit," and correlated with FeNo measures of all participants. VitD values were classified as sufficient (>30 ng/ml), insufficient (20-30 ng/ml), and deficient (<20 ng/mL) based on preceding reference [22]. ...
... In the latter decades exclusively, a cumulative bulk of data emphasized how vitD could control several biological activities; henceforth, vitD was revived being not simply the bones vitamin, but as well, multipurpose vitamin [9]. In this context, several epidemiological studies address the link between vitD and BA [5], [22], and the role of vitD insufficiency in asthma evolvement and exacerbations [23]. In our group of adults with BA, no correlation between reduced vitD levels and FeNo or HSCRP levels had reported, though HSCRP levels and FeNo index were significantly higher among BA patients compared to the control group. ...
Background: Bronchial asthma (BA) is a common lung illness and a significant health concern affecting over 315 million individuals globally. Asthma involves three main pathologies: airways hyperresponsiveness (AHR), inflammation, and remodeling. VitD has a forceful immunomodulatory effect able of reducing inflammatory responses in many cells intricate in BA. Deficiency of vitD has been linked with much inflammation and global worsening of asthmatic patients. C-reactive protein (CRP) is elevated in primary stages of inflammation of BA and high serum CRP values are observed with impaired pulmonary function and AHR. For that reason, it is sensible to explore the role of vitD in BA via its associations with CRP. This comparative study was aimed to evaluate the relationship between serum levels of HSCRP and vitD in patients with asthma. Patients and Methods: This is a case-control study conducted on 127 asthmatic patients with 113 (sex/aged matching) healthy control. The FeNo results had obtained in private centers, according to the ''guidelines of the American Thoracic Society (ATS)''. All participants had blood analysis of HSCRP and correlated with FeNo measures. VitD Values were classified as sufficient (>30ng/ml), insufficient (20 to 30ng/ml), and deficient (<20ng/mL) based on the preceding reference. Statistical Package for Social Sciences (SPSS/23-IBM) had used. The chi-squared test had used for univariate investigation, and a t-test had completed detecting variations between the studied groups, treatment groups, and genders. The outcomes had calculated at a 95% CI and had assigned as significant for all variables. The categorization accuracy of HSCRP, vitD, and FeNo measures had been investigated under the ''ROC curves'' for their diagnostic fitness to decide asthma prediction. Results Compared to the control group, the mean FeNo levels were significantly higher in asthmatics (p-0.001). Vitamin D mean levels were parallel between the study groups (p>0.05). The mean HSCRP levels were significantly (p-0.03) higher among asthmatics. Around 40% of all participants had lower than normal levels of serum VitD and <10% only revealed deficient levels. There was no effect of history of the treatment of BA on the blood levels of vitD and HSCRP. There was a positive non-significant correlation of vitD with FeNo results (r-0.067, p-0.54) and negative non-significant (r-0.082, p-0.086) correlation of vitD with HSCRP. ROC-curve analysis showed a significant ability (p-0.001) of FeNo to distinguish asthma, with high accuracy, sensitivity and specificity: 0.967, 93.5%, 93.2%, at 95% CI [0.946-1.000], respectively. Likewise, ROC analysis of HSCRP revealed significant ability (p-0.001), but with lower accuracy (0.881), sensitivity (87.1%), and specificity (76.3%) at 95% CI [0.812-0.950] to distinguish asthma patients from healthy subjects. Unlikely, VitD had a non-significant (p-0.085) and lower ability to predict asthma from healthy participants showing AUC (0.612), sensitivity (54.8%), and specificity (68.3%) at 95% CI [0.488 -0.736]. Conclusion No relation or minor conflicting correlations between serum levels of vitD with asthma severity, treatment history, and inflammation (as indicated by HSCRP). Highly sensitive CRP is correlated with asthma.
... This is in line with a previous study conducted in Costa Rica, which also found a statistically significant association between serum Vitamin D levels and inhaled steroids [12]. Similarly, a different study analyzing vitamin D levels in asthmatic children found a significant association between increased inhaled corticosteroids use, oral corticosteroids use, and total steroid dose with lower Vitamin D levels [20]. These findings, including in the current study, may suggest that low Vitamin D levels increase asthma severity, thereby increasing the need for pharmacological treatment such as inhaled and oral steroids, as also concluded in other studies [20]. ...
... Similarly, a different study analyzing vitamin D levels in asthmatic children found a significant association between increased inhaled corticosteroids use, oral corticosteroids use, and total steroid dose with lower Vitamin D levels [20]. These findings, including in the current study, may suggest that low Vitamin D levels increase asthma severity, thereby increasing the need for pharmacological treatment such as inhaled and oral steroids, as also concluded in other studies [20]. Although corticosteroid therapy proves beneficial to asthmatic patients, various laboratory studies suggest that long-term glucocorticoid therapy can eventually result in vitamin D deficiency, due to increased activity of 24-hydroxylase, which is responsible for degrading vitamin D metabolites [21,22]. ...
The role of vitamin D as an immunosuppressant and anti-inflammatory has been studied previously for different pathologies in different populations globally. Relationships between serum vitamin D levels and its effect on asthma exacerbations in the adolescent asthma population are not well studied in this region. Therefore, this study was conducted to determine the vitamin D status in pediatric and adolescent asthma patients, and its association with asthma exacerbations. A retrospective study was conducted at The Aga Khan University Hospital from 2016 to 2020. Children and adolescents who were diagnosed and admitted with acute asthma exacerbations and who had at least one measurement of 25 hydroxy-vitamin D (25 OHD) were included in the study. Serum vitamin D levels were documented for enrolled patients and their past 2-year data was analyzed for asthma exacerbations, mean length of stay per admission, and admission plus length of stay at High Dependency Unit. 114 patients were included in the study. 41 patients (35.96%) were found to be Vitamin D deficient, 38 patients (33.3%) were Vitamin D insufficient, and 35 patients (30.7%) were labeled as Vitamin D sufficient. The average number of exacerbations per year was significantly high in Vitamin D deficient group (2.82±1.11) in comparison with insufficient (2.05±0.92) and sufficient groups (1.37±0.59) (p<0.001). Vitamin D deficiency is related to an increased number of annual asthma exacerbations, length of stay per admission, and admission into High Dependency Unit (HDU).
... Asthma prevalence has been rising globally, primarily in Westernized and industrialized countries, with a trend toward higher prevalence farther away from the equator. Because of the high incidence of asthma, chronicity, morbidity, and mortality have become serious public health concerns [1]. Furthermore, new epidemiological research reveals that due to dietary and behavioral changes over the last few decades, vitamin D deficiency is rising in numerous nations and has been linked with various diseases [2]. ...
... Previous studies have shown that patients with mild to moderate asthma have low levels of serum vitamin D, inadequate control of asthma severity and disease attacks, rate of hospitalization, decreased lung function, decreased response to inhaled corticosteroids, and consequently, increased use of inhaled corticosteroids [6,13e16], which in terms could increase the risk of various infections [17]. In addition, serum vitamin D levels are inversely associated with increased airway response, airway repair, and response to glucocorticosteroids [1,18]. ...
Background & aims
Asthma prevalence has increased significantly since the 1960s. Increased airway hyperresponsiveness, decreased pulmonary function, poor asthma management, and steroid resistance have all been linked to vitamin D insufficiency. In addition, treatment with oral corticosteroids increases the risk of vitamin D deficiency. We studied patients with asthma regarding their vitamin D status and its association with disease severity.
Methods
Patients with asthma were included in the study. Spirometry results and serum levels of 25-hydroxyvitamin D, calcium, and phosphorus were measured.
Results
Of the 54 subjects, the majority (77.8%) were women, and the mean age was 49.71 ± 12.16 years. Among the patients, 19 (35.2%) had sufficient vitamin D levels, 18 (33.3%) had insufficient vitamin D, and 17 (31.5%) had vitamin D deficiency. The mean FEV/FVC in the group with vitamin D deficiency is significantly lower than those with insufficient vitamin D levels (P = 0.018). The mean calcium and phosphorus levels between the three groups were not different.
Conclusion
Vitamin D deficiency is common in patients with asthma but is not associated with lung function test results.
... Moreover, in children with asthma, decreased vitamin D status is associated with increased use of corticosteroids. (Searing et al., 2010) [61] . Hence it can suggested that maintaining optimum levels of vitamin D aids in good respiratory health and keeps the immune system strong and healthy and maintains factors like CRF and CRP. ...
... Moreover, in children with asthma, decreased vitamin D status is associated with increased use of corticosteroids. (Searing et al., 2010) [61] . Hence it can suggested that maintaining optimum levels of vitamin D aids in good respiratory health and keeps the immune system strong and healthy and maintains factors like CRF and CRP. ...
The world is dealing with a contagious disease caused by a newly identified virus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Coronavirus mainly targets the human respiratory system. Hence attacking the immunity system of a person. While data regarding nutrition in coronavirus infection (COVID-19) is on its way, in this review we aimed to explore the various vitamins and minerals which have been proven effective in previously occurred viral infections and epidemics (with special emphasis on respiratory infections) and also summarising the conclusion of results gained in the past 4 months from COVID-19 patients. Clinical trials conducted on COVID-19 patients using vitamins and minerals have also been summarised. The review also aims at changing the perspective towards the benefits of taking vitamins and minerals on daily basis in a daily diet. The study concludes that intake of a balanced diet with the recommended amount of fruits and vegetables on a daily basis which provides all the essential vitamins and minerals keeps the immune system strong. Infection-fighting abilities are better in subjects taking a balanced diet. While in case of weakened immune system and susceptibility to life-threatening diseases, including COVID-19, it has been found that large and or intravenous doses of certain vitamins and minerals have shown improvement in the patient's condition. Hence nutritional therapy can also be used in the treatment of COVID-19.
... There is evidence from observational cohort studies linking low 25-hydroxyvitamin D levels with asthma incidence in children [10,11]. A systematic review of the literature on studies examining the impact of vitamin D supplementation in children with early diagnosed asthma failed to show clear positive impact [12]. ...
... Also, there is unclear evidence around the link between severity of asthma and low 25-hydroxyvitamin D levels [10]. Importantly, prior to the Vitamin D Kids Asthma (VDKA) trial [13], other studies including either preschool or school-age children had not focused only on children with low 25-hydroxyvitamin D levels or on those who are at high risk for severe asthma exacerbations (assessed by poor asthma control) [11,14]. A recently published randomised controlled trial including younger children with vitamin D deficiency showed no positive impact of vitamin D 3 supplementation on incidence of asthma exacerbations and on asthma control [15]. ...
Vitamin D deficiency in children needs to be treated irrespective of asthma benefits. The VDKA trial showed that vitamin D supplementation in school-age asthmatic children with vitamin D insufficiency did not improve asthma control. https://bit.ly/2UF3j61.
... Therefore, the new steroid enhancement property of vitamin D is conformed. In addition, the result revealed that the low serum level of vitamin D in asthmatic patients was correlated to the poor therapeutic effect of corticosteroids, and that vitamin D could enhance the effect of glucocorticoids in mononuclear cells in peripheral blood of asthmatic patients, and enhance the immunosuppressive function of DXM in vitro (20). Moreover, exposure to vitamin D in the process of fetal development can affect the immune system of newborns, thereby protecting newborns from asthma and other related diseases, including the impact of infectious diseases. ...
... These results revealed that the expression of chemokines eotaxin and IL-8 increased in the culture supernatant of ASMCs treated with TNF-α, and that 1,25-(OH) 2 D 3 had obvious inhibition effect on this. Furthermore, the upregulated expression of VDR significantly downregulated the expression of ROCK, MLC 20 and P-MLC 20 . The influences of DXM on the above factors were much greater than those of 1,25-(OH) 2 D 3 , and the inhibitory effect of the combination of these two drugs was more obvious, suggesting that these two has a synergistic effect. ...
Background:
Bronchial asthma (referred to as asthma in the present study) is the most common chronic airway inflammatory disease in childhood. The present study aimed to investigate the effect of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] on VDR expression, which is closely associated with asthmatic airway smooth muscle cells (ASMCs), and explored its role and mechanism in the Rho-kinase signaling pathway.
Methods:
The acute asthma model was induced by ovalbumin (OVA) and pertussis bacillus, and ASMCs obtained from asthmatic rats were cultured in vitro. These cells were randomly divided into five groups: control (N) group, TNF-α (TNF) group, 1,25-(OH)2D3 (VD) group, dexamethasone (DXM) group, and 1,25-(OH)2D3 + DXM (L) group. The protein expression levels of VDR, ROCK, MLC20 and P-MLC20 were detected by western blot, and the mRNA expression levels of VDR, ROCK, MLC20 and P-MLC20 were detected by real-time quantitative PCR.
Results:
The expression of ROCK, MLC20 and P-MLC20 in each treatment group were significantly lower, when compared to the TNF group (P<0.05), but this remained stronger than (P<0.05) or similar to (P>0.05) that in the N group.
Conclusions:
The regulation mechanism of 1,25-(OH)2D3 in alleviating asthma should be correlated to its regulation of the expression of related signaling molecules in the Rho-kinase signaling pathway, and this effect may be achieved by regulating the mRNA and protein expression of the VDR gene.
... A inflamação via linfócitos Th2 é o perfil mais comum de asma na infância e caracteriza-se pela presença de eosinófilos e aumento nos níveis de IgE, que se relacionam à melhora da doença com corticosteroides. (1)(2)(3) A vitamina D, um micronutriente lipossolúvel (4) que age por meio do vitamin D receptor (VDR, receptor de vitamina D), (5) pode influenciar a cascata imunológica da asma suprimindo a resposta de linfócitos T2 alto e reduzindo a produção de IL-5, com diminuição do número de eosinófilos e dos níveis de IgE. (6) Usualmente a vitamina D não está presente na alimentação da maioria das pessoas, inclusive na dos brasileiros. ...
... O método de avaliação dos níveis séricos de 25-hidroxivitamina D3 (vitamina D) foi descrito previamente, (12,13) refletindo contribuições de todas as fontes dessa vitamina (ou seja, por via alimentar e exposição ao sol). (14) Os métodos de avaliação de eosinófilos séricos (3,13) , IgE, (15) nível de controle da asma, (1) diagnóstico de rinite alérgica (16) e espirometria (17,18) também já foram descritos anteriormente. A graduação da posologia de corticosteroides inalatórios e a sua padronização em dosagens equivalentes à budesonida foram feitas conforme descrito no GINA. ...
In this cross-sectional study, we investigated the relationship that levels of vitamin D had with eosinophil counts and IgE levels in 26 children with asthma (6-12 years of age) in the city of Londrina, Brazil. Vitamin D levels were found to correlate significantly, albeit moderately, with age (r = -0.51) and eosinophilia (r = -0.49), although not with IgE levels (r = -0.12). When we stratified the sample into two groups by the median vitamin D level (< or ≥ 24 ng/mL), we found that those in the < 24 ng/mL group were older, had higher eosinophil counts, and had higher IgE levels. To our knowledge, this is the first study to show an association between low levels of vitamin D and more pronounced eosinophilia in children with asthma in Brazil.
... Data related to the effects of maternal vitamin D on skeletal bone integrity and skin color in childhood (31,32). Maternal vitamin D deficiency was found to correlate with asthma and impaired lung function in offspring (33,34). Vitamin D acts as a neurosteroid with direct effects on brain development. ...
... A recent study provided supporting data for our point of view, since it showed that a better built-up efficacy of allergy immunotherapy was achieved in VD3-supplemented allergic patients [17]. Clinical studies have indicated that serum VD levels are inversely associated with the responsiveness to corticosteroids, with a lower VD level corresponding with a higher drug consumption [24]. Furthermore, dexamethasone-resistant patients showed IL-10-unproductive Tregs [25]. ...
The post hoc analysis presented here aimed to address the influence of endogenous vitamin D in the immunological mechanism underlying effective mite allergoid immunotherapy (AIT). Previously, we have shown that in allergic children, after 12 months of this immunoactive treatment, functionally potentiated memory regulatory T cells are identified. Indeed, AIT is the only known treatment that is able to reshape the detrimental immune response against the allergen into a non-noxious one. Besides, VD is widely considered an immunoregulatory molecule that is endogenously produced and exogenously provided by foods and supplements that might interact with the AIT mechanism, thus affecting its outcome. Therefore, a post hoc analysis of the clinical and immunological data from three different cohorts of allergic patients was performed. One cohort (N = 70) was on a standard symptom-controlling pharmacological treatment, while the other two (N = 60 and N = 35) were treated with AIT for 12 months. In the first cohort, a lower mean endogenous VD level (
... [7] In addition, Vitamin D levels were significantly and inversely associated with total IgE and eosinophil count. [16] Searing et al. [17] in a cross-sectional study of 100 asthmatic children showed that Vitamin D levels were inversely associated with serum IgE, the number of skin prick tests positive for perennial aeroallergens, lung function, and use of inhaled or oral corticosteroids. ...
Background: Vitamin D deficiency has been declared a public health problem for both adults and children worldwide. Asthma and related allergic disorders are leading causes of morbidity in children. The objective of this study was to estimate Vitamin D levels in children suffering from asthma and allergic rhinitis in North Kerala. Objectives: (1) To evaluate Vitamin D levels among children between the age group 5 and 18 years suffering from asthma and/or allergic rhinitis. (2) To study the factors associated with low levels of Vitamin D and (3) to study the correlation between Vitamin D levels, immunoglobulin E (IgE), and absolute eosinophil count (AEC). Materials and Methods: This is a retrospective analysis of hospital data in which data of children between the age group 5 and 18 years attending the pulmonology outpatient department of a tertiary care hospital in North Kerala are captured. The study period was 6 months from March 01, 2021, to August 31, 2021. Detailed clinical history, physical examination, and laboratory investigations including complete blood cell count, IgE, and 25 dihydroxyvitamin D3 (Vitamin D) level were done. Diagnosis of allergic rhinitis and asthma is made on the clinical presentation by an experienced pulmonologist. Family history of asthma or allergic rhinitis was also recorded. Data were entered into Microsoft Excel, and analysis was done using Epi Info 7. Means and standard deviation were calculated, and correlation was assessed between Vitamin D levels, IgE, AEC, and age of the children. Results: Thirty percent of children in the study group had Vitamin D deficiency, 56% had insufficient values, and 14% had normal values. Most of the children with low Vitamin D levels had raised values for IgE and AEC, but the association was not statistically significant. Conclusion: Most of the children in this part of the state presenting with respiratory allergy have low or insufficient levels of Vitamin D. This may be one of the reasons for poor control of symptoms and such children may require Vitamin D supplementation along with optimal treatment of respiratory allergy.
... A recent study provides supporting data to our point of view since it shows that better built-up efficacy of allergy immunotherapy is achieved in VD3-supplemented allergic patients [17]. Clinical studies indicate that VD serum levels are inversely associated with responsiveness to corticosteroids, with the lower level corresponding to the higher drug assumption [24]. Furthermore, dexamethasone-resistant patients show IL-10-unproductive Tregs [25]. ...
The post-hoc analysis presented here aimed to address the influence of endogenous vitamin D in the immunological mechanism underlying effective mite allergoid-immunotherapy (AIT). Previously, we have shown that one subpopulation of T regulatory cells results in phenotypically identifiable as functionally potentiated and memory cells in allergic children after 12 months of this immunoactive treatment. Indeed, AIT is the only known treatment able to reshape the detrimental immune response against the allergen into a not noxious one. Besides, VD is widely considered an immunoregulatory molecule endogenously produced and exogenously provided with foods and supplements that might interact with AIT mechanism and affect its outcome. Therefore, a post-hoc analysis of the clinical and immunological data of three different cohorts of allergic patients was performed. One cohort (N=70) was on standard symptoms-controlling pharmacological treatment while the other two (N=60 and N=35, respectively) were treated with AIT for 12 months. Among the first were observed a lower mean endogenous VD level (<22 ng/ml) along with worse symptoms and higher use of medications. Remarkably, the comparison between two sub-cohorts of patients with serum VD above (N=32) or below (N=28) a cut-off value set at mean value (27 ng/ml) revealed that optimal improvement of all clinical and immune parameters was achieved (as expected by effective AIT), irrespective of the VD level. Notably, the third analysis, carried out on one cohort of AIT patients also taking concomitantly VD3 as food supplement (N=19), was distinguished by uppermost overall treatment outcome (amelioration of symptoms, lowest medications requirement, and reduction of total and allergen-specific IgE) as well as the increase of allergen-specific tolerogenic memory T regulatory cells. These findings suggest that endogenous VD level affects allergy severity and allergen immunotherapy effectiveness. Also, VD3 might be investigated as an add-on supplement to get the best out of immunotherapy in VD deficient/insufficient allergic patients. The immunogenic but low-allergenic mite allergoid used as bioactive agent might have contributed to minimize allergic and highlight immunological effects described here.
... In relation to these mechanisms, vitamin D may also have a therapeutic effect in reducing asthma attacks. 26 Vitamin D deficiency may be associated with the development of LRTIs or a more severe prognosis in children without any chronic disease. 27 In this study, the rate of patients diagnosed with respiratory system diseases was 1.7%, and no significant difference was found in the point of the vitamin D level. ...
Objective:
In this study, we aimed to assess the frequency of vitamin D deficiency according to age and sex in children and to investigate their relationship with demographic characteristics, presentation complaints, and accompanying clinical findings.
Materials and methods:
Vitamin D levels and demographic and clinical characteristics of 1505 children aged 2-18 years who applied to the hospital between January 01, 2017, and December 31, 2017, were analyzed. Patients who had a disease that could negatively affect vitamin D absorption and metabolism, who were diagnosed with rickets, or who took vitamin D supplements were excluded from the study.
Results:
The median vitamin D level of children was 17.7 ng/mL, and the prevalence of vitamin D deficiency and insufficiency was 26.4% and 33.4%, respectively. Females were the group most at risk for vitamin D deficiency. Another group at risk for vitamin D deficiency was adolescents. Vitamin D deficiency or insufficiency was detected in approximately half of the school-age and preschool children. Of the patients, 18% were admitted to the hospital by their parents to have their vitamin D levels checked. No health problems were detected in 47.7% of the patients whose vitamin D level was checked. Neurological complaints were more common in patients with vitamin D deficiency or insufficiency when compared to the group with normal vitamin D levels (P < .001).
Conclusions:
The risk of vitamin D deficiency in children is highest in the female sex and adolescent age group. Neurological complaints are more likely to be associated with vitamin D deficiency or insufficiency.
... Further, IL-10 expression in both asthmatic models fed LVD diets was lower than those fed HVD diets. This is consistent with previous studies (49) suggested that vitamin D may help reduce airway inflammation and reverse steroid-resistance by increasing IL-10 expression. IL-6 and IL-17A expression were increased in the LVD + OVA + ozone group compared with the LVD + OVA group, suggesting that LVD + OVA + ozone seems to induce a greater inflammatory response than LVD + OVA. ...
Introduction
Asthma is primarily divided into two categories: type 2 (T2-high) and non-type 2 (T2-low). A relationship between asthma severity and vitamin D deficiency has been identified, but its impact on each asthma endotype remains unknown.
Methods
We clinically examined the influence of vitamin D on patients with T2-high (n = 60) or T2-low asthma (n = 36) compared with controls (n = 40). Serum 25(OH)D levels, inflammatory cytokines and spirometry were measured. Mouse models were then used to further analyze the effects of vitamin D on both asthmatic endotypes. BALB/c mice were fed with vitamin D-deficient (LVD), -sufficient (NVD), or -supplemented diets (HVD) throughout lactation and offspring followed the same diet after weaning. Offspring were sensitized/challenged with ovalbumin (OVA) to establish “T2-high” asthma or OVA combined with ozone exposure (OVA + ozone) to induce “T2-low” asthma. Spirometry and serum, bronchoalveolar lavage fluid (BALF), and lung tissues were analyzed.
Results
Serum 25(OH)D levels were decreased in asthmatic patients compared with controls. Patients with vitamin D deficiency (Lo) had varying degrees of elevation of the pro-inflammatory cytokines IL-5, IL-6, and IL-17A, decreased expression of the anti-inflammatory cytokine IL-10, and altered forced expiratory volume in the first second as a percentage of predicted value (FEV 1 %pred) in both asthmatic endotypes. Vitamin D status had a stronger correlation with FEV 1 %pred in T2-low asthma than T2-high asthma, and 25(OH)D level was only positively linked to maximal mid-expiratory flow as a percentage of predicted value (MMEF%pred) in the T2-low group. Inflammation, hyperresponsiveness, and airway resistance (R L ) was increased in both asthma models compared with controls while vitamin D deficiency further increased airway inflammation and airway obstruction. These findings were particularly prominent in T2-low asthma.
Discussion
The potential function and mechanisms of vitamin D and both asthma endotypes should be studied individually, and further analysis of the potential signaling pathways involved with vitamin D on T2-low asthma is warranted.
... Estudos recentes tem relacionado os baixos níveis séricos os baixos níveis séricos de 25-hidroxivitamina D (doravante, "vitamina D") a exacerbações graves de asma, diminuição da função pulmonar e resposta reduzida a corticosteroides (Ogeyingbo et al., 2021;Searing et al., 2010). A vitamina D é uma das vitaminas lipossolúveis exigidas pelo organismo, sendo obtida principalmente pela via de síntese da pele após a radiação ultravioleta B (UVB), e uma pequena parte dos alimentos (peixes oleosos, gema de ovo, cogumelo, fígado ou carne de órgãos) e suplementos. ...
Introdução: A asma é uma doença inflamatória crônica das vias aéreas na qual o processo inflamatório culmina em episódios recorrentes de sibilância, dispneia, aperto no peito e tosse. Estudos recentes tem relacionado os baixos níveis séricos de 25-hidroxivitamina D (vitamina D) a exacerbações graves de asma, diminuição da função pulmonar e resposta reduzida a corticosteroides. Objetivos: Analisar os efeitos do uso da vitamina D em pacientes com asma, com ou sem defeito desta vitamina. Métodos: Trata-se de uma revisão integrativa, que utilizou as bases de dados PUBMED, SciELO e LILACS. Os critérios de inclusão foram: responder à pergunta norteadora, estar disponível em português, inglês ou espanhol, artigos publicados nos últimos 5 anos, do tipo ensaio clínico, relato e séries de casos, estudos de coorte e estudos transversais. Após a triagem, foram selecionados 13 artigos. Resultados e discussão: Os resultados foram bastante divergentes quanto a eficácia da suplementação de vitamina D em pacientes asmáticos com ou sem deficiência desta, embora a maioria tenha indicado uma forte correlação entre a carência vitamínica e a exacerbação das crises de asma. Anda, fatores como o tipo e tamanho de amostra e tempo de seguimento podem influenciar nos resultados, sendo evidenciado que em crianças há uma correlação mais positiva do que em adultos. Conclusão: Os resultados divergentes na literatura disponível requerem que mais estudos primários sejam realizados, com uma amostra maior e mais homogênea, a fim de alcançar resultados mais fidedignos, que embasem, de fato, a eficácia na suplementação de vitamina D nestes pacientes.
... Searing et al, in a crosssectional study involving 100 asthmatic children, demonstrated inverse associations between vitamin D and serum IgE levels, [39] the number of positive skin tests for pneumallergens, lung function and use of corticosteroids by inhalation or orally. Other studies have also shown that lower levels of vitamin D are associated with poorer lung function and the presence of exerciseinduced bronchoconstriction [40] in children with asthma [41]. Bump et al [42] have shown in vitro that vitamin D increases the bioavailability of glucocorticoids in bronchial smooth muscle cells, suggesting an additional beneficial role of this vitamin in the prevention and treatment of asthma. ...
... The relationship between vitamin D deficiency and asthma has also been associated with decreased lung function. On average, children with vitamin D deficiency have a slightly lower FEV 1 than those with adequate vitamin D levels [33]. ...
Stunting, which results from chronic malnutrition, is common in children from low- and middle-income countries. Several studies have reported an association between obesity and asthma. However, only a handful of studies have identified stunting as a significant risk factor for wheezing, a symptom of asthma, although the underlying mechanism remains unclear. This article aimed to review possible mechanisms underlying asthma in stunted children. Overall, changes in diet or nutritional status and deficiencies in certain nutrients, such as vitamin D, can increase the risk of developing asthma. Vitamin D deficiency can cause linear growth disorders such as stunting in children, with lower levels of 25(OH)D found in underweight and stunted children. Stunted children show a decreased lean body mass, which affects lung growth and function. Low leptin levels during undernutrition cause a Th1–Th2 imbalance toward Th2, resulting in increased interleukin (IL)-4 cytokine production and total immunoglobulin E (IgE). Studies in stunted underweight children have also found an increase in the proportion of the total number of B cells with low-affinity IgE receptors (CD23+). CD23+ plays an important role in allergen presentation that is facilitated by IgE to T cells and strongly activates allergen-specific T cells and the secretion of Th2-driving cytokines. Stunted children present with low vitamin D and leptin levels, impaired lung growth, decreased lung function, and increased IL-4 and CD23+ levels. All of these factors may be considered consequential in asthma in stunted children.
... Cortisol and vitamin D are all derived from cholesterol metabolites. Clinical evidence had shown that elevated glucocorticoids use was associated with decreased serum 25 (OH)D levels among asthmatic children [20]. Additionally, experimental evidence has suggested that 1,25dihydroxyvitamin D3 regulates adipocyte cortisol levels by increasing 11beta-HSD1 expression [21]. ...
Background and aims:
The effects of cortisol on cardiovascular diseases (CVD) and CVD risk are unknown, especially in patients with type 2 diabetes mellitus (T2DM). Furthermore, it is unclear whether 25 (OH)D can alter the associations of cortisol with CVD and CVD risk factors. Thus, the present study was to investigate the associations of serum cortisol with CVD and CVD risk factors and whether 25 (OH)D altered these associations among patients with T2DM. Materials and methods. A total of 762 patients diagnosed with T2DM were recruited. The levels of serum cortisol and 25 (OH)D were measured with a liquid chromatography-tandem mass spectrometry. Logistic regression and linear regression were used to assess the association of cortisol with CVD and multiple cardiovascular risk factors. Modification analyses were performed to identify whether 25 (OH)D altered the above associations.
Results:
A 1 SD increase in cortisol was associated with a higher prevalence of stroke (odds ratio (OR): 1.25, 95% confidence interval (CI): 1.05, 1.50). Elevated cortisol was associated with related cardiovascular risk factors, including deceased ß cell function, high-density lipoprotein-cholesterol (HDL-C), and fasting insulin, as well as increased triglycerides (TG), low-density lipoprotein-cholesterol (LDL-C), fasting plasma glucose (FPG), and glycated hemoglobin (HbA1c). In addition, modification analyses suggested that the associations of cortisol with ß cell function, fasting insulin, FPG, and HbA1c were modified by 25 (OH)D.
Conclusions:
Serum cortisol was associated with the prevalence of stroke and cardiovascular risk factors, and the associations of cortisol with cardiovascular risk factors were moderated by 25 (OH)D, suggesting that T2DM patients with exposure to lower 25 (OH)D levels and higher cortisol levels were more susceptible to have higher cardiovascular risk factors.
... Corticosteroid use in a nationally representative cohort study has been associated with a 2-fold increased propensity for vitamin D deficiency compared with nonuse after multivariable statistical adjustment [106]. The usage of these anti-inflammatory drugs and subsequent vitamin D deficiency particularly affect the elderly, especially those with chronic pulmonary, rheumatic, and/or kidney diseases, as well as children with asthma [106,107]. Suboptimal concentrations of serum 25(OH)D 3 on the order of -0.5 ng/ml compared with healthy referents have been linked with the administration of glucocorticoids, a potent class of corticosteroids (e.g., dexamethasone, methylprednisolone, and prednisone) that bind to the glucocorticoid receptor [108,109]. On the other hand, dexamethasone treatment has been purported to mitigate the adverse effects of vitamin D deficiency in hospitalized COVID-19 patients [110]. ...
Vitamin D is an important immune-modulator with anti-inflammatory properties. While this prohormone has been studied extensively in the prevention and treatment of COVID-19, findings have been inconsistent regarding its overall benefit in patients hospitalized with COVID-19. Most studies to date have been observational in nature, not accounting for the use of corticosteroids. Furthermore, the few randomized clinical trials designed to examine the effect of vitamin D supplementation on COVID-19 outcomes have been relatively small and thus insufficiently powered to assure a balance of corticosteroid use between study arms. The current perspective addresses the interaction of vitamin D and corticosteroids as a potential explanation for the divergent results reported in the literature. Future research on vitamin D and COVID-19 will benefit by considering this interaction, especially among hospitalized patients requiring oxygen and mechanical ventilation.
... Administration of Vit D purportedly reverses the induction of interleukin 10 (IL-10)-secreting regulatory T cells in glucocorticoid-resistant patients, a mechanism particularly beneficial in the context of COVID-19 [67]. Vit D has also been shown to have a synergistic anti-inflammatory effect with CRTs by facilitating glucocorticoid induction of mitogen-activated protein kinase (MAPK) phosphatase 1 (MKP-1) and IL-10 in peripheral blood mononuclear cells (PBMCs) [68]. Granulocyte-macrophage colony-stimulating factor (GM-CSF) found in culture supernatants from clusters of differentiation 14-negative (CD14 -) cells and mediator complex subunit 14 (MED14) have been recognized as significant factors in this process, effectively reducing the dose of glucocorticoids needed to mitigate inflammatory effects [69]. ...
This data-based cohort consisted of 26,508 (7%) United States veterans out of the 399,290 who tested positive for SARS-CoV-2 from 1 March to 10 September 2020. We aimed to assess the interaction of post-index vitamin D (Vit D) and corticosteroid (CRT) use on 30-day mortality among hospitalized and non-hospitalized patients with coronavirus disease 2019 (COVID-19). Combination Vit D and CRT drug use was assessed according to four multinomial pairs (−|+, −|−, +|+, +|−). Respective categorical effects were computed on a log-binomial scale as adjusted relative risk (aRR). Approximately 6% of veterans who tested positive for SARS-CoV-2 died within 30 days of their index date. Among hospitalized patients, a significantly decreased aRR was observed for the use of Vit D in the absence of CRTs relative to patients who received CRTs but not Vit D (aRR = 0.30; multiplicity corrected, p = 0.0004). Among patients receiving systemically administered CRTs (e.g., dexamethasone), the use of Vit D was associated with fewer deaths in hospitalized patients (aRR = 0.51) compared with non-hospitalized patients (aRR = 2.5) (P-for-Interaction = 0.0071). Evaluating the effect of modification of these compounds in the context of hospitalization may aid in the management of COVID-19 and provide a better understanding of the pathophysiological mechanisms underlying this and future infectious disease outbreaks.
... Some studies observed an association between maternal intake of vitamin D during pregnancy and risk of childhood asthma in the offspring, and thus its supplementation may have beneficial effects during pregnancy, lung growth and development in neonates [20] . Another study found that the serum vitamin D was positively correlated with lung function and enhanced glucocorticoid action in peripheral blood mononuclear cells [21] . Moreover, vitamin D was inversely correlated with total IgE, the degree of atopy and the use of inhaled or oral steroids and might be potentially capable of overcoming the poor glucocorticoid responsiveness in severe asthmatics through the upregulation of interleukin-10 production (a potent anti-inflammatory cytokine) from CD4+ T cells. ...
Background: Asthma is a heterogeneous disease, usually characterized by chronic airway inflammation. The detrimental effects of vitamin D deficiency in pediatrics have become increasingly apparent and extend beyond skeletal health. Aims & Objectives: This study was carried out to evaluate the level of vitamin D and immunoglobulin E (IgE) in asthmatic patients of paediatric ages during exacerbation and after remission. Patients and Methods: This study was carried out on 56 bronchial asthma children of 4 to 14 years of age group attending the 'Pediatric outpatient department' of ICARE Institute of Medical Sciences, Haldia, with bronchial asthma diagnosed and classified according to Global Initiative for Asthma 2016 and 48 healthy age and sex matched individuals. Serum vitamin D and IgE were measured using enzyme-linked immunosorbent assay for all participants. Results: Serum IgE level was found significantly higher among bronchial asthma subjects with respect to controls (443.2 ± 237.3 versus 139.8 ± 82.06 IU/ml; P < 0.001). Moreover, serum 25 OH vitamin D levels were lower in bronchial asthma cases as compared to controls and were statistically significant (15.83 ± 7.44 versus 23.14 ± 8.29 ng/ml; P < 0.001). Serum vitamin D level showed an inverse correlation with IgE (r =-0.77; P < 0.0001) level among bronchial asthma subjects, but no significant correlation was observed in controls (r = 0.077; P = 0.689). Conclusion: Despite these limitations it has been observed that serum vitamin D levels were lower and IgE levels were higher in patients suffering from bronchial asthma. A clear strong inverse correlation between vitamin D and Ig E also indicates a strong relationship in the pathogenesis of the disease.
... Table 2; eFigure in Supplement 2). The proportion of participants whose inhaled corticosteroid dose could be reduced (halved) at the midpoint of the trial was not significantly different between the vitamin D 3 ...
... 15,27 It was observed that vitamin D deficiency and bone mineral density decreased in children with asthma who were using OCS. 28 Searing et al. 29 showed that the vitamin D level is lower in patients with asthma by using, not only OCS but also ICS. They also showed vitamin D enhancement of glucocorticoid action in PBMCs in patients with asthma in vitro. ...
Background: In recent years, interest in the effects of vitamin D on human health and the immune system has increased. Objective: This study aimed to investigate the relationship of vitamin D with asthma severity, attacks, and clinical and functional parameters in adult patients with asthma who were living in different geographic regions in Turkey. Methods: A total of 384 patients with stable asthma and 87 control subjects were included. A physical examination and a pulmonary function test were performed, and routine blood analyses and vitamin D levels were evaluated. Asthma Control Test was applied. The number of exacerbations in the previous year, asthma therapy, and medication adherence were recorded. Results: In our study, vitamin D levels were below the target values in both patients with asthma (median [minimum-maximum] 16.0 ng/mL [3.5-48 ng/ml]) and control subjects (median [minimum-maximum] 20.0 ng/mL [5.8-58.79 ng/mL]). However, it was lower in the patients with asthma than in the control subjects (p = 0.001). There was a negative relationship between the levels of vitamin D and the severity of asthma (Kendall τ = -0.146; p < 0.001). Furthermore, the patients with severe asthma were received The Global Initiative for Asthma (GINA) step 5 treatment showed significantly lower vitamin D compared with the patients who received GINA step 4 treatment (p = 0.037). Vitamin D levels correlated with forced vital capacity (FVC), forced expiratory volume in the first second of expiration (FEV1), and peak expiratory flow (r, 0.221-0.236; p ≤ 0.001). In addition, a positive relationship was found between Asthma Control Test and vitamin D (r = 0.229; p = 0.001). However, body mass index (BMI), asthma exacerbation, and hospitalization were inversely related to vitamin D (r, 0.198-0.233; p = 0.001). Multivariable regression analysis revealed that FVC (p = 0.002), FEV1 (p = 0.033), and BMI (p = 0.037) were independent determinants associated with vitamin D. Conclusion: This study suggested a high prevalence of vitamin D deficiency in adults with asthma living in different geographic areas in Turkey. Vitamin D deficiency is associated with asthma severity, poor control, and lower lung function.
... • Measurement of serum vitamin D concentration (measured as 25-hydroxyvitamin D) was once carried out by the use of a radioimmunoassay strategy using the Diasorin RIA (DiasorinInc, Stillwater, MN) by means of Quest Laboratories that take an interest within the vitamin D outside Quality Appraisal Conspire (DEQAS)). Values have been categorized as adequate (>30 ng/mL), inadequate (20-30 ng/mL), and poor (<20 ng/mL) based on past suggestions (Searing et al., 2010). • Spirometry for baseline functional respiratory tests: ...
Bronchial Asthma is outlined as a chronic irritation of the airways in children. Vitamin D is a real immune system regulator which has a potential part in allergy. Asymmetric Dimethyl Arginine (ADMA) is an endogenic Nitric Oxide Synthase (NOS) inhibitor. This study is to determine if there is a role of vitamin D deficiency, ADMA in the pathogenesis of asthma in children, And whether the decreased arginine bioavailability and NOS suppression by ADMA contribute to respiratory tract blockage or not. We measured serum vitamin D, ADMA, nitric oxide and plasma L-arginine in 30 asthmatic and 10 healthy children. Serum 25-hydroxy vitamin D, plasma L-Arginine and serum Nitric Oxide were decreased significantly in asthmatic patients compared to healthy children. On the other hand, ADMA serum levels were increased significantly in asthmatic patients. In asthmatic children, there were positive correlations between serum vitamin D concentration and forced expiratory volume in the first, second FEV1 (%predicted). Furthermore, there were negative correlations between serum ADMA concentration and FEV1 (%predicted). In conclusion, marked reduction of vitamin D and elevated ADMA serum levels in asthmatic children has contributed to NOS-related pathophysiology, therefore ADMA and vitamin D could be considered reliable in managing oxidative stress in asthma.
... The findings for a selective sweep for increased IVL observed in European populations that live in Northern latitudes suggests a possible link between cutaneous vitamin D production and IVL expression as a mechanism of environmental adaptation for the skin barrier. Vitamin D is known to stimulate the differentiation of keratinocytes [53][54][55] and promote the expression of IVL 56,57 ; it is possible that high rates of vitamin D deficiency in modern populations 58,59 could contribute to reduced skin barrier integrity and, subsequently, disease states including asthma 60 . ...
The genetic modules that contribute to human evolution are poorly understood. Here we investigate positive selection in the Epidermal Differentiation Complex locus for skin barrier adaptation in diverse HapMap human populations (CEU, JPT/CHB, and YRI). Using Composite of Multiple Signals and iSAFE, we identify selective sweeps for LCE1A-SMCP and involucrin (IVL) haplotypes associated with human migration out-of-Africa, reaching near fixation in European populations. CEU-IVL is associated with increased IVL expression and a known epidermis-specific enhancer. CRISPR/Cas9 deletion of the orthologous mouse enhancer in vivo reveals a functional requirement for the enhancer to regulate Ivl expression in cis. Reporter assays confirm increased regulatory and additive enhancer effects of CEU-specific polymorphisms identified at predicted IRF1 and NFIC binding sites in the IVL enhancer (rs4845327) and its promoter (rs1854779). Together, our results identify a selective sweep for a cis regulatory module for CEU-IVL, highlighting human skin barrier evolution for increased IVL expression out-of-Africa. Selection on alleles contributing to human evolution is not well understood. Here, the authors investigate positive selection on skin barrier adaptation, identifying a selective sweep on involucrin alleles associated with migration out of Africa, and confirming enhancer regulatory effects with functional assays.
... [16][17][18] Vitamin D deficiency has been shown to increase the incidence and severity of asthma with inhaled corticosteroids. 19 Vitamin D not only influences the immune system through its effects on helper T cell type 1 and 2 and regulatory T cells but also modulates chemokines secreted by airway smooth muscle cells. [20][21][22] The present study showed that asthmatics with insufficient Vitamin D had a higher absolute eosinophil count as compared to the sufficient group (p<0.0001). ...
Background: Asthma is the most common chronic respiratory disease among children characterized by reversible airway obstruction. Vitamin D plays an important role in many immune and allergic diseases and it may have a role in asthmatic patients, however this association yet remains uncertain. The present study was designed to assess the level of serum Vitamin D in patients with bronchial asthma and it’s correlation with disease severity.Methods: A prospective observational study was performed from April 2019 to February 2020 in the Paediatric OPD of LNMC and JK Hospital Bhopal. All 90 children with physician diagnosed bronchial asthma (mild, moderate and severe) aged 10 to 18 years of both genders who have come in the OPD (total enumeration sampling) during the above mentioned period were enrolled in to the study. The patients were grouped on the basis of Vitamin D sufficiency and Vitamin D levels were correlated with disease severity.Results: The study comprised 54 boys (60%) and 36 girls (40%) with mean age of 15.1±3.96. Out of 90 children enrolled, 46 had good control over asthma and 37 had uncontrolled asthma. As regards asthma control, 25-OH Vitamin D was lowest among patients with uncontrolled asthma.Conclusions: Vitamin D deficiency was highly prevalent in asthmatic patients and there was a direct and a significant relationship between serum Vitamin D levels, severity of asthma, control of asthma, serum IgE levels and blood eosinophils count. Thus, measuring serum levels of Vitamin D followed by supplementation could be considered in the routine assessment of patients with bronchial asthma.
... Also, the use of inhaled steroids, use of oral steroids, and the total steroid dose all showed significant inverse correlations with vitamin D levels. This findings support that vitamin D enhances the anti-inflammatory effects of glucocorticoids, and could be as a potential steroidsparing agent in patients with moderate-to-severe persistent asthma, as well as a modifier of asthma disease severity [157]. Furthermore, low serum levels of vitamin D at admission have been proposed as an independent prognostic biomarker for greater stroke severity, a poorer functional outcome at discharge, a higher risk of death at one or 2 y, and a greater risk of early recurrent stroke [158,159]. ...
Asthma is a heterogeneous disease, usually characterized by chronic airway inflammation, bronchial reversible obstruction and hyperresponsiveness to direct or indirect stimuli. It is a severe disease causing approximately half a million deaths every year and thus possessing a significant public health burden. Stroke is the second leading cause of death and a major cause of disability worldwide. Asthma and asthma medications may be a risk factors for developing stroke. Nevertheless, since asthma is associated with a variety of comorbidities, such as cardiovascular, metabolic and respiratory, the increased incidence of stroke in asthmatics may be due to a confounding effect. The purpose of this review is to analyze the complex relationship between asthma and stroke.
... [32] Children who are suffering from asthma, also having low serum 25(OH)D level, cognate with high use of corticosteroids. [69] Another study report shows that while the target group is having 50% deficient and 31% insufficient serum 25(OH)D level, the chances of the deficient one getting recurrent otitis media are higher than that of the sufficient one. [70] For a healthy respiratory system, "tight cell junction" is crucial during infectious stage. ...
Vitamin D has potential antimicrobial activity, the deficiency of which has
deleterious effects on the general well‑being and longevity, predisposing major
public health problem worldwide. About 1 billion people have Vitamin D
deficiency, which is prevalent among all ethnicities and age groups throughout
the world. In addition, the incidence of antimicrobial resistance has emerged as
a major threat to public health, and it is estimated to cause 10 million deaths
annually by 2050 throughout the world. Vitamin D, as a mighty antimicrobial
agent, may decrease the occurrence of infection through numerous pathways.
Vitamin D strengthens innate immunity by modulating the production of various
anti‑microbial peptide (AMPs), cytokine, chemokines and interleukin responses.
Vitamin D is responsible for the regulation of >200 genes, including cell
proliferation, differentiation, and apoptotic genes. It acts as the key holder for
modulating systemic inflammation, oxidative stress, and mitochondrial respiratory
functions. Thus, a Vitamin D replete state appears to benefit most infections.
As an antiviral agent, Vitamin D may constitute an inexpensive prophylactic
option either by itself or as a synergistic agent during the treatment of different
viral infections. The present review stipulates the importance of Vitamin D and
its possible mechanisms against treating any kind of viruses. Relevant published
articles were summarized by performing computerized literature searches (searches
were made in PubMed/Medline, EMBASE, ScienceDirect, and Scirus) of different
authentic databases using the following keywords: Vitamin D, VDR, infections,
antimicrobial peptides, viruses, and COVID‑19. The future for the sunshine
vitamin as an antiviral agent looks brighter. More scientific proposition entailing
in vitro, in vivo, or genomic studies are required to understand how important
Vitamin D is against viral infections.
... VDR is found in all tissues, including bronchial epithelial cells and lung fibroblasts (8). Several epidemiological and clinical studies have linked VitD deficiency to various respiratory diseases such as asthma (9)(10)(11), chronic obstructive pulmonary disease (12), cystic fibrosis, and respiratory infections (13). Prenatal VitD deficiency may cause diminished tracheal and bronchial cartilage formation and decreased large airway diameter, leading to increased airway resistance (14). ...
Vitamin D (VitD) has pleiotropic effects. VitD deficiency is closely involved with obesity, and may contribute to the development of lung fibrosis and aggravation of airway hyperresponsiveness (AHR). We evaluated the causal relationship between VitD deficiency and the lung pathologies associated with obesity. In vivo effect of VitD supplementation were analyzed using high fat diet (HFD) induced obese mice and TGF-β1 triple transgenic mice. Effects of VitD supplementation were also evaluated in both BEAS-2B and primary lung cells from the transgenic mice. Obese mouse had decreased 25-OH VitD and VitD receptor expressions with increases of insulin resistance, renin and angiotensin-2 system (RAS) activity, and leptin. In addition, lung pathologies such as a modest increase in macrophages, enhanced TGF-β1, IL-1β, and IL-6 expression, lung fibrosis, and AHR were found. VitD supplementation to HFD induced obese mice recovered these findings. TGF-β1-overexpressing transgenic mice enhanced macrophages in BALF, lung expression of RAS, epithelial mesenchymal transition markers, AHR, and lung fibrosis. VitD supplementation also attenuated these findings in addition to the attenuation of the expressions of TGF-β1, and phosphorylated Smad-2/3 in lung. Supplementing in vitro-stimulated BEAS-2B and primary lung cells with VitD inhibited TGF-β1 expression, supporting the suppressive effect of VitD for TGF-β1 expression. These results suggest that obesity leads to VitD deficiency and worsens insulin resistance while enhancing the expression of leptin, RAS, TGF-β1, and pro-inflammatory cytokines. These changes may contribute to the development of lung fibrosis and AHR. VitD supplementation rescues these changes and may have therapeutic potential for asthma with obesity.
... 11 Inhibition process of Allergic rhinitis pathophysiology by vitamin D may reduce the clinical nasal symptoms. 9,12,13 Recently, many studies reported that vitamin D plays a critical role in Allergic rhinitis, however, this association yet remains unclear. The study aimed to evaluate total nasal symptom scores (TNSS), serum IgE, serum absolute eosinophil count (AEC) in patients of AR, pre and post-treatment with and without supplementation of vitamin D. ...
... 13 Other studies in India have also found a high prevalence of vitamin D deficiency in asymptomatic Indian children. 6,14 However, the prevalence of deficiency in the control group is higher than that found in the Iranian study. 12 There was a statistically significant difference in vitamin D levels between the cases and the controls (p=0.008). ...
Background: Asthma is one of the most common chronic respiratory diseases worldwide. Its exact cause remains unknown. Vitamin D has been implicated as a critical regulator of immunity and found to be associated with several immune mediated diseases. Recently there has been increasing interest in the possible link between vitamin D and asthma. Hence, we planned this study to assess the existence of any correlation between asthma and vitamin D levels in India.Methods: Fifty consecutive cases of clinically diagnosed asthma attending asthma clinic and those admitted in IMCH Calicut, Kerala, India were included in the study and administered detailed questionnaire. Routine physical examination and investigation as per the protocol in asthma clinic were done. Blood was drawn for 25 hydroxy cholecalciferol and serum analyzed by Roche Elecsys chemiluminescence assay. Controls were selected only after all fifty cases were selected. Vitamin D levels were assayed in the same manner as in patients with asthma. Vitamin D levels were then analyzed with other parameters and variables. Statistical analysis was performed using SPSS software, version 16.Results: Prevalence of vitamin D deficiency is high in study population. The difference in vitamin D levels between cases and controls is significant.Conclusions: More studies need to be done to ascertain the relationship between asthma and vitamin D in developing countries like India.
... Associations between vitamin D deficiency and asthma has also been observed in other studies [9,10], but not consistently [11]. Vitamin D deficiency has been shown to increase the incidence and severity of asthma as well as the efficacy of preventive therapy with inhaled corticosteroids [12]. Vitamin D not only influences the immune system through its effects on helper T cell type 1 and 2 and regulatory T cells [13,14] but also modulates chemokines secreted by airway smooth muscle cells [15]. ...
Objective: To study the association between asthma control and serum 25OH Vitamin D
levels in children with moderate persistent asthma on preventer therapy. Methods:
Children aged 6-18 years, with moderate persistent asthma, on preventer therapy for ≥2
months were included. Control was categorized as good, partial or poor as per GINA
guidelines. Serum 25 (OH) Vitamin D levels were measured and their relationship with the
level of control was studied. Results: Out of 50 children enrolled, 22 had well-controlled
asthma, and 21 had partially controlled asthma. Vitamin D was deficient in 30 children and
insufficient in 18 children. Children with vitamin D deficiency had significantly less well-
controlled asthma as compared to those with insufficient or sufficient levels of 25 (OH)
vitamin D (13.3% vs 88.9 % vs 100%). Conclusion: Vitamin D deficiency is associated with
suboptimal asthma control.
... The use of vitamin D is justified by the growing evidence that normal values of this vitamin in infected patients can enhance immunity against pathogen and improve immune recovery during treatment with antiretroviral (99,(102)(103)(104)(105)(106)(107). In addition, previous studies have demonstrated the role of vitamin D in preventing asthma and in improving the severity of asthmatic symptoms (108). A systematic review and metaanalysis published in 2017 identified 25 eligible randomized, double-blind, placebo-controlled trials with a total of 11,321 participants, whose effect of vitamin D supplementation on the risk of acute respiratory tract infection was assessed. ...
The pandemic caused by the new coronavirus (SARS-Cov-2) has encouraged numerous in vitro studies and clinical trials around the world, with research groups testing existing drugs, novel drug candidates and vaccines that can prevent or treat infection caused by this virus. The urgency for an effective therapy is justified by the easy and fast viral transmission and the high number of patients with severe respiratory distress syndrome who have increasingly occupied intensive care hospital beds, leading to a collapse in health systems in several countries. However, to date, there is no sufficient evidence of the effectiveness of any researched therapy. The off-label or compassionate use of some drugs by health professionals is a reality in all continents, whose permission by regulatory agencies has been based on the results of some clinical trials. In order to guide decision-making for the treatment of COVID-19, this review aims to present studies and guidelines on the main therapies that have been and are currently being tested against SARS-CoV-2 and to critically analyze the reported evidences.
... Oral corticoid therapy for exacerbation control and hospitalization for acute asthma attack management were not found to be associated with a suboptimal serum 25-OH-VitD status. These findings are in contrast with other studies that reported that a suboptimal serum 25-OH-VitD level is associated with increased oral corticosteroid use [28]. Further, vitamin D 3 supplementation has been shown to lower the frequency of asthma attacks [29] and exacerbations requiring systemic corticosteroid therapy [30]. ...
Even though vitamin D is widely acknowledged as having a potential immunomodulatory role in asthma, its exact beneficial mechanisms are yet to be clarified. An optimal serum 25-hydroxy-vitamin D (25-OH-VitD) level in pediatric asthma patients might not rely solely on the effect of dose-dependent vitamin D 3 intake, but might also be influenced by factors related to insufficient asthma control. We aimed to survey the prevalence of serum 25-OH-VitD deficiency and analyze whether suboptimal levels were associated with asthma severity factors. The current cross-sectional study enrolled 131 pediatric asthma or asthma-suggestive recurrent wheezing patients, for whom serum 25-OH-VitD, IgE, and eosinophil count were assessed. The prevalence of suboptimal serum 25-OH-VitD was 58.8%. A suboptimal vitamin D status was associated with asthma exacerbation in the previous month (p = 0.02). Even under seasonal oral vitamin D 3 supplementation, patients with a positive history of asthma attack in the previous four weeks presented significantly lower serum 25-OH-VitD concentrations, compared to their peers with no disease exacerbation. In conclusion, sequential measurements of serum 25-OH-VitD might prove useful for future studies evaluating the dynamic changes in vitamin D 3 status in regard to asthma, especially in symptomatic patients.
... Por otro lado, la administración sostenida de glucocorticoides puede dar lugar a una alteración del metabolismo del cortisol, incluido el síndrome de Cushing y la disminución de los niveles séricos de vitamina D 74 , hecho asociado, a su vez, a un exceso de ECV 75,76 . La vitamina D es un modulador reconocido de la respuesta inmunitaria, que se requiere para proporcionar una respuesta fisiológica adecuada a las enfermedades inflamatorias y medidas por el sistema inmunitario. ...
Módulo 1
Asma
Patología intersticial
Patología vascular pulmonar
... Table 2; eFigure in Supplement 2). The proportion of participants whose inhaled corticosteroid dose could be reduced (halved) at the midpoint of the trial was not significantly different between the vitamin D 3 ...
Importance
Severe asthma exacerbations cause significant morbidity and costs. Whether vitamin D3 supplementation reduces severe childhood asthma exacerbations is unclear.
Objective
To determine whether vitamin D3 supplementation improves the time to a severe exacerbation in children with asthma and low vitamin D levels.
Design, Setting, and Participants
The Vitamin D to Prevent Severe Asthma Exacerbations (VDKA) Study was a randomized, double-blind, placebo-controlled clinical trial of vitamin D3 supplementation to improve the time to severe exacerbations in high-risk children with asthma aged 6 to 16 years taking low-dose inhaled corticosteroids and with serum 25-hydroxyvitamin D levels less than 30 ng/mL. Participants were recruited from 7 US centers. Enrollment started in February 2016, with a goal of 400 participants; the trial was terminated early (March 2019) due to futility, and follow-up ended in September 2019.
Interventions
Participants were randomized to vitamin D3, 4000 IU/d (n = 96), or placebo (n = 96) for 48 weeks and maintained with fluticasone propionate, 176 μg/d (6-11 years old), or 220 μg/d (12-16 years old).
Main Outcomes and Measures
The primary outcome was the time to a severe asthma exacerbation. Secondary outcomes included the time to a viral-induced severe exacerbation, the proportion of participants in whom the dose of inhaled corticosteroid was reduced halfway through the trial, and the cumulative fluticasone dose during the trial.
Results
Among 192 randomized participants (mean age, 9.8 years; 77 girls [40%]), 180 (93.8%) completed the trial. A total of 36 participants (37.5%) in the vitamin D3 group and 33 (34.4%) in the placebo group had 1 or more severe exacerbations. Compared with placebo, vitamin D3 supplementation did not significantly improve the time to a severe exacerbation: the mean time to exacerbation was 240 days in the vitamin D3 group vs 253 days in the placebo group (mean group difference, −13.1 days [95% CI, −42.6 to 16.4]; adjusted hazard ratio, 1.13 [95% CI, 0.69 to 1.85]; P = .63). Vitamin D3 supplementation, compared with placebo, likewise did not significantly improve the time to a viral-induced severe exacerbation, the proportion of participants whose dose of inhaled corticosteroid was reduced, or the cumulative fluticasone dose during the trial. Serious adverse events were similar in both groups (vitamin D3 group, n = 11; placebo group, n = 9).
Conclusions and Relevance
Among children with persistent asthma and low vitamin D levels, vitamin D3 supplementation, compared with placebo, did not significantly improve the time to a severe asthma exacerbation. The findings do not support the use of vitamin D3 supplementation to prevent severe asthma exacerbations in this group of patients.
Trial Registration
ClinicalTrials.gov Identifier: NCT02687815
D Vitamini Kimyasal Yapısı ve Metabolizması Hülya Cenk D Vitamini Ve Genetik Aydın Rüstemoğlu D Vitamininin Normal Serum Düzeyleri, D Vitamin Düzeylerini Etkileyen Faktörler Ve D Vitamini Yetmezliği Sabiye Akbulut Serum D Vitamininin Ölçümü Andaç Uzdoğan, Çiğdem Yücel D Vitamini Biyoyararlanımı ve Doğal Beslenme Kaynakları Atilla Çifci, Halil İbrahim Yakut Sistemik D Vitamini Tedavi Ajanları, Biyoyararlanımı ve Tedavi Yönetimi Işıl Deniz Oğuz Topikal D Vitamini Tedavisi, Tedavi Yönetimi ve Kullanıldığı Hastalıklar Dursun Türkmen Deride D Vitamini Sentezi Mekanizmaları Abdullah Demirbaş, Ömer Faruk Elmas Güneşten Koruyucu Kullanımı ve D Vitamini Nursel Dilek, Yunus Saral D Vitamininin Deri Yapısı ve Fizyolojisine Etkisi Pelin Hızlı Deri Yaşlanması ve D Vitamini Ülker Gül Psoriasis ve D Vitamini Ülker Gül Psöriatik Artrit ve D Vitamini Mehmet Uçar Atopik Dermatit ve D Vitamini Ayşegül Ertuğrul, İlknur Bostancı Mast Hücresi ve Kutanöz Mastositozda D Vitamini Selçuk Doğan, Tülin Çataklı, İlknur Bostancı Ürtiker ve D Vitamini Kemal Özyurt Kaşıntı ve D Vitamini Kübra Yüce Atamulu Likenoid Dermatozlar ve D Vitamini Nihal Altunışık Vitiligo ve D Vitamini Ayşe Akbaş Melasma ve D Vitamini İbrahim Etem Arıca Rozase ve D Vitamini Nalan Saraç Akne ve D Vitamini Selma Korkmaz Hidradenitis Süpürativa ve D Vitamini Yılmaz Ulaş Seboreik Dermatit ve D Vitamini Dilek Başaran Otoimmün Büllöz Hastalıklar ve D Vitamini Sezgi Sarıkaya Solak Bağ Doku Hastalıkları ve D Vitamini Kevser Gök Behçet Hastalığı ve D Vitamini Şule Ketenci Ertaş, Ragıp Ertaş İdiyopatik Fotodermatozlar ve D Vitamini Bülent Nuri Kalaycı İktiyozis ve D Vitamini Tubanur Çetinarslan Epidermolizis Bülloza ve Vitamin D Eda Haşal Kseroderma Pigmentozum, Epidermodisplasia Verrusiformis ve D Vitamini Derya Yayla Nevüsler ve D Vitamini Serpil Şener, Suat Sezer Aktinik Keratoz ve Seboreik Keratozda D Vitamini Mahmut Sami Metin Deri Maliniteleri ve D Vitamini Sevda Önder Vaskülitler ve Vitamin D Havva Hilal Ayvaz Venöz Trombozis ve D Vitamini Cahit Yavuz Yara İyileşmesi ve D Vitamini Bülent Nuri Kalaycı Diyabetik Ayak Ülseri ve D Vitamini Gözde Ulutaş Demirbaş, Abdullah Demirbaş Granülomatöz Hastalıklar ve D Vitamini Selma Bakar Dertlioğlu Deri Enfeksiyonları ve Vitamin D Atıl Avcı Oral Mukoza Hastalıkları ve D Vitamini Ali İhsan Güleç Tırnak Sağlığı ve Hastalıklarında D Vitamini Hülya Cenk Alopesiler ve D Vitamini Munise Daye Hirsutizm ve D Vitamini Efşan Gürbüz Yontar Sistemik Kortikosteroid Kullanımında D Vitamini Desteği Selma Korkmaz Fototerapi ve D Vitamini Tuğba Özkök Akbulut Covıd-19 Ve Vitamin D Sibel Altunışık Toplu D Vitamini Tedavisinin Yan Etkileri ve D Vitamini Tedavisi Sürecinde Dikkat Edilecek Hususlar Dursun Türkmen, Nihal Altunışık D Vitamini Ve İlaç İlaç Etkileşimleri Şule Gökşin D Vitamini İntoksikasyonu Bedriye Müge SÖNMEZ
Rationale:
The role and timing of vitamin D supplementation in the prevention of asthma has not been fully elucidated.
Objective:
Describe the association between prenatal and postnatal vitamin D with offspring asthma outcomes in participants of the Vitamin D Antenatal Asthma Reduction Trial.
Methods:
We classified 748 mother-offspring pairs into 4 groups based on mother's randomization to high-dose vs low-dose (4400 IU vs 400 IU) vitamin D supplementation during pregnancy, and offspring parent-reported high-dose vs low-dose (≥ 400 IU vs < 400 IU) vitamin D supplementation as estimated by intake of vitamin D drops or infant formula. We used logistic regression to test the association of the 4 vitamin D exposure groups, "Mother-low/Infant-low [reference]," "Mother-high/Infant-high," "Mother-high/Infant-low," and "Mother-low/Infant-high" with offspring asthma/recurrent wheeze by age 3 years, and active asthma and atopic asthma at age 6 years.
Results:
The risk of asthma/recurrent wheeze at 3 years was lowest in the "Mother-high/Infant-low" group (adjusted OR compared to "Mother-low/Infant-low" 0.39, 95% CI 0.16-0.88, p = .03). When stratifying by history of exclusive breastfeeding until age 4 months, the protective effect of the "Mother-high/Infant-low" group was seen only among exclusively breastfed infants (OR compared to "Mother-low/Infant-low" 0.19, 95% CI 0.04-0.68, p = .02). We did not observe any significant associations with active asthma at age 6 years or atopic asthma at age 6 years.
Conclusions:
We observe that high-dose prenatal and low-dose postnatal vitamin D supplementation may be associated with reduced offspring asthma or recurrent wheeze by age 3 years, however this association may be confounded by the protective effect of breastfeeding.
The obese asthma syndrome (OAS) is characterized by increased airway inflammation and impaired lung function. Obesity-induced inflammation, characterized by elevated pro-inflammatory cytokines and reduced anti-inflammatory adipokines, contributes to airway inflammation and asthma symptoms. Asthmatic patients with obesity often have a poor response to inhaled corticosteroids (ICS), which are the mainstay of asthma treatment. They achieve less asthma control, more hospitalizations, and experience a poorer quality of life. The detrimental effects of obesity on lung function and the additive or synergistic effects of systemic inflammation contribute to this reduced response to glucocorticoids. Additionally, studies have suggested a potential association between vitamin D deficiency, obesity, and asthma exacerbations. Low vitamin D levels have also been linked to glucocorticoid resistance, while in vitro evidence suggests that vitamin D can enhance the effectiveness of glucocorticoids. Weight loss through bariatric surgery shows promising results in improving asthma control and reducing airway inflammation.
For many years, vitamin D has been acknowledged for its role in maintaining calcium and phosphate balance. However, in recent years, research has assessed its immunomodulatory role and come up with conflicting conclusions. Because the vitamin D receptor is expressed in a variety of immune cell types, study into the precise role of this molecule in diseases, notably autoimmune disorders, has been made possible. The physiologically activated version of vitamin D also promotes a tolerogenic immunological condition in addition to modulating innate and acquired immune cell responses. According to a number of recent studies, this important micronutrient plays a complex role in numerous biochemical pathways in the immune system and disorders that are associated with them. Research in this field is still relatively new, and some studies claim that patients with severe autoimmune illnesses frequently have vitamin D deficiencies or insufficiencies. This review seeks to clarify the most recent research on vitamin D's immune system-related roles, including the pathophysiology of major disorders.
Vitamin D has anti-inflammatory properties by multiple mechanisms. Vitamin D deficiency has been associated with increased inflammation, exacerbations, and overall worse outcomes in pediatric asthma and is seen in asthmatic children with obesity. Also, given the increase in the prevalence of asthma over the last few decades, there has been enormous interest in vitamin D supplementation as a potential therapeutic option. However, recently there have been opposite results studies suggest no strong association between vitamin D levels or vitamin D supplements and childhood asthma. Additionally, recently there have been exciting reports that obesity and vitamin D deficiency has been associated with increased asthma symptoms. Thus, this review will summarize the findings from clinical trials regarding the role of vitamin D in pediatric asthma and analyze the study trend of vitamin D for two decades.
IntroductionIn this study, it was aimed to compare the effects of both melatonin and 25-hydroxyvitamin D3, defined as an immune modulator, on laboratory diagnostic criteria parameters and disease activity in patients with systemic lupus erythematosus (SLE).Methods
The study included 56 women with SLE and 40 healthy women (control group). Melatonin and 25-hydroxyvitamin D3 levels of patients and healthy individuals included in the study were examined. In addition, leukocytes, lymphocytes, platelets, C3, C4, anti-double-stranded DNA (Anti-dsDNA), antinuclear antibody, and SLE disease activity index (SLEDAI) were analyzed in women with SLE. Patients were divided into four subgroups according to SLEDAI.ResultsMelatonin and 25-hydroxyvitamin D3 levels of women with SLE were lower than healthy women (p < 0.001). Both melatonin and 25-hydroxyvitamin D3 levels were not correlated with laboratory diagnostic criteria parameters. Only 25-hydroxyvitamin D3 levels were correlated with leukocyte levels (p < 0.01). There was no significant difference between the melatonin levels of the subgroups. The 25-hydroxyvitamin D3 levels of the subgroup without disease activity were higher than levels of the subgroups with disease activity (p < 0.05). There was a negative correlation between SLEDAI score and 25-hydroxyvitamin D3 levels (p < 0.05).Conclusion
Women with SLE had lower melatonin and 25-hydroxyvitamin D3 levels than healthy women. On the other hand, parameters of laboratory diagnostic criteria of SLE disease were not related. Only 25-hydroxyvitamin D3 levels were inversely related leukocyte levels. SLE disease activity was not correlated with melatonin levels but negatively correlated with 25-hydroxyvitamin D3 levels.
Key Points
• Women with SLE have low levels of melatonin and 25-hydroxyvitamin D3.
• Melatonin and 25-hydroxyvitamin D3 levels are not related to the laboratory diagnostic criteria parameters for SLE disease.
• Low levels of melatonin and 25-hydroxyvitamin D3 may be a factor in the unbalanced immune system of SLE.
• Supplementation of melatonin and 25-hydroxyvitamin D3 may be recommended for women patients with SLE.
Latar belakang. Dampak vitamin D sebagai immunomodulator dan anti-inflamasi pada penderita asma dapat menjadi faktor proteksi yang baik. Dalam berbagai penelitian, prevalensi defisiensi vitamin D di Indonesia cukup tinggi. Oleh karena itu, perlu diteliti kadar vitamin D plasma dalam hubungannya dengan derajat kekerapan pada asma, sebagai pertimbangan pemberian terapi suportif pada pasien anak dengan asma.
Tujuan. Menganalisis pengaruh kadar vitamin D terhadap derajat kekerapan pada asma anak di RSUD Dr. Moewardi Surakarta.
Metode. Studi cross sectional terhadap pasien anak dengan asma bronkial berusia 6-18 tahun yang datang ke poliklinik anak di RSUD Dr. Moewardi, Surakarta. K Kadar 25(OH)D dalam darah diperiksa dan dianalisis korelasinya dengan derajat kekerapan asma menggunakan korelasi Spearman, dengan nilai signifikan bila p
Due to its imunomodulatory properties, vitamin D has a potentially growing role in chronic diseases: malignant, cardiovascular, autoimmune and chronic lung diseases. Asthma is chronic inflammatory disease of airways. Prevalence of asthma and prevalence of vitamin D insufficiency is constantly rising in past decades. According to the numerous study results we can hypothesize that vitamin D insufficiency can be important contributor to pathogenesis, stage, disease control and therapeutic response in asthma. Vitamin D has antimicrobial properties as well, because of its influence on catelicidin, human peptide produced by neutrophils, macrophages, skin, respiratory an digestive tract cells with wide antimicrobial activity (Gram-positive and Gram-negative bacteria, some viruses and fungus) (18). Recent studies provide growing evidence in favor of vitamin D supplementation in asthma.
Background: Allergic Rhinitis (AR) is one of the inflammatory diseases of the nasal mucosa, caused by immunoglobulin E (IgE) after allergens exposure, Severity measurement of the AR symptoms can be conducted subjectively by counting the total nasal symptom score (TNSS) and objectively by counting the serum IgE levels. Vitamin D (VD) plays a significant part in inborn and adaptive immunity; however, this is not completely understood. It is reported that over 900 genes are regulated by VD. The aim of this study is to assess the role of VD supplementation in AR. Methods: This prospective randomized controlled study was carried out on 90 patients Test group (n = 45): received standard medications and supplementation of oral VD3 (cholecalciferol; 1000 IU) for 3 months. Control group (n = 45): received standard medications without supplementation of oral VD3. Results: Comparison between both groups showed insignificant difference between both groups in VD level at the start of the study. According to TNSS in test group, there was significant improvement after 3 months compared to before the study. According to TNSS in control group, there was significant improvement after 3 months than before the study. There was significant improvement in test group than control group as regard to TNSS after 3 months. Conclusions: There was highly significant reduction in the TNSS after VD supplementation. Thus, VD supplementation alters the course of AR towards clinical improvement.
Asthma is chronic eosinophilic bronchitis with the dominancy of T helper 2 (Th2) inflammation. However, patients with asthma and metabolic dysfunction have pathogenic and pathological differences from those with Th2 inflammation. Metabolic dysfunction, typically presented as metabolic syndrome, has several important clinical components including central obesity, insulin resistance or glucose intolerance, dyslipidemia, and vitamin D deficiency. Data from large epidemiological studies support the significance of these components in the control of asthma and their contribution to airway remodeling, suggesting the presence of an asthma phenotype with metabolic dysfunction. These components are quite interactive with each other, so it is difficult to reveal the individual role of each. It is well known that asthma is difficult to treat in patients with obesity, due in part to inadequate response to inhaled corticosteroids. Additionally, vitamin D deficiency and insulin resistance have been regarded as aggravating factors of asthma control and airway remodeling. Recent clinical and in vivo studies have revealed the specific mechanisms of these components, which may aggravate asthma control and airway remodeling. In this review article, I summarize the recent studies and unmet needs for patients with asthma and metabolic dysfunction.
Assessment of asthma comorbidities, conditions that adversely affect the pathobiology of asthma or impair its response to therapies, is a fundamental step in the evaluation and management of patients with difficult-to-treat asthma. Identifying and effectively treating asthma comorbidities, such as obesity, obstructive sleep apnea, and chronic sinusitis with nasal polyps may improve asthma control and reduce exacerbations. Additionally, identifying comorbid T2 inflammatory conditions may help guide optimal selection of biologic therapies. Here, we describe common comorbid conditions found in adult and pediatric difficult-to-control asthma, discuss evidence for the association with asthma morbidity and treatment benefit, and provide information on how and when to assess comorbidities.
Bronchial asthma (BA) is a common disease of airways in children characterized by chronic inflammation, as well as respiratory symptoms varying in time and intensity. In recent years, an increase in the prevalence of BA has been seen, both among the adult and children’s population. The current trend stimulates scientists to continue studying the probable influence of various factors on this process, including the role of micronutrient deficiency, especially antioxidants, methylene donors and vitamin D (VD). Hypovitaminosis D has been considered as a provoking factor affecting the pathogenesis of various pathological processes. The results of numerous studies confirm the opinion that VD affects the intensity of inflammation, reducing the produc-tion of proinflammatory cytokines and secretion of mucus, and stimulates the secretion of the antiinflammatory cytokine IL-10. VD-regulated genes encode the synthesis of antimicrobial peptides that provide protection against bacteria and viruses provoking BA exacerbations. The article discusses the role of tissue growth factor (TGF-β) as an initiator of fibrosis in the epithelial cells of the respiratory tract through the activation of epithelial mesenchymal transition signals, and also discusses the inhibitory effect of VD on the processes of airway remodeling in BA. To-day it is known that VD can inhibit the progression of pulmonary fibrosis in various ways, in-cluding suppression of the expression of TGF, inhibition of the motility of epithelial cells induced by TGF-β, reduction of the excessive activation of RAS (antifibrotic effect), increase in the level of TGF antagonist. Separately, the issue of the possible strengthening of the antioxidant defense of the body in BA is considered through optimization of the supply of the organism with VD. Conclusion. Thus, taking into account the fact that to date, the results of clinical studies of the use of VD in the treatment of BA gave conflicting results, additional studies are needed to address controversial issues regarding the role of VD deficiency in the pathogenesis of BA and its control. Further understanding of the mechanisms underlying the airway remodeling will help develop a set of measures aimed at minimizing the risk of structural changes in AD.
Asthma in children is the most prevalent allergic disease worldwide that has become a major public health priority. The objective of this study was to examine the relationship between baseline serum vitamin D status, spirometry and Fractional exhaled Nitric Oxide levels (FeNO) in 64 Greek children with ‘mild asthma’ aged 5-12 years (51.6% male) in a dietary intervention study. We hypothesized that baseline serum vitamin D levels modify the beneficial response of fatty fish intake on pulmonary function in asthmatic children following a Mediterranean diet. The intervention group consumed two fatty fish meals/week (≥ 150 g cooked filleted fish/meal) as part of the Mediterranean diet for six months, and the control group, their usual diet. Baseline serum 25(OH)D was determined using Enzyme-Linked Immuno Assay and defined as sufficient levels of 25(OH)D ≥ 25 ng/mL. Only 36% of children were graded as sufficient in 25(OH)D levels on entry into the study with a higher proportion of girls insufficient than boys (61% vs 39% respectively). Participants with sufficient levels of serum 25(OH)D at baseline, consuming the intervention diet increased FEV1/FVC by 4.89 units (β = 4.89; 95%CI: 1.19- 8.61; p = 0.013) and FEF25-75% by 12.83 units (β = 12.83; 95%CI: 4.27-21.40; p = 0.006) compared to controls. No significant differences in pulmonary function or FeNO were observed for those with insufficient levels of 25(OH) D in the intervention or control groups. In conclusion, sufficient serum vitamin D levels enhanced ventilatory function in response to a dietary intervention in asthmatic children.
To determine the prevalence of 25-hydroxyvitamin D (25[OH]D) deficiency and associations between 25(OH)D deficiency and cardiovascular risk factors in children and adolescents.
With a nationally representative sample of children aged 1 to 21 years in the National Health and Nutrition Examination Survey 2001-2004 (n = 6275), we measured serum 25(OH)D deficiency and insufficiency (25[OH]D <15 ng/mL and 15-29 ng/mL, respectively) and cardiovascular risk factors.
Overall, 9% of the pediatric population, representing 7.6 million US children and adolescents, were 25(OH)D deficient and 61%, representing 50.8 million US children and adolescents, were 25(OH)D insufficient. Only 4% had taken 400 IU of vitamin D per day for the past 30 days. After multivariable adjustment, those who were older (odds ratio [OR]: 1.16 [95% confidence interval (CI): 1.12 to 1.20] per year of age), girls (OR: 1.9 [1.6 to 2.4]), non-Hispanic black (OR: 21.9 [13.4 to 35.7]) or Mexican-American (OR: 3.5 [1.9 to 6.4]) compared with non-Hispanic white, obese (OR: 1.9 [1.5 to 2.5]), and those who drank milk less than once a week (OR: 2.9 [2.1 to 3.9]) or used >4 hours of television, video, or computers per day (OR: 1.6 [1.1 to 2.3]) were more likely to be 25(OH)D deficient. Those who used vitamin D supplementation were less likely (OR: 0.4 [0.2 to 0.8]) to be 25(OH)D deficient. Also, after multivariable adjustment, 25(OH)D deficiency was associated with elevated parathyroid hormone levels (OR: 3.6; [1.8 to 7.1]), higher systolic blood pressure (OR: 2.24 mmHg [0.98 to 3.50 mmHg]), and lower serum calcium (OR: -0.10 mg/dL [-0.15 to -0.04 mg/dL]) and high-density lipoprotein cholesterol (OR: -3.03 mg/dL [-5.02 to -1.04]) levels compared with those with 25(OH)D levels > or =30 ng/mL.
25(OH)D deficiency is common in the general US pediatric population and is associated with adverse cardiovascular risks.
Maternal vitamin D intake during pregnancy has been inversely associated with asthma symptoms in early childhood. However, no study has examined the relationship between measured vitamin D levels and markers of asthma severity in childhood.
To determine the relationship between measured vitamin D levels and both markers of asthma severity and allergy in childhood. Methods: We examined the relation between 25-hydroxyvitamin D levels (the major circulating form of vitamin D) and markers of allergy and asthma severity in a cross-sectional study of 616 Costa Rican children between the ages of 6 and 14 years. Linear, logistic, and negative binomial regressions were used for the univariate and multivariate analyses.
Of the 616 children with asthma, 175 (28%) had insufficient levels of vitamin D (<30 ng/ml). In multivariate linear regression models, vitamin D levels were significantly and inversely associated with total IgE and eosinophil count. In multivariate logistic regression models, a log(10) unit increase in vitamin D levels was associated with reduced odds of any hospitalization in the previous year (odds ratio [OR], 0.05; 95% confidence interval [CI], 0.004-0.71; P = 0.03), any use of antiinflammatory medications in the previous year (OR, 0.18; 95% CI, 0.05-0.67; P = 0.01), and increased airway responsiveness (a < or =8.58-mumol provocative dose of methacholine producing a 20% fall in baseline FEV(1) [OR, 0.15; 95% CI, 0.024-0.97; P = 0.05]).
Our results suggest that vitamin D insufficiency is relatively frequent in an equatorial population of children with asthma. In these children, lower vitamin D levels are associated with increased markers of allergy and asthma severity.
Given the recent spate of reports of vitamin D deficiency, there is a need to reexamine our understanding of natural and other sources of vitamin D, as well as mechanisms whereby vitamin D synthesis and intake can be optimized. This state-of-the-art report from the Drug and Therapeutics Committee of the Lawson Wilkins Pediatric Endocrine Society was aimed to perform this task and also reviews recommendations for sun exposure and vitamin D intake and possible caveats associated with these recommendations.
Pharmacologic doses of corticosteroids impair intestinal calcium absorption and contribute to negative calcium balance. However, the relationship between the impaired calcium absorption and a possible defect in the conversion of vitamin D to its physiologically active form, 1,25-dihydroxyvitamin D, is unknown. We compared fractional calcium absorption (double-isotope method, 100-mg carrier) and serum 25-hydroxyvitamin D (25-OH-D) (Haddad method) in 27 patients receiving pharmacologic doses of prednisone with 27 age-, sex-, and season-matched normal subjects. In patients receiving high daily doses of prednisone (15-100 mg/day), calcium absorption (P < 0.02) and serum 25-OH-D (P < 0.001) were decreased. However, in patients receiving low doses (8-10 mg/day) or high doses (30-100 mg) of prednisone on an alternate-day schedule, both of these parameters were normal. Calcium absorption in the patients treated with daily prednisone correlated inversely with the dose of corticosteroids (r = -0.52, P < 0.025) and, in all steroid-treated patients, correlated directly with serum 25-OH-D (r = 0.58, P < 0.01). In four patients who received high-dose corticosteroid therapy for an average of 4 wk, serum 25-OH-D decreased by 35.5% from pretreatment values. Administration of a physiologic or near-physiologic dose of synthetic 1,25-dihydroxyvitamin D(3) (0.4 mug daily for 7 days) to patients receiving high-dose corticosteroids led to an increase in calcium absorption in all patients. These results suggest that calcium malabsorption in the corticosteroid-treated patients is due to a dose-related abnormality of vitamin D metabolism and not to a direct effect of corticosteroids on depressing transmucosal intestinal absorption of calcium.
We previously reported that human CD4+ Tregs secrete high levels of IL-10 when stimulated in the presence of dexamethasone and calcitriol (vitamin D3). We now show that following stimulation by allergen, IL-10-secreting Tregs inhibit cytokine secretion by allergen-specific Th2 cells in an IL-10-dependent manner. A proportion of patients with severe asthma fail to demonstrate clinical improvement upon glucocorticoid therapy, and their asthma is characterized as glucocorticoid resistant (SR, abbreviation derived from "steroid resistant"). Dexamethasone does not enhance secretion of IL-10 by their CD4+ T cells. Addition of vitamin D3 with dexamethasone to cultures of SR CD4+ T cells enhanced IL-10 synthesis to levels observed in cells from glucocorticoid-sensitive patients cultured with dexamethasone alone. Furthermore, pretreatment with IL-10 fully restored IL-10 synthesis in these cells in response to dexamethasone. Vitamin D3 significantly overcame the inhibition of glucocorticoid-receptor expression by dexamethasone while IL-10 upregulated glucocorticoid-receptor expression by CD4+ T cells, suggesting potential mechanisms whereby these treatments may overcome poor glucocorticoid responsiveness. We show here that administration of vitamin D3 to healthy individuals and SR asthmatic patients enhanced subsequent responsiveness to dexamethasone for induction of IL-10. This strongly suggests that vitamin D3 could potentially increase the therapeutic response to glucocorticoids in SR patients.
To investigate whether exposure to high maternal concentrations of 25(OH)-vitamin D in pregnancy poses any risk to the child.
Prospective study.
Princess Anne Maternity Hospital, Southampton, UK.
A group of 596 pregnant women were recruited. A total of 466 (78%) children were examined at birth, 440 (74%) at age 9 months and 178 (30%) at age 9 years.
Maternal 25 (OH)-vitamin D concentrations were measured in late pregnancy. Anthropometry of the child was recorded at birth, 9 months and 9 years. At 9 months, atopic eczema was assessed. At 9 years, children had an echocardiogram and a dual energy x-ray absorptiometry scan, blood pressure, arterial compliance and carotid intima-media thickness were measured and intelligence and psychological function assessed.
There were no associations between maternal 25(OH)-vitamin D concentrations and the child's body size or measures of the child's intelligence, psychological health or cardiovascular system. Children whose mothers had a 25(OH)-vitamin D concentration in pregnancy >75 nmol/l had an increased risk of eczema on examination at 9 months (OR 3.26, 95% CI 1.15-9.29, P=0.025) and asthma at age 9 years (OR 5.40, 95% CI, 1.09-26.65, P=0.038) compared to children whose mothers had a concentration of <30 nmol/l.
Exposure to maternal concentrations of 25(OH)-vitamin D in pregnancy in excess of 75 nmol/l does not appear to influence the child's intelligence, psychological health or cardiovascular system; there could be an increased risk of atopic disorders, but this needs confirmation in other studies.
Maternal intake of vitamin D in pregnancy is a potentially modifiable but understudied risk factor for the development of asthma in children.
We investigated whether maternal vitamin D intake in pregnancy is associated with decreased risks of wheezing symptoms in young children.
Subjects were from a birth cohort recruited in utero with the primary objective of identifying associations between maternal diet during pregnancy and asthma and allergies in children. A random sample of 2000 healthy pregnant women was recruited while attending antenatal clinics at the Aberdeen Maternity Hospital, Scotland, at approximately 12 wk gestation. Maternal vitamin D intake was ascertained from a food-frequency questionnaire completed at 32 wk of gestation. The main outcome measures were wheezing symptoms, spirometry, bronchodilator response, atopic sensitization, and exhaled nitric oxide at 5 y.
Respiratory details through 5 y and maternal food-frequency-questionnaire data were available for 1212 children. In models adjusted for potential confounders, including the children's vitamin D intake, a comparison of the highest and lowest quintiles of maternal total vitamin D intake conferred lower risks for ever wheeze [odds ratio (OR): 0.48; 95% CI: 0.25, 0.91], wheeze in the previous year (OR: 0.35; 95% CI: 0.15, 0.83), and persistent wheeze (OR: 0.33; 95% CI: 0.11, 0.98) in 5-y-old children. In addition, lower maternal total vitamin D intakes in pregnancy were also associated with decreased bronchodilator response (P = 0.04). No associations were observed between maternal vitamin D intakes and spirometry or exhaled nitric oxide concentrations.
Increasing maternal vitamin D intakes during pregnancy may decrease the risk of wheeze symptoms in early childhood.
Vitamin D deficiency and asthma are common at higher latitudes. Although vitamin D has important immunologic effects, its relation with asthma is unknown.
We hypothesized that a higher maternal intake of vitamin D during pregnancy is associated with a lower risk of recurrent wheeze in children at 3 y of age.
The participants were 1194 mother-child pairs in Project Viva-a prospective prebirth cohort study in Massachusetts. We assessed the maternal intake of vitamin D during pregnancy from a validated food-frequency questionnaire. The primary outcome was recurrent wheeze, ie, a positive asthma predictive index (>or=2 wheezing attacks among children with a personal diagnosis of eczema or a parental history of asthma).
The mean (+/-SD) total vitamin D intake during pregnancy was 548 +/- 167 IU/d. By age 3 y, 186 children (16%) had recurrent wheeze. Compared with mothers in the lowest quartile of daily intake (median: 356 IU), those in the highest quartile (724 IU) had a lower risk of having a child with recurrent wheeze [odds ratio (OR): 0.39; 95% CI: 0.25, 0.62; P for trend < 0.001]. A 100-IU increase in vitamin D intake was associated with lower risk (OR: 0.81; 95% CI: 0.74, 0.89), regardless of whether vitamin D was from the diet (OR: 0.81; 95% CI: 0.69, 0.96) or supplements (OR: 0.82; 95% CI: 0.73, 0.92). Adjustment for 12 potential confounders, including maternal intake of other dietary factors, did not change the results.
In the northeastern United States, a higher maternal intake of vitamin D during pregnancy may decrease the risk of recurrent wheeze in early childhood.
Highlights of the National Asthma Education and Prevention Program's Expert Panel Report 3 (EPR-3): Guidelines for the Diagnosis and Management of Asthma-Full Report 2007 are presented in this EPR-3 summary report. The updated guidelines emphasize the importance of asthma control. Asthma control is the degree to which the manifestations of asthma are minimized by therapeutic intervention and the goals of therapy are met. Because asthma is highly variable, the level of control must be monitored on a periodic basis to determine whether therapy should be maintained or adjusted (stepped up if necessary, stepped down if possible). On the other hand, asthma severity is the intrinsic intensity of the disease process, most easily and directly measured in a patient not receiving long-term control therapy. For managing asthma, the recommendation is to assess severity to initiate therapy and assess control to adjust therapy. Recommendations for managing asthma include an expanded section on childhood asthma with addition of an age group 5 to 11 years old (earlier guidelines combined this group with adults). The guidelines provide new recommendations on patient education in settings beyond the physician's office, and new advice for controlling environmental factors that can cause asthma symptoms. The concepts of current impairment (frequency and intensity of symptoms, low lung function, and limitations of daily activities) and future risk (likelihood of exacerbations, progressive loss of lung function, or adverse side effects from medications) support a new approach to assessing and monitoring the patient's level of asthma control through use of multiple measures. The guidelines stress that some patients can still be at high risk for frequent exacerbations even if they have few day-to-day effects of asthma.Moreover, EPR-3 confirms the importance of teaching patients skills to self-monitor and manage asthma and to use a written asthma action plan, which should include instructions for daily treatment and ways to recognize and handle worsening asthma. New recommendations encourage expanding educational opportunities to reach patients in a variety of settings, such as pharmacies, schools, community centers, and patients' homes. A new section addresses the need for clinician education programs to improve communication with patients and to use system-wide approaches to integrate the guidelines into health care practice. The guidelines describe new evidence for using multiple approaches to limit exposure to allergens and other substances that can worsen asthma; research shows that single steps are rarely sufficient. EPR-3 also expands the section on common conditions that can affect asthma and notes that management of these conditions may help to improve asthma control. Expert Panel Report 3 continues the use of a stepwise approach to control asthma. When assessing the level of asthma control to determine the need for adjusting therapy, EPR-3 reconfirms the importance of assessing patient adherence to medication, inhaler technique, and environmental control measures before making a step up in therapy. The stepwise approach expands from 4 steps to 6 steps of care. Medications have been repositioned within these 6 steps. Recommendations on medications are updated to reflect the latest evidence on effectiveness and safety. EPR-3 reaffirms that patients with persistent asthma need both long-term control medications to control asthma and prevent exacerbations and quick-relief medication for symptoms, as needed. EPR-3 also reaffirms that inhaled corticosteroids are the most effective long-term control medication across all age groups. New recommendations on treatment options such as leukotriene receptor antagonists and cromolyn for long-term control; long-acting beta-agonists as adjunct therapy with inhaled corticosteroids; omalizumab for severe asthma; and albuterol, levalbuterol, and corticosteroids for acute exacerbations are included.
Objective
To appraise the data on systemic adverse effects of inhaled corticosteroids.
Methods
A computerized database search from January 1, 1966, through July 31, 1998, using MEDLINE, EMBASE, and BIDS and using appropriate indexed terms. Reports dealing with the systemic effects of inhaled corticosteroids on adrenal gland, growth, bone, skin, and eye, and reports on pharmacology and pharmacokinetics were reviewed where appropriate. Studies were included that contained evaluable data on systemic effects in healthy volunteers as well as in asthmatic children and adults. A statistical meta-analysis using regression was performed for parameters of adrenal suppression in 27 studies.
Results
Marked adrenal suppression occurs with high doses of inhaled corticosteroid above 1.5 mg/d (0.75 mg/d for fluticasone propionate), although there is a considerable degree of interindividual susceptibility. Meta-analysis showed significantly greater potency for dose-related adrenal suppression with fluticasone compared with beclomethasone dipropionate, budesonide, or triamcinolone acetonide, whereas prednisolone and fluticasone propionate were approximately equivalent on a 10:1-mg basis. Inhaled corticosteroids in doses above 1.5 mg/d (0.75 mg/d for fluticasone propionate) may be associated with a significant reduction in bone density, although the risk for osteoporosis may be obviated by postmenopausal estrogen replacement therapy. Although medium-term growth studies showed suppressive effects with 400-µg/d beclomethasone dipropionate, there was no evidence to support any significant effects on final adult height. Long-term, high-dose inhaled corticosteroid exposure increases the risk for posterior subcapsular cataracts, and, to a much lesser degree, the risk for ocular hypertension and glaucoma. Skin bruising is most likely to occur with high-dose exposure, which correlates with the degree of adrenal suppression.
Conclusions
All inhaled corticosteroids exhibit dose-related systemic adverse effects, although these are less than with a comparable dose of oral corticosteroids. Meta-analysis shows that fluticasone propionate exhibits greater dose-related systemic bioactivity compared with other available inhaled corticosteroids, particularly at doses above 0.8 mg/d. The long-term systemic burden will be minimized by always trying to achieve the lowest possible maintenance dose that is associated with optimal asthmatic control and quality of life.
To determine the prevalence of vitamin D deficiency and to examine whether 25-hydroxyvitamin D (25OHD) concentration varies as a function of skin pigmentation, season, sun exposure, breastfeeding, and vitamin D supplementation.
Cross-sectional sample.
Urban primary care clinic.
Healthy infants and toddlers (N = 380) who were seen for a routine health visit.
Primary outcomes were serum 25OHD and parathyroid hormone levels; secondary measures included data on sun exposure, nutrition, skin pigmentation, and parental health habits. Wrist and knee radiographs were obtained for vitamin D-deficient participants.
The prevalence of vitamin D deficiency (< or =20 ng/mL) was 12.1% (44 of 365 participants), and 146 participants (40.0%) had levels below an accepted optimal threshold (< or =30 ng/mL). The prevalence did not vary between infants and toddlers or by skin pigmentation. There was an inverse correlation between serum 25OHD and parathyroid hormone levels (infants: r = -0.27, P < .001; toddlers: r = -0.20, P = .02). In multivariable models, breastfeeding without supplementation among infants and lower milk intake among toddlers were significant predictors of vitamin D deficiency. In vitamin D-deficient participants, 3 participants (7.5%) exhibited rachitic changes on radiographs, whereas 13 (32.5%) had evidence of demineralization.
Suboptimal vitamin D status is common among otherwise healthy young children. Predictors of vitamin D status vary in infants vs toddlers, information that is important to consider in the care of these young patients. One-third of vitamin D-deficient participants exhibited demineralization, highlighting the deleterious skeletal effects of this condition.
Microbial superantigens induce human T-cell resistance to corticosteroids.
Understanding the molecular pathways resulting in corticosteroid-resistant T cells is important because this condition can complicate the treatment of inflammation.
The response of human PBMCs to steroids was assessed by using proliferation assays after stimulation with superantigens or anti-CD3 in the presence of various kinase inhibitors. Glucocorticoid receptor alpha (GCRalpha) localization was defined on the basis of intracellular staining. Protein phosphorylation was measured by means of Western blotting.
In the current study we found that PBMCs stimulated with superantigen, but not anti-CD3, induced corticosteroid-resistant T cells. However, the purified T cells stimulated either with staphylococcal enterotoxin B (SEB) or anti-CD3 are susceptible to corticosteroid inhibition. These results imply that signals on antigen-presenting cells might act in concert with the T-cell receptor to cause steroid resistance. Blockade of CD40-CD40 ligand interaction had no effect on superantigen-induced corticosteroid resistance. However, CD28 costimulation with T-cell receptor activation induced corticosteroid resistance of human T cells in a dose-dependent manner. Superantigen stimulation, compared with anti-CD3 stimulation, was found to induce a more rapid and sustained phosphorylation of mitogen-activated extracellular signal-regulated kinase (ERK). Treatment with PD98059 and UO126 (specific mitogen-activated protein kinase kinase [MEK]/ERK inhibitors), but not a p38 inhibitor or a c-Jun N-terminal kinase inhibitor, restored the response to steroids, as indicated by proliferation assays. Furthermore, purified ERK1 and ERK2 were able to phosphorylate recombinant human GCRalpha directly in an in vitro kinase assay. Of note, superantigen-induced corticosteroid resistance was associated with abrogation of GCRalpha nuclear translocation. This effect could be reversed by treatment with MEK/ERK pathway inhibitors.
These data are compatible with the hypothesis that superantigen-induced corticosteroid resistance involves the Raf-MEK-ERK1/ERK2 pathway of T-cell receptor signaling, which leads to GCRalpha phosphorylation and inhibition of dexamethasone-induced GCRalpha nuclear translocation.
The objective of this study was to determine the vitamin D status and its relationship with disease and therapy features and with bone mineral density in women with systemic lupus erythematosus. Non-pregnant systemic lupus erythematosus women with dual-energy X-ray absorptiometry and vitamin D measurements performed between May 1 2005 and August 31 2006 were studied. In each patient, the lowest T-score of the first dual-energy X-ray absorptiometry scan during the study period was used. In postmenopausal women, a T-score > or = 1.0 standard deviation was considered normal, between -1.0 and -2.5 standard deviations osteopenia and < or = 2.5 standard deviations osteoporosis; in premenopausal women a T-score > or = 2.5 standard deviations was normal and < or = 2.5 standard deviations defined as reduced bone density. 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels were determined at the time of dual-energy X-ray absorptiometry. A 25-hydroxyvitamin D level of <80 nmol/L was defined as sub-optimal and a level <40 nmol/L as deficient. Demographic and clinical variables were investigated for association with vitamin D levels by univariate and multivariate analyses. One-hundred and twenty-four systemic lupus erythematosus women had dual-energy X-ray absorptiometry scans and vitamin D assays performed during the study period. Sub-optimal 25-hydroxyvitamin D levels were found in 82 (66.7%) and deficient 25-hydroxyvitamin D levels in 22 (17.9%) patients. The disease-related features examined at the time of vitamin D assays or bone mineral density showed no correlation with vitamin D levels by univariate analyses. Neither 25-hydroxyvitamin D nor 1,25-dihydroxyvitamin D was associated with bone mineral density status among these patients. A multivariate logistic regression model identified season, cumulative glucocorticoid exposure, and serum creatinine as being associated with 25-hydroxyvitamin D levels, whereas ethnicity, glucocorticoid exposure, and serum creatinine were associated with 1,25-dihydroxyvitamin D levels. In conclusion, sub-optimal vitamin D status is common in women with systemic lupus erythematosus and is related to season, cumulative glucocorticoid dose, and serum creatinine.
Our skin is constantly challenged by microbes but is rarely infected. Cutaneous production of antimicrobial peptides (AMPs) is a primary system for protection, and expression of some AMPs further increases in response to microbial invasion. Cathelicidins are unique AMPs that protect the skin through 2 distinct pathways: (1) direct antimicrobial activity and (2) initiation of a host response resulting in cytokine release, inflammation, angiogenesis, and reepithelialization. Cathelicidin dysfunction emerges as a central factor in the pathogenesis of several cutaneous diseases, including atopic dermatitis, in which cathelicidin is suppressed; rosacea, in which cathelicidin peptides are abnormally processed to forms that induce inflammation; and psoriasis, in which cathelicidin peptide converts self-DNA to a potent stimulus in an autoinflammatory cascade. Recent work identified vitamin D3 as a major factor involved in the regulation of cathelicidin. Therapies targeting control of cathelicidin and other AMPs might provide new approaches in the management of infectious and inflammatory skin diseases.
To appraise the data on systemic adverse effects of inhaled corticosteroids.
A computerized database search from January 1, 1966, through July 31, 1998, using MEDLINE, EMBASE, and BIDS and using appropriate indexed terms. Reports dealing with the systemic effects of inhaled corticosteroids on adrenal gland, growth, bone, skin, and eye, and reports on pharmacology and pharmacokinetics were reviewed where appropriate. Studies were included that contained evaluable data on systemic effects in healthy volunteers as well as in asthmatic children and adults. A statistical meta-analysis using regression was performed for parameters of adrenal suppression in 27 studies.
Marked adrenal suppression occurs with high doses of inhaled corticosteroid above 1.5 mg/d (0.75 mg/d for fluticasone propionate), although there is a considerable degree of interindividual susceptibility. Meta-analysis showed significantly greater potency for dose-related adrenal suppression with fluticasone compared with beclomethasone dipropionate, budesonide, or triamcinolone acetonide, whereas prednisolone and fluticasone propionate were approximately equivalent on a 10:1-mg basis. Inhaled corticosteroids in doses above 1.5 mg/d (0.75 mg/d for fluticasone propionate) may be associated with a significant reduction in bone density, although the risk for osteoporosis may be obviated by post-menopausal estrogen replacement therapy. Although medium-term growth studies showed suppressive effects with 400-microg/d beclomethasone dipropionate, there was no evidence to support any significant effects on final adult height. Long-term, high-dose inhaled corticosteroid exposure increases the risk for posterior subcapsular cataracts, and, to a much lesser degree, the risk for ocular hypertension and glaucoma. Skin bruising is most likely to occur with high-dose exposure, which correlates with the degree of adrenal suppression.
All inhaled corticosteroids exhibit dose-related systemic adverse effects, although these are less than with a comparable dose of oral corticosteroids. Metaanalysis shows that fluticasone propionate exhibits greater dose-related systemic bioactivity compared with other available inhaled corticosteroids, particularly at doses above 0.8 mg/d. The long-term systemic burden will be minimized by always trying to achieve the lowest possible maintenance dose that is associated with optimal asthmatic control and quality of life.
Although vitamin D deficiency has been documented as a frequent problem in studies of young adults, elderly persons, and children in other countries, there are limited data on the prevalence of this nutritional deficiency among healthy US teenagers.
To determine the prevalence of vitamin D deficiency in healthy adolescents presenting for primary care.
A cross-sectional clinic-based sample.
An urban hospital in Boston.
Three hundred seven adolescents recruited at an annual physical examination to undergo a blood test and nutritional and activity assessments.
Serum levels of 25-hydroxyvitamin D (25OHD) and parathyroid hormone, anthropometric data, nutritional intake, and weekly physical activity and lifestyle variables that were potential risk factors for hypovitaminosis D.
Seventy-four patients (24.1%) were vitamin D deficient (serum 25OHD level, </=15 ng/mL [</=37.5 nmol/L]), of whom 14 (4.6%) were severely vitamin D deficient (25OHD level, </=8 ng/mL [</=20 nmol/L]). By using a broader definition (25OHD level, </=20 ng/mL [</=50 nmol/L]), 129 patients (42.0%) were vitamin D insufficient. Serum 25OHD levels were inversely correlated with parathyroid hormone levels (r = -0.29), and were 24% lower during winter compared with summer. In a final multivariate model, season, ethnicity, milk and juice consumption, body mass index, and physical activity were significant independent predictors of hypovitaminosis D.
Vitamin D deficiency was present in many US adolescents in this urban clinic-based sample. The prevalence was highest in African American teenagers and during winter, although the problem seems to be common across sex, season, and ethnicity.
Age, gender, height, ethnicity, and smoking are important determinants of lung function but do not explain all of the variation between individuals. Low concentrations of vitamin D have been associated with a number of diseases, including osteoporosis, hypertension, and type I diabetes. It is possible that serum concentrations of vitamin D might also influence pulmonary function.
To determine the relationship between serum concentrations of 25-hydroxy vitamin D and pulmonary function.Design, setting and participants: The analysis was conducted using data from the Third National Health and Nutrition Examination Survey, which was a cross-sectional survey of the US civilian population that was conducted from 1988 to 1994. The analyses were restricted to 14,091 people who > or = 20 years of age, were interviewed at mobile examination centers, and had undergone spirometry, and in whom serum 25-hydroxy vitamin D levels had been measured.
After adjustment for age, gender, height, body mass index, ethnicity, and smoking history, the mean FEV1 was 126 mL (SE, 22 mL), and the mean FVC was 172 mL (SE, 26 mL) greater for the highest quintile of serum 25-hydroxy vitamin D level (> or = 85.7 nmol/L) compared with the lowest quintile (< or = 40.4 nmol/L; p < 0.0001). With further adjustment for physical activity, the intake of vitamin D supplements, milk intake, and the level of serum antioxidants, the mean difference between the highest and lowest quintiles of 25-hydroxy vitamin D was 106 mL (SE, 24 mL) for FEV1, and 142 mL (SE, 29 mL) for FVC (p < 0.0001).
There is a strong relationship between serum concentrations of 25-hydroxy vitamin D, FEV1, and FVC. Further studies are necessary to determine whether supplementation with vitamin D is of any benefit in patients with respiratory disease.
Oral vitamin D supplementation has been introduced into modern medicine to prevent rickets without the knowledge that this may have profound immunological consequences. The main vitamin D metabolite calcitriol suppresses dendritic cell maturation and consecutive Th(1) cell development, which has independently described as a key mechanism of allergy development. Animal studies and epidemiological surveys now provide a first link of early vitamin D supplementation and later allergy where several vitamin D regulated genes seem to be involved. A randomized clinical trial of vitamin D supplementation could be a further step to follow up the vitamin hypothesis.
Previous studies have found an association between the use of inhaled corticosteroids and fracture, but the extent to which this association is due to inhaled corticosteroids or to related factors, such as the severity of airflow obstruction, is disputed. We report a new approach in which we combine data on people with airflow obstruction from a large Medical Research Council study of the assessment and management of older people in the community with longitudinal data from their computerized general practice records.
Our cohort includes 1,671 study participants with a diagnosis of asthma or COPD (mean age, 80.6 years). We determined the dose-response relationship between inhaled corticosteroid exposure and time to first fracture using Cox regression, allowing for a wide range of potential confounding factors.
During a mean follow-up period of 9.4 years, 982 patients (59%) received a prescription for an inhaled corticosteroid and 187 patients had a fracture. After adjusting for the effects of age and gender, we found a dose-related increase in fracture risk with exposure to inhaled corticosteroids (rate ratio for mean daily dose > 601 mug, 2.53; 95% confidence interval [CI], 1.65 to 3.89; overall trend p < 0.0001). The results were similar after adjusting for oral corticosteroid exposure, airflow obstruction diagnosis, historical fracture, and bronchodilator use (rate ratio, 4.21; 95% CI, 2.19 to 8.13), and also in the subset of people with no exposure to oral corticosteroids (rate ratio, 4.54; 95% CI, 1.23 to 16.74).
Our findings provide further evidence that inhaled corticosteroid use is an independent risk factor for fracture.
The epidemiology of anaphylaxis is uncertain, especially its geographic distribution.
To address this deficit, we examined regional rates of EpiPen prescriptions in the United States.
EpiPen prescriptions in 2004 were obtained for all 50 states and Washington, DC, from NDCHealth, Pharmaceutical Audit Suite (Alpharetta, Ga). Data included the number of total filled prescriptions, including refills, and the actual number of EpiPens prescribed. Several data sets were used to obtain state-specific populations, as well as multiple demographic, health, and weather characteristics. State population was used to calculate the average number of prescriptions written per person.
Overall, there were 1,511,534 EpiPen prescriptions filled during 2004. These prescriptions accounted for 2,495,188 EpiPens. On average, there were 5.71 EpiPens prescribed per 1000 persons. Massachusetts had the highest number of prescriptions per 1000 persons (11.8), whereas Hawaii had the lowest (2.7). In addition to state-to-state variation, there was an obvious regional difference: New England (Connecticut, Rhode Island, Massachusetts, Vermont, New Hampshire, Maine) had the highest values, with 8 to 12 EpiPen prescriptions per 1000 persons, whereas the southern states (between and including California and Mississippi) had only 3 prescriptions per 1000 persons. The New England finding persisted even when controlling for all available factors (eg, population demographic characteristics, number of health care providers, prescriptions for other medications).
A strong north-south gradient was observed for the prescription of EpiPens in the United States, with the highest rates found in New England.
The regional differences in EpiPen prescribing may provide important etiologic clues (vitamin D status) and merit further investigation.
In the 1960s, the prevalence of asthma and allergic diseases began to increase worldwide. Currently, the burden of the disease is more than 300 million people affected. We hypothesize that as populations grow more prosperous, more time is spent indoors, and there is less exposure to sunlight, leading to decreased cutaneous vitamin D production. Coupled with inadequate intake from foods and supplements, this then leads to vitamin D deficiency, particularly in pregnant women, resulting in more asthma and allergy in their offspring. Vitamin D has been linked to immune system and lung development in utero, and our epidemiologic studies show that higher vitamin D intake by pregnant mothers reduces asthma risk by as much as 40% in children 3 to 5 years old. Vitamin D deficiency has been associated with obesity, African American race (particularly in urban, inner-city settings), and recent immigrants to westernized countries, thus reflecting the epidemiologic patterns observed in the asthma epidemic. Providing adequate vitamin D supplementation in pregnancy may lead to significant decreases in asthma incidence in young children.
Asthma is a serious health problem throughout the world. During the past two decades, many scientific advances have improved our understanding of asthma and ability to manage and control it effectively. However, recommendations for asthma care need to be adapted to local conditions, resources and services. Since it was formed in 1993, the Global Initiative for Asthma, a network of individuals, organisations and public health officials, has played a leading role in disseminating information about the care of patients with asthma based on a process of continuous review of published scientific investigations. A comprehensive workshop report entitled "A Global Strategy for Asthma Management and Prevention", first published in 1995, has been widely adopted, translated and reproduced, and forms the basis for many national guidelines. The 2006 report contains important new themes. First, it asserts that "it is reasonable to expect that in most patients with asthma, control of the disease can and should be achieved and maintained," and recommends a change in approach to asthma management, with asthma control, rather than asthma severity, being the focus of treatment decisions. The importance of the patient-care giver partnership and guided self-management, along with setting goals for treatment, are also emphasised.
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