Keywords
allergic rhinitis - immunoglobulin E - vitamin D - adult
Introduction
Allergic diseases such as asthma and allergic rhinitis are associated with an immune
mediated reaction after exposure to the related allergen. Allergic rhinitis is a common
health problem that interferes with the social and professional lives and decreases
the quality of life of the patients.[1] The prevalence of allergic rhinitis in Turkey is not known clearly, but in Europe
the prevalence is ∼ 17 and 25% of the population.[2] Besides, prevalence can be changed according to the socioeconomic status of the
population, and to the geographic and aeroallergen diversity in a specific region.
Industrialized populations spend significant amounts of time indoors, which causes
the deficiency of essential vitamins, such as vitamin D. Vitamin D is a steroid hormone
primarily synthesized in the skin through a chemical reaction that is dependent on
sun exposure. During its metabolism, the kidneys play an important role and convert
it to its active form, known as 1α-25-dihydroxyvitamin D3. This form of vitamin D
regulates both humoral and cellular immune responses in the human body.[3]
[4] It is supposed that an increase in cases of allergic rhinitis is closely related
to the deficiency of vitamin D in industrialized populations. There are several previous
studies that have investigated this relationship. Wjst et al[5] claimed that high levels of vitamin D cause allergic rhinitis, whereas Litonjua
et al[3] stated that low levels of vitamin D lead to allergic diseases. Besides, epidemiologic
studies about vitamin D supplementation and allergic diseases have provided inconsistent
results, causing confusion.[6]
[7]
[8] Allergic rhinitis and its relationship with the active form of vitamin D, which
has an important role in the metabolism have never been investigated in adult subjects,
according to our knowledge. The objective of the present study is to investigate the
levels of 1α-25-dihydroxyvitamin D3 in allergic rhinitis patients and to compare them
to the levels found in the normal population. We also want to investigate the relationship
between the allergens and 1α-25-dihydroxyvitamin D3 levels in the Ankara region in
Turkey.
Materials and Methods
The present study was conducted at our hospital's otorhinolaryngology outpatient clinic
(Etimesgut State Hospital ENT Department) between December 2014 and May 2015. A total
of 256 patients was included in the study, and they were divided into two groups:
patients with allergic rhinitis (65 male and 60 female) and control subjects (70 male
and 61 female). The diagnosis of the allergic rhinitis patients was determined by
the Allergic Rhinitis and Its Impact on Asthma (ARIA) 2008 guidelines. Allergic rhinitis
patients were detected as presenting one or more of the following criteria: nasal
obstruction, rhinorrhea, nasal itching and sneezing, all of which were supported by
a skin prick test.[9] The control group was composed of healthy volunteers who did not present any allergic
symptoms and did not present any reaction to the skin prick test.
Subjects who presented chronic diseases such as diabetes, chronic renal insufficiency,
vitamin D metabolism disorder, malignant diseases, asthma history, were overweight
or obese (body mass index [BMI] > 25), used medications such as antihistamines or
anti-allergy drugs, and were aged over 65 years old were excluded from the study.
The BMI of all participants was calculated using the following formula: BMI = weight
(kg)/[height (m)]2.
The allergy test included 15 different allergens supplied by Stallergenes Greer Laboratories
(Antony, France). The allergen extracts were composed of pollen, weeds, grasses (maize,
oat, wheat and barley), mold spores, mites (Dermatophagoides farina and Dermatophagoides pteronyssinus), epithelia, allergens derived from insects and other animals (feather mix, dog hair,
cat hair and cockroach). Skin prick tests were applied to the forearms of all participants
after cleaning the skin with alcohol. Each allergen was standardly diluted (1:50),
and histamine hydrochloride 10 mg/ml and 50% glycerol-saline solutions were used as
positive and negative controls respectively. The results were graded after 20 minutes
as +, ++, +++ and ++ + +, according to the level of erythema and the severity of the
reaction.
A blood sample of each participant was collected at the end of the allergy test. Serum
levels of the active form of vitamin-D (1α-25-hydroxyvitamin D3) were measured using
an enzyme immunoassay kit (Immunodiagnostic Systems Holdings PLC, Tyne and Wear, UK).
Afterwards, the levels detected in the allergic rhinitis patients and in the control
subjects were compared.
Total serum levels of immunoglobulin E (IgE) and eosinophil counts from both groups
were also measured using the IMMULITE 1000 Immunoassay System (Siemens, Munich, Germany).
Peripheral blood eosinophil counts were conducted using fluorescent flow cytometry
performed by a XT-1800i Automated Hematology Analyzer (Sysmex, Mundelein, IL, USA).
The data was compiled using the Statistical Package for the Social Sciences (SPSS,
IBM Corp., Armonk, NY, US), version 22.0. The groups were compared through analysis
of variance (ANOVA) and Pearson correlation analysis, and values of p < 0.05 were considered statistically significant.
The present study was approved by our hospital's ethical committee (Dr. Lutfi Kırdar
Kartal Education and Research Hospital Ethical Committee) and informed consent was
taken from each participant.
Results
The study sample was composed of 256 subjects divided into two groups: a study group
consisting of patients presenting allergic rhinitis (125 patients = 65 male and 60
female) and a control group (131 subjects = 70 male and 61 female). The mean age of
the study group was 44.5 years old, and the mean age of the control group was 42.4
years old. The groups were similar according to age, gender and BMI distribution (p > 0.05) ([Table 1]). The mean value of serum 1α-25-hydroxyvitamin D3 in the allergic rhinitis group
was 25.5 ± 3.74 (female = 24.4 ± 3.31 and male = 24.9 ± 3.29). On the other hand,
the mean value of serum 1α-25-hydroxyvitamin D3 was 31.58 ± 3.85 (females = 31.12 ± 3.62
and males =31.9 ± 3.49) in the control subjects. This difference reveals statistically-decreased
levels in the allergic rhinitis group (p < 0.05) ([Table 1]). Eosinophil cationic protein (ECP) levels in both groups were similar, whereas
total IgE levels were statistically increased in the allergic rhinitis group (p < 0.05). Additionally, the IgE levels were negatively correlated with the levels
of serum 1α-25-hydroxyvitamin D3 (r = -0.259, p < 0.05). The frequencies of positive skin prick test results of the allergic rhinitis
patients are presented on [Table 2]. According to this data, the most significant allergens are D. pteronyssinus, D.farina, Alternaria alternata and Alnus betulaceae (29.6, 28.6, 28.3 and 27.6 respectively). Although we have detected allergens in
the allergic rhinitis group, we could not detect any correlation between vitamin D
levels and the severity of the allergic reaction.
Table 1
The descriptives of allergic rhinitis and control subjects
|
Variable
|
Allergic rhinitis (n = 125)
|
Control (n = 131)
|
p value
|
|
Age (years)
|
44.5 ± 12.6
|
42.4 ± 14.6
|
0.512
|
|
(mean ± SD)
(minimum-maximum)
|
(32–57)
|
(28–58)
|
|
Gender (male/female)
|
65/60
|
70/61
|
0.698
|
|
Serum 1α-25-hydroxyvitamin D3
(ng/mL)
|
25.5 ± 3.74
|
31.58 ± 3.85
|
0.048*
|
|
Male
24.9 ± 3.29
|
Female
24.4 ± 3.31
|
p > 0.895
|
Male
31.9 ± 3.49
|
Female
31.12 ± 3.62
|
p > 0.952
|
|
|
ECP (μg/L)
|
25.2 ± 31.5
|
24.9 ± 29.28
|
0.854
|
|
IgE (IU/mL)
|
453.6 ± 15.3
|
123.6 ± 23.5
|
0.01*
|
|
Body mass index (kg/m2)
|
21.5 ± 3.45
|
22.1 ± 3.05
|
0.654
|
Abbreviations: ECP, eosinophil cationic protein; IgE, immunoglobulin E; SD, standard
deviation.
Table 2
The distribution of positive skin prick test in allergic rhinitis
|
Specific allergen
|
Frequency (%)
|
|
Dermatophagoides pteronyssinus
|
29.6
|
|
Dermatophagoides farina
|
28.6
|
|
Alternaria alternata
|
28.3
|
|
Alnus betulaceae
|
27.6
|
|
Mixture of Cereals
|
25.4
|
|
Grasses
|
21.2
|
|
Feather mix
|
20.9
|
|
Aspergillus mix
|
20.1
|
|
Cladosporium
|
18.2
|
|
Cat hair
|
17.6
|
|
Dog hair
|
17.5
|
|
Cockroach
|
15.3
|
|
Penicillium mix
|
14.2
|
|
Compositae
|
10.7
|
|
A. fagacees
|
8.3
|
Discussion
Allergic rhinitis is one of the most common causes of the allergic condition, provoking
a decrease in the quality of life.[10] Allergens commonly leading to this response are pollen, dust, mite, and others.[11] In the present study, the most frequent allergens in our region are D. pteronyssinus, D. farina, A. alternata and A. betulaceae, which had never been researched before. After exposure to these specific allergens,
symptoms such as sneezing, nasal congestion, nasal itching and rhinorrhea, in any
combination, could be seen in the clinical setting.[12] According to the ARIA classification, allergic rhinitis is classified either as
seasonal or perennial. The allergens affect the disease process, affecting the severity
of the symptoms, which are classified as mild, moderate and severe, based on the disturbance
in daily and social life.[9] Patients with seasonal or perennial allergic rhinitis are less comfortable during
allergen exposure in the Spring. The coincidence of this condition also fits with
the reduced exposure to sunlight after winter, as in the Northern hemisphere. Turkey
is located on a geographically fortunate area that provides enough exposure to sunlight
during the summer, which is crucial for the biosynthesis of vitamin D. In order to
prevent this effect, we have conducted the study between December and May, so we have
measured the lowest vitamin D levels in both study groups.
According to our knowledge, the level of vitamin D in allergic rhinitis populations,
including the adult population in Turkey, had never been investigated. In the present
study, we found lower 1α-25-dihydroxyvitamin D3 levels in the allergic rhinitis patients
than in the healthy control subjects. There is only one study that has investigated
the role of 1α-25-dihydroxyvitamin D3 among children, and it revealed an increased
risk of disease when there is vitamin D deficiency.[13] There are also several studies that have researched the role of 1α-25-dihydroxyvitamin
D3 in the allergic response. Some of these studies supported the conclusion that a
deficiency of this form of vitamin D leads to an increase in the allergic response,
whereas other reports support the opposite.[14]
[15]
[16] Therefore, the role of 1α-25-dihydroxyvitamin D3 deficiency in allergic diseases
is not currently clear. We believe that this situation is related to the assessment
of the inactivated type of the vitamin D form. These studies were also performed in
the children population. Epidemiologic studies have shown that reference Vitamin D
levels change with age.[17] All of this data may with the result of inconsistent findings about the role of
vitamin D in allergic rhinitis.
Another problem in identifying the ideal level of vitamin D is the weight and fat
storage of the participant. Vitamin D is a fat soluble vitamin, and it can be present
in lower levels in obese patients.[18] In previous reports, there is not sufficient data in the methodology sections about
the BMI values of the participants. This bias may be one of the reasons for the inconsistent
results. To avoid this effect, we have excluded overweight and obese patients from
the present study.
Vitamin D is a key hormone that modulates the immune response at the tissue level,
participating both in innate and humoral immunity. Macrophages, dendritic cells (DCs)
and lymphocytes possess receptors activated by the active form of vitamin D (1α-25-dihydroxyvitamin
D3).[19] 1α-25-dihydroxyvitamin D3 protects the activation and maturation of the DCs, resulting
in the suppression of antigen presentation. The 1α-25-dihydroxyvitamin D3 level is
important in the pathogenesis of the allergic diseases. Our findings support this
data.
Environmental antigens, also known as allergens, cause increased synthesis of IgE.
Immunoglobilin plays an important role in type-1 hypersensitivity reactions, such
as allergic rhinitis, in which the IgE levels increased. The relationship between
IgE levels and 1α-25-dihydroxyvitamin D3 has been investigated before, and the results
both in total and specific IgE levels.[20]
[21] These inconsistent results may be related to the age of the selected study group,
the duration of exposure to sunlight, and the changes in allergen diversity. In the
present study, we have found increased levels of IgE in the allergic rhinitis patients.
We have also found a relationship in which the IgE levels are increased when the 1α-25-dihydroxyvitamin
D3 levels decrease, which also supports our findings.
Vitamin D, which is crucial for biosynthesis and immune reactions in the human body,
can be synthesized through a chemical reaction that is dependent on sun exposure.
The role of vitamin D in allergic diseases such as allergic rhinitis has been investigated
in previous reports, which have reached a clear conclusion. We thought that this is
related to the selected experiment group (age, BMI) and the measurement of inactive
vitamin D in the tissue level. We tried to exclude this effect in our study, and confirmed
the relationship between 1α-25-dihydroxyvitamin D3 and allergic rhinitis in the adult
population, but there were limitations in the present study as well. Firstly, the
vitamin deficiency should be measured and followed-up throughout the year. Secondly,
we should provide a 1α-25-dihydroxyvitamin D3 supplement to the patients with 1α-25-dihydroxyvitamin
D3 deficiency and follow the therapeutic response of the allergic rhinitis.
Conclusion
In the present study, we have shown the decreased level of 1α-25-dihydroxyvitamin
D3 in allergic rhinitis in the adult population with specific features. Furthermore,
this decrease is closely related with IgE levels. According to our knowledge, there
is no similar study in the literature. We believe that future studies including large
patient groups should be performed. These studies should cover the one-year measurement
of 1α-25-dihydroxyvitamin D3 and of vitamin D replacement in allergic rhinitis patients
with vitamin D deficiency and detect their response to it.
