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Effect of environmental exposures on allergen sensitization and the development of childhood allergic diseases: A large-scale population-based study

  • Chian-Feng Huang
    Affiliations
    Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei 10055, Taiwan

    Miaoli General Hospital, Ministry of Health and Welfare, Miaoli 36054, Taiwan
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  • Wei-Chu Chie
    Affiliations
    Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei 10055, Taiwan
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  • I-Jen Wang
    Correspondence
    Corresponding author. Department of Pediatrics, Taipei Hospital, Ministry of Health and Welfare, 127 Su-Yuan Road, Hsin-Chuang Dist., New Taipei City 242, Taiwan
    Affiliations
    Department of Pediatrics, Taipei Hospital, Ministry of Health and Welfare, New Taipei City 24213, Taiwan

    School of Medicine, National Yang-Ming University, Taipei 112, Taiwan

    College of Public Health, China Medical University, Taichung 40402, Taiwan

    National Institute of Environmental Health Sciences, National Health Research Institutes, Miaoli 350, Taiwan

    National Taiwan University Hospital, National Taiwan University,Taipei 100, Taiwan
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Open AccessPublished:January 06, 2021DOI:https://doi.org/10.1016/j.waojou.2020.100495

      Abstract

      Background

      Changing environmental factors are likely responsible for the rising prevalence of allergic diseases in children. However, whether environmental exposures induce allergen sensitizations, and which allergen sensitization is related to the development of allergic diseases, is not clear. The study is aimed to investigate the association between environmental exposure, allergen sensitization, and the development of allergic diseases for further preventive intervention.

      Methods

      We conducted the Taiwan Childhood Environment and Allergic diseases Study (TCEAS) in kindergarten children in Taiwan. Skin prick tests for 6 allergens were performed. Information on the development of allergic diseases and environmental exposure was collected using standardized questionnaires. Multiple logistic regressions were used to estimate the association between environmental factors, allergen sensitization, and the development of allergic diseases.

      Results

      A total of 3192 children were recruited. 485 (15.2%) children had atopic dermatitis (AD), 1126 (35.3%) had allergic rhinitis (AR), and 552 (17.3%) had asthma. Children with environmental tobacco smoke exposure and fungi on the house wall had a higher risk of asthma, with ORs (95% CIs) of 1.25 (1.03–1.52) and 1.22 (1.01–1.47), respectively. The mite sensitization rate was found to be the highest. Mite sensitization was associated with significant increases in the risks of AD, AR, and asthma, with ORs (95% CIs) of 2.15 (1.53–3.03), 1.94 (1.46–2.58), and 2.31 (1.63–3.29), respectively. Cockroach sensitization also increased the risk of asthma, with an OR (95% CI) of 2.38 (1.01–5.61). Mite sensitization was associated with carpet in the home and fungi on the house wall, and milk sensitization was associated with breastfeeding duration.

      Conclusion

      Environmental exposures play a role in the development of allergic diseases. Allergen sensitizations were associated with certain environmental exposures. Early environmental interventions are urgently needed to prevent the development of childhood allergic diseases.

      Keywords

      Abbreviations:

      OR (odd ratio), CI (confidence interval), AD (atopic dermatitis), AR (allergic rhinitis), ISAAC (International Study of Asthma and Allergies in Childhood), ETS (environmental tobacco smoke), SPTs (skin prick tests), HDMs (house dust mites)

      Introduction

      Over the past few decades, the prevalence of allergic diseases in children has rapidly increased in industrialized countries.
      • Hansen T.E.
      • Evjenth B.
      • Holt J.
      Increasing prevalence of asthma, allergic rhinoconjunctivitis and eczema among schoolchildren: three surveys during the period 1985-2008.
      ,
      • de Marco R.
      • Cappa V.
      • Accordini S.
      • et al.
      Trends in the prevalence of asthma and allergic rhinitis in Italy between 1991 and 2010.
      In Taiwan, the prevalence of asthma may have increased dramatically,
      • Lee Y.L.
      • Hwang B.F.
      • Lin Y.C.
      • Guo Y.L.
      Time trend of asthma prevalence among school children in Taiwan: ISAAC phase I and III surveys.
      and asthma is the most common chronic illness among children.
      • Liang P.H.
      • Shyur S.D.
      • Huang L.H.
      • et al.
      Risk factors and characteristics of early-onset asthma in Taiwanese children.
      Most previous studies of atopic diseases conducted in Taiwan and abroad have investigated allergic asthma, which was found in about 38% of asthmatic patients.
      • Lawson J.A.
      • Chu L.M.
      • Rennie D.C.
      • et al.
      Prevalence, risk factors, and clinical outcomes of atopic and nonatopic asthma among rural children.
      However, the incidence of atopic dermatitis (AD) in the developed world has also increased over the past several decades. AD is a chronic inflammatory skin disease with a peak onset in infancy, and a large majority of patients presenting skin symptoms in the first few years of life.
      • Diepgen T.L.
      Is the prevalence of atopic dermatitis increasing?.
      ,
      • Moore M.M.
      • Rifas-Shiman S.L.
      • Rich-Edwards J.W.
      • et al.
      Perinatal predictors of atopic dermatitis occurring in the first six months of life.
      In addition, allergic rhinitis (AR) is one of the most common chronic diseases in children.
      • Meltzer E.O.
      Allergic rhinitis: managing the pediatric spectrum.
      Because population genetic variability does not change with such rapidity, changing environmental factors are likely responsible for the increase in the number of individuals diagnosed with asthma, AD, and AR.
      • Gaffin J.M.
      • Phipatanakul W.
      The role of indoor allergens in the development of asthma.
      Children with atopic diseases are most likely to have considerable school absences, family stress, and health care expenditures. Nowadays, most young children live in an indoor environment where many allergens exist. Therefore, the identification of indoor environmental factors among genetically susceptible children in Taiwan is urgently required.
      Among environmental exposures, allergens are among the most important factors. Common indoor allergens for asthma include host dust mites, cockroaches, animal dander, and mold.
      • Arshad S.H.
      Does exposure to indoor allergens contribute to the development of asthma and allergy?.
      Some studies have evaluated the environmental predictors of the early-life presentation of AD.
      • Moore M.M.
      • Rifas-Shiman S.L.
      • Rich-Edwards J.W.
      • et al.
      Perinatal predictors of atopic dermatitis occurring in the first six months of life.
      For example, sensitization to food allergens (egg, milk, wheat, soy, and peanut) is associated with atopic dermatitis and is related to disease severity.
      • Eigenmann P.A.
      • Sicherer S.H.
      • Borkowski T.A.
      • Cohen B.A.
      • Sampson H.A.
      Prevalence of IgE-mediated food allergy among children with atopic dermatitis.
      Furthermore, other reported environmental factors, including cats, dogs, secondary tobacco smoke exposure, and air pollution, may trigger respiratory allergic diseases.
      • Matsui E.C.
      • Sampson H.A.
      • Bahnson H.T.
      • et al.
      Story RE, Visness CM and Inner-city Asthma Consortium. Allergen-specific IgE as a biomarker of exposure plus sensitization in inner-city adolescents with asthma.
      ,
      • Gehring U.
      • Wijga A.H.
      • Brauer M.
      • et al.
      Traffic-related air pollution and the development of asthma and allergies during the first 8 years of life.
      Many studies of allergen sensitization in allergic asthma, AR, and AD have been conducted, although allergens and their associations with AD remain controversial. However, a large-scale environmental factors evaluation is lacking. Therefore, this study evaluated the relationships between environmental exposures, allergen sensitization, and allergic diseases in children. We conducted a cross-sectional study to investigate the prevalence of allergic diseases and allergen sensitization in a representative pediatric population in Taipei. We also investigated the associations among allergen sensitization of 6 chosen indoor allergens, environmental exposures, and the development of allergic diseases—asthma, AD, and AR.

      Methods

      Study population

      We conducted a school-based survey for allergic diseases in kindergarten children in 2010. Schools were chosen through stratified systematic sampling in New Taipei City to ensure a degree of geographical and social diversity and provide a reasonably representative estimate. In each school, subjects were selected through cluster sampling. Children were recruited, and their written informed consent documents or those from their guardian were obtained. Parents were invited to complete a structured questionnaire. The exclusion criteria were inability to answer questions in Chinese, prematurity, and congenital and chronic diseases.

      Case definition

      Asthma was defined as a positive response to physician-diagnosed asthma together with a positive response to nocturnal cough or exercise-induced wheezing in the past 12 months by using the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire. Cases of AD were defined using the questions “Has your child ever had AD diagnosed by a physician?” and” Has your child ever had a recurrent itchy rash for at least 6 consecutive half-month periods over the elbows, knees, face, wrists, neck, periauricular areas, or eyebrow areas?” Cases of AR were defined using the questions “Has your child ever been diagnosed as having AR by a physician?” and “Has your child ever had a problem with sneezing or a runny or blocked nose when your child did not have a cold or the flu?”

      Exposure measurements

      The standard ISAAC-Chinese version questionnaire with the addition of questions concerning environmental allergen exposures were taken home by children and answered by their parents. Some information on basic demographic characteristics, residential environmental factors (such as environmental tobacco smoking, pets and cockroaches in the home, dampness of the house, fungus on the house wall, and carpets in the home), and family history of atopic diseases was also collected using the questionnaire.

      Skin prick test

      Skin prick tests (SPTs) for 6 common allergens were performed, including house dust mites (HDMs mix, including Dermatophagoides pteronyssinus [Der p], Dermatophagoides farinae [Der f], Dermatophagoides microceras [Der m] and Blomia tropicalis [Blo t] allergens), dog dander, cockroaches, egg, milk, and crab allergens (ALK-Abelló, Round Rock, TX, USA). With a positive reaction to an allergen, the skin becomes itchy within a few minutes and then becomes red and swollen with a in the center. Histamine (0.1%) in phosphate buffered saline and normal saline were used as positive and negative controls, respectively. Children were advised to not take antihistamines for 72 h before the clinic appointment. The tests results were recorded in 15 min, and the mean wheal diameters were calculated (sum of the longest diameter and the diameter perpendicular to it divided by 2). In the presence of a positive control (>3 mm), a mean wheal diameter of at least 3 mm greater than the negative control was taken as positive for an allergen.

      Statistical analysis

      Multiple logistic regressions were performed to estimate the association between environmental factors, allergen sensitization, and the development of allergic diseases, with adjustments made for potential confounders. The effect of environmental exposures on allergen sensitization was also evaluated. The confounders adjusted for in the model were selected based on the literature, and the standard statistical procedures 10% change in point estimate. All tests assumed a two-sided alternative hypothesis and a 0.05 significance level. All hypothesis tests were two-sided at the significance level of 0.05 and performed with SAS software version 9.1 (SAS Institute, Cary, NC, USA).

      Results

      A total of 3192 children were recruited. Table 1 provides the demographic characteristics of the study population. Specifically, 485 (15.2%) children had AD, 1126 (35.3%) had AR, and 552 (17.3%) had asthma. Of all the risk factors collected, children with fungi on house walls had higher risks of AD [OR (95% CI): 1.27 (1.04–1.55)], AR [OR (95% CI): 1.18 (1.01–1.37)], and asthma [OR (95% CI): 1.22 (1.01–1.47)] (Table 2). Children with environmental tobacco smoke (ETS) exposure had higher risks of both AR and asthma, with ORs (95% CIs) of 1.23 (1.06–1.43) and 1.23 (1.06–1.52), respectively. Breastfeeding duration is the last risk factor noted. A breastfeeding duration of more than 6 months had a strong association with AD [OR (95% CI): 1.66 (1.20–4.31)].
      Table 1Demographic characteristics of participants
      All eligible participants (n = 3192)
      n%
      Children
      Infant gender (%)
       Male172554.1
       Female146745.9
      Premature birth (<37 weeks) (%)
      Number of participants does not add up to total N because of missing data
       Yes2618.2
       No283388.8
       Missing983.0
      Birth body weight (gm)
       Mean ± SD3106.07 ± 457.961
      Mother
      Maternal age at delivery (years)
       Mean ± SD29.32 ± 4.49
      Maternal education (%)
       Junior high school and below1855.8
       Senior high school and above300794.2
      Maternal Nationality (%)
       Taiwan300594.1
       Foreign countries1875.9
      Maternal history of atopy (%)
       Yes106033.2
       No213266.8
      Family income per month (NT$)∗ (%)
       < 600,00093029.2
       ≥600,000226270.8
      Abbreviations: SD, standard deviation; ∗NT$ per year.
      a Number of participants does not add up to total N because of missing data
      Table 2Environmental risk factors for allergic diseases (N = 3192)
      CharacteristicsNo. of SubjectAD Rate (%)OR95% CIAR Rate (%)OR95% CIAsthma Rate (%)OR95% CI
      Environment
      Duration of breast feeding (%)
       No66911.41.0029.61.0010.81.00
       < 6 months157715.21.39(1.06–1.84)∗32.71.16(0.95–1.41)13.01.24(0.93–1.65)
       ≥ 6 months53517.61.66(1.20–4.31)∗27.70.91(0.71–1.17)14.41.39(0.99–1.97)
      Older siblings (%)
       No86616.11.0037.61.0016.91.00
       < 2163115.70.97(0.78–1.22)35.10.90(0.75–1.06)16.70.99(0.79–1.23)
       ≥ 256313.50.82(0.60–1.10)32.70.80(0.64–1.01)18.11.09(0.83–1.44)
      Day care (%)
       No232814.81.0034.81.0016.71.00
       Yes70417.81.25(1.00–1.56)35.81.05(0.88–1.25)17.01.03(0.82–1.29)
      Furry pets at home (%)
       No250016.11.0035.71.0016.81.00
       Yes55013.60.82(0.63–1.08)33.60.91(0.75–1.11)17.31.03(0.81–1.32)
      Cockroaches at home
       No55714.91.0034.51.0014.71.00
       Yes254115.31.03(0.80–1.34)35.51.07(0.82–1.39)17.61.23(0.96–1.59)
      Carpets at home (%)
       No294715.01.0032.31.0016.81.00
       Yes19617.91.23(0.84–1.80)35.71.01(0.75–1.3721.91.40(0.98–1.98)
      Fungi on house walls (%)
       No187314.41.0033.81.0015.81.00
       Yes116817.61.27(1.04–1.55)∗37.61.18(1.01–1.37)∗18.61.22(1.01–1.47)∗
      Environmental tobacco smoke exposure (%)
       No128215.91.0032.41.0015.21.00
       Yes175815.00.93(0.76–1.13)37.11.23(1.06–1.43)∗18.31.25(1.03–1.52)∗
      Incense burning at home (%)
       No138214.81.0033.91.0016.81.00
       Yes161216.51.14(0.94–1.39)36.41.12(0.96–1.30)17.91.08(0.90–1.31)
      Residence location
       Urban100917.11.0047.41.0018.41.00
       Country387.90.41(0.13–1.36)35.50.61(0.32–1.17)15.60.82(0.35–1.89)
      Living near main road
       <1 km32614.41.0035.01.0017.81.00
       ≥1 km252415.71.11(0.80–1.53)37.70.89(0.70–1.13)17.00.95(0.70–1.28)
      ∗P < 0.05.
      Number of participants does not add up to total N because of missing data
      Of all the allergens tested, the mite sensitization rate was found to be the highest, with mite sensitization found in 29% of all participants. The prevalence of other allergen sensitization by SPTs was lower than 4% for each one. The gender difference for allergen sensitization was not significant, except for mite; mite sensitization was slightly higher in boys (Table 3).
      Table 3The prevalence of allergen sensitizations based on skin prick tests
      CharacteristicsTotalBoys%Girls%P value
      House dust mite31920.007
      2266119169.0107573.3
      +92653531.039126.7
      Cockroach0.549
      3092166996.7142397.1
      +100573.3432.9
      Dog dander0.926
      3175171799.5145899.5
      +1790.580.5
      Milk0.983
      3166171299.2145499.2
      +26140.8120.8
      Egg0.366
      3170171299.2145899.5
      +22140.880.5
      Crab0.366
      3170171299.2145899.5
      +22140.880.5
      The association between allergen sensitization and allergic diseases was significant for some aeroallergens. Mite sensitization was associated with significant increases in the risks of AD, AR, and asthma, with ORs (95% CIs) of 2.15 (1.53–3.03), 1.94 (1.46–2.58), and 2.31 (1.63–3.29), respectively. Cockroach sensitization also increased the risk of asthma, with an OR (95% CI) of 2.38 (1.01–5.61) (Table 4). However, the association of other aeroallergen and food allergen sensitization with allergic diseases failed to reach statistical significance after adjustments were made for confounding variables.
      Table 4Association of aeroallergen and food allergen sensitizations with allergic diseases
      Skin prick testAtopic dermatitis N = 485Allergic rhinitis N = 1126Asthma N = 552
      Total N = 3192n (%)OR (95% CI)Adjusted OR (95% CI)n (%)OR (95% CI)Adjusted OR (95% CI)n (%)OR (95% CI)Adjusted OR (95% CI)
      Aeroallergen

      Mite (−)
      2266277 (57.1)1.001.00669 (59.4)1.001.00309 (56.0)1.001.00
      (+)926208 (42.9)2.08 (1.71–2.54)∗2.15 (1.53–3.03)∗457 (40.6)2.33 (1.99–2.72)∗1.94 (1.46–2.58)∗243 (44.0)2.25 (1.87–2.72)∗2.31 (1.63–3.29)∗
      Cockroach (−)3092466 (96.1)1.001.001080 (95.9)1.001.00522 (94.6)1.001.00
      (+)10019 (3.9)1.32 (0.79–2.20)0.89 (0.30–2.63)46 (4.1)1.59 (1.06–2.37)∗1.75 (0.79–3.85)30 (5.4)2.11 (1.36–3.27)∗2.38 (1.01–5.61)∗
      Animal (−)

      Dander
      3175481 (99.2)1.001.001119 (99.4)1.001.00548 (99.3)1.001.00
      (+)174 (0.8)1.72 (0.56–5.31)1.39 (0.15–12.65)7 (0.6)1.29 (0.49–3.39)1.27 (0.21–7.76)4 (0.7)1.48 (0.48–4.54)1.62 (0.18–14.80)
      Food allergen Milk (−)3166479 (98.8)1.001.001110 (98.6)1.001.00543 (98.4)1.001.00
      (+)266 (1.2)1.68 (0.67–4.21)2.41 (0.45–13.02)16 (1.4)2.96 (1.34–6.55)∗1.17 (0.25–5.58)9 (1.6)2.56 (1.13–5.77)∗2.06 (0.38–11.07)
      Egg (−)3170479 (98.8)1.001.001116 (99.1)1.001.00549 (99.5)1.001.00
      (+)226 (1.2)2.11 (0.82–5.41)1.60 (0.16–15.65)10 (0.9)1.53 (0.66–3.56)0.55 (0.06–5.40)3 (0.5)0.75 (0.22–2.56)
      Crab (−)3170482 (99.4)1.001.001116 (99.1)1.001.00548 (99.3)1.001.00
      (+)223 (0.6)0.88 (0.26–2.99)0.98 (0.11–8.44)10 (45.5)1.53 (0.66–3.56)0.36 (0.04–3.11)4 (0.7)1.06 (0.36–3.15)
      Abbreviations: OR, odd ratio; CI, confidence interval; ∗P < 0.05.
      #Model adjusted for gender, ETS exposure, fungi on house walls, and residence location
      Mite sensitization was associated with carpets at home and fungi on the house wall, with ORs (95% CIs) of 1.44 (1.06–1.94) and 1.24 (1.06–1.46), respectively (Table 5). Cockroach sensitization was associated with cockroaches at home, and milk sensitization was associated with breastfeeding duration (Table 6). Nevertheless, no difference was observed in sensitization to animal dander and furry pets at home.
      Table 5Association of environment exposures with mite sensitizations
      CharacteristicsTotal N = 3192Mite sensitizationOR (95% CI)
      N%
      Day care (%)
       No232867128.81.00
       Yes70419728.00.96 (0.80–1.16)
      Furry pets at home (%)
       No250073129.21.00
       Yes55015127.50.92 (0.75–1.13)
      Cockroaches at home
       No55716529.61.00
       Yes254173528.90.97 (0.79–1.18)
      Carpets at home (%)
       No294783528.31.00
       Yes1967136.21.44 (1.06–1.94)∗
      Fungi on house walls (%)
       No187350627.01.00
       Yes116836831.51.24 (1.06–1.46)∗
      Environmental tobacco smoke exposure (%)
       No175850528.71.00
       Yes128237229.01.01 (0.87–1.19)
      Incense burning at home (%)
       No138238728.01.00
       Yes161248530.11.11 (0.94–1.30)
      Residence location
       Urban100927427.21.65 (0.72–3.79)
       Country38718.41.00
      Living near main road
       <1 km252473529.10.96 (0.74–1.23)
       ≥1 km3269830.11.00
      ∗P < 0.05.
      Number of participants does not add up to total N because of missing data
      Table 6Association of environment exposures determined using a questionnaire with allergen sensitizations by skin prick tests
      Environment exposuresTotal N = 3192Cockroach sensitizationOR (95% CI)
      N%
      Cockroaches at home
       No557101.91.00
       Yes2541883.51.96 (1.02–3.80)∗
      Animal dander sensitizationOR (95% CI)
      N%
      Furry pets at home (%)
       No2500130.51.00
       Yes55040.71.40 (0.46–4.32)
      Milk sensitizationOR (95% CI)
      N%
      Duration of breast feeding (%)
       No66910.11.00
       < 6 months1577120.85.12 (0.67–39.47)
       ≥ 6 months535101.912.72 (1.62–99.71)∗
      ∗P < 0.05.
      Number of participants does not add up to total N because of missing data

      Discussion

      This study demonstrated a fast-growing prevalence of allergic diseases in children in Taiwan. Participants with fungi on houses wall were found to have a higher risk of such diseases. Among the allergens selected, mite sensitization had the highest prevalence and was associated with significant increases in the risks of asthma, AR, and AD. Environmental tobacco smoke exposure, carpets at home, and breastfeeding duration were also important risk factors.
      According to previous studies, childhood AD prevalence in Taiwan considerably increased from 7.2% in 1998 to 18% in 2002.
      • Wang J.Y.
      • Liu L.F.
      • Chen C.Y.
      • Huang Y.W.
      • Hsiung C.A.
      • Tsai H.J.
      Acetaminophen and/or antibiotic use in early life and the development of childhood allergic diseases.
      ,
      • Liao M.F.
      • Huang J.L.
      • Chiang L.C.
      • Wang F.Y.
      • Chen C.Y.
      Prevalence of asthma, rhinitis, and eczema from ISAAC survey of schoolchildren in Central Taiwan.
      In 2008, Ho et al revealed a prevalence of 10.7%.
      • Ho C.L.
      • Chang L.I.
      • Wu W.F.
      The prevalence and risk factors of atopic dermatitis in 6–8 year-old first graders in taipei.
      Our study found a prevalence of 15.2% in preschool children, which is compatible with the reported trend. The statistic is close to those reported in similar urbanization regions in Asia: 12%–13% in Japan
      • Takeuchi S.
      • Esaki H.
      • Furue M.
      Epidemiology of atopic dermatitis in Japan.
      and more than 11% in Korea.
      • Lee J.
      • Yang H.
      • Kim M.
      • Kim J.
      • Ahn K.
      Is the prevalence of atopic dermatitis in Korean children decreasing? Analysis of the national statistics data, 2009–2014.
      The prevalence of AR in industrialized countries has also dramatically increased to 20%–40% in children.
      • Salarnia S.
      • Momen T.
      • Jari M.
      Prevalence and risk factors of allergic rhinitis in primary school students of isfahan, Iran.
      It is consistent with our finding of 35.3%, which is higher than the previous Taiwan survey finding of 27.6% in 2002.
      • Liao P.F.
      • Sun H.L.
      • Lu K.H.
      • Lue K.H.
      Prevalence of childhood allergic diseases in central Taiwan over the past 15 years.
      For asthma, the present study revealed a prevalence of 17%, which is slightly higher than not only previous data from Taipei but also data from other industrialized countries.
      • Ma Y.C.
      • Lin C.C.
      • Li C.I.
      • Chiang J.H.
      • Li T.C.
      • Lin J.G.
      Time-trend analysis of prevalence, incidence and traditional Chinese medicine use among children with asthma: a population-based study.
      ,
      • Griffiths L.J.
      • Lyons R.A.
      • Bandyopadhyay A.
      • et al.
      Childhood asthma prevalence: cross-sectional record linkage study comparing parent-reported wheeze with general practitioner-recorded asthma diagnoses from primary care electronic health records in Wales.
      The allergic phenotype of asthma was estimated as 42%, which is also slightly higher than the previous literature. It may be attributed to differences in air pollution, humidity, lifestyle, temperature, and housing conditions.
      The fast growing prevalence implies that environmental factors play a stronger role than genetics. Among all the risk factors collected in our study, children with ETS exposure and fungi on the house wall had higher risks of asthma and AR (Table 2). Our survey showed an increased risk of over 20% in children with ETS exposure, which is consistent with that in a previous meta-analysis.
      • Burke H.
      • Leonardi-Bee J.
      • Hashim A.
      • et al.
      Prenatal and passive smoke exposure and incidence of asthma and wheeze: systematic review and meta-analysis.
      Another exposure, fungi on house walls, can be interpreted as visible mold and dampness. Our results are in line with those of previous European cohort studies,
      • Mendell M.J.
      • Mirer A.G.
      • Cheung K.
      • Tong M.
      • Douwes J.
      Respiratory and allergic health effects of dampness, mold, and dampness-related agents: a review of the epidemiologic evidence.
      ,
      • Thacher J.D.
      • Gruzieva O.
      • Pershagen G.
      • et al.
      Mold and dampness exposure and allergic outcomes from birth to adolescence: data from the BAMSE cohort.
      which demonstrated a higher risk in children exposed to any mold or dampness.
      For AD, our study revealed significant odds ratios for breastfeeding duration and fungi on the house wall. Munblit D et al. claimed that conflicting evidence exists related to breastfeeding being a protector against allergic diseases among children.
      • Munblit D.
      • Peroni D.G.
      • Boix-Amorós A.
      • et al.
      Human milk and allergic diseases: an unsolved puzzle.
      Based on the data, it may even be a risk factor for AD; however, we cannot exclude other potential benefits of breastfeeding; the association between breastfeeding and allergic disease development requires further investigation. In addition, there might exist a reverse causation when mothers whose children have AD tend to breastfeed their children.
      Notably, in this study, the prevalence of mite sensitization was the highest among all allergens tested (Table 3). In addition to asthma and AR, our study showed that HDMs were crucial triggers of AD (Table 4). Because the allergy-related process of mites mainly occurs through the airway, it is widely accepted that the process predominantly influences asthma and AR. Whether HDM sensitization plays a role in the development of AD is still controversial. In a meta-analysis, Bremmer et al revealed no evidence of dust mite avoidance for AD prevention.
      • Bremmer S.F.
      • Simpson E.L.
      Dust mite avoidance for the primary prevention of atopic dermatitis: a systematic review and meta-analysis.
      However, the present study result supports the positive association between mite sensitization and AD. This may be explained by skin barrier destruction, thus rendering children vulnerable to contact with the allergen, or by systemic hypersensitivity to mites through IgE process. We highly suspect that there is a subgroup of potential children with AD who can benefit from mite avoidance; this requires further exploration.
      Risk factors for specific allergen sensitization were identified in this study. We found that mite sensitization was associated with carpets in the home and fungi on house walls (Table 5). This result implies that an awareness of indoor humidity and routine carpet management are vital. Although we may not comprehensively remove all possible allergen particles, this would eliminate some important risk factors; measures for this include setting up a dehumidifier, simply removing any carpet-like furniture or other mite-avoidance procedures.
      • Bremmer S.F.
      • Simpson E.L.
      Dust mite avoidance for the primary prevention of atopic dermatitis: a systematic review and meta-analysis.
      ,
      • Wilson J.M.
      • Platts-Mills T.A.E.
      Home environmental interventions for house dust mite.
      Notably, only fungi on the house wall had a significant association with allergic diseases, not carpets in the home. Carpet-like furniture might be considered an allergens reservoir,
      • Salo P.M.
      • Wilkerson J.
      • Rose K.M.
      • et al.
      Bedroom allergen exposures in US households.
      which may enhance penetration of the causal pathway from mite exposure to mite sensitization and allergic diseases.
      In the present study, we observed significantly higher HDM sensitization in boys than in girls (Table 3). Our study supports previous findings of a gender difference. Keller et al
      • Keller T.
      • Hohmann C.
      • Standl M.
      • et al.
      The sex-shift in single disease and multimorbid asthma and rhinitis during puberty - a study by MeDALL.
      suggested that male participants have a higher risk of being allergic in childhood, perhaps due to anatomical differences and immune response profiles, which may cause boys to be more sensitive to allergens.
      Furthermore, we demonstrated that only sensitization to particular allergens was associated with the same environmental exposures (Table 6). For example, cockroach sensitization was associated with cockroaches in the home. Because cockroaches may not appear when people are awake, a positive SPT finding may be indicative of a problem. Although no allergic symptom is noted yet, cockroaches at home are still a potential hazard and possibly induce allergic diseases, especially asthma.
      • Togias A.
      • Fenton M.J.
      • Gergen P.J.
      • Rotrosen D.
      • Fauci A.S.
      Asthma in the inner city: the perspective of the national Institute of allergy and infectious diseases.
      Another strong association noted in the study was that between milk sensitization and breastfeeding duration.
      To investigate the associations among environmental exposures, allergen sensitization, and allergic disease development, we conducted SPTs as opposed to multiple allergen simultaneous tests (MASTs) through blood. Although it is noteworthy that a certain population had negative SPT results but had allergic symptoms or diseases, for kindergarten participants, SPT is preferred because it is painless, simple, and well tolerated. Furthermore, it is less expensive and more sensitive, and the results are available onsite within 20 min. We use SPTs as a convenient and noninvasive surrogate to evaluate the effect of whole environmental exposures on children in a population scale (Table 5). Our study showed that the SPT is informative and may serve as a convenient tool for detection of allergen sensitization after environmental exposures. This may help early prevention of the development of allergic diseases.
      The present study has some potential limitations that may affect the interpretation of our results. First, we used a questionnaire for exposure evaluation without objective data. However, the validity of the questionnaire for exposure measurement, such as ETS and pet exposure, has been recognized, and it is an acceptable substitute for laboratory results.
      • Gavarkovs A.G.
      • Risica P.M.
      • Parker D.R.
      • Jennings E.
      • Mello J.
      • Phipps M.
      Self-reported environmental tobacco smoke exposure and avoidance compared with cotinine confirmed tobacco smoke exposure among pregnant women and their infants.
      ,
      • Waser M.
      • Von Mutius E.
      • Riedler J.
      • et al.
      Exposure to pets, and the association with hay fever, asthma, and atopic sensitization in rural children.
      Moreover, some researchers have suggested that participants tend to underestimate exposures,
      • Jaakkola J.J.
      • Hwang B.F.
      • Jaakkola M.S.
      Home dampness and molds as determinants of allergic rhinitis in childhood: a 6-year, population-based cohort study.
      which made the results toward the null. Thus, the questionnaire is still a suitable measure in such a large population. Secondly, some environmental risk factors were evaluated in an indirect way. However, it is very difficult to perform direct environmental exposure assessment in such a large-scale, population-based epidemiological study. Thus, SPTs were used as a convenient and noninvasive surrogate for allergen sensitization in a population scale, especially in children. We can still use the indirect evidences to inform a resident in the community through allergen sensitization profile that there might be some specific environmental risk factors for allergic diseases. Recall bias is another limitation, especially for respiratory outcomes. However, the recall of allergic disease status was assessed in a subgroup of the study population, and parental reports and medical records had favorable concordance. Finally, the cross-sectional study failed to demonstrate the causal relationship. Further follow-up is warranted.
      Nevertheless, the study has several strengths. We performed the first population-based study demonstrating the relationships between allergic diseases, environmental risk factors, and allergen sensitization. This largest cross-sectional preschool survey in Taiwan included a considerable number of participants. No significant demographic difference was noted between the study cohort and the Taiwanese population of the same age. Our study also elaborated on comprehensive environmental factors with regards to potential health risks related to the pathway of the atopic process, which included both the skin and airways. These environmental exposures have common risk factors with great generalizability for further comparison with those in different countries. In addition, we administered an allergen sensitization survey through SPTs to identify many essential allergens. We discovered that both mite sensitization and fungi on house walls were significantly associated with all three common allergic diseases. Furthermore, mite sensitization had the highest prevalence. The results support the supposition that the avoidance of mites and house dampness might be beneficial for preventing the development of allergic diseases. Thus, our contribution can provide relevant information for patients in medical systems, for public education in communities and mass media, and for long-term health policy making.

      Conclusions

      Environmental exposures play a role in the development of allergic diseases. Reduction in indoor allergen exposure and environmental risk factors may prevent the development of allergic diseases. Early environmental interventions are urgently needed.

      Availability of data and materials

      The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to their containing information that could compromise the privacy of research participants.

      Author contributions

      C.-F.H. analyzed and interpreted the data, and wrote the manuscript. W.-C.C. interpreted the data and revised the manuscript. I.-J.W. collected, analyzed, and interpreted the data. I.-J.W. designed the research and wrote and revised the manuscript. All authors read and approved the final manuscript.

      Ethics approval

      The study protocol was approved by the Institutional Review Board of Taipei Hospital, Ministry of Health and Welfare, Taiwan (TH-IRB-08-06), and it complied with the principles outlined in the Helsinki Declaration.

      Consent for publication

      All the authors agree with the publication of this manuscript.

      Declaration of competing interest

      The authors declare no competing interests.

      Acknowledgments

      This study was supported by grants from the National Science Council (NSC102-2628-B-192-001-MY3) and Taipei Hospital, Ministry of Health and Welfare in Taiwan. We also thank all the participants in this study and the study groups in the CEAS.

      References

        • Hansen T.E.
        • Evjenth B.
        • Holt J.
        Increasing prevalence of asthma, allergic rhinoconjunctivitis and eczema among schoolchildren: three surveys during the period 1985-2008.
        Acta Paediatr. 2013; 102: 47-52
        • de Marco R.
        • Cappa V.
        • Accordini S.
        • et al.
        Trends in the prevalence of asthma and allergic rhinitis in Italy between 1991 and 2010.
        Eur Respir J. 2012; 39: 883-892
        • Lee Y.L.
        • Hwang B.F.
        • Lin Y.C.
        • Guo Y.L.
        Time trend of asthma prevalence among school children in Taiwan: ISAAC phase I and III surveys.
        Pediatr Allergy Immunol. 2007; 18: 188-195
        • Liang P.H.
        • Shyur S.D.
        • Huang L.H.
        • et al.
        Risk factors and characteristics of early-onset asthma in Taiwanese children.
        J Microbiol Immunol Infect. 2006; 39: 414-421
        • Lawson J.A.
        • Chu L.M.
        • Rennie D.C.
        • et al.
        Prevalence, risk factors, and clinical outcomes of atopic and nonatopic asthma among rural children.
        Ann Allergy Asthma Immunol. 2017; 118: 304-310
        • Diepgen T.L.
        Is the prevalence of atopic dermatitis increasing?.
        in: Williams H.C. Epidemiology of Atopic Eczema. Cambridge University Press, Cambridge, United Kingdom2000: 96-109
        • Moore M.M.
        • Rifas-Shiman S.L.
        • Rich-Edwards J.W.
        • et al.
        Perinatal predictors of atopic dermatitis occurring in the first six months of life.
        Pediatrics. 2004; 113: 468-474
        • Meltzer E.O.
        Allergic rhinitis: managing the pediatric spectrum.
        Allergy Asthma Proc. 2006; 27: 2-8
        • Gaffin J.M.
        • Phipatanakul W.
        The role of indoor allergens in the development of asthma.
        Curr Opin Allergy Clin Immunol. 2009; 9: 128-135
        • Arshad S.H.
        Does exposure to indoor allergens contribute to the development of asthma and allergy?.
        Curr Allergy Asthma Rep. 2010; 10: 49-55
        • Eigenmann P.A.
        • Sicherer S.H.
        • Borkowski T.A.
        • Cohen B.A.
        • Sampson H.A.
        Prevalence of IgE-mediated food allergy among children with atopic dermatitis.
        Pediatrics. 1998; 101: e8
        • Matsui E.C.
        • Sampson H.A.
        • Bahnson H.T.
        • et al.
        Story RE, Visness CM and Inner-city Asthma Consortium. Allergen-specific IgE as a biomarker of exposure plus sensitization in inner-city adolescents with asthma.
        Allergy. 2010; 65: 1414-1422
        • Gehring U.
        • Wijga A.H.
        • Brauer M.
        • et al.
        Traffic-related air pollution and the development of asthma and allergies during the first 8 years of life.
        Am J Respir Crit Care Med. 2010; 181: 596-603
        • Wang J.Y.
        • Liu L.F.
        • Chen C.Y.
        • Huang Y.W.
        • Hsiung C.A.
        • Tsai H.J.
        Acetaminophen and/or antibiotic use in early life and the development of childhood allergic diseases.
        Int J Epidemiol. 2013; 42: 1087-1099
        • Liao M.F.
        • Huang J.L.
        • Chiang L.C.
        • Wang F.Y.
        • Chen C.Y.
        Prevalence of asthma, rhinitis, and eczema from ISAAC survey of schoolchildren in Central Taiwan.
        J Asthma. 2005; 42: 833-837
        • Ho C.L.
        • Chang L.I.
        • Wu W.F.
        The prevalence and risk factors of atopic dermatitis in 6–8 year-old first graders in taipei.
        Pediatr. Neonatol. 2019; 60: 166-171
        • Takeuchi S.
        • Esaki H.
        • Furue M.
        Epidemiology of atopic dermatitis in Japan.
        J Dermatol. 2014; 41: 200-204
        • Lee J.
        • Yang H.
        • Kim M.
        • Kim J.
        • Ahn K.
        Is the prevalence of atopic dermatitis in Korean children decreasing? Analysis of the national statistics data, 2009–2014.
        Asian Pac J Allergy Immunol. 2017; 35: 144-149
        • Salarnia S.
        • Momen T.
        • Jari M.
        Prevalence and risk factors of allergic rhinitis in primary school students of isfahan, Iran.
        Adv Biomed Res. 2018; 7: 157
        • Liao P.F.
        • Sun H.L.
        • Lu K.H.
        • Lue K.H.
        Prevalence of childhood allergic diseases in central Taiwan over the past 15 years.
        Pediatr Neonatol. 2009; 50: 18-25
        • Ma Y.C.
        • Lin C.C.
        • Li C.I.
        • Chiang J.H.
        • Li T.C.
        • Lin J.G.
        Time-trend analysis of prevalence, incidence and traditional Chinese medicine use among children with asthma: a population-based study.
        J Publ Health. 2016; 38: e263-e271
        • Griffiths L.J.
        • Lyons R.A.
        • Bandyopadhyay A.
        • et al.
        Childhood asthma prevalence: cross-sectional record linkage study comparing parent-reported wheeze with general practitioner-recorded asthma diagnoses from primary care electronic health records in Wales.
        BMJ Open Respir Res. 2018; 5e000260
        • Burke H.
        • Leonardi-Bee J.
        • Hashim A.
        • et al.
        Prenatal and passive smoke exposure and incidence of asthma and wheeze: systematic review and meta-analysis.
        Pediatrics. 2012; 129: 735-744
        • Mendell M.J.
        • Mirer A.G.
        • Cheung K.
        • Tong M.
        • Douwes J.
        Respiratory and allergic health effects of dampness, mold, and dampness-related agents: a review of the epidemiologic evidence.
        Environ Health Perspect. 2011; 119: 748-756
        • Thacher J.D.
        • Gruzieva O.
        • Pershagen G.
        • et al.
        Mold and dampness exposure and allergic outcomes from birth to adolescence: data from the BAMSE cohort.
        Allergy. 2017; 72: 967-974
        • Munblit D.
        • Peroni D.G.
        • Boix-Amorós A.
        • et al.
        Human milk and allergic diseases: an unsolved puzzle.
        Nutrients. 2017; 9: 894
        • Bremmer S.F.
        • Simpson E.L.
        Dust mite avoidance for the primary prevention of atopic dermatitis: a systematic review and meta-analysis.
        Pediatr Allergy Immunol. 2015; 26: 646-654
        • Wilson J.M.
        • Platts-Mills T.A.E.
        Home environmental interventions for house dust mite.
        J Allergy Clin Immunol Pract. 2018; 6: 1-7
        • Salo P.M.
        • Wilkerson J.
        • Rose K.M.
        • et al.
        Bedroom allergen exposures in US households.
        J Allergy Clin Immunol. 2018; 141 (e14): 1870-1879
        • Keller T.
        • Hohmann C.
        • Standl M.
        • et al.
        The sex-shift in single disease and multimorbid asthma and rhinitis during puberty - a study by MeDALL.
        Allergy. 2018; 73: 602-614
        • Togias A.
        • Fenton M.J.
        • Gergen P.J.
        • Rotrosen D.
        • Fauci A.S.
        Asthma in the inner city: the perspective of the national Institute of allergy and infectious diseases.
        J Allergy Clin Immunol. 2010; 125: 540-544
        • Gavarkovs A.G.
        • Risica P.M.
        • Parker D.R.
        • Jennings E.
        • Mello J.
        • Phipps M.
        Self-reported environmental tobacco smoke exposure and avoidance compared with cotinine confirmed tobacco smoke exposure among pregnant women and their infants.
        Int J Environ Res Publ Health. 2018; 15: 871
        • Waser M.
        • Von Mutius E.
        • Riedler J.
        • et al.
        Exposure to pets, and the association with hay fever, asthma, and atopic sensitization in rural children.
        Allergy. 2005; 60: 177-184
        • Jaakkola J.J.
        • Hwang B.F.
        • Jaakkola M.S.
        Home dampness and molds as determinants of allergic rhinitis in childhood: a 6-year, population-based cohort study.
        Am J Epidemiol. 2010; 172: 451-459