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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 unclear. In particular, large-scale, population-based studies
examining this relationship in adult Asian populations are lacking. Objective: To evaluate the association between serum vitamin
D levels and allergic conditions in the general adult Korean population. Methods: A cross-sectional study was performed by
using data collected from 15,212 individuals 19 years or older who participated in the Korean National Health and Nutrition
Examination Survey from 2008 to 2010. The confounder- adjusted mean serum 25-hydroxyvitamin D (25[OH]D) levels of
participants with and without allergic conditions (including atopic dermatitis, asthma, allergic rhinitis, and increased total and
allergen-specific serum IgE) were compared by using multiple linear regression analyses. Multiple logistic regression analyses
with confounder adjustment estimated the odds ratios (ORs) for developing each condition according to adequate, inadequate, or
deficient serum 25(OH)D levels. Results: After adjusting for potential confounders, mean serum 25(OH)D levels were
significantly lower in participants diagnosed with atopic dermatitis than in those without this diagnosis (mean 6 SE, 18.58 6 0.29
ng/mL vs 19.20 6 0.15 ng/ mL; P 5 .02). Compared with participants with adequate vitamin D levels (>_20 ng/mL), confounder-
adjusted ORs of atopic dermatitis were significantly higher in those with inadequate (12-19.99 ng/mL) or deficient (<12 ng/mL)
levels (OR [95% CI], 1.50 [1.10-2.06] and 1.48 [1.04-2.12], respectively; P 5 .02). This relationship was not observed in
participants with the other allergic conditions. Conclusion: Vitamin D–insufficient adult individuals within the general Korean
population have an increased likelihood of atopic dermatitis, but not asthma, allergic rhinitis, or IgE sensitization. (J Allergy Clin
Immunol 2014;133:1048-55.)
Key words: Vitamin D, allergy, atopic dermatitis, asthma, allergic rhinitis, IgE, Asian, Korean, adult, KNHANES
Vitamin D receptors are expressed on nearly all types of immune cells, including T cells, B cells, neutrophils, macro- phages,
and dendritic cells.1 The function of vitamin D––known to regulate calcium and phosphate homeostasis––is thought to be highly
complex, and its potential roles in cardiovascular, neoplastic, infectious, and autoimmune diseases have been investigated in
recent studies.2-5
Vitamin D exerts its immunomodulatory effects on both the innate and adaptive immune systems,6 and its suppressive effects
are known to play a role in various autoimmune diseases.4 Reduced vitamin D levels have been reported in conditions such as
rheumatoid arthritis, type 1 diabetes mellitus, inflamma- tory bowel disease, and multiple sclerosis, all of which are commonly
mediated by T
H
1 cells.4 Indeed, using vitamin D analogues to treat psoriasis is now common clinical practice.
However, the effect of vitamin D on allergic conditions is less clear.
Previous experimental studies show that vitamin D may enhance which direct ever, clinical effect shifts T H
2 on the studies cell naive balance responses show T-cell of varying differentiation T not cells only results.1 toward by into
inhibiting T
While H 2,7 T H
2 but some cells.8 T also H
1 studies How- cells, via a
report a protective role of vitamin D in atopic dermatitis (AD),9 asthma,10 allergic rhinitis (AR),11 and allergic sensitization12
in childhood, others support a deleterious effect.13-15 Furthermore, studies thus far have largely focused on evaluating children
or pregnant mothers in white, African-American, or Hispanic popu- lations. To date, there are insufficient numbers of large-scale,
population-based studies examining the association between allergic conditions and serum vitamin D levels, particularly
From
a
Royal Perth Hospital, Perth, Western Australia;
b
the Department of Family Medicine, Kangwon National University Hospital,
Chuncheon; cthe Department of Dermatology, Dongtan Sacred Heart Hospital, Hallym University College of Medi- cine,
Hwaseong; dthe Department of Dermatology, Asan Medical Center, University
among adult Asian populations. Thus, the present study aimed to evaluate the association between serum vitamin D levels and
allergic conditions, namely, AD, asthma, and AR as well as IgE 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. Available online December 31, 2013. Corresponding author: Gyeong-Hun Park,
MD, PhD, Department of Dermatology, Dong- tan Sacred Heart Hospital, Hallym University College of Medicine 7,
Keunjaebong-gil, Hwaseong-si, Gyeonggi-do 445-170, Korea. E-mail: borelalgebra@gmail.com. 0091-6749/$36.00
Nutrition Examination Survey (KNHANES), a survey conducted by the Korea Center for Disease Control and Prevention to
garner nationally representative and reliable statistical data regarding the health, behavior associated with health, nutrition, and
food intake status of the Korean population. Data were collected from 2008 to 2010, which corresponded to the second and third
years © 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
Abbreviations used
25(OH)D: 25-Hydroxyvitamin D
AD: Atopic dermatitis AR: Allergic rhinitis BMI: Body mass index KNHANES: Korean National Health and Nutrition
Examination
Survey OR: Odds ratio RSV: Respiratory syncytial virus
examination, and blood tests. The institutional review board at the Korea Centers for Disease Control and Prevention approved
the protocol, and all participants signed informed consent forms.
Both KNHANES IV and V adopted the stratified multistage cluster sampling design by using the rolling-survey sampling
method. Therefore, the rolling sample collected during each year is the probability sample representing the general Korean
population, and they are homogeneous and independent from each other. In 2008, 2009, and 2010, a total of 36,188 individuals
(12,528, 12,722, and 10,938, respectively) were sampled, and 29,235 of these individuals (9,744, 10,533, and 8,958, respectively)
participated in the surveys. Among the 29,235 participants, we subsequently 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, asthma, AR, occupation, income, education, physical activity, regular walking, or
smoking (n 5 3,607); those without body mass index (BMI) measurement (n 5 46); and those with a chronic disease that might
affect vitamin D metabolism, including liver cirrhosis, renal failure, pulmonary tuberculosis, and malignancies (n 5 243). Thus, a
final total of 15,212 participants was eligible for our study (Fig 1).
Variable definitions
The following question was used to assess physician-diagnosed AD for each participant: ‘‘Have you been diagnosed with AD
by a doctor?’’ Physician- diagnosed asthma and AR were also determined by using similar questions. The season in which the
examination occurred was classified as follows: spring (March to May), summer (June to August), autumn (September to
November), and winter (December to February). The region of residence for each participant was grouped as follows: urban
(Seoul, Gyeonggi, Busan, Daegu, Incheon, Gwangju, Daejeon, and Ulsan) and rural (Gangwon, Chungbuk, Chungnam, Jeonbuk,
Jeonnam, Gyeongbuk, Gyeongnam, and Jeju), as described previously.16 Occupation was classified on the basis of Korean
Standard Classification of Occupations as follows: group 1 (managers, professionals, and related workers); group 2 (clerks);
group 3 (service and sales workers); group 4 (skilled agricultural, forestry, and fishery workers); group 5 (craft, equipment, and
machine operating and assembling workers); group 6 (elementary workers); and group 7 (housewives, students, and the
unemployed). In this study, groups 1, 2, 3, and 7 were merged into a single group and groups 4, 5, and 6 were also merged,
because the latter groups were previously reported to have significantly higher serum 25(OH)D levels than the former groups.17
Participants who performed moderate physical activity for more than 30 minutes per day on more than 5 days per week 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 minutes per day on more than 5 days
per week, as described previously.16 In- come was defined as the log transformation of the monthly equivalent house- hold
income (in US $), which was calculated by dividing the household income by the square root of the number of household
members in accordance with the method recommended by the Organization for Economic Co- operation and Development.18
Before log transformation, US $1 was added to the monthly equivalent household income to retain the participants who re- ported
no income. Education level was classified into the following categories:
J ALLERGY CLIN IMMUNOL VOLUME 133, NUMBER 4
graduation from elementary school or lower, middle school, high school, and college and above. Cigarette smoking was indicated
as ‘‘yes’’ for participants who had smoked 100 cigarettes or more during their lifetime and ‘‘no’’ for those who had never
smoked or smoked fewer than 100 cigarettes during their lifetime.
Height and weight were measured as described previously,19 and the BMI was calculated in kilograms per square meter. The
BMI was categorized as normal or underweight (<23 kg/m2), overweight (ranging from 23 kg/m2 to <25 kg/m2), and obese
(>_25 kg/m2) according to the modified World Health 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 as described previously21 and
categorized as adequate (>_20 ng/mL), inade- quate (ranging from 12 to <20 ng/mL), or deficient (<12 ng/mL) according to the
guidelines set by the Food and Nutrition Board of the Institute of Medicine.22 Total and allergen-specific serum IgE levels
against Dermatopha- goides farinae, cockroach, and dog allergens were obtained in 2010 from 1588 participants who were
randomly sampled from every age and sex group in each district to represent the general Korean population. IgE levels were
measured by using a 1470 Wizard gamma-counter (PerkinElmer, Turku, Finland) with ImmunoCAP 100 (Phadia, Uppsala,
Sweden). Total IgE levels of more than 150 U/mL were defined as increased,23 and participants with allergen- specific IgE
levels of 0.35 kU/L or more were regarded as sensitized.12
Statistical analyses
Statistical analyses were performed by using the statistical software package R version 3.0.1 (The R Foundation for Statistical
Computing, Vienna, Austria), and 2-sided P values of less than .05 were considered statistically significant. To produce unbiased
national estimates representing the general Korean population, we used KNHANES sample weights accounting for the 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 level according to their AD,
asthma, AR, and increased total and allergen- specific serum IgE level status. The differences in the participant characteris- tics
according to the presence of these conditions were analyzed by using the design-based Wilcoxon rank-sum test for complex
sample survey data or the Pearson x2 test with Rao-Scott adjustment.
To estimate the mean serum 25(OH)D levels in participants with and without the above-mentioned allergic conditions, we
performed simple and multiple linear regression analyses by using the generalized linear model for a complex survey design. The
estimated means of serum 25(OH)D levels were calculated in the following ways: no adjustment for potential confounders;
confounder adjustment for age and sex (model 1); and confounder adjustment for age, sex, season at blood sampling, region of
residence, occupation, regular exercise, and regular walking (model 2).
To estimate odds ratios (ORs) of AD, asthma, AR, and increased total and allergen-specific serum IgE levels according to
serum 25(OH)D levels, we conducted simple and multiple logistic regression analyses by using the generalized linear model for a
complex survey design. The ORs and 95% CIs were calculated in the following ways: no adjustment for potential confounders;
confounder adjustment for age and sex (model 1); and confounder adjustment for age, sex, region of residence, income,
education, smoking, and BMI (model 2).
RESULTS General characteristics
A total of 15,212 participants were included in the study, and the general characteristics of this study population are presented
in Table I. Of these 15,212 participants, 1,588 were further tested for total and allergen-specific serum IgE levels for D farinae,
cockroach, and dog allergens; these IgE measurements are presented in Table II.
CHENG ET AL 1049
Differences in mean serum 25(OH)D levels based on the presence of AD, asthma, AR, and allergic sensitization
From this adult Korean population, we determined whether vitamin D (25[OH]D) levels correlated with any of the allergic
conditions by comparing the estimated mean values. Without 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
levels (Table III). However, when adjusted for confounding factors by using model 1 (age and sex) and model 2 (age, sex, season
at blood sampling, region of residence, occupation, regular exercise, and regular walking), mean 25(OH)D levels were
significantly lower only in participants diagnosed with AD compared with those without an AD diagnosis. Thus, regardless of the
adjustment model, the association remained significant between mean serum 25(OH)D levels and AD diagnosis, but not with
asthma, AR, or increased total or allergen-specific serum IgE levels.
Differences in the risk of developing AD, asthma, AR, and allergic sensitization based on serum 25(OH)D levels
We also evaluated whether the different 25(OH)D levels were associated with any of the allergic diseases by estimating OR
values and found a similar trend as above (Table IV). Without adjusting for potential confounders, the odds of AD and AR diag-
nosis were significantly higher in participants with inadequate or deficient 25(OH)D levels. Also, without adjusting for potential
confounders, the odds of increased total serum IgE level was significantly lower in those with inadequate or deficient 25(OH) D
levels. When adjusted for confounding factors by using model 1 (age and sex) and model 2 (age, sex, region of residence,
income, education, smoking, and BMI), only the odds for AD
1050 CHENG ET AL
FIG 1. Flowchart of the study population.
remained significantly higher in participants with both inadequate and deficient 25(OH)D levels. Thus, the association between
lower-than-normal 25(OH)D levels and AD diagnosis was signif- icant using both adjustment models. Again, however, this
relationship was not observed in asthma, AR, or increased total or allergen-specific serum IgE levels.
DISCUSSION
In this study, we set out to determine whether vitamin D levels correlated with any of the well-known allergic diseases in an adult
Asian population, which has not yet been addressed in previous studies. Our results demonstrate that study participants diagnosed
with AD had significantly lower vitamin D levels. Likewise, the odds of being diagnosed with AD were also significantly higher
in participants with inadequate or deficient vitamin D levels. Neither of these findings was observed in asthma, AR, or IgE
sensitization 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 or AR.25 Furthermore, our results can be extrapolated to the general adult Korean population because the present
study used data from a nationally representative sampling of the population. The pathogenesis of AD is attributed to immune and
skin- barrier abnormalities,26 and vitamin D may play beneficial roles in ameliorating both abnormalities. Vitamin D decreases
inflam- matory responses through helping to tolerize dendritic cells and convert CD41 T cells into regulatory T cells.4In addition,
vitamin D inhibits IL-12, IL-2, and IFN-g production, thereby reducing T
H
1 cell production, activation, and function.4 T
H
1-mediated inflammatory responses predominate in chronic lichenified
lesions,27 which are a characteristic of adult AD.28 Furthermore, vitamin D is important in maintaining the epidermal
permeability barrier29 and in promoting antimicrobial activity,30 both of which
J ALLERGY CLIN IMMUNOL APRIL 2014
are well recognized as defective in patients with AD.26 Mice null for 25(OH)D 1a-hydroxylase exhibit decreased filaggrin
expres- sion in their epidermis,29 which is known to increase the risk of allergen penetration and AD development.31 Vitamin D
enhances the expression of the antimicrobial peptide, cathelicidin,30 which has broad-spectrum antimicrobial activity against
bacteria, viruses, and fungi.32 Because colonization or infection by patho- gens, including Staphylococcus aureus, weakens the
permeability barrier and exacerbates AD,26 the antimicrobial effects of vitamin D can potentially play beneficial roles in AD.
The association between vitamin D and asthma has been studied extensively in recent years and has been observed by many, if
not all, studies among children.10,33 In contrast, this as- sociation has not been observed in many adult studies.25,34-36 A
significant proportion of childhood wheezing is associated with respiratory viral agents, particularly respiratory syncytial
TABLE I. General characteristics of the total study population
Characteristic Total
AD
P
AR
P No Yes value
No Yes 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.
CHENG ET AL 1051
J ALLERGY CLIN IMMUNOL VOLUME 133, NUMBER 4
virus (RSV).37 While RSV infection produces only cold-like symptoms in healthy adults, it can involve the lower respiratory
tract in infants and young children.38 RSV infection, including bronchiolitis, has been suggested to increase respiratory mucosal
permeability, enhance allergic sensitization to aeroallergens, and contribute to asthma development.37 Because vitamin D can
decrease the predisposition of children to respiratory viral infec- tions (RSV in particular)39 and can also decrease the inflamma-
tory response to RSV infection,40 adequate vitamin D levels may be associated with reduced wheezing or asthma development in
children. In adults, however, many studies found no association between vitamin D and asthma,25,34-36 consistent with the
results of the present study.
In contrast to AD and asthma, relatively few studies have investigated the role of vitamin D in AR,41 but many clinicians now
subscribe to the ‘‘united airways disease hypothesis,’’ which
Asthma
P value
posits that AR and asthma are the result of a single inflammatory process.42 On the basis of this concept, we can extrapolate the
pathophysiology of asthma to that of AR.43 Similar to asthma,
TABLE II. General characteristics of participants with total and allergen-specific serum IgE measurements
Characteristic Total
Sensitization to Dermatophagoides farinae
P value
Sensitization to dogs
P No Yes No Yes No Yes 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
sampling
Increased serum total IgE
P value
Sensitization to cockroaches
P value
.04 .06 .13 .01
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
residence
.002 .03 .09 .20
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, 3, and 7
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
Groups 4, 5,
and 6
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
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 school or less
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
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 above
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
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
less (<23)
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
Overweight (23-<25)
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
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
level (ng/mL)
.03 .02 .69 .21
Adequate (>_20)
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
Inadequate (12-<20)
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
Deficient
(<12)
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
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 x
2
test with Rao-Scott adjustment.
1052 CHENG ET AL
J ALLERGY CLIN IMMUNOL APRIL 2014
the association between vitamin D deficiency and AR in adults is weak based on current evidence. While an Iranian study, which
did not account for any confounders, showed a strong association
between them,44 a large cohort study found that higher vitamin D levels were associated with an increased prevalence of AR.45
The prevalence of AR in adulthood was also higher in participants who received vitamin D supplements as infants.15 The present
study found no association between vitamin D and AR in an adult Korean population, and further studies are needed to determine
the precise role of vitamin D in the pathogenesis of AR.
Consistent with our results showing that low vitamin D levels did not associate with IgE sensitization to allergens, large cross-
sectional studies of adults in the United States also showed no association.12,45 In children and adolescents, howev- er, low
serum vitamin D levels were significantly associated with allergic sensitization to most allergens.12 A study of asthma patients
also demonstrated that serum vitamin D levels inversely correlated with serum IgE levels in the pediatric, but not adult, group.46
Furthermore, the association in the pediatric group was stronger in younger (6-12 years old) than in older (13-17 years old)
children, where the association became statis- tically insignificant in the older children.46 The mechanism underlying the age-
related difference for this association, how- ever, remains to be elucidated. Because vitamin D contributes to maintaining the
epidermal permeability barrier and mucosal integrity as well as protecting against pathogenic microorgan- isms,29,30,47 vitamin
D deficiency may increase the chances of allergen exposure in childhood. However, because most allergies are initiated in
childhood, serum vitamin D levels in adults may not closely correlate to their allergic sensitization status.46
CHENG ET AL 1053
J ALLERGY CLIN IMMUNOL VOLUME 133, NUMBER 4
TABLE III. The estimated mean serum 25(OH)D levels (ng/mL) and their differences according to each condition
Condition
Mean 6 SE
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.
A cross-sectional study showed that serum vitamin D levels inversely associated with the prevalence of asthma in white, but
not African American, women.48 In addition, specific genotypes for several genes could modify the association between vitamin
D and allergy risk.49 Furthermore, a recent study reported the association between vitamin D receptor gene polymorphisms and
severe AD in adults.50 Therefore, the role of vitamin D in allergic diseases was speculated to differ on the basis of race.
However, an insufficient number of investigations have been con- ducted from which to draw any firm conclusions regarding
whether differences in ethnicity affect the association between serum vitamin D levels and allergic conditions. To our knowl-
edge, the present study is the first large-scale, population-based study describing the associations between serum vitamin D levels
and several allergic conditions in an adult East Asian population. Additional studies will be needed to clarify the effect of
ethnicity on the relationship between vitamin D and allergy.
Owing to the overall design of this study, several limitations exist. Because of the cross-sectional nature of the collected data,
temporal relationships among the conditions cannot be established. In addition, the method for absorbing vitamin D was also not
accounted for, because the information about sun exposure and the use of oral vitamin D supplements was not fully collected as
part of the study. The study is also subjected to recall bias because diagnoses of the conditions were self-reported.
In summary, we found an increased likelihood of AD among vitamin D–deficient individuals in the general adult Korean
population, but no apparent association of vitamin D status with
asthma, AR, or IgE sensitization. Further cohort studies will be needed to establish whether vitamin D has a possible therapeu- tic
effect to reduce the incidence and disease progression of AD in adults.
Key messages
d
Vitamin D insufficiency is associated with an increased risk of atopic dermatitis, but not asthma, allergic rhinitis, or IgE
sensitization, in the general adult Korean population.
d
The role of vitamin D in the pathogenesis and manage- ment of atopic dermatitis in adults warrants further investigation.
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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
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