The incidence of atopic manifestations varies
significantly depending on the vitamin D status in our population of younger
Algerian children. Average vitamin D concentrations were lower in children who
developed these disorders. As a result, vitamin D deficiency would expose to
the risk of the occurrence of allergic manifestations in our population
confirming the results of the majority of studies published on this topic. Our
comments will cover several aspects. We will first make a critical analysis of
the approach adopted and the problems encountered during the investigation. We
will compare our results with the data in the literature in second step by
discussing them. Our study presents some positive points. The sample size is
quite large and both sexes were well represented. Vitamin D plasma
concentrations were assessed during the 4 seasons demonstrating the effect of
seasonality on the variation in the level of 25 OHD. The 25 OHD assay technique
has been validated by several expert reports and allows the determination of
the two forms of vitamin D used for all patients. The study suffer some
weaknesses and limitations. This survey made by a questionnaire suffers from
its declarative and therefore subjective character. Thus, the low incidence of
food allergies in our study could be explained by this declarative nature and
questioning only the parents. The study is limited to the commune of Hussein
Dey alone. There is no standard definition of vitamin D status. Currently, many
experts support a 25 OHD threshold greater than 30 ng / ml to consider a normal
level [3]. This threshold is justified by the wish to allow the subjects to
benefit from the effect of vitamin D on the bone but also on other pathologies
while others fix the threshold of 20 ng / ml as minimum threshold in order to
optimize calcium absorption [4]. Several pediatric consensus define in children
the deficit at the threshold of 20 ng / ml and the vitamin D deficiency at the
threshold of 10 ng / ml [5]. The diversity of the populations studied, in
particular in terms of latitude, geographic origin or age, the variability of
the assay techniques and the lack of real consensus on the reference thresholds
for defining the deficit makes international comparisons difficult. However,
there is an increase in the vitamin D deficit in all latitudes and all
continents [6,7]. Several studies dedicated to the relationship between vitamin
D, asthma and allergies have increased significantly. Experimental evidence in
rats shows that fetal type II alveolar epithelial cells express vitamin D
receptor (VDR), suggesting that lung maturation is sensitive to exposure to
vitamin D [8,9]. In humans, Kho et al. examined gene expression profiles during
human fetal lung development and identified a number of genes associated with
the vitamin D signaling pathway whose expression was developmentally regulated
[10]. Although the exact role of these vitamin D-linked genes in fetal lung
development remains to be fully explored, several genes (LAMP3 PIP5K1B, SCRAB2
and TXNIP) have also been found to be significantly overexpressed in cells
derived from asthmatic children, suggesting thus a link between the vitamin D
pathway genes, fetal development and asthma, [11]. Zosky studied the effects of
vitamin D deficiency in a mouse model. The offspring of vitamin D deficient
mice had reduced lung volume compared to that of mice with optimal vitamin D
status. Vitamin D also appears to affect the development of the immune system
in utero. Chi et al [12] using data from the Urban Environment and Childhood
Asthma study, showed that vitamin D concentrations in cord blood were inversely
associated with the proportion of CD25 +, CD25 Bright and CD25 + FoxP3
regulatory T cells. After birth, vitamin D has immunomodulatory effects on the
allergen-induced inflammatory pathways by acting on the VDR expressed on
various immune cells, including B cells, T cells, dendritic cells and
macrophages [13,14]. Many of these cells, such as activated macrophages and
dendritic cells, are able to synthesize biologically active vitamin D from
circulating 25 OHD [15,16]. This mechanism allows immune cells to rapidly
increase local levels of vitamin D, which are potentially needed to shape
adaptive immune responses [17,18]. Low levels of vitamin D seem to be inversely
correlated with the severity of atopic dermatitis. Sharief et al have shown
that higher levels of IgE are associated with vitamin D deficiency in children
and adolescents [19]. Similarly, in another publication, mean serum 25 (OH) D
levels were lower in children with moderate to severe atopic dermatitis [20].
Which is consistent with our results. A small trial aimed to explore the impact
of vitamin D supplementation in the pediatric population on allergic diseases.
A study as part of a larger pilot study of vitamin D supplementation
investigated the effect of this supplementation on atopic dermatitis in 11
children [21]. The children were randomized to 1000 IU per day of
ergocalciferol or placebo for 1 month. There was a tendency to improve scores
for atopic dermatitis, but due to the small number and short duration of the
trial, the results were not statistically significant. Few studies have
investigated vitamin D status in allergic rhinitis and food allergy in children
[22]. May et al. [23] studied the relationship between the serum 25OHD level
and the incidence of allergic rhinitis. The study included a random sample of
the population (N = 1351), serum 25OHD levels <20 ng / ml were associated
with an increased risk of allergic rhinitis (OR adjusted to 2.55, p = 0.001),
these results are similar to ours. It has been suggested that a vitamin D
deficiency could alter the integrity of the epithelial barrier, which would
lead to increased and inappropriate exposure of the mucosa to food antigens as
well as an immune imbalance favoring sensitization, which would compromise
immunological tolerance. Therefore, early correction of vitamin D deficiency
could enhance mucosal defense, maintain healthy microbial ecology and tolerance
to allergens, and reduce the risk of food allergies in children. Mullins et al
[24] and Vassallo et al [25] reported significantly higher food allergy rates
in children born in autumn / winter, suggesting a relationship between food
allergy rates and monthly exposure to Sun. Two studies used data from the
National Health and Nutrition Survey (NHANES) conducted in the United States
[26,27]. In an analysis of 3136 children and adolescents, allergic
sensitization to 11 allergens was more frequent in those with a vitamin D
deficiency (<15 ng / ml) after a multivariate adjustment. Awareness included
food allergens (peanuts and shrimp), indoor allergens (dog, cockroach,
Alternaria sp) and pollen (oak, birch). The prevalence of vitamin D deficiency
in asthmatic and non-asthmatic children was determined in several case-control
studies, it varied considerably between the different studies ranging from 3%
to 77%, and moreover children without asthma had more vitamin D levels
sufficient compared to asthmatic children consistent with the results of our
study. Several studies have been carried out on African-American, [28] Qataris,
[29] Iranian children, [30] and all show that the prevalence of vitamin D
deficiency is higher in asthmatic children than in controls. Bener et al [31]
had carried out in 2012 a case-control study including 966 healthy children and
in asthmatics of equal age [32]. The authors found that vitamin D deficiency
was associated with an increased risk of asthma (adjusted OR: 4.82 CI:
2.4-8.6). Another analysis of 6,857 participants 6 years aged and older showed
that vitamin D levels were inversely associated with asthma [33]. Several
studies have studied the association between 25OHD and asthma exacerbations
measured in terms of hospitalizations and treatment with oral corticosteroids.
Except the study of Gergen, all studies have shown that a low serum vitamin D
concentration is associated with an increased risk of exacerbation of asthma
(RR = 0.64 CI: 0.5-0.8). Asthma control studies. Have evaluated control and
exacerbations based on the frequency of dosing and dosage of treatments, or the
number of emergencies. Brehm et al [34] correlated their data with vitamin D
concentrations. Gergen and Van Oeffelen found that a high serum 25OHD
concentration was associated with a reduction in the severity of asthma whereas
Chinellato and Gupta did not found any association. In the PIAMA birth cohort
of more than 300 children, serum vitamin D concentrations were inversely
associated with the prevalence of asthma in children from four to 8 years old
[35]. Hollams et al [36], in a cohort of more than 600 Australian children,
have shown that higher levels of vitamin D at 6 years protect against the
development of asthma, rhino-conjunctivitis and allergy. Several studies have
examined the relationship between vitamin D deficiency and exacerbations of
asthma [37]. Brehm et al were the first to show that vitamin D deficiency
(<30 ng / ml) was associated with an increased risk of severe asthma
exacerbations leading to emergency visits or hospitalizations after an analysis
of data collected from 1024 participants of the childhood asthma management
program (CAMP) [38]. Searing et al, in a cross-sectional 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 exercise-induced 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 role of vitamin D in preventing asthma
and allergies in children remains controversial. Although most of the published
data report a protective effect of higher vitamin D levels or vitamin D
consumption, some studies do not find this link. Thus, five prospective studies
on large cohorts evaluated the relationship between 25OHD levels and asthma,
and found no association. Other clinical trials would be useful to resolve
these inconsistencies [43].