Vitamin D Status in Children with Recurrent Wheeze

Background: it has been shown that low serum 25-hydroxyvitamin D concentration was associated with a higher risk of upper and lower respiratory infections in children Aim to evaluate vitamin D concentration and selected biochemical markers in infants and children with recurrent wheeze. Methods: a case-control study has been carried out to measure serum vitamin Concentration; on 33 patients with recurrent wheeze, their ages ranged from 4-60 months; over the period from the1of March 2014 to the end of June 2014. Forty-two age and sex matched healthy children were selected as control group. List of investigation was measured by spectrophotometer as serum calcium, phosphorus, alkaline phosphatase and 25-OH vitamin. Result: Frequency of breast feeding in the first two years of life was low in wheezy children and significantly shorter duration of breast feeding less than 4 months in wheezy children than control group, P value 0.01. Vitamin D concentration was significantly low in children with recurrent wheeze than the control group; (21.69 ng/ml, 39.36 ng/ml) respectively with p-value 0.000. The severity of vitamin D deficiency was significant in children with recurrent wheeze, severe deficiency of vitamin D < 5 ng/ml recorded in 4(100%), p-value of 0.001.while mean serum calcium, phosphorus and alkaline phosphatase shows no significant difference. There is no significant relation observed between mean Vitamin D concentration and selected variables of infants and children with wheeze (P value > 0.05) Conclusion: vitamin D supplementation may be considered in infants and children with recurrent wheeze.


Introduction
here are many studies highlighting associations between childhood asthma and vitamin D deficiency. The hypothesis is that vitamin D could have a central role in these pathological situations and that it may represent a novel preventive and/or therapeutic strategy. 1 Meta-analysis data of published clinical trials concluded that vitamin D supplementation decreased the risk of asthma exacerbations in those with 25OHD levels less than 10ng/ml. The evidence suggests that there is a protective effect of higher vitamin D level primary prevention of asthma and itsexacerbations. 2 Almost all cells in the body possess vitamin D receptors, including cells of the immune system. This has fueled more research and hypotheses that vitamin D may be integral to immune system regulatory T

RESEARCH PAPER
The Medical Journal of Basrah University (2020); 38(1): [29][30][31][32][33][34][35][36] Vitamin D in Children with Recurrent Wheeze functions. Vitamin D deficiency can affect Th1 and Th2 cytokines, which may also contribute to the development of atopy. 3 Vitamin D, can modulate the innate and adaptive immune responses; 1, 25-Dihydroxyvitamin D stimulates innate (macrophage) immunity by enhancing bacterial killing but it also modulates adaptive (lymphocyte) immunity to minimize inflammation and autoimmune disease. 4 During a bacterial infection, macrophages acquire the capacity to convert circulating 25 vitamin D into 1, 25 OH vitamin D, which is a direct inducer of the expression of genes encoding for antimicrobial peptides and cathlicid in antimicrobial peptide in particular. This peptide is central in host defense against respiratory tract pathogens. 5 Deficiency in vitamin D is associated with increased autoimmunity as well as an increased susceptibility to infection. Many studies in adults and children found a higher prevalence of vitamin D deficiency in asthmatics than in the normal population; in addition, low vitamin D levels are associated with increasing severity of asthma and impaired pulmonary function. Patients with vitamin D deficiency have shown to have increased airway hyper-responsiveness and increased corticosteroid requirements. 6

Subjects and Methods
A Case-control study has been carried out to measure serum level of vitamin D; 33 infants and children with recurrent wheeze (more than 3 attacks) 7,8 who were admitted to Basra Maternity and Children Hospital and Basra teaching Hospital or those who visit pediatric emergency room, their ages ranged from 4-60 months; over the period from the 1 st of March to the end of June 2014 were included. Fortytwo infants and children visiting AL-Razi primary health care center for routine checkup and vaccination were age and sex matched as control group.
Exclusion criteria including history of: 1. Congenital heart diseases, chronic lung disease, immunodeficiency, neurologic or metabolic disease. 2. Prematurity with or without admission to neonatal care unit 3. Vitamin D supplements for the last 3 weeks. 9 4. Steroids treatment for previous one month. 10 Especial Questionnaire was designed for the purpose of the study. An informed consent was obtained from the parents for recruitment in the study. All patients underwent general and systemic examination, and anthropometric measurements were assessed and applied to appropriate charts. 11 Laboratory Data Blood samples (3 milliliters) from recruited subjects were collected using, Clot Activator with Gel Tube. A List of investigations was measured by spectrophotometer for the patients and control group: Serum calcium (Ca), phosphorus (Ph), Alkaline Phosphatase. Serum 25-OH Vitamin Dmeasurement by Euroimmun25-OH Vitamin D by ELISA kitEuroimmun AG, Seekamp 31,23560 lübeck, Germany. 12 Reference values 13 Severe deficiency (<5 ng/ml), deficiency (<15 ng/ml), insufficient (15-20 ng/ml) and sufficient > 20 Data were analyzed using SPSS version 18

Results
A total of 75 infants and children, their ages ranged from 4-60 months are included in this study; 33 infants and children with history of

Selected characteristics of patients with wheeze and control group
High frequency of breast feeding reported in the control group than children with recurrent wheeze, (38.1%,27.3%) respectively but statistically non-significant result, with significantly shorter duration of breast feeding less than 4 months in wheezy children than control group (39.1%,5.6%) respectively p value 0.01. There is no significant difference in children with recurrent wheeze and control group regarding history of atopy (48.5%, 33.3%) with significant family history of allergic rhinitis and conjunctivitis (48.5%, 39.3%) in wheezy children than control group (14.3%,7.1%) respectively as shown in (Table -1

Vitamin D status
Higher frequency of vitamin D deficiency; severe deficiency (12.1%) deficient (12.1%) and insufficiency (21.3%) recorded in children with recurrent wheeze than control group (4%); as well as sufficient level of vitamin D >20 ng/ml was recorded with higher frequency in control group than children with wheeze (97.6%,54.5%) respectively with statistically significant result (P-value 0.001). (Table-3

Table 3. Vitamin D status in patients and control group
Vitamin D and selected characteristics of patients with wheezes (Table-4), shows no significant relation observed between mean Vitamin D level and selected variables of studied infants and children with recurrent wheeze; as age, sex, feeding history, history of atopy (p value > 0.0

Discussion
The effects of vitamin D deficiency in pediatrics have become increasingly apparent and extend beyond skeletal health. Vitamin D modifies airway inflammation and appears to be important in building immunity against respiratory infections, so is potentially beneficial in asthma. 14 The present study reveals that; the frequency and duration of breast feeding was reported less in wheezy child than control group, this is in consistent with Silvers et al 15  has focused on the strong association between atopic tendency and childhood wheezing. 19 Current study shows no significant difference of atopic tendency in children with recurrent wheeze and control group; similar result was concluded by Linneberg, et al study in Denmark. 20 They found most risk factors had opposite direction of their effects on wheeze and atopic dermatitis. For example, breast-feeding was associated with a decreased risk of wheezing but an increased risk of atopy. Hence, these findings support the hypothesis that wheeze and atopic dermatitis have a different etiology. In contrast to a study carried out in Hong Kong by Wang SS etal 21 who concludes that vitamin D deficiency is associated with childhood atopic dermatitis. There was no significant difference regarding family history of atopic dermatitis and asthma among wheezy children and control group in contrast to a study carried out in Italy by Esposito, et al 22 , a family history of atopy was significantly frequent among children with wheeze than the controls as well as in UK study bySherriff et al 23 ; atopy and a family history of asthma emerged as the main predictors of wheeze that developed after 6 months of age. In this study there is significant family history of allergic rhinitis and conjunctivitis in wheezy children ,these finding is inconsistent with other study in Singapore done byTan TN et al 24 29 In this study history of atopic dermatitis in wheezy children with low vitamin D is not significant. A study in Australiaby Allen, et al. 30 also did not find significant association between eczema and low serum 25(OH) D levels. While Lee et al, in Korea found an inverse correlation between serum concentration of vitamin D and severity of the disease in children with atopic dermatitis associated with food allergy. 31 We conclude that vitamin D supplementation may be considered in infants and children with recurrent wheeze.