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Table of Contents
ORIGINAL ARTICLE
Year : 2022  |  Volume : 1  |  Issue : 2  |  Page : 115-120

The Association Between Vitamin D Deficiency and Childhood Asthma


1 Department of Pharmacology, College of Medicine, University of Kerbala, Karbala, Iraq
2 Department of Pediatric, College of Medicine, University of Kerbala, Karbala, Iraq
3 Department of Pharmacology, University of Kerbala, Karbala, Iraq
4 Department of Family and Community Medicine, College of Medicine, University of Kerbala, Karbala, Iraq
5 Department of Pediatric, Karbala Health Directorate, Karbala, Iraq

Date of Submission18-Feb-2022
Date of Acceptance19-May-2022
Date of Web Publication15-Jun-2022

Correspondence Address:
Dr. Nabaa Mohammed Jawad Al-Tuama
University of Kerbala, Karbala
Iraq
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jpdtsm.jpdtsm_13_22

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  Abstract 


BACKGROUND: Asthma, a major public health issue, is one of the most common diseases affecting millions of population globally. It is a chronic respiratory disease characterized by increased airway inflammation and hyper-responsiveness. Vitamin D deficiency has become a global public health concern. Vitamin D is of particular interest in asthma due to its immunomodulatory effects. Serum 25-hydroxyvitamin D deficiency is found to be a risk factor in the development of serious chronic diseases where inflammatory mechanisms play a role in the pathogenesis. Several researches have reported positive associations between Vitamin D and asthma. On the other hand, others have reported contrasting effects of Vitamin D on asthma.
OBJECTIVE: The aim of this study is to determine whether asthmatic patients attending Kerbala teaching hospital for pediatrics have Vitamin D deficiency or not.
MATERIALS AND METHODS: In a case–control study, patients with asthma and healthy volunteers between the ages 1 and 14 years were enrolled into the study as patient and control groups, respectively. Fifty patients with asthma and 66 healthy children were included. For both groups, demographic information and body mass index were recorded. We measured 25-hydroxyvitamin D levels in serum collected from all 116 children. For asthmatic patients, clinical findings were recorded and total Immunoglobulin E (IgE) were determined for all patients.
RESULTS: Fifty patients with asthma and 66 healthy children were included. Compared to the control group, decreased serum Vitamin D levels were significantly detected in patient group. Forty six (92%) of asthmatic patients have were Vitamin D insufficient, as defined by a level of 30 ng/mL or less 25-hydroxyvitamin D. In compare to the control group, forty six (69.7%) have Vitamin D insufficiency (odds ratio = 5, P < 0.001). No significant correlation was found between Vitamin D levels and age, gender, obesity, sun exposure, and dietary intake in asthmatic patients.
CONCLUSION: The frequency of Vitamin D deficiency and insufficiency was higher in children with asthma, compared to the controls.

Keywords: Asthma, asthma control, asthma severity, children, Vitamin D


How to cite this article:
Al-Tuama NM, Almusawi ZM, Abood HA, Abutiheen A, Al-tuama KM. The Association Between Vitamin D Deficiency and Childhood Asthma. J Prev Diagn Treat Strategies Med 2022;1:115-20

How to cite this URL:
Al-Tuama NM, Almusawi ZM, Abood HA, Abutiheen A, Al-tuama KM. The Association Between Vitamin D Deficiency and Childhood Asthma. J Prev Diagn Treat Strategies Med [serial online] 2022 [cited 2022 Jun 26];1:115-20. Available from: http://www.jpdtsm.com/text.asp?2022/1/2/115/347538




  Introduction Top


Asthma is a chronic immunological disorder of the lungs characterized by reversible airway obstruction, airway inflammation, and increased airway hyper responsiveness in response to provocative challenges.[1] Asthma is one of the most common chronic, noncommunicable diseases in children and adults.[2]

In susceptible individuals, airway inflammation may cause recurrent or persistent bronchospasm, which causes symptoms that include wheezing, breathlessness, chest tightness, and cough, particularly at night (early morning hours) or after exercise.[3] The factors particularly responsible for asthma are not very clear because of its different presentation in both adults and children.[4] Interleukins (IL)-4, IL-5, and IL-13 (T-helper cell Type-2 cytokines) are regulated in the asthmatic airway and are related with increased eosinophilia,[4] mast cell degranulation, and increased levels of IgE.[4] Characterized by episodic or persistent symptoms of wheezing, dyspnea, and cough.[5] The complex interaction between cells and inflammatory mediators and impairment of immunogenic tolerance promotes airway injury (remodeling). This remodeling involves hypertrophy of smooth muscle, hyperplasia of epithelial goblet cell, and deposition of airway extracellular matrix proteins which may lead to increase airflow obstruction and finally causing the respiratory symptoms.[6]

Several dietary hypotheses have been proposed in context with asthma[7],[8] and among them, Vitamin D status is of particular interest. Studies suggest that there is a probable relationship between Vitamin D status and asthma-related symptoms presumably through the immune-modulatory effects of Vitamin D.[8] The prevalence of childhood asthma in Iraq is 16.4% in school age children.[4] Numerous risk factors of asthma can be divided into host and environmental factors. Host factors, genetic,[6],[7],[8] obesity,[7],[9] and gender childhood asthma are found to be common in boys than girls and by adulthood, this is reversed. Environmental factors include Allergens. It relies on the allergen, the dose, the time of exposure and the age of the child, and genetics can also play a role, infections, tobacco smoke, outdoor/indoor pollutants, and diet. Diagnosis depends on careful history and physical examination; the most important diagnostic tests are pulmonary function tests: Spirometry. Radiography reveals hyperinflation and increased bronchial markings, total IgE, and specific IgE can identify allergic factors that may significantly contribute to asthma.[10]

Ethical approval

The study protocol was approved by the ethical committee in the Karbala Health Directorate. In addition, verbal approval was taken from the patients and/or their parents before taking the sample. Health measures and safety were taken when sampling.


  Subjects and Method Top


This study has been approved by the ethical committee of the institute in which study was carried out on 9/5/2019. This is a case–control study included 116 subjects divided into two groups, first group included 50 (18 females, 32 males) asthmatic patients attended asthma outpatient clinic of Karbala teaching Hospital for pediatric from July 2018 to February 2019. Their ages range from 1 to 15 years.

First group (asthmatic patients): inclusion criteria were being more than 1 year old, clinical finding and spirometry interpretation consistent with the diagnosis of bronchial asthma and both gender; exclusion criteria were history of intake of Vitamin D and any chronic disease.

The second group (control) included 66 apparently healthy children (21 females, 45 males) their age range from 1 to 15 years with no history of chronic disease, and the age and gender were nearly consistent with the study group; the sample selection was randomly. All subjects in this study were submitted to a detailed survey including sociodemographic information, anthropometric measurements including body weight, height, and body mass index (BMI) of all patients were recorded. BMI was calculated as weight (kg)/height (m2) and BMI percentile range was evaluated. Z Score = ((BMI/M) L-1)/(L * S), all of them were calculated by using Medscape application. All the kids whose selected in the current study were chosen after careful taken the consideration of their exposure to the sun, amount of milk, egg yolk and any fish (tuna) intake, type of feeding (for child <2 years).

Specific questions for asthmatic patients, length and properties of asthma symptoms, drugs administered for asthma treatment, asthma control and severity for them, and asking about passive smoking.

Blood sampling and laboratory analysis

Informed consent was obtained from the parents of all patient. Peripheral venous blood samples from all subjects were obtained to determine serum Vitamin D levels. Two milliliters of the venous blood samples were transferred into tube with EDTA Blood samples placed in tubes. Following that samples were centrifuged. Then, they were frozen at −80°C until all serum samples can be analyzed. Before analyses, samples were rested at −20°C and then thawed at +4°C. Serum level of 25 (OH) D levels was determined with mini VIDAS® 25 OH Vitamin D Total is an automated quantitative test for the determination of 25-hydroxyvitamin D Total in human serum or plasma using the (Enzyme-Linked Fluorescent Assay) technique. It reflects Vitamin D produced cutaneously and that obtained from food and supplements for a reliable indication of Vitamin D.

Statistical analysis

Results were presented as mean ± standard deviation for quantitative variables and were summarized by absolute frequencies and percentages for categorical variables. Categorical variables were compared using Chi-square test or Fisher's exact test. Quantitative variables were also compared with t-test (Analysis of Variance [ANOVA]) tests. The association between quantitative variables was tested using correlation test. We used the multivariable regression modeling to assess the relation between Vitamin D deficiency and severity of asthma with the presence of confounders. For the statistical analysis, the statistical software SPSS version 21 for window was used.


  Results Top


Fifty patients with asthma and 66 healthy children were enrolled into the study as patient and control groups, respectively. The mean ages of the asthmatic and healthy control children were 7.28 ± 3.91 years and 6.55 ± 3.04 years, respectively (P = 0.257) [Table 1]. Gender, age, BMI, and residences of both groups are found in [Table 1].
Table 1: Demographic information of patients and control

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  • Data related to Vitamin D levels for asthma patients and control groups are presented in [Table 2]. A significant difference was found when serum Vitamin D levels between asthma patients and control groups were compared. Mean serum Vitamin D levels in the asthma patient and control group were detected as 17.12 ± 8.65 ng/ml and 27.41 ± 18.10 ng/ml, respectively, with P (<0.0001) odds ratio between two groups 5. Detailed investigation of our study groups revealed that 14 (28%) patients in asthma patient group and 8 (12%) subjects in control group had Vitamin D deficiency. Thirty-two (64%) patients in asthma patients group and 38 (58%) had Vitamin D insufficiency [Table 2] and [Table 3].
Table 2: Mean and standard deviation for serum Vitamin D in asthmatic patients and control groups

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Table 3: Evaluation of asthma patient and control groups based on Vitamin D levels

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Comparison of Vitamin D levels according to the gender, there was no significant difference between two groups. Mean serum Vitamin D levels in the asthma patient group were detected as 18.45 ± 9.20 ng/ml and 14.761 ± 6.89 ng/ml for males and females, respectively (P = 0.145). In the control group, however, no significant difference between average serum Vitamin D levels between females (26.34 ± 12.61 ng/ml) and males (27.95 ± 20.42 ng/ml) (P = 0.736). No significant correlation was found between Vitamin D and residency for both groups. The correlation between Vitamin D with gender and residency for each group is shown in [Table 4].
Table 4: Correlation between Vitamin D with gender and residency for each group

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When groups were classified in terms of Vitamin D deficiency based on mean ages in asthmatic group, there was no significant correlation (P = 0.157).

While there was a significant negative correlation for control group (P ≤ 0.001),

the same results were found between Vitamin D and BMI. There was a significant negative correlation (P = 0.02) for control group, while no significant correlation was found in asthmatic group.

There was increase in the prevalence of Vitamin D deficiency and insufficiency with increase in asthma severity but it was insignificant (P = 0.65). Examining patients being followed for asthma for correlation between Vitamin D deficiency and asthma control, no significant difference between Vitamin D deficiency and asthma management was detected (P = 0.13). Detailed analysis of asthma patient group for asthma severity and asthma control status according to Vitamin D deficiency also resulted in no significant difference [Table 5].
Table 5: Asthma characters and Vitamin D level

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[Table 5] shows asthma characters and Vitamin D level.

We also tried to determine the relationship between Vitamin D level and sun exposure. There was no significant relation between sun exposure and Vitamin D level (P = 0.173) for cases and (P = 0.523) for control.

By using ANOVA, there was no correlation between Vitamin D level and sun exposure (P = 0.899), cups of milk drinking per week (P = 0.11), fish intake (P = 0.09), and egg intake (P = 0.10) in both asthmatic patient and control group. For children below 2 years, there was no significant association between breastfeeding, artificial and mixed feeding (P = 0.899).


  Discussion Top


Vitamin D deficiency has been shown to be a risk factor in the development of serious chronic diseases where inflammatory mechanisms play a role in the pathogenesis. In our study, we planned to investigate the correlation between serum Vitamin D level and asthma. In our study, the mean age in both case and control groups was approximately the same [Table 1]; also, the gender between two groups was nearly the same, there are male predominance in both groups [Table 1] as well as (BMI) for both group was approximately the same [Table 1]. In our study, the average serum Vitamin D levels in asthma patient was found to be significantly lower than control group (P < 0.001) [Table 2]. This results agree with other studies found that the frequency of Vitamin D deficiency and insufficiency was higher in children with asthma, compared to the control.[11] A multicenter research presumed that the inadequacy in Vitamin D is predominant in asthmatic kids live in Iraq. Moreover, the asthma in Iraqi children has a direct relationship with the concentration of Vitamin D in serum. The research also concluded that the low concentration of the vitamin in serum with lead to developed asthma seriousness in Iraqi children.[12] Some case-controlled studies could show the association between Vitamin D deficiency and asthma in children. In a study by Arikoglu et al., the association between Vitamin D deficiency and increased risk for asthmatic attack in children was indicated.[13] In another study by Hatami et al., similar to our finding, there was a significant decrease in the concentration of serum 25-hydroxy (OH) Vitamin D in the asthmatic patients as compared.[14] The main point of the study was that the presence of Vitamin D deficiency could effectively predict increased risk for childhood asthma. Because Vitamin D promotes steroid sensitivity in the body, can down regulate an inflammatory state through gene expression and cytokines production, its action could be directly on the airway.[15] Deficiency of Vitamin D could be associated with an inability to switch off the inflammatory state, following an acute inhalational insult, with up regulation of prostaglandin, leukotrienes, macrophages, T cell activity and recruitment. Vitamin D also inhibits the formation of matrix metalloproteinase as well as fibroblast proliferation and influences collagen synthesis, therefore, suggesting the role of 1, 25-dihydroxy Vitamin D in tissue remodeling and probably lung function.[16] In a review on observational studies including 3 prospective, 16 case–control and 14 cross-sectional studies, it was suggested a pooled positive association of Vitamin D levels with better asthma control, reduced use of asthma medication, fewer asthma exacerbation, and lower utilization of health-care facilities for urgent treatment.[17] In a meta analysis by Riverin et al. in 2015 and by reviewing eight randomized controlled trial including 573 children aged 3–18 years, it was revealed that the use of Vitamin D supplement leads to a reduced risk of asthma exacerbations.[18] The findings from meta-analysis have shown that the relation between the level of Vitamin D and the incidence of asthma, asthma control, and lung functions is inconclusive. However, the severity or control status of this event could not be predicted by confirming Vitamin D deficiency only many factors contribute to the severity and level of asthma control.[19] In our study, the average serum Vitamin D level in asthmatic and control group was found to be similar in both gender [Table 4]. Similar to our finding, a gender-based grouped records done in Erbil did not show any effect on Vitamin D level.[20] In our study, asthmatic patients showed no significant association between those who are overweight or obese and those who are normal weight while control group show significant association. SIMON Vanlint found that the association between reduced 25D concentrations and obesity is well established and correction of low 25D concentrations in obese individuals requires higher doses than those often advocated for the general population.[21] Mohan Kumaratne[22] found that obesity is recognized to be associated with Vitamin D deficiency as adipose tissue sequesters 25 (OH) D, resulting in an inverse relationship between Vitamin D and BMI. Therefore, our results are in agreement with previous researchers who concluded that Vitamin D deficiency is more prevalent in those who are obese. After Vitamin D3 supplement in a study, the change in the BMI produces improvement in endogenous Vitamin D status parallel to the change in the heart BMI and markedly improvement in asthma control. Rasha Saeed[23] found that the reduction in the BMI after Vitamin D3 treatment was positively correlated with asthma control. That results support our finding in healthy control while asthmatic children not show the same result in both age and BMI finding that may be due to sample size or accompanied by different degrees of changes in VDR gene polymorphism, which is negatively correlated with of polymorphic genes that code for key enzymes which regulate the synthesis and metabolism of Vitamin D (i.e., CYP27A1, GC, CYP27B1, and CYP24A1) and of genes that encode for downstream mediators of Vitamin D signaling (i.e., VDR, RXR, PPAR, NCOA, and SMAD) Although many observations suggested that evaluation of serum Vitamin D concentrations should be considered in obese asthmatic patients that respond suboptimally to inhaled corticosteroid, and recently give promising preventive strategy that anti-inflammatory and antioxidant effect of Vitamin D3 supplementation could result in improvement of these phenotypic variables in the subset of subjects with asthma who are Vitamin D deficient.[24],[25] Vitamin D deficiency is a common problem obese and overweight adolescents, and this may help to explain the relationship between obesity and several chronic diseases that are associated with poor Vitamin D status.[26] A systematic review of 23 observational studies found that mean Vitamin D levels were significantly lower in asthmatic children compared to nonasthmatic children, but correlation between Vitamin D levels with incidence/prevalence of asthma, lung functions, and control of asthma was not uniform among the studies. Wide range of Vitamin D deficiency may be explained by variation in nutritional status, difference in sun exposure, fortification of food items, use of supplements, geographical location of country, and many other factors in different countries.[27],[28],[29],[30]


  Conclusions and Recommendations Top


Vitamin D deficiency and insufficiency are strongly associated with childhood asthma in karbala province without significant impact on disease severity and level of control.

Acknowledgment

The authors would like to thank all children and their parents who participated in this study (asthmatic patients and healthy control) and Karbala teaching hospital for children for its support.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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