1

ISSN: 2644-2981

DOI: 10.33552/GJNFS.2022.03.000571

Global Journal of
Nutrition & Food Science
Research Article

Copyright © All rights are reserved by Hiroyuki Nakamura

Association of Immunoglobulin E Levels with Smoking
and Trace Element Intake: A Cross-sectional Analysisof the Shika Study
Koji Katano1, Fumihiko Suzuki2,3, Hiromasa Tsujiguchi1,2,4, Akinori Hara1,2,4, Sakae Miyagi5, Takayuki Kannon4,6,
Keita Suzuki2, Yukari Shimizu7, Thao Thi Thu Nguyen8, Kim-Oanh Pham1, Atsushi Asai1, Tomoko Kasahara1,
Masaharu Nakamura2, Chie Takazawa1, Koichiro Hayashi1, Toshio Hamagishi2, Aki Shibata2, Tadashi Konoshita9,
Yasuhiro Kambayashi10, Hirohito Tsuboi11, Atsushi Tajima4,6, Takayuki Kobayashi2 and Hiroyuki Nakamura1,2,4*
Graduate School of Medical Science, Kanazawa University, Japan1

Department of Hygiene and Public Health, Kanazawa University, Japan

2

Community Medicine Support Dentistry, Ohu University Hospital, Japan

3

Advanced Preventive Medical Sciences Research Center, Kanazawa University, Japan

4

Innovative Clinical Research Center, Kanazawa University, Japan

5

Department of Bioinformatics and Genomics, Kanazawa University, Japan

6

Department of Nursing, Komatsu University, Japan

7

Faculty of Public Health, Haiphong University of Medicine and Pharmacy, Vietnam

8

Third Department of Internal Medicine, University of Fukui Faculty of Medical Sciences, Japan

9

Department of Public Health, Okayama University of Science, Japan10

Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Japan

11*Corresponding author: Hiroyuki Nakamura, Department of Hygiene and Public
Health, Graduate School of Medical Science, Kanazawa University, Kanazawa,
Ishikawa, Japan.

Received Date: March 04, 2022
Published Date: March 16, 2022

Abstract
Introduction: Although many epidemiological studies have investigated the relationship between smoking and immunoglobulin E (IgE)
levels, few have reported a relationship with the intake of trace elements. Therefore, this epidemiological study examined the relationship between
smoking and IgE antibody titers, with the factor of trace element intake, in middle-aged and elderly inhabitants living in Shika town, Ishikawa, Japan.
Methods: Participants comprised 771 inhabitants of Shika town and included 363 males and 408 females with mean ages of 61.93 years
and 62.13 years, respectively. Non-specific IgE was obtained from the medical checkups. Smoking status was asked using the questionnaire. Traceelement intakes were investigated using the brief-type self-administered diet history questionnaire.

Results: Trace elements that showed interactions in a two-way analysis of covariance were copper and manganese. A post hoc analysis using
the Bonferroni method demonstrated that copper intake was significantly higher in the low-IgE group than in the high-IgE group of current smokers
only. A multiple logistic regression analysis showed that copper and manganese significantly contributed to higher IgE levels in current smokers only.
Conclusions: Our cross-sectional study of middle-aged and elderly community residents, among males, revealed lower manganese andcopper intakes in the high-IgE group of current smokers only, suggesting that IgE levels are more easily increased by allergens in smokers with low
manganese and copper intakes.

This work is licensed under Creative Commons Attribution 4.0 License GJNFS.MS.ID.000571.

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Global Journal of Nutrition & Food Science

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Keywords: Cigarette smoking; Serum immunoglobulin; Copper; Manganese; Cross-sectional study

Abbreviations: ANCOVA-Analysis of covariance; BDHQ-Brief-type self-administered Diet History Questionnaire; BMI-Body Mass Index; CIConfidence Interval; IgE-Immunoglobulin E; OR-Odds Ratio; SD-Standard Deviation

Introduction
Although the prevalence of allergic diseases, such as bronchialasthma, allergic rhinitis, atopic dermatitis, and food allergy, isapproximately 20% [1,2], it has rapidly increased in recent decades[3,4]. The causative agents of allergic diseases are allergens, such aspollen, microorganisms, dust mites, house dust, or pets. Exposure
to airborne particulates, such as environmental chemicals andtobacco, may also exacerbate allergic reactions [3]. In recent
years, increases in these chemicals in the environment have beensuggested to aggravate allergic diseases [5]. Since most cases ofallergic rhinitis and asthma are genetically predisposed to produce
immunoglobulin E (IgE) antibodies to common environmental
allergens, allergy is known as an IgE-mediated disease [6].

Tobacco tar or polycyclic aromatic hydrocarbons [7,8], which

are involved in allergic reactions, may increase the number ofmemory B cells, which are the source of IgE production, throughproduction [16]. This mechanism is supported by findings showing

a marked increase in B lymphocytes in the spleens of copperdeficient rats [17]. Although adequate intakes of manganese andcopper may inhibit increases in IgE antibodies and B cells, which

produce IgE antibodies, the findings of epidemiological studies
have been inconclusive. Combining the above-mentioned previous

studies, we hypothesized that smokers who have insufficient

intake of the trace elements elevate IgE antibody which is related
to various allergic diseases. Therefore, this epidemiological study

investigated the association of immunoglobulin E levels with andwithout smoking and trace elements intake in middle-aged andelderly inhabitants.

Materials and Methods
Participants

We utilized cross-sectional data from the Shika study [18-20].

the effects of nicotinic receptors, including the alpha4 and alpha7

Participants were recruited between October 2013 and January

congestion, and rhinorrhea [10]. Epidemiological studies reported

in Shika town, Ishikawa prefecture, Japan (population, 21,061,

subunits, in B cell lines [9], and exacerbate the IgE-mediatedsymptoms of allergic rhinitis, such as sneezing, itching, nasal

a dose-dependent relationship between the number of cigarettes
smoked and IgE antibody titers [11] and demonstrated that IgElevels increased with not only active smoking, but also passive
smoking [12]. On the other hand, a cross-sectional study on

untreated patients diagnosed with allergic rhinitis showed thatnasal obstruction in patients with moderate to severe symptoms

and quality of life due to rhinitis did not significantly differ between
smokers and non-smokers [13]. Therefore, the relationshipbetween smoking and IgE levels remains unclear.

Although few epidemiological studies have investigated therelationship between trace element intake and IgE levels, Tsuji, et al.

[14] reported a negative correlation between animal dander-specificIgE and blood manganese levels in pregnant women. Furthermore,

Oluwole et al. [15] revealed that serum concentrations of manganese
negatively correlated with asthma in schoolchildren. A clinicalstudy on healthy adults also demonstrated that a low-copper dietincreased the percentage of circulating B cells, the source of IgE

2017. The target population was residents living in 4 model

districts (Horimatsu, Higashimasuho, Tsuchida, and Togi districts)
population aged 65 years and older on 1 September 2020, 8499

(aging rate 42.2%)) [21]. The 4 districts were randomly selected,
and approximately 50% of the population of the town live in these

districts. A total of 5013 residents aged 40 years and older live inthe model districts. Written informed consent was obtained fromall 5013 participants. Among the participants who underwent a
medical examination, 1184 agreed to take part in this study. Amongthe participants who underwent a medical examination, 1184

agreed to take part in this study. Four hundred and thirty patientswere excluded for the following reasons: IgE levels were notexamined, the questionnaire was not answered, or energy records
were not within 600–4000 Kcal on the brief-type self-administered
diet history questionnaire (BDHQ). Figure 1 shows inclusion
criteria. In total, 771 participants (363 males and 408 females withmean (SD) ages of 61.93 (11.01) years and 62.13 (11.07) years,
respectively) were included in the analysis. No one received thetreatment with anti-IgE antibodies (Figure 1).

Citation: Koji Katano, Fumihiko Suzuki, Hiromasa Tsujiguchi, Akinori Hara, Hiroyuki Nakamura etc all. Association of Immunoglobulin
E Levels with Smoking and Trace Element Intake: A Cross-sectional Analysis of the Shika Study. Glob J Nutri Food Sci. 3(5): 2022. GJNFS.
MS.ID.000571. DOI: 10.33552/GJNFS.2022.03.000571.

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Global Journal of Nutrition & Food Science

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Figure 1: Participant recruitment chart.
Note: a This reference value was selected for the following reasons: less than 600 kcal/day is equivalent to half the energy intake required
for the lowest physical activity category; more than 4000 kcal/day is equivalent to 1.5-fold the energy intake required for the medium physicalactivity category. Abbreviations: BMI, Body Mass Index; BDHQ, Brief-Type Self-Administered diet history questionnaire

IgE levels
Blood samples were collected during medical checkups in

the Shika study mostly from December to January annually. Nonspecific IgE levels were measured by SRL Inc. (Tokyo, Japan) usinga Phadia5000 instrument (Thermo Fisher Scientific/Phadia AB,
Uppsala, Sweden) according to the manufacturer’s instructions.

BDHQ

Trace elements were assessed using the BDHQ [22,23]. The

BDHQ is a four-page structured questionnaire that assesses theconsumption frequencies of 58 foods and beverages commonly
consumed by the general Japanese population. The BDHQ also

estimates dietary intake in the last month using an ad hoc computer
algorithm. The validity of the BDHQ has been demonstrated inprevious studies [22,23]. To analyze nutrient data, the density
method was employed for estimations of intake per 1000 Kcal.

Questionnaire on demographics

Participants completed a self-administered questionnaire on

their lifestyle and medical history, including age, sex, BMI, lack of
exercise, sleep deprivation, current drinker, and current smoker.

Statistical analysis

Participants were classified as current and non-smokers. The

two IgE groups were classified into the low- and high-IgE groups
based on the median of participants in the present study. [24] IBMSPSS Statistics version 25 for Windows (IBM, Armonk, NY, USA) wasused for statistical analyses. The Student’s t-test was performed to
examine relationships between continuous variables, while the chi-squared test was conducted to investigate relationships between

categorical variables. A two-way analysis of covariance (ANCOVA)

was performed to examine the main effects and interactions
between the two smoking groups and two IgE groups on traceelement intake. Adjustments were performed for the following
confounding factors: age, lack of exercise, sleep deprivation,

current drinker, and BMI. In order to confirm the trace elementsthat showed an interaction between the two smoking groups andthe two IgE groups, we performed multiple logistic regression

analysis stratified by smoking status with IgE as the dependent
variable. The forced input method was used for variable selection.
The significance level was set to 5%.

Sample size

We used the free software G-power to calculate the sample sizeand statistical power. For the F-tests of ANCOVA, the effect size,alpha error probability, power, number of groups, and number ofcovariates were set to 0.25, 0.05, 0.8, 4, and 5, respectively. The total
sample size and actual power were 128 and 0.801, respectively. For

the Z-tests for logistic regression, tails, odds ratio, mull hypothesis,
alpha error probability, power, X distribution, X parm π were set
to Two, 0.2, 0.25, 0.05, 0.8, Binomial, 0.5, respectively. The total

sample size and actual power were found to be 124 and 0.800,

respectively. Therefore, the sample size of this study was confirmed
to be sufficient.

Ethics statement

The present study was conducted with the approval of the Ethics

Committee of Kanazawa University (No. 1491). Written informed
consent was obtained from all participants prior to participation.

Citation: Koji Katano, Fumihiko Suzuki, Hiromasa Tsujiguchi, Akinori Hara, Hiroyuki Nakamura etc all. Association of Immunoglobulin
E Levels with Smoking and Trace Element Intake: A Cross-sectional Analysis of the Shika Study. Glob J Nutri Food Sci. 3(5): 2022. GJNFS.
MS.ID.000571. DOI: 10.33552/GJNFS.2022.03.000571.

Page 3 of 9

Global Journal of Nutrition & Food Science

Volume 3-Issue 4

Results

females were current smokers (p < 0.001). On the other hand, theParticipant characteristics
Participant characteristics, the smoking status, IgE levels, andtrace element intake are shown in Table 1. Among 771 participants,

363 were male and 408 were female with mean (SD) ages of
61.93 (11.01) years and 62.13 (11.07) years, respectively, and no

significant sex differences. IgE levels (p < 0.001) was significantly
higher in males than in females. Significantly more males than
S1 Table: Comparison of IgE levels with and without allergic disease.

intakes of iron (p < 0.001), zinc (p < 0.001), copper (p < 0.001), andmanganese (p < 0.001) were significantly higher in females.

A comparison of IgE levels with and without allergic disease

is shown in S1 Table. IgE levels were significantly higher in the

100 participants of any allergic disease group than in the 648
participants of the non-allergic disease group (p < 0.001) and in the
67 participants of the pollinosis group than in the 681 participantsof the non-pollinosis group (p = 0.004).
Without disease

With disease

SD

Mean

SD

Any allergic disease (without 648, with: 100), IU/mL

200.34440.37436.4

1302.8<0.001

Pollinosis (without 681, with: 67), IU/mL

213.7

458.96416.941520.40.004

Allergic asthma (without 717, with: 31), IU/mL

225.04

Atopic dermatitis (without 741, with: 7), IU/mL

230.02

Food allergy (without 741, with: 7), IU/mL

228.73633.87390.59633.13430.59627.73572.39The mean (SD) number of cigarettes smoked per day among

0.115

485.74568.01

0.465

994.71

Notes: One-way analysis of variance. Covariates adjusted for sex and age. Abbreviations: SD, Standard deviationaP-value a

Mean

0.149

provide a concise and precise description of the experimental

current smokers was 20.35 (11.05) for males and 13.81 (7.72) for

results, their interpretation, as well as the experimental

females. This section may be divided by subheadings. It should

conclusions that can be drawn (Table 1).

Table 1: Participant characteristics.

Total (n = 771)

Male (n = 363)

Female (n = 408)

P-value a

Mean / n

SD / %

Mean / n

SD / %

Mean / n

SD / %

Age, years

62.04

11.04

61.93

11.01

62.13

11.07

Lack of exercise, n

611

79.25

278

76.58

333

81.62

365

47.34

264

72.73

101

24.75

<0.001

341.37<0.001

BMI, kg/m2

Sleep deficiency, nCurrent drinker, nCurrent smoker, n

23.09
547
136

3.02

70.95
17.64

23.66
248
118

2.95

68.32
32.51

22.59
299
22

IgE, IU/ml

229.92623.66334.38821.97136.98

Zinc, mg/1000 Kcal

4.48

0.72

4.26

0.69

4.67

Iron, mg/1000 Kcal

Copper, mg/1000 Kcal

Manganese, mg/1000 Kcal

4.21
0.65
1.63

1.19
0.12
0.45

3.84
0.61
1.57

1.03
0.11
0.42

4.53
0.68
1.69

0.806

2.98

<0.001

73.28

0.131

5.32
1.23
0.7

0.12
0.46

0.087

<0.001<0.001<0.001<0.001<0.001

Notes: p-values were calculated using the Student’s t-test for continuous variables and the chi-squared test for categorical variables. Abbreviaa

tions: BMI, body mass index; SD, standard deviation.

Comparison of IgE levels
No significant differences were observed in mean age between

the 550 participants in the low-IgE group and the 221 participantsin the high-IgE group (62.15 years versus 61.76 years, respectively).

The proportion of females (p < 0.001) and the intakes of zinc (p =0.003), and copper (p = 0.029) were significantly higher in the lowIgE group than in the high-IgE group. In contrast, the proportion ofcurrent smokers (p < 0.001) was significantly higher in the high-IgEgroup than in the low-IgE group (Table 2).

Citation: Koji Katano, Fumihiko Suzuki, Hiromasa Tsujiguchi, Akinori Hara, Hiroyuki Nakamura etc all. Association of Immunoglobulin
E Levels with Smoking and Trace Element Intake: A Cross-sectional Analysis of the Shika Study. Glob J Nutri Food Sci. 3(5): 2022. GJNFS.
MS.ID.000571. DOI: 10.33552/GJNFS.2022.03.000571.

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Global Journal of Nutrition & Food Science

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Table 2: Characteristics of low-IgE and high-IgE groups.
Low-IgE (n = 550)

High-IgE (n = 221)

Mean / n

95%CI / n

Mean / n

95%CI / nAge, years

62.15(61.24, 63.06)

61.76(60.27, 63.26)

BMI, kg/m2

22.95(22.70, 23.20)

23.45(23.05, 23.86)

Sleep deficiency, n

397

72.18

150

67.87

Sex (female), n
Lack of exercise, nCurrent drinker, nCurrent smoker, n

330
436

60

79.27

223
76

40.55

78

175
142

13.82

60

<0.001

79.19

0.978

<0.00127.15

666.37(528.80, 803.94)

Zinc, mg/1000 Kcal

4.53

(4.47, 4.59)

4.36(4.26, 4.46)(1.60, 1.68)

1.63

Copper, mg/1000 Kcal

Manganese, mg/1000 Kcal

0.65
1.64

(0.64, 0.66)

4.1

0.63

0.243

<0.001(51.07, 58.03)(4.15, 4.34)

0.037

64.25

54.55
4.25

0.664

35.29

IgE, IU/ml

Iron, mg/1000 Kcal

P-value a(3.94, 4.27)(0.61, 0.65)(1.57, 1.69)<0.001
0.128
0.003
0.029
0.715

Notes: a p-values were calculated using the Student’s t-test for continuous variables and the chi-squared test for categorical variables. Abbreviations: BMI, body mass index; CI, confidence interval.

Comparison of current smokers
The mean age of 635 non-smokers was significantly higher

than that of 136 current smokers (62.94 years versus 57.80 years,

p < 0.001). The proportion of females (p < 0.001) and the intakesof iron (p < 0.001), zinc (p = 0.001), and copper (p < 0.001) weresignificantly higher in non-smokers than in current smokers. In

contrast, IgE levels (p = 0.018) was significantly higher in current

smokers than in non-smokers. Since there were 110 male smokers
and only 26 female smokers, two-way ANCOVA and multiple logistic

regression analyses were performed only for the male group (Table
3).

Table 3: Characteristics of non-smoker and current smoker groups.

Non-smoker (n = 635)

Current smoker (n = 136)

P-value a

Mean / n

95%CI / %Mean / n

95%CI / %Age, years

62.94(62.09, 63.80)

57.8(56.11, 59.49)<0.001

BMI, kg/m2

23.08(22.85, 23.31)

23.18(22.63, 23.74)

0.701

Sleep deficiency, n

446

70.24

101

74.26

Sex (female), n
Lack of exercise, nCurrent drinker, n

382
492
269

60.16
77.48
42.36

26

119
96

19.12
87.5

(3.70, 4.11)

0.001(156.33, 251.98)

350.22(240.63, 459.81)

Zinc, mg/1000 Kcal

4.52

(4.47, 4.57)

4.29(4.15, 4.43)(1.61, 1.68)

1.6

Copper, mg/1000 Kcal

Manganese, mg/1000 Kcal

0.65
1.64

(4.18, 4.36)(0.65, 0.66)

3.9
0.6

0.336

<0.001204.16
4.27

0.003

70.59

IgE, IU/ml

Iron, mg/1000 Kcal

<0.001(0.58, 0.62)(1.52, 1.68)

0.018
0.001

<0.001
0.295

Notes: a p-values were calculated using the Student’s t-test for continuous variables and the chi-squared test for categorical variables. Abbreviations: BMI, body mass index; CI, confidence interval.

ANCOVA between two smoking groups and two IgEgroups on trace element intake in males
Table 4 shows the results of a two-way ANCOVA with the twocurrent smoking groups (non-smokers and current smokers) and

two IgE groups (low and high) as fixed factors and adjustments forage, BMI, lack of exercise, sleep deprivation, and current drinkers.

When 253 non-current smokers were subclassified, 160 were in the
low-IgE group and 93 were in the high-IgE group. Similarly, among

110 current smokers, 60 were in the low-IgE group and 50 were in

the high-IgE group. The trace element that showed a main effectin the two IgE groups was copper (p = 0.044). The trace elementsthat showed an interaction between the two groups of current

Citation: Koji Katano, Fumihiko Suzuki, Hiromasa Tsujiguchi, Akinori Hara, Hiroyuki Nakamura etc all. Association of Immunoglobulin
E Levels with Smoking and Trace Element Intake: A Cross-sectional Analysis of the Shika Study. Glob J Nutri Food Sci. 3(5): 2022. GJNFS.
MS.ID.000571. DOI: 10.33552/GJNFS.2022.03.000571.

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smoking and IgE levels were copper (p = 0.048) and manganese(p = 0.007). Therefore, high intakes of copper and manganese incurrent smokers appeared to result in low IgE levels (Table 4). In
Table 4: Two-way ANCOVA of smoker and IgE groups in males.

multiple comparisons using the Bonferroni method, copper intake

was significantly higher in the low-IgE group than in the high-IgEgroup within current smokers (Figure 2).

Male (n = 363)
Non-smoker (n = 253)

Low-IgE (n = 160)
Iron, mg/1000 Kcal
Zinc, mg/1000 Kcal
Copper, mg/1000 Kcal
Manganese, mg/1000 Kcal

Mean (95%CI)
3.87

High-IgE (n = 93)
Mean (95%CI)
3.77

Current smoker (n = 110)

Low-IgE (n = 60)
Mean (95%CI)
3.95

High-IgE (n = 50)
Mean (95%CI)
3.77(3.72 - 4.02)(3.57 - 3.97)(3.70 - 4.20)(3.50 - 4.04)(4.19 - 4.40)(4.08 - 4.35)(4.17 - 4.51)(3.96 - 4.33)(0.59 - 0.63)(0.59 - 0.63)(0.60 - 0.65)(0.55 - 0.61)(1.46 - 1.59)(1.55 - 1.71)(1.54 - 1.75)(1.39 - 1.61)

4.3

0.61
1.53

4.22
0.61
1.63

4.34
0.63
1.65

4.14
0.58
1.5

P1

P-value a
P2

P3

0.733

0.216

0.719

0.858

0.077

0.435

0.692

0.044

0.048

0.923

0.619

0.007

Notes: a Two-way ANCOVA. Adjusted for age, lack of exercise, sleep deprivation, current drinker, and BMI. P1: current smoker, P2: IgE, P3: current
smoker × IgE. Abbreviations: CI, confidence interval; ANCOVA, analysis of covariance.

Figure 2: Interaction between current smoking status and IgE on copper intake.
Notes: Post hoc Bonferroni analysis. Adjusted for age, lack of exercise, sleep deprivation, current drinker, and BMI. Error bar: 95% CI.
Abbreviations: BMI, Body Mass Index; CI, Confidence Interval; IgE, Immunoglobulin E.

Relationship between trace element intake and IgElevels stratified by the current smoking status in males
The results of a multiple logistic regression analysis stratified by

the two groups of current smokers, with IgE levels as the dependent
variable, are shown in Table 5. When covariates were adjusted forage, BMI, a lack of exercise, sleep deprivation, and current drinkers,
and each independent factor was entered separately, copper (oddsratio (OR) 0.002, 95% confidence interval (CI), ≤ 0.001 - 0.206, p =0.008) and manganese (OR 0.252, 95% CI, 0.070 - 0.910, p = 0.035)
were identified as significant independent variables, whereas noneof the trace elements were significant independent variables in non-smokers. Therefore, similar to the results of the two-way ANCOVA,
higher copper and manganese intakes were associated with lower
IgE levels in current smokers (Table 5).

Citation: Koji Katano, Fumihiko Suzuki, Hiromasa Tsujiguchi, Akinori Hara, Hiroyuki Nakamura etc all. Association of Immunoglobulin
E Levels with Smoking and Trace Element Intake: A Cross-sectional Analysis of the Shika Study. Glob J Nutri Food Sci. 3(5): 2022. GJNFS.
MS.ID.000571. DOI: 10.33552/GJNFS.2022.03.000571.

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Global Journal of Nutrition & Food Science

Volume 3-Issue 4

Table 5: Relationship between trace elements and IgE levels stratified by current smokers in males.
Male (n = 363)

Non-smoker (n = 635)

Current smoker (n = 136)

OR

95%CI

P

Iron, mg/1000 Kcal

0.897

(0.682 - 1.180)

0.438

Copper, mg/1000 Kcal

1.041

(0.076 - 14.282)

0.976

0.761

(0.481 - 1.204)

Zinc, mg/1000 Kcal

Manganese, mg/1000 Kcal
Iron, mg/1000 Kcal

Zinc, mg/1000 Kcal

Copper, mg/1000 Kcal

Manganese, mg/1000 Kcal

0.825
1.802
0.576
0.002
0.252

(0.552 - 1.232)(0.958 - 3.391)(0.310 - 1.073)(0.000 - 0.206)(0.070 - 0.910)

0.347
0.068
0.244
0.082
0.008
0.035

Notes: Adjusted for age, lack of exercise, sleep deficiency, current drinker, and BMI. Abbreviations: BMI, body mass index; CI, confidence interval;
OR, odds ratio.

Discussion
The present results showed that IgE levels were significantly

higher in current smokers than in non-smokers in the univariate

analysis. Furthermore, the percentage of current smokers was
significantly higher in the high-IgE group, classified by median IgElevels in participants, than in the low-IgE group. In other words, wefound a definite relationship between smoking and IgE levels. In aprevious epidemiological study that investigated the relationshipbetween smoking and IgE levels [11], a dose-dependent relationshipwas observed between smoking and serum IgE levels in a crosssectional analysis of the relationship between urinary cotinine
concentrations and serum IgE levels in adult men. A case-control[10] based on the correlation between IgE levels and symptoms

such as nasal discharge [28,29]. On the other hand, a meta-analysis

by Saulyte, et al. [30], which investigated the relationship between

smoking and allergic diseases, reported that those associations
were very modest in adults, and that the associations wererelated to passive smoking in allergic rhinitis, active and passive
smoking in allergic dermatitis, and indirect smoking in food allergy,

respectively. This study also showed that 100 participants withany allergy of pollinosis, allergic asthma, atopic dermatitis, or foodallergy, showed significantly higher serum total IgE levels as anindicator of the exacerbation of allergy.

The main results from the two-way ANCOVA and multiple

study by Ahmed, et al. [12] revealed increases in IgE levels not only

logistic regression analysis in the present study demonstrated

et al. [9] showed that the effects of nicotinic receptors, including the

A review by Mahfuzur, et al. [31] demonstrated that manganesewith active smoking, but also with passive smoking. Regarding themechanism by which smoking increases IgE levels, a review by Qiu,
alpha4 and alpha7 subunits, in human B cell lines may increase thenumber of memory B cells, which are the source of IgE production.
The present results support a mechanism by which smoking is
involved in IgE production because the percentage of smokers was

significantly higher in the high-IgE group than in the low-IgE group.

The prevalence of allergies, such as bronchial asthma [25,26]

and cedar pollinosis [27], is higher in smokers than in non-smokers. A review conducted on the relationship between smoking
and asthma by Stapleton et al. [25] showed that smoking was

significantly and inversely associated with long-term asthma
control and that current smoking is associated with more asthma

attacks and nocturnal asthma symptoms. In addition, a crosssectional study by Kim, et al. [26] reported that asthma was also

positively associated with e-cigarettes. An epidemiological surveyof Japanese cedar pollinosis and smoking status by Tanigawa, etal. [27] indicated that lymphocyte subpopulations in smokers
increased more than those in nonsmokers. In the case of cedar

pollinosis, smoking is known to exacerbate IgE-mediated allergies

that manganese and copper intakes among current smokers weresignificantly lower in the high-IgE group than in the low-IgE group.
is a trace element necessary for maintaining good health and is
involved in various physiological functions in the body, including

defense against oxidative stress, digestion, and immune response.
In addition, a review by Wang, et al. [32] demonstrated that theabnormal metabolism of copper, which cannot be producedor synthesized in the body, leads to many diseases, such as
impaired immune function, diabetes, coronary heart disease, andosteoporosis. Regarding the relationship between trace elements
and IgE levels, a case-control study of 1,562 children by Oluwole,
et al. [15] revealed that serum concentrations of manganese
negatively correlated with asthma. Furthermore, in a clinical study

on 11 healthy men, Kelley, et al. [16] demonstrated that a low-copper diet increased the percentage of circulating B cells, similar

to manganese. This mechanism is supported by the percentageof B lymphocytes in the spleen being significantly increased inexperiments on copper-deficient rats by Bala, et al [17]. Therefore,
when manganese and copper are sufficiently consumed within therange of appropriate intake, they may suppress increases in IgECitation: Koji Katano, Fumihiko Suzuki, Hiromasa Tsujiguchi, Akinori Hara, Hiroyuki Nakamura etc all. Association of Immunoglobulin
E Levels with Smoking and Trace Element Intake: A Cross-sectional Analysis of the Shika Study. Glob J Nutri Food Sci. 3(5): 2022. GJNFS.
MS.ID.000571. DOI: 10.33552/GJNFS.2022.03.000571.

Page 7 of 9

Global Journal of Nutrition & Food Sciencelevel or B cells, the source of its production. Based on these findings,

we speculated that IgE levels are elevated by smoking because low
manganese and copper intakes did not inhibit IgE production.

Although the cessation of smoking effectively suppressed smokinginduced allergies, we consider the appropriate intake of traceelements to be meaningful as health guidance for those withdifficulty quitting smoking.

Regarding the limitations of the present study, firstly, due to its

cross-sectional nature, it was not possible to elucidate the causal

relationship between the intake of trace elements and smoking
on IgE production. Secondly, since the intakes of manganese andcopper were based on a questionnaire, we did not directly measure
their blood levels. Thirdly, participants were volunteers; therefore,

the possibility of selection bias needs to be considered. Fourthly,
because we did not examine a large number of subjects, we wereunable to analyze associations in each allergy disease, namely,

pollinosis, allergic asthma, atopic dermatitis, and food allergy.
Fifthly, since we did not perform a two-way ANCOVA and multiple

regression analysis because of fewer females with current smoking,it is unclear whether our conclusions would be true to females.

Finally, since we analyzed the data based on current smoking status,

the correlation between the number of cigarettes smoked and IgE isunclear. Therefore, further longitudinal epidemiology studies witha larger sample size of each allergic disease are needed.

Conclusion

In a cross-sectional study of middle-aged and elderly community

residents, only among males, the high-IgE group of current smokers

had significantly lower intakes of manganese and copper than the

low-IgE group. Therefore, it is suggested that IgE levels are moreeasily increased by allergens in smokers with low manganese andcopper intakes. Further large-scale longitudinal studies are needed
to prove this causal relationship.

Institutional Review Board Statement

The present study was conducted according to the Declarationof Helsinki and approved by the Ethics Committee of Kanazawa

University (protocol code, 1491; date of approval, 18 December2013).

Informed Consent Statement

Informed consent was obtained from all subjects involved in

the study.

Data Availability Statement

Data in the present study are available upon request from thecorresponding author. Data are not publicly available due to privacy
and ethical policies.

Acknowledgement

The authors thank all the participants in the Shika town study

Volume 3-Issue 4

and appreciate the collaborations by all field survey staff andexperimental staff.

Conflict of Interest

Author declare no conflict of interest.

References

1. Kay AB (2001) Allergy and allergic diseases. First of two parts. N Engl J
Med 344(1): 30-37.

2. Bantz S, Zhu Z, Zheng T (2014) The atopic march: progression fromatopic dermatitis to allergic rhinitis and asthma. J Clin Cell Immunol
5(2): 202.

3. Burbank AJ, Sood AK, Kesic MJ, Peden DB, Hernandez ML (2017)
Environmental determinants of allergy and asthma in early life. J Allergy
Clin Immunol 140(1): 1-12.
4. Platts-Mills TAE (2015) The allergy epidemics: 1870–2010. J Allergy Clin
Immunol 36(1): 3-13.
5. Anyenda EO, Higashi T, Kambayashi Y, Nguyen TTT, Michigami Y, etal. (2016) Associations of cough prevalence with ambient polycyclicaromatic hydrocarbons, nitrogen and sulphur dioxide: a longitudinal
study. Int J Environ Res Public Health 13(8): 800.

6. Murrison LB, Brandt EB, Myers JB, Hershey GKK (2019) Environmental
exposures and mechanisms in allergy and asthma development. J Clin
Invest 129(4): 1504-1515.

7. Rosa MJ, Jung KH, Perzanowski MS, Kelvin EA, Darling KW, et al. (2011)
Prenatal exposure to polycyclic aromatic hydrocarbons, environmental
tobacco smoke and asthma. Respir Med 105(6): 869-876.
8. Klingbeil EC, Hew KM, Nygaard UC, Nadeau KC (2014) Polycyclicaromatic hydrocarbons, tobacco smoke, and epigenetic remodeling inasthma. Immunol Res 58(2-3): 369-373.
9. Qiu F, Liang CL, Liu H, Zeng YQ, Hou S, et al. (2017) Impacts of cigarettesmoking on immune responsiveness: Up and down or upside down.
Oncotarget 8(1): 268-284.
10. Skoner DP (2001) Allergic rhinitis: definition, epidemiology,
pathophysiology, detection, and diagnosis. J Allergy Clin Immunol
108(1): S2-8.

11. Dong JJ, Shen JJ, Lee YJ (2019) Dose-dependent effect of cotinine-verified
tobacco smoking on serum immunoglobulin E Levels in Korean adultmales. Nicotine Tob Res 21(6): 813-817.

12. Ahmed NJ, Husen AZ, Khoshnaw N, Getta HA, Hussein ZS, et al. (2020)
The Effects of smoking on IgE, oxidative stress and haemoglobin
concentration. Asian Pac J Cancer Prev 21(4): 1069-1072.
13. Bousquet PJ, Cropet C, Klossek JM, Allaf B, Neukirch F, et al. (2009)
Effect of smoking on symptoms of allergic rhinitis. Ann Allergy Asthma
Immunol 103(3): 195-200.
14. Tsuji M, Koriyama C, Ishihara Y, Yamamoto M, Yamamoto-Hanada K,
et al. (2019) Associations between metal levels in whole blood andIgE concentrations in pregnant women based on data from the Japanenvironment and children’s study. J Epidemiol 29(12): 478-486.

15. Oluwole O, Arinola OG, Adu MD, Adepoju A, Adedokun BO, et al. (2014)
Relationships between plasma micronutrients, serum IgE, and skin test
reactivity and asthma among school children in rural southwest Nigeria.
J Biomarkers 2014: 1-9.
16. Kelley D, Daudu P, Taylor P, Mackey B, Turnlund J (1995) Effects of lowcopper diets on human immune response. Am J Clin Nutr 62(2): 412416.
17. Bala S, Failla M, Lunney J (1990) Phenotypic and functional alterations
in peripheral blood mononuclear cells of copper‐deficient rats. Ann N Y
Acad Sci 587: 283-285.

Citation: Koji Katano, Fumihiko Suzuki, Hiromasa Tsujiguchi, Akinori Hara, Hiroyuki Nakamura etc all. Association of Immunoglobulin
E Levels with Smoking and Trace Element Intake: A Cross-sectional Analysis of the Shika Study. Glob J Nutri Food Sci. 3(5): 2022. GJNFS.
MS.ID.000571. DOI: 10.33552/GJNFS.2022.03.000571.

Page 8 of 9

Global Journal of Nutrition & Food Science

18. Shimizu Y, Kambayashi Y, Tsujiguchi H, Hara A, Hori D, et al. (2018)
Relationship between the Use of Parabens and Allergic Diseases inJapanese Adults—A Cross-Sectional Study. J 1(1): 148-158.
19. Suzuki F, Morita E, Miyagi S, Tsujiguchi H, Hara A, et al. (2021) Protein
intake in inhabitants with regular exercise is associated with sleep
quality: Results of the Shika study. PLoS One 16(2): e0247926.

20. Yamada Y, Nakamura H, Tsujiguchi H, Hara A, Miyagi S, et al. (2021)
Relationships among the β3-adrenargic receptor gene Trp64Arg
polymorphism, hypertension, and insulin resistance in a Japanese
population. PLoS One 16(8): e0255444.
21. Shika Town population (2020).

22. Kobayashi S, Murakami K, Sasaki S, Okubo H, Hirota N, et al. (2011)
Comparison of relative validity of food group intakes estimatedby comprehensive and brief-type self-administered diet history
questionnaires against 16 d dietary records in Japanese adults. Public
Health Nutr 14(7): 1200-1211.
23. Kobayashi S, Honda S, Murakami K, Sasaki S, Okubo H, et al. (2012) Both
comprehensive and brief self-administered diet history questionnaires
satisfactorily rank nutrient intakes in Japanese adults. J Epidemiol
22(2): 151-159.

24. Bousquet J, Cabrera P, Berkman N, Buhl R, Holgate S, et al. (2005) The
effect of treatment with omalizumab, an anti-IgE antibody, on asthma
exacerbations and emergency medical visits in patients with severe
persistent asthma. Allergy 60(3): 302-308.

Volume 3-Issue 4

25. Stapleton M, Howard-Thompson A, George C, Hoover RM, Self TH (2011)
Smoking and asthma. J Am Board Fam Med 24(3): 313-322.
26. Kim SY, Sim S, Choi HG (2017) Active, passive, and electronic cigarettesmoking is associated with asthma in adolescents. Sci Reports 7(1):17789.
27. Tanigawa T, Araki S, Nakata A, Sakurai S, Miki A (2010) Effects ofsmoking and Japanese cedar pollinosis on lymphocyte subpopulations.
Arch Environ Health 54(2): 119-123.

28. Yoshida T, Usui A, Kusumi T, Inafuku S, Sugiyama T, et al. (2005) A
quantitative analysis of cedar pollen-specific immunoglobulins in nasal
lavage supported the local production of specific IgE, not of specific IgG.
Microbiol Immunol 49(6): 529-534.

29. Sakaida H, Masuda S, Takeuchi K (2014) Measurement of Japanese cedarpollen-specific IgE in nasal secretions. Allergol Int 63(3): 467-473.
30. Saulyte J, Regueira C, Montes-Martínez A, Khudyakov P, Takkouche B(2014) Active or passive exposure to tobacco smoking and allergic
rhinitis, allergic dermatitis, and food allergy in adults and children: asystematicreview and meta-analysis. PLoS Med 11(3): e1001611.
31. Miah MR, Ijomone OM, Okoh COA, Ijomone OK, Akingbade GT, etal. (2020) The effects of manganese overexposure on brain health.
Neurochem Int 135: 104688.
32. Wang P, Yuan Y, Xu K, Zhong H, Yang Y, et al. (2021) Biological applicationsof copper-containing materials. Bioact Mater 6(4): 916-927.

Citation: Koji Katano, Fumihiko Suzuki, Hiromasa Tsujiguchi, Akinori Hara, Hiroyuki Nakamura etc all. Association of Immunoglobulin
E Levels with Smoking and Trace Element Intake: A Cross-sectional Analysis of the Shika Study. Glob J Nutri Food Sci. 3(5): 2022. GJNFS.
MS.ID.000571. DOI: 10.33552/GJNFS.2022.03.000571.

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