Low vitamin D levels are associated with atopic dermatitis

,
but not allergic rhinitis, asthma, or IgE sensitization, in the
adult Korean population
Hui Mei Cheng, MD,a Sunmi Kim, MD,b Gyeong-Hun Park, MD, PhD,c Sung Eun Chang, MD, PhD,d
Seunghyun Bang, PhD,e Chong Hyun Won, MD, PhD,d Mi Woo Lee, MD, PhD,d Jee Ho Choi, MD, PhD,d and
Kee Chan Moon, MD, PhDd Perth, Australia, and Chuncheon, Hwaseong, and Seoul, Korea

Background: The effect of vitamin D on allergic conditions is Key words: Vitamin D, allergy, atopic dermatitis, asthma, allergic
unclear. In particular, large-scale, population-based studies rhinitis, IgE, Asian, Korean, adult, KNHANES
examining this relationship in adult Asian populations are
lacking.
Objective: To evaluate the association between serum vitamin D Vitamin D receptors are expressed on nearly all types of
levels and allergic conditions in the general adult Korean immune cells, including T cells, B cells, neutrophils, macro-
population. phages, and dendritic cells.1 The function of vitamin D––known
Methods: A cross-sectional study was performed by using data to regulate calcium and phosphate homeostasis––is thought to be
collected from 15,212 individuals 19 years or older who highly complex, and its potential roles in cardiovascular,
participated in the Korean National Health and Nutrition neoplastic, infectious, and autoimmune diseases have been
Examination Survey from 2008 to 2010. The confounder- investigated in recent studies.2-5
adjusted mean serum 25-hydroxyvitamin D (25[OH]D) levels of Vitamin D exerts its immunomodulatory effects on both the
participants with and without allergic conditions (including innate and adaptive immune systems,6 and its suppressive effects
atopic dermatitis, asthma, allergic rhinitis, and increased total are known to play a role in various autoimmune diseases.4
and allergen-specific serum IgE) were compared by using Reduced vitamin D levels have been reported in conditions
multiple linear regression analyses. Multiple logistic regression such as rheumatoid arthritis, type 1 diabetes mellitus, inflamma-
analyses with confounder adjustment estimated the odds ratios tory bowel disease, and multiple sclerosis, all of which are
(ORs) for developing each condition according to adequate, commonly mediated by TH1 cells.4 Indeed, using vitamin D
inadequate, or deficient serum 25(OH)D levels. analogues to treat psoriasis is now common clinical practice.
Results: After adjusting for potential confounders, mean serum However, the effect of vitamin D on allergic conditions is less
25(OH)D levels were significantly lower in participants clear.
diagnosed with atopic dermatitis than in those without this Previous experimental studies show that vitamin D may
diagnosis (mean 6 SE, 18.58 6 0.29 ng/mL vs 19.20 6 0.15 ng/ enhance TH2 cell responses not only by inhibiting TH1 cells,
mL; P 5 .02). Compared with participants with adequate which shifts the balance of T cells toward TH2,7 but also via a
vitamin D levels (>_20 ng/mL), confounder-adjusted ORs of direct effect on naive T-cell differentiation into TH2 cells.8 How-
atopic dermatitis were significantly higher in those with ever, clinical studies show varying results.1 While some studies
inadequate (12-19.99 ng/mL) or deficient (<12 ng/mL) levels report a protective role of vitamin D in atopic dermatitis (AD),9
(OR [95% CI], 1.50 [1.10-2.06] and 1.48 [1.04-2.12], asthma,10 allergic rhinitis (AR),11 and allergic sensitization12 in
respectively; P 5 .02). This relationship was not observed in childhood, others support a deleterious effect.13-15 Furthermore,
participants with the other allergic conditions. studies thus far have largely focused on evaluating children or
Conclusion: Vitamin D–insufficient adult individuals within the pregnant mothers in white, African-American, or Hispanic popu-
general Korean population have an increased likelihood of lations. To date, there are insufficient numbers of large-scale,
atopic dermatitis, but not asthma, allergic rhinitis, or IgE population-based studies examining the association between
sensitization. (J Allergy Clin Immunol 2014;133:1048-55.) allergic conditions and serum vitamin D levels, particularly
among adult Asian populations. Thus, the present study aimed
From aRoyal Perth Hospital, Perth, Western Australia; bthe Department of Family to evaluate the association between serum vitamin D levels and
Medicine, Kangwon National University Hospital, Chuncheon; cthe Department of
Dermatology, Dongtan Sacred Heart Hospital, Hallym University College of Medi-
allergic conditions, namely, AD, asthma, and AR as well as IgE
cine, Hwaseong; dthe Department of Dermatology, Asan Medical Center, University sensitization to allergens, in an adult Korean population.
of Ulsan College of Medicine, Seoul; and eAsan Institute for Life Sciences, Seoul.This
report was presented at the 9th Asian Dermatological Congress in Hong Kong, on July
10-13, 2013.
Disclosure of potential conflict of interest: The authors declare that they have no relevant METHODS
conflicts of interest. Study population
Received for publication August 23, 2013; revised October 27, 2013; accepted for pub- This study was based on data acquired from the Korean National Health and
lication October 29, 2013. Nutrition Examination Survey (KNHANES), a survey conducted by the Korea
Available online December 31, 2013.
Center for Disease Control and Prevention to garner nationally representative
Corresponding author: Gyeong-Hun Park, MD, PhD, Department of Dermatology, Dong-
and reliable statistical data regarding the health, behavior associated with
tan Sacred Heart Hospital, Hallym University College of Medicine 7, Keunjaebong-gil,
Hwaseong-si, Gyeonggi-do 445-170, Korea. E-mail: borelalgebra@gmail.com. health, nutrition, and food intake status of the Korean population. Data were
0091-6749/$36.00 collected from 2008 to 2010, which corresponded to the second and third years
Ó 2013 American Academy of Allergy, Asthma & Immunology of KNHANES IV (2007-2009) and the first year of KNHANES V (2010-
http://dx.doi.org/10.1016/j.jaci.2013.10.055 2012). The survey included a health interview, a nutritional survey, a physical

1048
J ALLERGY CLIN IMMUNOL CHENG ET AL 1049
VOLUME 133, NUMBER 4

graduation from elementary school or lower, middle school, high school, and
Abbreviations used college and above. Cigarette smoking was indicated as ‘‘yes’’ for participants
25(OH)D: 25-Hydroxyvitamin D who had smoked 100 cigarettes or more during their lifetime and ‘‘no’’ for
AD: Atopic dermatitis those who had never smoked or smoked fewer than 100 cigarettes during their
AR: Allergic rhinitis lifetime.
BMI: Body mass index Height and weight were measured as described previously,19 and the BMI
KNHANES: Korean National Health and Nutrition Examination was calculated in kilograms per square meter. The BMI was categorized as
Survey normal or underweight (<23 kg/m2), overweight (ranging from 23 kg/m2 to
OR: Odds ratio <25 kg/m2), and obese (> _25 kg/m2) according to the modified World Health
RSV: Respiratory syncytial virus Organization criteria for the Asia-Pacific region.20
Blood samples were collected from the antecubital veins, refrigerated
immediately, transported to the central testing facility in cold storage, and
analyzed within 24 hours of sampling. Serum 25(OH)D levels were measured
examination, and blood tests. The institutional review board at the Korea as described previously21 and categorized as adequate (> _20 ng/mL), inade-
Centers for Disease Control and Prevention approved the protocol, and all quate (ranging from 12 to <20 ng/mL), or deficient (<12 ng/mL) according
participants signed informed consent forms. to the guidelines set by the Food and Nutrition Board of the Institute of
Both KNHANES IV and V adopted the stratified multistage cluster Medicine.22 Total and allergen-specific serum IgE levels against Dermatopha-
sampling design by using the rolling-survey sampling method. Therefore, goides farinae, cockroach, and dog allergens were obtained in 2010 from 1588
the rolling sample collected during each year is the probability sample participants who were randomly sampled from every age and sex group in each
representing the general Korean population, and they are homogeneous and district to represent the general Korean population. IgE levels were measured
independent from each other. In 2008, 2009, and 2010, a total of 36,188 by using a 1470 Wizard gamma-counter (PerkinElmer, Turku, Finland) with
individuals (12,528, 12,722, and 10,938, respectively) were sampled, and ImmunoCAP 100 (Phadia, Uppsala, Sweden). Total IgE levels of more than
29,235 of these individuals (9,744, 10,533, and 8,958, respectively) 150 U/mL were defined as increased,23 and participants with allergen-
participated in the surveys. Among the 29,235 participants, we subsequently specific IgE levels of 0.35 kU/L or more were regarded as sensitized.12
excluded the following participants: younger than 19 years (n 5 7,424);
those whose 25-hydroxyvitamin D (25[OH]D) levels were not measured
(n 5 2,703); those who did not completely answer questions regarding AD, Statistical analyses
asthma, AR, occupation, income, education, physical activity, regular Statistical analyses were performed by using the statistical software
walking, or smoking (n 5 3,607); those without body mass index (BMI) package R version 3.0.1 (The R Foundation for Statistical Computing, Vienna,
measurement (n 5 46); and those with a chronic disease that might affect Austria), and 2-sided P values of less than .05 were considered statistically
vitamin D metabolism, including liver cirrhosis, renal failure, pulmonary significant. To produce unbiased national estimates representing the general
tuberculosis, and malignancies (n 5 243). Thus, a final total of 15,212 Korean population, we used KNHANES sample weights accounting for the
participants was eligible for our study (Fig 1). complex sampling design to each participant.24 We estimated the means and
SDs or the proportions and SEs of the participants’ demographic variables,
socioeconomic factors, health behavior factors, BMI, and serum 25(OH)D
Variable definitions level according to their AD, asthma, AR, and increased total and allergen-
The following question was used to assess physician-diagnosed AD for specific serum IgE level status. The differences in the participant characteris-
each participant: ‘‘Have you been diagnosed with AD by a doctor?’’ Physician- tics according to the presence of these conditions were analyzed by using the
diagnosed asthma and AR were also determined by using similar questions. design-based Wilcoxon rank-sum test for complex sample survey data or the
The season in which the examination occurred was classified as follows: Pearson x2 test with Rao-Scott adjustment.
spring (March to May), summer (June to August), autumn (September to To estimate the mean serum 25(OH)D levels in participants with and
November), and winter (December to February). The region of residence for without the above-mentioned allergic conditions, we performed simple and
each participant was grouped as follows: urban (Seoul, Gyeonggi, Busan, multiple linear regression analyses by using the generalized linear model for a
Daegu, Incheon, Gwangju, Daejeon, and Ulsan) and rural (Gangwon, complex survey design. The estimated means of serum 25(OH)D levels were
Chungbuk, Chungnam, Jeonbuk, Jeonnam, Gyeongbuk, Gyeongnam, and calculated in the following ways: no adjustment for potential confounders;
Jeju), as described previously.16 Occupation was classified on the basis of confounder adjustment for age and sex (model 1); and confounder adjustment
Korean Standard Classification of Occupations as follows: group 1 (managers, for age, sex, season at blood sampling, region of residence, occupation, regular
professionals, and related workers); group 2 (clerks); group 3 (service and exercise, and regular walking (model 2).
sales workers); group 4 (skilled agricultural, forestry, and fishery workers); To estimate odds ratios (ORs) of AD, asthma, AR, and increased total and
group 5 (craft, equipment, and machine operating and assembling workers); allergen-specific serum IgE levels according to serum 25(OH)D levels, we
group 6 (elementary workers); and group 7 (housewives, students, and the conducted simple and multiple logistic regression analyses by using the
unemployed). In this study, groups 1, 2, 3, and 7 were merged into a single generalized linear model for a complex survey design. The ORs and 95% CIs
group and groups 4, 5, and 6 were also merged, because the latter groups were calculated in the following ways: no adjustment for potential
were previously reported to have significantly higher serum 25(OH)D levels confounders; confounder adjustment for age and sex (model 1); and
than the former groups.17 Participants who performed moderate physical confounder adjustment for age, sex, region of residence, income, education,
activity for more than 30 minutes per day on more than 5 days per week smoking, and BMI (model 2).
and/or strenuous physical activity for more than 20 minutes per day on
more than 3 days per week were assigned to the regular exercise group. Reg-
ular walking was designated as ‘‘yes’’ for those who walked for more than 30 RESULTS
minutes per day on more than 5 days per week, as described previously.16 In-
General characteristics
come was defined as the log transformation of the monthly equivalent house-
A total of 15,212 participants were included in the study, and
hold income (in US $), which was calculated by dividing the household
income by the square root of the number of household members in accordance the general characteristics of this study population are presented
with the method recommended by the Organization for Economic Co- in Table I. Of these 15,212 participants, 1,588 were further tested
operation and Development.18 Before log transformation, US $1 was added for total and allergen-specific serum IgE levels for D farinae,
to the monthly equivalent household income to retain the participants who re- cockroach, and dog allergens; these IgE measurements are
ported no income. Education level was classified into the following categories: presented in Table II.
1050 CHENG ET AL J ALLERGY CLIN IMMUNOL
APRIL 2014

FIG 1. Flowchart of the study population.

Differences in mean serum 25(OH)D levels based on remained significantly higher in participants with both inadequate
the presence of AD, asthma, AR, and allergic and deficient 25(OH)D levels. Thus, the association between
sensitization lower-than-normal 25(OH)D levels and AD diagnosis was signif-
From this adult Korean population, we determined whether icant using both adjustment models. Again, however, this
vitamin D (25[OH]D) levels correlated with any of the allergic relationship was not observed in asthma, AR, or increased total
conditions by comparing the estimated mean values. Without or allergen-specific serum IgE levels.
adjusting for potential confounders, the mean 25(OH)D levels
were significantly lower in participants diagnosed with AD or AR
and significantly higher in participants with increased serum IgE DISCUSSION
levels (Table III). However, when adjusted for confounding factors In this study, we set out to determine whether vitamin D levels
by using model 1 (age and sex) and model 2 (age, sex, season at correlated with any of the well-known allergic diseases in an adult
blood sampling, region of residence, occupation, regular exercise, Asian population, which has not yet been addressed in previous
and regular walking), mean 25(OH)D levels were significantly studies. Our results demonstrate that study participants diagnosed
lower only in participants diagnosed with AD compared with with AD had significantly lower vitamin D levels. Likewise, the
those without an AD diagnosis. Thus, regardless of the adjustment odds of being diagnosed with AD were also significantly higher in
model, the association remained significant between mean serum participants with inadequate or deficient vitamin D levels. Neither
25(OH)D levels and AD diagnosis, but not with asthma, AR, or of these findings was observed in asthma, AR, or IgE sensitization
increased total or allergen-specific serum IgE levels. to allergens in the confounder-adjusted regression models. These
results are consistent with findings from a previous association
study showing that vitamin D–deficient participants in a primarily
adult obese population had an increased risk of AD but not asthma
Differences in the risk of developing AD, asthma, or AR.25 Furthermore, our results can be extrapolated to the
AR, and allergic sensitization based on serum general adult Korean population because the present study used
25(OH)D levels data from a nationally representative sampling of the population.
We also evaluated whether the different 25(OH)D levels were The pathogenesis of AD is attributed to immune and skin-
associated with any of the allergic diseases by estimating OR barrier abnormalities,26 and vitamin D may play beneficial roles
values and found a similar trend as above (Table IV). Without in ameliorating both abnormalities. Vitamin D decreases inflam-
adjusting for potential confounders, the odds of AD and AR diag- matory responses through helping to tolerize dendritic cells and
nosis were significantly higher in participants with inadequate or convert CD41 T cells into regulatory T cells.4 In addition, vitamin
deficient 25(OH)D levels. Also, without adjusting for potential D inhibits IL-12, IL-2, and IFN-g production, thereby reducing
confounders, the odds of increased total serum IgE level was TH1 cell production, activation, and function.4 TH1-mediated
significantly lower in those with inadequate or deficient 25(OH) inflammatory responses predominate in chronic lichenified
D levels. When adjusted for confounding factors by using model lesions,27 which are a characteristic of adult AD.28 Furthermore,
1 (age and sex) and model 2 (age, sex, region of residence, vitamin D is important in maintaining the epidermal permeability
income, education, smoking, and BMI), only the odds for AD barrier29 and in promoting antimicrobial activity,30 both of which
J ALLERGY CLIN IMMUNOL CHENG ET AL 1051
VOLUME 133, NUMBER 4

TABLE I. General characteristics of the total study population
AD P Asthma P AR P
Characteristic Total No Yes value No Yes value No Yes value

Total
n 15,212 14,820 392 14,737 475 13,421 1,791
% 100.0 97.0 6 0.2 3.0 6 0.2 97.1 6 0.2 2.9 6 0.2 86.8 6 0.4 13.2 6 0.4
Age (y) 44.0 6 15.1 44.3 6 15.1 35.5 6 13.7 <.001 43.9 6 15.0 47.9 6 17.8 .002 45.0 6 15.2 37.9 6 12.5 <.001
Sex .45 .09 .03
Male 50.6 6 0.4 50.6 6 0.4 48.3 6 3.0 50.7 6 0.4 45.5 6 3.0 51.0 6 0.5 47.6 6 1.4
Female 49.4 6 0.4 49.4 6 0.4 51.7 6 3.0 49.3 6 0.4 54.5 6 3.0 49.0 6 0.5 52.4 6 1.4
Season at blood sampling .12 .22 .40
Spring 25.7 6 2.1 25.7 6 2.1 27.1 6 3.5 25.6 6 2.1 30.0 6 3.5 25.4 6 2.1 27.5 6 2.6
Summer 27.0 6 2.1 27.0 6 2.1 25.4 6 3.3 27.0 6 2.1 25.8 6 3.1 27.1 6 2.1 26.5 6 2.6
Autumn 24.6 6 2.0 24.7 6 2.0 19.9 6 2.8 24.6 6 2.0 25.2 6 3.1 24.8 6 2.0 22.9 6 2.3
Winter 22.7 6 2.0 22.6 6 2.0 27.6 6 3.6 22.8 6 2.0 19.0 6 2.9 22.7 6 2.0 23.1 6 2.5
Region of residence .67 .01 .04
Urban 70.5 6 1.1 70.4 6 1.1 71.6 6 2.9 70.3 6 1.1 76.3 6 2.3 70.1 6 1.1 73.0 6 1.7
Rural 29.5 6 1.1 29.6 6 1.1 28.4 6 2.9 29.7 6 1.1 23.7 6 2.3 29.9 6 1.1 27.0 6 1.7
Occupation <.001 .053 <.001
Groups 1, 2, 3, and 7 73.5 6 0.7 73.2 6 0.7 82.7 6 2.2 73.4 6 0.7 78.2 6 2.3 72.1 6 0.8 82.7 6 1.1
Groups 4, 5, and 6 26.5 6 0.7 26.8 6 0.7 17.3 6 2.2 26.6 6 0.7 21.8 6 2.3 27.9 6 0.8 17.3 6 1.1
Regular exercise .69 .24 .80
No 84.1 6 0.4 84.1 6 0.4 83.2 6 2.2 84.1 6 0.4 81.5 6 2.4 84.1 6 0.5 83.8 6 1.0
Yes 15.9 6 0.4 15.9 6 0.4 16.8 6 2.2 15.9 6 0.4 18.5 6 2.4 15.9 6 0.5 16.2 6 1.0
Regular walking .63 .09 .046
No 67.2 6 0.5 67.2 6 0.5 65.9 6 2.7 67.3 6 0.5 62.3 6 3.0 66.8 6 0.6 69.5 6 1.2
Yes 32.8 6 0.5 32.8 6 0.5 34.1 6 2.7 32.7 6 0.5 37.7 6 3.0 33.2 6 0.6 30.5 6 1.2
Income (log US $) 7.0 6 0.9 7.0 6 0.9 7.0 6 1.1 .26 7.0 6 0.9 6.8 6 0.9 <.001 7.0 6 0.9 7.2 6 0.8 <.001
Education <.001 <.001 <.001
Elementary school or less 17.6 6 0.5 17.9 6 0.5 9.1 6 1.5 17.2 6 0.5 32.1 6 2.7 19.3 6 0.6 6.8 6 0.6
Middle school 10.2 6 0.3 10.3 6 0.3 6.1 6 1.4 10.1 6 0.3 11.6 6 1.6 10.7 6 0.3 6.6 6 0.6
High school 40.2 6 0.6 40.0 6 0.6 45.4 6 2.9 40.5 6 0.6 29.9 6 2.9 39.6 6 0.7 44.4 6 1.5
College or above 32.0 6 0.7 31.8 6 0.7 39.4 6 2.8 32.2 6 0.7 26.4 6 2.6 30.4 6 0.7 42.2 6 1.5
Smoking .17 .07 <.001
No 54.9 6 0.4 54.8 6 0.4 58.8 6 2.8 54.8 6 0.4 60.0 6 2.8 54.2 6 0.5 59.9 6 1.3
Yes 45.1 6 0.4 45.2 6 0.4 41.2 6 2.8 45.2 6 0.4 40.0 6 2.8 45.8 6 0.5 40.1 6 1.3
BMI (kg/m2) .25 .06 <.001
Normal or less (<23) 45.1 6 0.5 45.0 6 0.5 49.8 6 2.8 45.3 6 0.5 39.1 6 2.8 44.4 6 0.5 49.6 6 1.4
Overweight (23-<25) 23.1 6 0.4 23.2 6 0.4 20.2 6 2.5 23.1 6 0.4 23.6 6 2.5 23.2 6 0.4 22.8 6 1.1
Obese (>_25) 31.8 6 0.5 31.8 6 0.5 30.0 6 2.8 31.6 6 0.5 37.3 6 2.6 32.4 6 0.5 27.6 6 1.3
Serum 25(OH)D level (ng/mL) <.001 .38 <.001
Adequate (>_20) 34.2 6 1.0 34.6 6 1.0 21.9 6 2.6 34.3 6 1.0 31.1 6 2.6 35.1 6 1.0 28.6 6 1.5
Inadequate (12-<20) 48.2 6 0.7 47.9 6 0.7 56.1 6 3.0 48.2 6 0.7 49.4 6 2.7 47.5 6 0.7 52.6 6 1.5
Deficient (<12) 17.6 6 0.7 17.4 6 0.7 22.0 6 2.4 17.5 6 0.7 19.6 6 2.4 17.4 6 0.7 18.8 6 1.3

Data are expressed as mean 6 SD or % 6 SE.
P values were calculated by design-based Wilcoxon rank-sum test for complex sample survey data or Pearson x2 test with Rao-Scott adjustment.

are well recognized as defective in patients with AD.26 Mice null virus (RSV).37 While RSV infection produces only cold-like
for 25(OH)D 1a-hydroxylase exhibit decreased filaggrin expres- symptoms in healthy adults, it can involve the lower respiratory
sion in their epidermis,29 which is known to increase the risk of tract in infants and young children.38 RSV infection, including
allergen penetration and AD development.31 Vitamin D enhances bronchiolitis, has been suggested to increase respiratory mucosal
the expression of the antimicrobial peptide, cathelicidin,30 which permeability, enhance allergic sensitization to aeroallergens, and
has broad-spectrum antimicrobial activity against bacteria, contribute to asthma development.37 Because vitamin D can
viruses, and fungi.32 Because colonization or infection by patho- decrease the predisposition of children to respiratory viral infec-
gens, including Staphylococcus aureus, weakens the permeability tions (RSV in particular)39 and can also decrease the inflamma-
barrier and exacerbates AD,26 the antimicrobial effects of vitamin tory response to RSV infection,40 adequate vitamin D levels
D can potentially play beneficial roles in AD. may be associated with reduced wheezing or asthma development
The association between vitamin D and asthma has been in children. In adults, however, many studies found no association
studied extensively in recent years and has been observed by between vitamin D and asthma,25,34-36 consistent with the results
many, if not all, studies among children.10,33 In contrast, this as- of the present study.
sociation has not been observed in many adult studies.25,34-36 In contrast to AD and asthma, relatively few studies have
A significant proportion of childhood wheezing is associated investigated the role of vitamin D in AR,41 but many clinicians
with respiratory viral agents, particularly respiratory syncytial now subscribe to the ‘‘united airways disease hypothesis,’’ which
1052 CHENG ET AL J ALLERGY CLIN IMMUNOL
APRIL 2014

TABLE II. General characteristics of participants with total and allergen-specific serum IgE measurements
Sensitization to
Increased serum Dermatophagoides Sensitization Sensitization
total IgE P farinae P to cockroaches P to dogs P
Characteristic Total No Yes value No Yes value No Yes value No Yes value

Total
n 1588 1044 544 978 610 1277 311 1505 83
% 100.0 64.5 6 1.7 35.5 6 1.7 60.9 6 1.5 39.1 6 1.5 78.5 6 1.5 21.5 6 1.5 93.6 6 0.9 6.4 6 0.9
Age (y) 44.8 6 15.4 43.7 6 15.0 46.9 6 15.9 .004 46.1 6 15.4 42.8 6 15.1 .003 44.7 6 15.3 45.3 6 15.6 .66 45.2 6 15.3 38.4 6 15.3 .002
Sex <.001 <.001 <.001 <.001
Male 49.4 6 1.1 40.9 6 1.5 65.0 6 2.2 43.1 6 1.5 59.3 6 2.3 43.7 6 1.3 70.5 6 3.3 48.1 6 1.1 68.5 6 5.1
Female 50.6 6 1.1 59.1 6 1.5 35.0 6 2.2 56.9 6 1.5 40.7 6 2.3 56.3 6 1.3 29.5 6 3.3 51.9 6 1.1 31.5 6 5.1
Season at blood .04 .06 .13 .01
sampling
Spring 24.7 6 3.9 22.1 6 3.7 29.3 6 4.9 24.2 6 4.1 25.4 6 4.2 23.5 6 3.9 28.9 6 5.7 24.4 6 3.9 28.2 6 7.6
Summer 27.5 6 4.0 29.7 6 4.4 23.6 6 4.1 30.3 6 4.3 23.2 6 3.9 29.4 6 4.2 20.6 6 4.5 28.7 6 4.2 10.6 6 4.5
Autumn 20.4 6 3.2 19.9 6 3.2 21.4 6 4.0 19.1 6 3.2 22.4 6 3.8 19.9 6 3.2 22.4 6 4.3 20.5 6 3.2 19.1 6 5.6
Winter 27.4 6 4.1 28.3 6 4.3 25.7 6 4.5 26.4 6 4.1 29.0 6 4.6 27.2 6 4.1 28.1 6 5.1 26.4 6 4.0 42.0 6 8.4
Region of .002 .03 .09 .20
residence
Urban 70.0 6 2.5 73.7 6 2.6 63.3 6 3.4 72.4 6 2.7 66.2 6 3.0 71.5 6 2.6 64.4 6 4.2 69.5 6 2.5 77.9 6 5.8
Rural 30.0 6 2.5 26.3 6 2.6 36.7 6 3.4 27.6 6 2.7 33.8 6 3.0 28.5 6 2.6 35.6 6 4.2 30.5 6 2.5 22.1 6 5.8
Occupation <.001 .01 .001 .69
Groups 1, 2, 71.8 6 1.9 77.2 6 1.9 62.0 6 3.1 74.5 6 2.1 67.7 6 2.6 74.2 6 2.0 63.1 6 3.4 72.0 6 2.0 69.7 6 5.6
3, and 7
Groups 4, 5, 28.2 6 1.9 22.8 6 1.9 38.0 6 3.1 25.5 6 2.1 32.3 6 2.6 25.8 6 2.0 36.9 6 3.4 28.0 6 2.0 30.3 6 5.6
and 6
Regular exercise .02 .12 .42 .43
No 85.2 6 1.2 87.4 6 1.2 81.1 6 2.5 86.8 6 1.5 82.7 6 2.1 85.7 6 1.3 83.3 6 2.8 84.9 6 1.3 88.9 6 4.2
Yes 14.8 6 1.2 12.6 6 1.2 18.9 6 2.5 13.2 6 1.5 17.3 6 2.1 14.3 6 1.3 16.7 6 2.8 15.1 6 1.3 11.1 6 4.2
Regular walking .12 .67 .51 .13
No 71.2 6 1.4 73.0 6 1.6 67.9 6 2.8 71.7 6 1.7 70.4 6 2.5 71.7 6 1.5 69.3 6 3.3 71.7 6 1.4 63.1 6 6.0
Yes 28.8 6 1.4 27.0 6 1.6 32.1 6 2.8 28.3 6 1.7 29.6 6 2.5 28.3 6 1.5 30.7 6 3.3 28.3 6 1.4 36.9 6 6.0
Income (log US $) 7.2 6 0.9 7.2 6 0.9 7.1 6 0.9 .01 7.1 6 0.9 7.2 6 0.9 .50 7.2 6 0.9 7.1 6 0.9 .11 7.2 6 0.9 7.2 6 0.6 .62
Education .01 .04 .87 .35
Elementary 19.2 6 1.5 16.8 6 1.5 23.6 6 3.0 21.0 6 1.9 16.5 6 2.1 19.0 6 1.7 19.9 6 2.9 19.8 6 1.6 10.9 6 4.2
school or
less
Middle school 11.0 6 0.9 10.2 6 1.1 12.4 6 1.7 11.8 6 1.2 9.7 6 1.5 11.4 6 1.0 9.3 6 2.4 11.1 6 1.0 9.9 6 4.0
High school 39.2 6 1.5 42.2 6 1.8 33.7 6 2.3 39.5 6 1.9 38.6 6 2.4 39.0 6 1.8 39.7 6 3.1 39.0 6 1.6 41.7 6 6.4
College or 30.6 6 1.6 30.8 6 1.8 30.3 6 2.5 27.7 6 1.8 35.2 6 2.2 30.5 6 1.9 31.1 6 3.5 30.2 6 1.6 37.5 6 5.7
above
Smoking <.001 <.001 <.001 .005
No 54.9 6 1.3 62.8 6 1.7 40.5 6 2.3 60.3 6 1.7 46.5 6 2.3 58.7 6 1.5 41.3 6 3.6 56.2 6 1.3 36.4 6 6.6
Yes 45.1 6 1.3 37.2 6 1.7 59.5 6 2.3 39.7 6 1.7 53.5 6 2.3 41.3 6 1.5 58.7 6 3.6 43.8 6 1.3 63.6 6 6.6
BMI (kg/m2) .09 .53 .03 .54
Normal or 46.0 6 1.5 48.6 6 2.1 41.2 6 2.6 47.2 6 2.0 44.1 6 2.4 48.3 6 1.7 37.6 6 3.2 46.3 6 1.6 41.8 6 6.7
less (<23)
Overweight 20.2 6 1.2 19.9 6 1.5 20.9 6 2.3 20.4 6 1.6 20.0 6 1.9 19.3 6 1.3 23.7 6 3.1 19.9 6 1.2 25.7 6 5.7
(23-<25)
Obese (>_25) 33.8 6 1.5 31.5 6 1.9 37.9 6 2.6 32.4 6 2.0 35.9 6 2.6 32.4 6 1.6 38.7 6 3.4 33.9 6 1.6 32.4 6 5.8
Serum 25(OH)D .03 .02 .69 .21
level
(ng/mL)
Adequate 32.4 6 2.1 29.5 6 2.3 37.8 6 2.9 29.5 6 2.3 36.9 6 2.7 31.7 6 2.3 34.9 6 3.5 32.5 6 2.1 31.5 6 5.7
_20)
(>
Inadequate 51.5 6 1.8 53.4 6 2.1 48.2 6 3.0 54.5 6 2.0 47.0 6 2.7 52.2 6 1.9 49.1 6 4.2 52.0 6 1.9 44.5 6 6.6
(12-<20)
Deficient 16.0 6 1.5 17.2 6 1.9 14.0 6 2.0 16.0 6 1.9 16.1 6 1.9 16.1 6 1.6 16.0 6 3.1 15.5 6 1.5 24.0 6 5.9
(<12)

Data are expressed as mean 6 SD or % 6 SE.
P values were calculated by design-based Wilcoxon rank-sum test for complex sample survey data or Pearson x2 test with Rao-Scott adjustment.

posits that AR and asthma are the result of a single inflammatory the association between vitamin D deficiency and AR in adults
process.42 On the basis of this concept, we can extrapolate the is weak based on current evidence. While an Iranian study, which
pathophysiology of asthma to that of AR.43 Similar to asthma, did not account for any confounders, showed a strong association
J ALLERGY CLIN IMMUNOL CHENG ET AL 1053
VOLUME 133, NUMBER 4

TABLE III. The estimated mean serum 25(OH)D levels (ng/mL) and their differences according to each condition
Mean 6 SE
Condition Without disease With disease Difference, mean (95% CI) P value

AD
Unadjusted 18.27 6 0.16 16.54 6 0.35 21.73 (22.39 to 21.07) <.001
Model 1* 18.23 6 0.16 17.31 6 0.34 20.92 (21.56 to 20.28) .005
Model 2  19.20 6 0.15 18.58 6 0.29 20.62 (21.15 to 20.08) .02
Asthma
Unadjusted 18.23 6 0.16 17.94 6 0.37 20.29 (20.96 to 0.38) .39
Model 1* 18.22 6 0.16 17.72 6 0.37 20.50 (21.17 to 0.17) .14
Model 2  19.19 6 0.15 18.90 6 0.35 20.29 (20.91 to 0.33) .35
AR
Unadjusted 18.34 6 0.17 17.42 6 0.22 20.92 (21.31 to 20.54) <.001
Model 1* 18.24 6 0.16 18.00 6 0.23 20.23 (20.61 to 0.15) .23
Model 2  19.18 6 0.15 19.17 6 0.20 20.01 (20.34 to 0.33) .96
Increased total serum IgE
Unadjusted 17.53 6 0.36 18.85 6 0.44 1.32 (0.40-2.24) .005
Model 1* 17.85 6 0.36 18.30 6 0.43 0.45 (20.44 to 1.34) .32
Model 2  18.88 6 0.39 19.31 6 0.48 0.43 (20.41 to 1.26) .32
Sensitization to Dermatophagoides farinae
Unadjusted 17.69 6 0.37 18.48 6 0.41 0.79 (20.09 to 1.67) .08
Model 1* 17.78 6 0.36 18.38 6 0.40 0.60 (20.23 to 1.43) .15
Model 2  18.79 6 0.39 19.41 6 0.47 0.61 (20.19 to 1.42) .14
Sensitization to cockroaches
Unadjusted 17.78 6 0.34 18.79 6 0.52 1.01 (20.01 to 2.04) .053
Model 1* 17.96 6 0.34 18.20 6 0.53 0.23 (20.82 to 1.29) .66
Model 2  18.96 6 0.38 19.37 6 0.57 0.40 (20.62 to 1.42) .44
Sensitization to dogs
Unadjusted 18.01 6 0.32 17.83 6 0.97 20.17 (22.06 to 1.72) .86
Model 1* 18.03 6 0.32 17.78 6 0.89 20.25 (21.99 to 1.48) .78
Model 2  19.02 6 0.37 19.66 6 0.93 0.65 (21.01 to 2.30) .44
*Model 1: adjusted for age and sex.
 Model 2: adjusted for age, sex, season at blood sampling, region of residence, occupation, regular exercise, and regular walking.

between them,44 a large cohort study found that higher vitamin D A cross-sectional study showed that serum vitamin D levels
levels were associated with an increased prevalence of AR.45 The inversely associated with the prevalence of asthma in white, but
prevalence of AR in adulthood was also higher in participants not African American, women.48 In addition, specific genotypes
who received vitamin D supplements as infants.15 The present for several genes could modify the association between vitamin
study found no association between vitamin D and AR in an adult D and allergy risk.49 Furthermore, a recent study reported the
Korean population, and further studies are needed to determine association between vitamin D receptor gene polymorphisms
the precise role of vitamin D in the pathogenesis of AR. and severe AD in adults.50 Therefore, the role of vitamin D in
Consistent with our results showing that low vitamin D levels allergic diseases was speculated to differ on the basis of race.
did not associate with IgE sensitization to allergens, large However, an insufficient number of investigations have been con-
cross-sectional studies of adults in the United States also ducted from which to draw any firm conclusions regarding
showed no association.12,45 In children and adolescents, howev- whether differences in ethnicity affect the association between
er, low serum vitamin D levels were significantly associated serum vitamin D levels and allergic conditions. To our knowl-
with allergic sensitization to most allergens.12 A study of edge, the present study is the first large-scale, population-based
asthma patients also demonstrated that serum vitamin D levels study describing the associations between serum vitamin D levels
inversely correlated with serum IgE levels in the pediatric, but and several allergic conditions in an adult East Asian population.
not adult, group.46 Furthermore, the association in the pediatric Additional studies will be needed to clarify the effect of ethnicity
group was stronger in younger (6-12 years old) than in older on the relationship between vitamin D and allergy.
(13-17 years old) children, where the association became statis- Owing to the overall design of this study, several limitations
tically insignificant in the older children.46 The mechanism exist. Because of the cross-sectional nature of the collected data,
underlying the age-related difference for this association, how- temporal relationships among the conditions cannot be
ever, remains to be elucidated. Because vitamin D contributes established. In addition, the method for absorbing vitamin D
to maintaining the epidermal permeability barrier and mucosal was also not accounted for, because the information about sun
integrity as well as protecting against pathogenic microorgan- exposure and the use of oral vitamin D supplements was not fully
isms,29,30,47 vitamin D deficiency may increase the chances collected as part of the study. The study is also subjected to recall
of allergen exposure in childhood. However, because most bias because diagnoses of the conditions were self-reported.
allergies are initiated in childhood, serum vitamin D levels in In summary, we found an increased likelihood of AD among
adults may not closely correlate to their allergic sensitization vitamin D–deficient individuals in the general adult Korean
status.46 population, but no apparent association of vitamin D status with
1054 CHENG ET AL J ALLERGY CLIN IMMUNOL
APRIL 2014

TABLE IV. ORs and 95% CIs of AD, asthma, AR, and allergic sensitization according to serum 25(OH)D levels
Serum 25(OH)D level
Condition _20 ng/mL)
Adequate (> Inadequate (12-<20 ng/mL) Deficient (<12 ng/mL) P for trend

AD
Unadjusted 1 (reference) 1.85 (1.37-2.51) 2.00 (1.42-2.82) <.001
Model 1* 1 (reference) 1.50 (1.10-2.06) 1.48 (1.04-2.12) .02
Model 2  1 (reference) 1.50 (1.10-2.06) 1.48 (1.04-2.12) .02
Asthma
Unadjusted 1 (reference) 1.13 (0.89-1.44) 1.23 (0.90-1.70) .18
Model 1* 1 (reference) 1.21 (0.94-1.55) 1.32 (0.94-1.87) .08
Model 2  1 (reference) 1.19 (0.92-1.53) 1.29 (0.91-1.82) .12
AR
Unadjusted 1 (reference) 1.36 (1.19-1.56) 1.33 (1.12-1.59) <.001
Model 1* 1 (reference) 1.14 (0.98-1.31) 1.03 (0.85-1.24) .59
Model 2  1 (reference) 1.11 (0.96-1.29) 1.01 (0.84-1.23) .71
Increased total serum IgE
Unadjusted 1 (reference) 0.71 (0.53-0.94) 0.64 (0.43-0.95) .01
Model 1* 1 (reference) 0.90 (0.66-1.23) 0.87 (0.58-1.31) .44
Model 2  1 (reference) 0.91 (0.66-1.24) 0.88 (0.58-1.33) .47
Sensitization to Dermatophagoides farinae
Unadjusted 1 (reference) 0.69 (0.53-0.89) 0.80 (0.56-1.15) .07
Model 1* 1 (reference) 0.72 (0.54-0.96) 0.83 (0.59-1.18) .13
Model 2  1 (reference) 0.74 (0.55-0.98) 0.86 (0.61-1.21) .19
Sensitization to cockroaches
Unadjusted 1 (reference) 0.85 (0.59-1.23) 0.91 (0.57-1.45) .54
Model 1* 1 (reference) 1.08 (0.72-1.62) 1.22 (0.73-2.04) .44
Model 2  1 (reference) 1.09 (0.72-1.63) 1.25 (0.75-2.06) .40
Sensitization to dogs
Unadjusted 1 (reference) 0.88 (0.48-1.62) 1.60 (0.80-3.20) .32
Model 1* 1 (reference) 0.91 (0.49-1.71) 1.61 (0.83-3.12) .26
Model 2  1 (reference) 0.89 (0.48-1.67) 1.58 (0.80-3.11) .29
*Model 1: adjusted for age and sex.
 Model 2: adjusted for age, sex, region of residence, income, education, smoking, and body mass index.

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