Home environment, lifestyles behaviors, and rhinitis in childhood

Home environment, lifestyles behaviors, and rhinitis in childhood

Accepted Manuscript Title: Home Environment, Lifestyles Behaviors, and Rhinitis in Childhood Author: Xueying Wang Wei Liu Yu Hu Zhijun Zou Li Shen Che...

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Accepted Manuscript Title: Home Environment, Lifestyles Behaviors, and Rhinitis in Childhood Author: Xueying Wang Wei Liu Yu Hu Zhijun Zou Li Shen Chen Huang PII: DOI: Reference:

S1438-4639(15)00157-1 http://dx.doi.org/doi:10.1016/j.ijheh.2015.11.007 IJHEH 12891

To appear in: Received date: Revised date: Accepted date:

28-9-2015 5-11-2015 25-11-2015

Please cite this article as: Wang, X., Liu, W., Hu, Y., Zou, Z., Shen, L., Huang, C.,Home Environment, Lifestyles Behaviors, and Rhinitis in Childhood, International Journal of Hygiene and Environmental Health (2015), http://dx.doi.org/10.1016/j.ijheh.2015.11.007 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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Home Environment, Lifestyles Behaviors, and Rhinitis in Childhood Xueying Wang1,†, Wei Liu1,†, Yu Hu2, Zhijun Zou1, Li Shen3, Chen Huang1, * 1 Department of Building Environment and Energy Engineering, School of Environment and

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Architecture, University of Shanghai for Science and Technology, Shanghai, PR China 2 Tongji Architectural Design (Group) Company Limited (TJAD), Shanghai, PR China

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* Corresponding Author:

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† These authors contributed equally for this paper.

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3 R&B Technology (Shanghai) Company Limited, Shanghai, PR China

Prof. Chen Huang

School of Environment and Architecture,

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E-mail: [email protected]; [email protected]

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University of Shanghai for Science and Technology

516 Jungong Road, Yangpu District, Shanghai, PR China.

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Tel: 021-55273409

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Fax: 021-55270680

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Abstract The prevalence of children allergic rhinitis has been increasing in China and associated factors still are not clear. In the present paper, we selected 13,335 parent-reported

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questionnaires of 4-6 years-old children, in a cross-sectional study from April 2011 to April 2012 in Shanghai city, and investigated associations of various factors with parent-reported

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allergic rhinitis (doctor-diagnosed) and rhinitis symptoms in childhood. After adjusted by age,

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sex, family history of atopy, and respondent of questionnaire, we find that no siblings, mother in older age during pregnancy, shorter breastfeeding, using antibiotics in the first year, and

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home dampness-related exposures, had significant associations with increased prevalence of

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the studied diseases. Location, type, building area, decoration materials and construction period of the residence, also had significant associations with these diseases. Current parental

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smoking and pet-keeping had no significant associations with the studied diseases. Incense-burning and using mosquito coils had significant associations with reduced risk of

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allergic rhinitis and with increased risk of rhinitis symptoms. Using air cleaner and cleaning the residence in high frequency had associations with increased risk, but eating fast food and

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ice cream often had associations with the reduced risk, of the studied diseases. Families with children being diagnosed allergic rhinitis likely change their lifestyle behaviors. In conclusion, childhood rhinitis could be influenced by heredity and many “environmental exposures”. Avoidance behaviors and reverse causation in parental smoking, pet-keeping, and dietary habits for childhood rhinitis should be carefully considered.

Keywords Home, Allergic rhinitis, Avoidance behavior, Reverse causation, Children, Shanghai

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1. Introduction Allergic rhinitis is a common airway disorder among children and had great influence on the patient’s quality of life and study at school (Greiner et al., 2011). In China, more preschool

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children were diagnosed allergic rhinitis by a doctor than earlier periods (Zhang et al., 2013a). International Study of Asthma and Allergies in Childhood (ISAAC) phrase one (1994-1995)

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and phrase three (2001), which was conducted both in Beijing and Guangzhou, found that the

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prevalence of hay fever (ever) in 13-14 year old children increased from 6% to 7.6% in Beijing and 2.9% to 4.1% in Guangzhou (Asher et al., 2006). A cross-sectional study on

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childhood allergic diseases in 2009 found that the prevalence of childhood among 0-14 year

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old children were 20.42% in Chongqing, 14.46% in Beijing, and 7.83% in Guangzhou of China (Zhao et al., 2010). National-averaged prevalence of allergic rhinitis for these children

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increased to higher than the worldwide-averaged level in the past 20 years (Greiner et al., 2011). Meanwhile, dwelling characteristics, home environment, family lifestyles, and dietary

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habits in China have been largely changed, along with the rapid development of building industry and the improvement of economic status (Weschler 2009; Zhang et al., 2013b).

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Therefore, there may be some associations between increasing of allergic rhinitis prevalence and changing of these environmental factors and lifestyle behaviors. Many related studies have been conducted and found that environmental exposures are notably associated with childhood allergic rhinitis among children in different countries or regions (Brunekreef 1992, 2012; Spengler et al., 1994, 2004; Bornehag et al., 2005; Dong et al., 2008; Naydenov et al., 2008a; Sun and Sundell, 2013; Dalibalta et al., 2015; Keet et al., 2015; Wang et al., 2015). The substantial differences in home environment and lifestyles among the families in various 3

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areas and in different socioeconomic status provided a fantastic chance for us to reveal these associations of environmental factors and lifestyles and childhood airway diseases in China. However, the related studies in China were still limited (Zhang et al., 2013a).

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From 2011 to 2012, we conducted a large-scale questionnaire study in Shanghai (Huang et al.,

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2013, 2015), which was a part of the national study (CCHH: China, Children, Homes, Health) in more than ten large cities of China (Zhang et al., 2013a). In our previous articles, we have

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analysed part of the data and found that furred pet-keeping in the current residence or in the

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early residence at the child’s birth (Huang et al., 2013), parental smoking (Liu et al., 2013b), dwelling characteristics and family natural ventilation habits (Liu et al. 2014b; Zhao et al.,

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2013), and dampness-related exposures (Hu et al., 2014; Wang et al., 2013a, 2013b, 2015;

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Zhao et al., 2013) had significant associations with childhood asthma and related symptoms. Although some of these articles have included allergic rhinitis and rhinitis symptoms (Wang

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et al., 2013a, 2013b, 2015; Zhao et al., 2013; Hu et al., 2014), there were no compassion for the factors with childhood diseases by data in our entire questionnaire. Therefore, in the present paper, we focused on childhood allergic rhinitis and related symptoms and

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investigated their associations with all factors we had collected in the questionnaire and which involved individual and maternal characteristics, early nursing, dwelling characteristics, environmental exposures, family lifestyle behaviors, and children’s dietary habits. We also investigated dose-response relationships of several selected factors, which had been revealed in the previous studies (Huang et al., 2013; Liu et al., 2013a, 2014b; Hu et al., 2014; Liu et al., 2015a), with childhood allergic rhinitis and related symptoms. We also tried to find the interaction effect of these selected factors on the studied diseases. 4

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2. Methods 2.1. The CCHH study in Shanghai From April 2011 to April 2012, we sampled 17,898 parents or guardians of 1-8-year-old

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preschool children in 72 kindergartens from five districts of Shanghai city, by a multistage hierarchical approach. Method for the selection of the surveyed kindergartens were as follows:

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firstly, three urban districts (Hong-Kou, Jing-An, and Zha-Bei) and two suburban districts

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(Bao-Shan and Feng-Xian) were selected from 18 districts (10 urban districts and 8 suburbs) of Shanghai city; secondly, all kindergartens in the selected districts were numbered and

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about 15 kindergartens were randomly chose in each district. More detailed distributions of

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these chose kindergartens in each district were shown in our previous article (Huang et al. 2015). Questionnaire was performed by two methods: 1) on-site distributed to parents or

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guardians of children at teacher-parent meetings at the kindergartens by our members; 2) posted to the children’s teachers, who then distributed the questionnaires with an explanatory

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handout and guidance via the children to parents.

Questions about diseases and symptoms were the same as in the International Study of

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Asthma and Allergies in Childhood (ISAAC). Questions for children’s individual and maternal characteristics, early nursing of the children, dwelling characteristics, early and current home environmental exposures, family lifestyle behaviors, and children’s dietary habits, were similar to the DBH (Dampness in Buildings and Health) study in Sweden (Bornehag et al. 2005), the ALLHOME study in Bulgaria (Naydenov et al., 2008a, 2008b), and the study in Northeast Texas, USA (Sun and Sundell, 2013). More information about the CCHH study in Shanghai were provided in our previous articles (Huang et al., 2013; Hu et al. 5

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2014; Liu et al., 2013a, 2014b). The entire questionnaire was presented in the supplemental materials of a previous paper (Zhang et al., 2013a). All participants verbally consented for themselves and for the preschool children for whom they responded to questionnaires. The

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questionnaire and proposal for the CCHH study in Shanghai were approved by the ethical

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committee in the School of Public Health, Fudan University in Shanghai, China.

2.2. Definitions of exposures and diseases

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All information which involved in this paper was provided by parents or guardians of the

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children. Questions about the studied “exposures” were provided in the previous article (Zhang et al., 2013a). Children were defined as having the “exposure” when their

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questionnaires were answered “Yes” to these questions. Herein the early residence or early

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indicators were defined as refer to the household at the child’s birth; and the current residence or current indicators were defined as the home the surveyed child currently live in. Questions

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about allergic rhinitis and related symptoms were as follows: 1) Doctor-diagnosed allergic rhinitis, ever: Has your child been diagnosed with hay fever or allergic rhinitis by a doctor?; 2) Rhinitis symptoms, ever: Has your child ever had sneezing, or a runny nose or a blocked

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nose without a cold or flu at any time in the past?; 3) Rhinitis symptoms, during last year: Has your child ever had sneezing, or a runny nose or a blocked nose without a cold or flu in the last 12 months?. Children were defined as having the disease or symptom when their questionnaires were answered “Yes” to these questions. Family history of atopy (FHA) was defined as that at least one of the child’s sibling, parent or grandparent having had at least one of the following: asthma, and/or eczema, and/or allergic nose or eye problems.

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2.3. Statistical analysis Statistical analyses were performed with using Statistical Product and Service Solutions (SPSS) (version 17.0, SPSS Ltd., USA). Pearson’s chi-squared test was applied to compare

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prevalence of allergic rhinitis and rhinitis symptoms for different factors. Bivariate and multiple logistic regression models were used to investigate associations and dose-response

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relationships between “exposures” and childhood allergic rhinitis and rhinitis symptoms, and

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results were presented by crude odds ratio and adjusted odds ratio, respectively. Confidence intervals of 95% are also shown, with the criterion for significance in statistical analysis set at

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p<0.05. Multiple regression models were constructed by one studied disease (as dependent

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variable, Yes vs. No), one target factor (as independent variable, Yes vs. No) and potential confounders, which included respondent of questionnaire, the child’s sex and age, and FHA.

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If the target factor had more than two categories, one of the categories was selected as permanent reference (equivalently “No”) and another category as corresponding variable

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(equivalently “Yes”) in each regression model. Multiple regression models, which were constructed by setting the two variables we want to test interaction effect and their

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multiplicative item as independent variables, were also used to reveal the multiplicative interaction effect of the selected factors on studied diseases.

3. Results

3.1. Demographic data and Basic prevalence We selected 13,335 questionnaires of 4-6 year-olds children from the finally returned 15,266 questionnaires of 1-8 year-olds children (response rate: 85.3%), since the amount of children 7

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in 1-3 and 7-8 year-olds were very small (Huang et al., 2013, 2015; Liu et al., 2014b). Most (94.2%) of these questionnaires were filled out by the children’s parents. Boys and girls had similar sample sizes, and 23.9% of children had FHA. More demographic data for the CCHH

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study in Shanghai and in China were provided in previous articles (Huang et al., 2013, 2015; Zhang et al., 2013a). A total of 12.6%, 54.1%, and 42.7% had doctor-diagnosed allergic

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rhinitis ever, rhinitis symptoms ever, and rhinitis symptoms in the last year, respectively.

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3.2. Associations as relate to children’s individual characteristics

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Children whose questionnaires were filled out by the fathers/mothers had the lowest prevalence of the diseases than others. Boys had higher prevalence than girls. Children with

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FHA had substantially higher prevalence than children without FHA. In the logistic

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regression analyses, the children’s sex and FHA had strongly positive associations with the studied diseases. The mother’s occupation (were employed) and age (> 30 year-old) during

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pregnancy, duration of breastfeeding (≤ 6 months), the child’s age for first introduction of infant formula, gruel, or porridge (≤ 6 month-old), number of siblings (none), and guardian before the children attends kindergarten (not parents), had positive associations with the

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studied diseases. Birth season, gestational periods, and birth weight had no any significant associations with these diseases (Table 1).

3.3. Associations as relate to building characteristics of the residence Ownership (owner), location (urban), type (Multi-store apartment dwellings), building area (> 60 m2), and total floors of the residential building (≥ 7 floors), had significant and positive associations with the studied diseases. Layers of window glass (≥ two layers) and window 8

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frame material (not wooden) of the residence, and whether the bathroom has an exhaust fan (Yes) also had significant and positive associations with these diseases. The type of fuel for cooking (not electricity) had significant association and positive with allergic rhinitis.

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Whereas buying new furniture during one year before pregnancy, during 0-1 year-old, and during ≥ 1 year-old had significant and positive associations with rhinitis symptoms.

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Renovation of residence during ≥ 1 year-old had significant and positive associations with

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rhinitis symptoms. Using non-cement as material of floor covering and using non-cement as material of wall covering (reference: cement) in the child’s bedroom was significantly and

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positively associated with all studied diseases (Table 2).

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3.4. Associations as relate to home environmental exposures

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Residences close to commercial district within 200 meters had significant and positive associations with the studied diseases. Finding mosquitoes/flies and cockroach in the

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residence were positively and significantly associated with rhinitis symptoms ever. For the home dampness-related exposures, each of related indicators in the current residence and in the early residence were significantly and positively associated with rhinitis symptoms, but

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not doctor-diagnosed allergic rhinitis (Table 3).

3.5. Associations as relate to family lifestyle behaviors Family smoking had no significant associations with all studied diseases, and current pet-keeping had no significant association with allergic rhinitis and rhinitis symptoms ever. Also, parental smoking and pet keeping in the early residence had no significant associations with these diseases. However, family avoidance behaviors of furred pet-keeping and 9

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changing of the cleaning routines had strongly positive associations with these diseases. Using incense/mosquito coils in the residence had negative associations with allergic rhinitis, whether using incense had positive associations with rhinitis symptoms ever. Using of air

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humidifier/cleaner had positive associations with all studied diseases. Airing the beddings under the sun not often had positive associations with rhinitis symptoms. Few significant

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associations were found of frequencies of opening the windows of the child room during

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3.6. Associations as relate to dietary habits

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night with the studied diseases (Table 4).

Children who had different averaged frequency of eating fast food per month currently had

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significantly different prevalence of allergic rhinitis, but had no notable different prevalence

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of rhinitis symptoms. We also found that those children who often ate fast food and who often drank sugared beverage had notably and significantly lower prevalence of allergic

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rhinitis and rhinitis symptoms than other children. Children who ate ice cream often had lower prevalence, whereas children who often ate cookies, bread, sweet cake, frozen food, organ meat, and jam had higher prevalence, than other children. In logistic regression

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analyses, eating fast food ≥ 2 times per month had negative association with allergic rhinitis. Eating chips, French fries, instant noodle, pop-corn, ice cream, and soft drink often had negative associations with the diseases, whereas currently eating cookies, bread, frozen food, and organ meat had positive associations with rhinitis symptoms (Table 5).

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3.7. Dose-response relationships Compared to other children, children who had shorter exclusive breastfeeding had higher prevalence; Children in the families who bought furniture or renovated the residence in more

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periods had higher prevalence of rhinitis symptoms; children in the families who found more dampness-related indicators had significantly higher prevalence. Prevalence had no

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significant differences among children with different numbers of smokers in current

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residence. In the logistic regression analysis, exclusive breastfeeding had inverse and significant, whereas home dampness-related indicators had strongly positive and significant,

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dose-response relationships with the diseases. Current pet-keeping and parental smoking had

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no dose-response relationships with the diseases (Table 6).

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3.8. Interaction effect

Few significant interaction effects of nine selected factors on the studied diseases were found

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(Table 7). Only total number of periods for buying new furniture and total number of dampness indicators in the current residence had negative interaction effect on allergic rhinitis (doctor-diagnosed). Pet-keeping in early and current residence had negative

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interaction effect both on rhinitis (ever) and rhinitis (in the last year). Total number (n) of periods when new furniture was bought and total number (n) of smokers in current or early residence had negative interaction effect both on rhinitis (ever) and rhinitis (in the last year).

4. Discussion In this study, we found that many factors, with respect to the child’s individual characteristics, building characteristics, home environmental exposures, family lifestyle behaviors and the 11

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child’s dietary habits, had significant associations with childhood allergic rhinitis and rhinitis symptoms. Boys had higher prevalence of allergic rhinitis than girls. Those children with parental atopy had notable higher prevalence than others. These results indicated that sex and heredity could be strongly associated with childhood allergic rhinitis in Shanghai, which was

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consistent with the CCHH parallel studies in Texas of America (Sun and Sundell, 2013), in

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Urumqi (Wang et al., 2013a), in Taiyuan (Zhao et al., 2013), and in Beijing (Qu et al., 2013).

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Several individual characteristics of the child, such as duration of exclusive breastfeeding (van Odijk et al. 2003; Grimshaw et al., 2009; Chen et al., 2012; Hörnell et al., 2013; Nwaru

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et al., 2013; Qu et al., 2013), the number of siblings (Ponsonby et al., 1999; Karmaus et al.,

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2002; Strachan et al., 2015), and age for kindergarten-attend (Celedon et al., 1999; Kramer et al., 1999; Hägerhed-Engman et al., 2006; Chen et al., 2012;) had significant associations with

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childhood allergic rhinitis and related symptoms, are consistent with many previous studies. Strachan et al. found that those children with siblings had significant lower risk in getting

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allergic diseases (Strachan et al., 2015). A review for studies on breastfeeding and childhood allergic diseases from 1996 to 2001 had concluded that longer exclusive breastfeeding could be protective against respiratory diseases during childhood (van Odijk et al. 2003). A recent

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review also found that shorter breastfeeding could be a strong risk factor for childhood allergic rhinitis (Hörnell et al., 2013), as our results (Table 6) indicated. Our parallel studies in Beijing (Qu et al. 2013) and in Shanghai (Liu et al. 2015) also found that longer breastfeeding could be protective against asthma among children without FHA. These findings suggested that more exclusive breastfeeding in infancy could be a strong protective factor for childhood allergic diseases, and mothers should try to provide exclusive 12

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breastfeeding at least 4 months for their children as the China’s national recommendation (Xu et al. 2009). However, our findings, that gestational period and birth weight had no significant associations with allergic rhinitis, are not consistent with the previous studies

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which found shorter gestational period and lower birth weight could be risk factors for childhood respiratory health (Boyle et al., 2012; Chen et al., 2012; Paranjothy et al., 2013;

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Been et al., 2014; Xu et al., 2014; Sonnenschein-van der Voort et al., 2014). In the present

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study, we found that only 4.1% (n=533) and 2.9% (n=371) of the studied children had gestational period < 36 weeks and had birth weight < 2.5 kg, respectively. Among these

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children, the sample sizes (54 and 39, respectively) for children who had been diagnosed

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allergic rhinitis were very small; but the sample sizes for children who had been reported rhinitis symptoms (ever: 299 and 208, respectively; in the last 12 months: 229 and 162,

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respectively) were relatively large. Thus, we inferred that our “unexpected” findings and weak statistical power on associations of gestational period or birth weight with childhood

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allergic rhinitis in multiple logistic regression analysis were due to the small sample sizes.

We found that building characteristics, which included ownership, location, type, building

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area, and construction period, total floors of the residence, and material of floor and wall covering in the child’s bedroom also had significant associations with childhood allergic rhinitis and rhinitis symptoms. These findings are consistent with many studies (Spengler et al., 1994, 2004; Dong et al., 2008; Zuraimi et al., 2011; Sun and Sundell 2011, 2013; Liu et al., 2014b). On the one hand, these building characteristics could partly indicate the family socioeconomic status, which could have great effect on the diagnosis and treatment of allergic diseases (Liu et al. 2014b; Keet et al. 2015). For example, families with ownership of 13

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the current residence should have higher socioeconomic status than families without ownership and children in families with ownership of the current residence (Liu et al. 2014b, 2015). On the other hand, these building characteristics have notably effect on environmental

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exposures, such as indoor air pollution (Zhang and Yoshino 2010; Lewis et al., 2013) and dampness-related exposures (Hägerhed-Engman et al., 2009; Reponen et al., 2013; Liu et al.,

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2015), which were revealed to be significantly associated with childhood respiratory health in

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present study (Tables 2 and 6), in our previous study (Hu et al., 2014), and in other studies (Brunekreef 1992; Bornehag et al., 2005; Dong et al., 2008; Naydenov et al., 2008a; Quansah

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et al., 2012; Sun and Sundell, 2013; Wang et al., 2015).

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With respect to family lifestyle behaviors and the child’s dietary habits, we had several novel

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and “unexpected” findings. Firstly, we found that parental smoking in the current residence and in the early residence had no significant associations with childhood allergic rhinitis and

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rhinitis symptoms, although many studies (Dong et al., 2008; Henderson et al., 2008; Öerg et al., 2011; Sun and Sundell, 2013) verified that parental smoking is a strongly risk factor for childhood respiratory health and our previous study found that maternal smoking has a

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positive and significant association with childhood wheezing symptoms (Liu et al., 2013). More interesting, we also found that incense-burning and using mosquito coils had significant associations with a reduced risk of doctor-diagnosed allergic rhinitis, but with an increased risk of rhinitis symptoms. These findings are inconsistent with many other studies, which found that incense-burning and mosquito coils could be strongly risk factors for respiratory health (Liu et al., 2003; Cohen et al., 2013; Dalibalta et al., 2015). Secondly, children in families who often opened window during night, that probably indicated home ventilation 14

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status should be better than other families, had higher prevalence of allergic rhinitis and rhinitis symptoms than other families, although the associations lost significance in multiple logistic regression analyses. Besides, using air cleaner and cleaning the residence in more

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frequency had strongly associations with the increased risk of all studied diseases. This finding is consistent with our previous study on building characteristics and lifestyles and

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asthma (Liu et al., 2014b). Thirdly, be inconsistent with many previous studies (Naydenov et

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al., 2008; Takkouche et al., 2008; Sun and Sundell, 2011; Brunekreef et al., 2012), we found that current pet-keeping had no significant associations with childhood allergic rhinitis and

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rhinitis symptoms, and that the current residence had more than two pets even had significant

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associations with a reduced risk of allergic rhinitis (Table 6). This finding is consistent with our previous study, in which we also found that early furred pet-keeping, but not current

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pet-keeping had significant associations with the studied diseases (Huang et al, 2013).

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It is unlikely that parental smoking had no any significant associations with the studied diseases; incense-burning, using mosquito coils, currently keeping more pets, and eating more fast food and ice cream even could reduce the risk of doctor-diagnosed allergic rhinitis;

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whereas improving the home ventilation during night, using air cleaner in the residence, and cleaning the residence in more frequency could increase the risk of rhinitis. An explanation is that parents whose children with the doctor-diagnosed allergic rhinitis would change their lifestyle behaviors, which they think or are advised by the doctor as risk factors or protective factors for the child’s allergic rhinitis. In other word, there is a family avoidance behavior in parental smoking, incense-burning, using mosquito coils, and eating different foods, that analogous to pet avoidance behavior (Huang et al., 2013). After being diagnosed allergic 15

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rhinitis by a doctor, parents would avoid smoking around the children and burning incense and mosquito coils in the residence, and restricting the child to eat fast food and ice cream, as well as start using air cleaner and adding frequency in cleaning the residence which were

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considered to be benefit for their children’s health. Consequently, parents of children with rhinitis reported less potential risk factors, but more potential protective factors, than other

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children without doctor-diagnosed allergic rhinitis. Therefore, when we analyze the

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parent-reported data, these “unexpected” effects of these factors on allergic rhinitis were seen. These deductions could be verified by our findings that family avoidance behaviors in furred

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pet-keeping (Huang et al., 2013) and changing in the cleaning routines had strongly positive

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and significant associations with all studied diseases in the present study (Table 4). Therefore, we suggest that avoidance behavior and reverse causation for the different factors should be

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considered, especially in questionnaire-based cross-sectional study. For no significant associations of parental smoking with the studied diseases, another explanation is that the rate

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of maternal smoking is very small (0.9%, n=123) in Shanghai (Liu et al., 2013a), whereas many studies suggested maternal smoking, but not paternal smoking, has robust associations

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with childhood respiratory health (Henderson, 2008; Liu et al., 2013a; Öerg et al., 2011).

Furthermore, only some factors, which included pet-keeping, parental smoking, breastfeeding, buying new furniture, and renovating the residence, had significant interaction effect on one or all studied diseases in different combination. This finding seemingly indicated that most of the factors we investigated had independent effect on childhood rhinitis; both pet-keeping and parental smoking in the early and current residences could interact with their independent effect on childhood rhinitis (Liu et al., 2013b). 16

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All results in this paper indicated that both environmental factors and non-environmental factors included life habits and early nursing in infancy are strongly associated with childhood rhinitis. More environmental factors had great impact on childhood rhinitis than

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life habits and early nursing in infancy. Family avoidance behaviors of life habits; the materials of wall or floor, building area and location of building characteristics; the mother’s

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occupation during pregnancy, who take care of the child before the child starts to attend

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kindergarten of early nursing in infancy, all had more notable and positive correlation with

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childhood allergic rhinitis and rhinitis symptoms than other factors in this paper.

This study had some limitations. Firstly, no causal inference can be made about associations

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of the studied factors with allergic rhinitis and rhinitis symptoms, as in all cross-sectional

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epidemiological studies. Secondly, prevalences of the studied diseases, as well as status of the studied factors were derived from children’s guardian responses to questionnaires. Moreover,

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while allergic rhinitis was doctor-diagnosed, rhinitis symptoms was derived from parental observation and without doctor confirmation. Thirdly, because we had no related questions, we cannot deduce either family avoidance behaviors or Reverse Causation behaviors with

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certainty except for pet-keeping.

Nevertheless, this study also has several strengths. This study of 13,335 children from 72 randomly selected kindergartens is one of the largest cross-sectional study on the home environment and childhood health conducted in China (Zhang et al., 2013a; Huang et al., 2013). The questionnaire we used has been validated previously with regard to health questions and home environment in studies in Sweden (Bornehag et al., 2005), Bulgaria 17

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(Naydenov et al., 2008a) and Northeast Texas of USA (Sun and Sundell 2011, 2013). Therefore, although there can be no inference made about causality between exposure and health problems, and there is also a potential error resulting from over-reporting those risk

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factors that respondents are aware of, a response rate of 85.3% makes the present study likely gave a valid and reliable picture of the home environment and lifestyles and childhood

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respiratory health in Shanghai, China.

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5. Conclusions

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Childhood allergic rhinitis and rhinitis symptoms could be comprehensively influenced by heredity, individual characteristics, environmental exposures in the early and current

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residences, and dietary habits, especially by early nursing in infancy and the decorated

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materials of wall/floor in the residence. Family avoidance behaviors on the potential risk factors and reverse causation behaviors on the potential protective factors, especially for

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children with the studied doctor-diagnosed diseases, should be carefully considered when the related cross-sectional questionnaire studies are conducted.

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Acknowledgements

This work is financially supported by The National Natural Science Foundation of China (51278302), Hujiang Foundation of China (D14003), The Innovation Program of Shanghai Municipal Education Commission (14ZZ132), and The Innovation Fund Project for Graduate Student of Shanghai (JWCXSL1401). The authors thank the Shanghai Municipal and District Bureau of Education for their supports, and greatly appreciate the helps from Prof. Jan Sundell (Tsinghua University), Dr. Yuexia Sun (Tianjin University) and Dr. Zhuohui Zhao 18

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(Fudan University) in preparation of the questionnaire, and also express their thanks to all of the parents, and others who involved in the survey.

Competing Interests

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YH and LS were master students in their school and conducted the questionnaire study

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together with other authors during 2011 to 2012, and are employed by the company after the survey. The company has no role in study design, data collection and analysis, decision to

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publish, or preparation of the manuscript. The authors have declared that no competing

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interests exist.

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Authors’ contributions

CH, WL, YH, and ZJZ conceived and designed the questionnaire; CH, WL, YH, ZJZ, and LS

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performed the survey; XYW and WL analyzed the data, drafted and prepared the paper;

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XYW, WL, ZJZ, and CH contributed reagents/materials/analysis tools.

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References

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introduction of complementary foods during infancy in relation to the risk of asthma and atopic diseases up to 10 years. Clin Exp Allergy. 2013; 43: 1263-1273. Öerg, M., Jaakkola, M.S., Woodward, A., Peruga, A., Prüss-Ustün, A., 2011. Worldwide burden of disease from exposure to second-hand smoke: A retrospective analysis of data from 192 countries. Lancet 377, 139-146. Paranjothy, S., Dunstan, F., Watkins, W.J., Hyatt, M., Demmler, J.C., Lyons, R.A., et al., 2013. Gestational age, birth weight, and risk of respiratory hospital admission in childhood. Pediatrics 132(6), 1562-1529. Ponsonby, A.L., Couper, D., Dwyer, T., Carmichael, A., Kemp, A., 1999. Relationship between early life respiratory illness, family size over time, and the development of asthma and hay fever: a seven year follow up study. Thorax 54(8), 664-669. Qu, F., Weschler, L.B., Sundell, J., Zhang, Y.P., 2013. Increasing prevalence of asthma and allergy in Beijing pre-school children: Is exclusive breastfeeding for more than 6 months protective?. Chin. Sci. Bull. 58, 4190-4202. Quansah, R., Jaakkola, M.S., Hugg, T.T., Heikkinen, S.A.M., Jaakkola, J.J.K., 2012. Residential dampness and molds and the risk of developing asthma: a systematic review and meta-analysis. PLoS ONE 7(11), e47526. Reponen, T., Levin, L., Zheng, S., Vesper, S., Ryan, P., Grinshpun, S.A., et al., 2013. Family and home characteristics correlate with mold in homes. Environ. Res. 124, 67-70. Sonnenschein-van der Voort, A.M., Arends, L.R., de Jongste, J.C., Annesi-Maesano, I., Arshad, S.H., Barros, H., 2014. Preterm birth, infant weight gain, and childhood asthma risk: a meta-analysis of 147,000 European children. J. Allergy Clin. Immunol 33(5), 1317-1329. Spengler, J.D., Jaakkola, J.J.K., Parise, H., Katsnelson, B.A., Privalova, L.I., Kosheleva, A.A., 2004. Housing characteristics and children’s respiratory health in the Russian Federation. Am. J. Public Health 94, 657-662. Spengler, J.D., Neas, L., Nakai, S., Dockery, D., Speizer, F., Ware, J., et al., 1994. Respiratory symptoms and housing characteristics. Indoor Air, 4, 72-82. Strachan, D.P., Aït-Khaled, N., Foliaki, S., Mallol, J., Odhiambo, J., Pearce, N., et al., 2015. Siblings, asthma, rhinoconjunctivitis and eczema: a worldwide perspective from the International Study of Asthma and Allergies in Childhood. Clin. Exp. Allergy 45(1), 126-136. Sun, Y., Sundell, J., 2013. On associations between housing characteristics, dampness and asthma and allergies among children in Northeast Texas. Indoor Built Environ. 22, 678-684. Sun, Y., Sundell, J., 2011. Life style and home environment are associated with racial disparities of asthma and allergy in Northeast Texas children. Sci. Total Environ. 409, 4229-4234. Takkouche, B., González-Barcala, F.J., Etminan, M., Fitzgerald, M., 2008. Exposure to furry pets and the risk of asthma and allergic rhinitis: A meta-analysis. Allergy, 63, 857-864. van Odijk, J., Kull, I., Borres, M.P., Brandtzaeg, P., Edberg, U., Aanson, L.A., et al., 2003. Breastfeeding and allergic disease: a multidisciplinary review of the literature (1966–2001) on the mode of early feeding in infancy and its impact on later atopic manifestations. Allergy 58(9), 833-843. Wang, H., Li, B.Z., Yang, Q., Yu, W., Wang, J., Liu, Y.L., et al., 2013a. Dampness in dwellings and its associations with asthma and allergies among children in Chongqing: A cross-sectional study. Chin. Sci. Bull. 58, 4259-4266. Wang, H., Li, B.Z., Yu, W., Wang, J., Norback, D., 2015. Early-life exposure to home dampness associated with health effects among children in Chongqing, China. Build. Environ. 94, 327-334. 22

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Wang, T.T., Zhao, Z.H., Yao, H., Wang, S.L., Norback, D., Chen, J., et al., 2013b. Housing characteristics and indoor environment in relation to children’s asthma, allergic diseases and pneumonia in Urumqi, China. Chin. Sci. Bull. 58, 4237-4244. Weschler, C.J., 2009. Changes in indoor pollutants since the 1950s. Atmos. Environ. 43,153-169. Xu, F., Qiu, L., Binns, C.W., Liu, X., 2009. Breastfeeding in China: a review. Int. Breastfeed J. 4, 6. Doi: 10.1186/1746-4358-4-6. Xu, X.F., Li, Y.J., Sheng, Y.J, Liu, J.L., Tang, L.F., Chen, Z.M., 2014. Effect of low birth weight on childhood asthma: a meta-analysis. BMC Pediatr. 14. 275. http://www.biomedcentral.com/1471-2431/14/275 Zhang, H., Yoshino, H., 2010. Analysis of indoor humidity environment in Chinese residential buildings. Build. Environ. 45, 2132-2140. Zhang, Y.P., Li, B.Z., Huang, C., Yang, X., Qian, H., Deng, Q.H., et al., 2013a. Ten cities cross-sectional questionnaire survey of children asthma and other allergies in China. Chin. Sci. Bull. 58, 4182-4189. Zhang, Y.P., Mo, J.H., Weschler, C.J., 2013b. Reducing health risks from indoor exposures in rapidly developing urban China. Environ. Health Perspect. 121, 751-755. Zhao, Z.H., Zhang, X., Liu, R.R., Norback, D., Wieslander, G., Chen, J., et al., 2013. Prenatal and early life home environment exposure in relation to preschool children’s asthma, allergic rhinitis and eczema in Taiyuan, China. Chin. Sci. Bull. 58, 4245-4251. Zhao J, Bai J, Shen K, Xiang L, Huang S, Chen A, et al., 2010. Self-reported prevalence of childhood allergic diseases in three cities of China: a multicenter study. BMC Public Health. 10:551. Zuraimi, M.S., Tham, K.W., Chew, F.T., Ooi, P.L., Koh, D., 2011. Home air conditioning, traffic exposure, and asthma and allergic symptoms among preschool children. Pediatr. Allergy Immunol. 22, 112-118.

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Table 1 Demographic data and prevalences of the studied diseases Items

Sample size, n (%)

Sex Boys

1702 (50.9)

Girls

1642 (49.1)

4

5561 (41.7)

5

4399 (33.0)

6

3375 (25.3)

ip t

Age (year-olds)

Yes

703 (21.4)

No

2583 (78.6)

cr

Family history of atopy

Respondent of the questionnaire 3108 (24.0)

Mother

us

Father

9082 (70.2)

b

Others

748 (5.8)

Yes

1624 (12.6)

No

11301 (87.4)

an

Allergic rhinitis (doctor-diagnosed), ever

Yes

6003 (45.0)

No

7076 (53.1)

Rhinitis symptoms, in last year 7436 (57.3)

No

5532 (42.7)

ce pt

Includes grandmother, grandfather, or others.

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b

ed

Yes

M

Rhinitis symptoms, ever

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Table 2 Associations of diseases with maternal/infant characteristics and nursing of the children Allergic rhinitis, ever Rhinitis symptoms, ever Rhinitis symptoms, in last year Itemsa Prevalence, % AOR, 95%CIb Prevalence, % AOR, 95%CIb Prevalence, % AOR, 95%CIb (1) Number of children (< 8 year-olds) live in the current residence Only one vs. ≥ 2 13.5 vs. 7.5# 1.94, 1.53-2.46 54.5 vs. 50.1* 1.17, 1.03-1.32 43.7 vs. 36.5# 1.30, 1.14-1.48 (2) Who take care of the child before the child starts to attend kindergarten Parents 9.9 Reference 51.8 Reference 38.9 Reference Grandparents 14.6 1.46, 1.29-1.64 55.8 1.13, 1.05-1.22 45.5 1.25, 1.16-1.35 Others 17.0# 1.55, 1.12-2.13 59.9# 1.29, 1.02-1.62 48.0# 1.30, 1.03-1.64 (3) Whether he mothers were employed during pregnancy Yes vs. No 14.9 vs. 9.0# 1.54, 1.36-1.74 57.1 vs. 49.3# 1.32, 1.22-1.42 46.5 vs. 36.7# 1.40, 1.29-1.51 (4) Duration of breastfeeding (months) ≤ 6 vs. > 6 14.6 vs. 9.9# 1.47, 1.30-1.65 56.0 vs. 51.6# 1.16, 1.08-1.25 44.8 vs. 39.5# 1.19, 1.11-1.29 (5) The mother’s age during pregnancy (year-olds) ≥ 30 vs. < 30 14.7 vs. 11.8# 1.25, 1.10-1.41 56.9 vs. 53.2# 1.13, 1.04-1.22 46.0 vs. 41.6# 1.15, 1.06-1.25 (6) Whether the child lived in Shanghai city since birth Yes vs. No 13.6 vs. 6.3# 1.25, 1.11-1.40 54.7 vs. 50.7** 1.09, 1.01-1.17 44.0 vs. 35.8# 1.04, 0.96-1.12 (7) Whether use of antibiotics during the first year of life Yes vs. No 16.3 vs. 11.7# 1.23, 1.09-1.40 57.3 vs. 53.5# 1.08, 0.99-1.17 47.9 vs. 41.8# 1.17, 1.07-1.28 (8) Age for first introduction of infant formula, gruel or porridge (month-olds) ≤ 6 vs. > 6 14.7 vs. 11.6# 1.22, 1.09-1.38 56.1 vs. 52.9# 1.09, 1.01-1.18 46.2 vs. 40.8# 1.19, 1.10-1.28 (9) The child’s birth season Spring (Mar.-May) 12.2 Reference 52.7 Reference 42.2 Reference Summer (Jun.-Aug.) 11.8 1.00, 0.85-1.18 53.3 0.99, 0.89-1.10 42.2 0.99, 0.89-1.10 Autumn (Sep.-Nov.) 13.8 1.08, 0.92-1.28 56.1 1.07, 0.96-1.18 44.6 1.07, 0.96-1.19 Winter (Dec.-Feb.) 12.6 1.03, 0.87-1.21 53.2 0.98, 0.88-1.09 41.6 0.97, 0.87-1.08 (10) The child’s age for firstly attend the kindergarten (year-olds) < 3 vs. ≥ 3 12.5 vs. 13.2 0.99, 0.85-1.16 58.6 vs. 53.2# 1.23, 1.11-1.36 45.9 vs. 42.0** 1.15, 1.04-1.27 (11) The child’s birth weight (kilograms) < 2.5 vs. ≥ 2.5 10.8 vs. 12.6 0.85, 0.60-1.21 56.8 vs. 54.0 1.17, 0.94-1.45 44.6 vs. 42.7 1.14, 0.92-1.42 (12) Age for first introduction of fruit and vegetables (month-olds) ≤ 6 vs. > 6 11.5 vs. 12.8 0.78, 0.61-1.02 58.2 vs. 53.9 1.18, 1.00-1.39 44.4 vs. 42.6 1.06, 0.90-1.25 (13) The child’s gestational period at birth (weeks) < 36 vs. ≥ 36 10.4 vs. 12.7 0.73, 0.54-1.00 57.4 vs. 54.0 1.14, 0.95-1.38 44.6 vs. 42.7 1.08, 0.90-1.31 a Prevalences of the disease/symptoms before and after “vs.” are corresponding to the options for different items. The latter options are references in the logistic regression analyses except for the specific indication. b AOR: adjusted odds ratio; CI: confidence interval. Adjusted factors included respondent of questionnaire, age, sex, and

Ac

family history of atopy. * 0.01 ≤ p <0.05; ** 0.001 ≤ p <0.01; # p <0.001 in chi-square test.

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Table 3 Associations of the studied diseases as related to dwelling characteristics Allergic rhinitis, ever Rhinitis symptoms, ever Rhinitis symptoms, in last year Itemsa Prevalence, % AOR, 95%CIb Prevalence, % AOR, 95%CIb Prevalence, % AOR, 95%CIb 1. Building characteristics as related to the current residence (1) Type of the residence DHSFc 8.8 Reference 52.6 Reference 38.5 Reference MSADd 14.6 1.56, 1.35-1.82 55.2 1.05, 0.96-1.15 45.0 1.24, 1.13-1.35 Others 7.3# 0.90, 0.67-1.20 50.4** 0.98, 0.85-1.14 35.6# 0.95, 0.81-1.11 (2) Location of the residence Urban vs. Suburban 14.6 vs. 8.4# 1.52, 1.32-1.74 57.5 vs. 46.7# 1.44, 1.33-1.56 46.3 vs. 34.7# 1.45, 1.34-1.58 (3) Total floors of the residential building ≥ 7 vs. < 7 floors 16.8 vs. 10.5# 1.42, 1.27-1.59 59.5 vs. 51.5# 1.28, 1.18-1.38 49.8 vs. 39.1# 1.38, 1.27-1.49 (4) Ownership of the residence Owner vs. Tenant 14.2 vs. 9.7# 1.40, 1.24-1.59 55.4 vs. 52.0# 1.08, 1.00-1.16 45.3 vs. 38.6# 1.23, 1.14-1.33 (5) Building area of the residence ≤ 60 m2 9.6 Reference 52.3 Reference 38.9 Reference 61-100 m2 12.9 1.25, 1.08-1.44 54.3 1.04, 0.95-1.14 43.6 1.17, 1.07-1.28 ≥ 101 m2 15.7# 1.51, 1.31-1.75 56.1** 1.10, 1.00-1.20 46.3# 1.24, 1.13-1.36 (6) Type of fuel for cooking Electricity 10.0 Reference 52.3 Reference 39.6 Reference Natural gas 12.8 1.25, 1.04-1.49 54.3 1.03, 0.92-1.14 43.2 1.09, 0.98-1.22 Othersf 13.5** 1.25, 1.03-1.52 54.4 1.02, 0.90-1.14 43.1* 1.06, 0.94-1.20 (7) Type of home heating in winter Electric heater 13.5 Reference 58.6 Reference 44.9 Reference Air conditioner 12.6 1.11, 0.89-1.38 53.8 1.23, 1.07-1.42 42.8 1.10, 0.95-1.27 Otherse 15.1** 1.20, 1.04-1.38 56.3** 1.08, 0.98-1.20 45.5 1.08, 0.98-1.19 (8) Whether the residence was renovated during the following periods (Yes vs. No) One year before 14.8 vs. 11.9# 1.16, 1.00-1.35 56.7 vs. 52.4** 1.11, 1.00-1.23 44.9 vs. 41.3 1.09, 0.98-1.21 pregnancy During pregnancy 14.3 vs. 12.0 1.12, 0.84-1.50 55.0 vs. 52.3 1.05, 0.87-1.28 45.2 vs. 41.3 1.11, 0.91-1.36 During 0-1year-old 17.3 vs. 12.0** 1.30, 0.94-1.81 58.2 vs. 52.3* 1.19, 0.94-1.51 45.3 vs. 41.3 1.06, 0.84-1.35 During ≥ 1 year-old 14.2 vs. 12.0** 1.11, 0.95-1.29 57.5 vs. 52.2# 1.21, 1.09-1.34 47.9 vs. 41.0# 1.29, 1.16-1.43 (9) Whether new furniture was bought during the following periods (Yes vs. No) One year before 14.0 vs. 11.6** 1.15, 1.01-1.31 57.1 vs. 51.1# 1.22, 1.12-1.33 45.3 vs. 40.4# 1.17, 1.08-1.28 pregnancy During pregnancy 13.7 vs. 11.9 1.06, 0.89-1.27 54.4 vs. 51.6* 1.08, 0.96-1.21 44.6 vs. 40.7** 1.13, 1.00-1.27 During 0-1year-old 13.1 vs. 12.1 1.02, 0.85-1.22 57.7 vs. 51.2# 1.27, 1.13-1.43 45.9 vs. 40.6# 1.22, 1.08-1.37 During ≥ 1 year-old 12.7 vs. 12.1 0.93, 0.82-1.05 56.3 vs. 51.3# 1.19, 1.09-1.29 44.7 vs. 40.5# 1.15, 1.06-1.25 (10) Construction period of the residence Prior to 1990 11.5 Reference 54.4 Reference 40.6 Reference 1991-2000 12.1 1.03, 0.87-1.20 54.6 0.99, 0.89-1.09 43.4 1.10, 0.99-1.22 2001-present 14.0** 1.14, 0.98-1.32 54.3 0.97, 0.88-1.06 44.2** 1.12, 1.01-1.23 2. Building characteristics as related to the child’s room in the current residence (1) Material of floor covering Cement 3.5 Reference 46.1 Reference 29.4 Reference Laminate wood 15.0 3.78, 2.52-5.66 57.0 1.42, 1.20-1.68 46.6 1.77, 1.48-2.12 Solid wood 13.7 3.55, 2.42-5.20 54.9 1.29, 112-1.49 44.1 1.62, 1.39-1.89 Tiles or stone 7.0 2.01, 1.24-3.26 49.6 1.16, 0.95-1.41 35.4 1.23, 0.99-1.52 Others 10.3# 2.38, 1.42-3.96 53.7# 1.27, 1.00-1.61 40.6# 1.40, 1.09-1.80 (2) Material of wall covering Cement 6.2 Reference 46.8 Reference 31.9 Reference Wallpaper 10.9 1.44, 0.93-2.21 55.7 1.37, 1.10-1.70 42.7 1.44, 1.14-1.81 Oil paint 13.7 1.95, 1.29-2.94 54.8 1.30, 1.06-1.60 43.5 1.49, 1.19-1.86 Lime 6.5 0.93, 0.59-1.46 50.9 1.15, 0.93-1.42 35.5 1.13, 0.90-1.42 Latex paint 15.0 2.06, 1.39-3.05 55.7 1.31, 1.08-1.59 46.1 1.64, 1.34-2.02 Others 8.8# 1.34, 0.85-2.13 47.9# 1.05, 0.83-1.33 33.6# 1.34, 0.85-2.13 (3) Floor of the child’s bedroom in the residential building 1-3 10.5 Reference 52.4 Reference 39.6 Reference 4-7 13.1 1.18, 1.03-1.35 53.9 1.03, 0.95-1.12 43.5 1.13, 1.03-1.23 ≥8 17.0# 1.44, 1.24-1.67 59.4# 1.23, 1.12-1.36 50.0# 1.38, 1.25-1.53 a Prevalences of the disease/symptoms before and after “vs.” are corresponding to the options for different items. The latter options are references in the logistic regression analyses except for the specific indication. b AOR: adjusted odds ratio; CI: confidence interval. Adjusted factors included respondent of questionnaire, age, sex, and family history of atopy. c Detached housings for single families. d Multi-store apartment dwellings. d Included coal stove, heat wall (Kang), fire pan, radiant floor heating, central or splitting heating, and others. e Included coal, wood, and others. f Included bamboo, PVC (Polyvinyl chloride), and carpet (chemical fibre, pure wool, or hemp rug). * 0.01 ≤ p <0.05; ** 0.001 ≤ p <0.01; # p <0.001 in chi-square test. 26

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Table 4 Associations of the studied diseases as related to home environmental exposures Allergic rhinitis, ever Rhinitis symptoms, ever Rhinitis symptoms, in last year Items a Prevalence, % AOR,95%CIb Prevalence, % AOR,95%CIb Prevalence, % AOR, 95%CIb 1. Environmental exposures as related to the current residence (Yes vs. No) (3) Dampness-related indicators in the residence Water damage 15.7 vs. 11.9# 1.19, 1.03-1.37 59.6 vs. 52.5# 1.23, 1.11-1.36 49.0 vs. 41.2# 1.24, 1.13-1.37 # damp clothing 12.7 vs. 12.5 0.94, 0.84-1.05 57.7 vs. 51.4 1.28, 1.19-1.38 45.6 vs. 40.6# 1.19, 1.11-1.29 # moldy odor 12.9 vs. 12.0 1.07, 0.95-1.22 56.4 vs. 52.3 1.16, 1.07-1.26 45.4 vs. 40.8# 1.19, 1.10-1.30 (1) Surrounding environment (within 200 meters) of the residence high way 13.5 vs. 11.9** 1.09, 0.97-1.23 55.2 vs. 53.7 1.01, 0.94-1.09 44.6 vs. 41.7 1.06, 0.98-1.14 commercial district 14.4 vs. 11.8** 1.18, 1.04-1.34 57.3 vs. 53.0# 1.17, 1.08-1.27 45.5 vs. 41.7# 1.14, 1.05-1.24 river or lake 12.0 vs. 12.6 1.00, 0.83-1.20 53.6 vs. 54.4 0.98, 0.87-1.10 42.6 vs. 42.9 1.01, 0.89-1.14 industrial district 10.8 vs. 12.7 0.91, 0.71-1.16 53.6 vs. 54.4 0.99, 0.86-1.15 40.1 vs. 43.0 0.93, 0.80-1.09 (2) Whether any animals, stated below, were found in the residence mice 8.4 vs. 12.9# 0.66, 0.55-0.79 53.3 vs. 53.3 1.03, 0.93-1.14 38.8 vs. 42.8# 0.89, 0.80-0.99 # mosquitoes or flies 12.7 vs. 11.7 0.96, 0.82-1.14 54.6 vs. 50.2 1.13, 1.02-1.25 43.5 vs. 37.9# 1.17, 1.05-1.30 # cockroach 12.0 vs. 13.2 0.88, 0.78-0.99 55.2 vs. 52.0 1.12, 1.03-1.20 42.9 vs. 41.9 1.03, 0.95-1.11 2. Dampness-related exposures in the child’s room of the current residence (Yes vs. No) mold spots 14.5 vs. 12.4 1.09, 0.89-1.34 61.2 vs. 53.3# 1.31, 1.14-1.51 49.9 vs. 41.0 # 1.28, 1.11-1.47 # # damp stains 14.9 vs. 12.2 1.11, 0.95-1.29 60.3 vs. 52.7 1.27, 1.15-1.41 48.1 vs. 41.6# 1.20, 1.08-1.33 windows pane 15.0 vs. 9.9# 1.32, 1.16-1.51 57.2 vs. 51.1# 1.18, 1.08-1.28 47.8 vs. 37.6# 1.39, 1.27-1.51 condensation 3. Dampness-related exposures as related to early residence at the child’s birth (Yes vs. No) Mold spots/stains 15.0 vs. 12.2** 1.20, 1.03-1.40 61.6 vs. 52.9# 1.38, 1.24-1.54 48.4 vs. 41.9# 1.25, 1.12-1.39 windows pane 14.4 vs. 10.4# 1.19, 1.06-1.34 57.4 vs. 50.4# 1.23, 1.14-1.32 47.1 vs. 37.8# 1.33, 1.24-1.44 condensation Moldy odor 15.3 vs. 12.2** 1.28, 1.04-1.56 62.1 vs. 52.7# 1.47, 1.27-1.70 48.2 vs. 41.6# 1.27, 1.10-1.46 a Prevalences of the disease/symptoms before and after “vs.” are corresponding to the options for different items. The latter options are references in the logistic regression analyses. b AOR: adjusted odds ratio; CI: confidence

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Table 5 Associations of the studied diseases as related to family lifestyle behaviors Allergic rhinitis, ever Rhinitis symptoms, ever Rhinitis symptoms, in last year Items a Prevalence, % AOR,95%CIb Prevalence, % AOR,95%CIb Prevalence, % AOR, 95%CIb 1. Lifestyle behaviors as related to the current residence (1) whether any equipment, stated below, were used in the residence Air humidifier 16.8 vs. 12.1# 1.27, 1.10-1.46 60.5 vs. 53.0 1.30, 1.17-1.43 50.0 vs. 41.6# 1.29, 1.17-1.42 Air cleaner 20.3 vs. 12.3# 1.59, 1.33-1.91 63.4 vs. 53.5# 1.42, 1.23-1.63 53.8 vs. 42.1# 1.49, 1.30-1.71 Printer/photocopy 12.5 vs. 13.0 0.86, 0.72-1.00 56.4 vs. 54.1 1.09, 0.97-1.22 45.3 vs. 42.8 1.08, 0.96-1.21 machine Air conditioner 12.9 vs. 12.1 0.92, 0.68-1.25 54.2 vs. 56.8 0.81, 0.66-0.98 43.1 vs. 42.3 0.92, 0.75-1.12 (2) Whether the beddings were took to sunshine Not often vs. Often 14.2 vs. 12.2** 1.10, 0.96-1.27 58.7 vs. 53.1# 1.23, 1.12-1.36 46.1 vs. 42.0# 1.13, 1.03-1.25 (3) Whether any furred animals / pets existed in the present residence Yes vs. No 14.0 vs. 12.2* 1.04, 0.91-1.19 56.1 vs. 53.4* 1.08, 0.98-1.18 45.4 vs. 41.9** 1.10, 1.00-1.21 (4) Whether there any family members smoke in the present residence Yes vs. No 12.6 vs. 12.6 1.04, 0.93-1.17 53.9 vs. 54.0 1.00, 0.93-1.08 42.6 vs. 42.8 1.01, 0.94-1.09 (5) whether mosquito coils were used in the residence Yes vs. No 12.3 vs. 13.8* 0.85, 0.74-0.97 54.0 vs. 53.5 1.01, 0.92-1.11 42.7 vs. 42.0 1.03, 0.93-1.12 (6) whether incense were burned in the residence Yes vs. No 11.0 vs. 12.9* 0.75, 0.62-0.90 58.5 vs. 53.3# 1.19, 1.06-1.33 45.9 vs. 42.2** 1.12, 1.00-1.26 2. Lifestyle behaviors as related to the child’s room in the current residence (1) How often do vacuum clean, sweep or mop (wet) the floor in the child’s room Everyday vs. 13.2 vs. 11.7* 1.16, 1.03-1.30 54.4 vs. 53.8 1.03, 0.95-1.11 42.5 vs. 43.1 0.97, 0.90-1.05 ≤ twice a week (2) How often does the window open when the child is sleeping during night Spring often 13.6 Reference 55.5 Reference 43.6 Reference Sometimes 11.5 0.86, 0.76-0.97 53.2 0.93, 0.86-1.01 41.9 0.97, 0.89-1.05 Never 13.1** 0.94, 0.78-1.13 52.3* 0.87, 0.77-0.98 42.9 0.96, 0.85-1.09 Summer often 12.4 Reference 53.4 Reference 41.9 Reference Sometimes 12.5 1.05, 0.93-1.19 54.4 1.05, 0.97-1.14 42.9 1.06, 0.97-1.15 Never 14.8 1.15, 0.95-1.40 57.6* 1.13, 0.99-1.29 48.0** 1.22, 1.06-1.39 Autumn often 13.6 Reference 54.9 Reference 43.3 Reference Sometimes 11.5 0.83, 0.74-0.94 53.3 0.95, 0.87-1.02 42.0 0.97, 0.90-1.05 Never 13.7** 1.00, 0.83-1.21 53.0 0.91, 0.80-1.03 44.2 1.03, 0.91-1.18 Winter often 13.5 Reference 56.0 Reference 44.3 Reference Sometimes 11.7 0.84, 0.72-0.99 54.0 0.91, 0.82-1.01 41.7 0.89, 0.80-0.99 Never 13.4* 0.93, 0.79-1.09 52.9 0.84, 0.75-0.94 43.4 0.91, 0.81-1.01 3. Lifestyle behaviors as related to the early residence at the child’s birth (1) Whether any furred animals and/or pets existed in the residence Yes vs. No 14.2 vs. 12.3* 1.09, 0.93-1.28 56.7 vs. 53.6* 1.08, 0.97-1.21 45.2 vs. 42.2* 1.07, 0.96-1.20 (2) Whether father and/or mother smoke during the child’s birth Yes vs. No 12.6 vs. 12.4 1.04, 0.93-1.17 53.8 vs. 54.2 1.00, 0.93-1.08 42.2 vs. 43.0 1.01, 0.94-1.09 4. Other behaviors (1) Have the cleaning routines changed due to allergies in the family Yes vs. No 26.8 vs. 8.6# 2.72, 2.38-3.12 69.4 vs. 48. 7# 2.02, 1.82-2.24 58.2 vs. 37.7# 1.88, 1.70-2.07 (2) Have refrained from procuring any furred animals/pets due to allergic illnesses in the family Yes vs. No 21.6 vs. 10.1# 2.20, 1.86-2.61 64.8 vs. 51.4# 1.61, 1.42-1.83 52.8 vs. 39.6# 1.57, 1.39-1.78 (3) Have got rid of any furred animals/pets due to allergic illnesses in the family Yes vs. No 24.5 vs. 9.4* 1.77, 1.45-2.18 66.2 vs. 50.5# 1.51, 1.29-1.77 55.8 vs. 38.8# 1.37, 1.17-1.60 a Prevalences of the disease/symptoms before and after “vs.” are corresponding to the options for different items. The latter options are references in the logistic regression analyses except for the specific indication. b AOR: adjusted odds ratio; CI: confidence interval. The bold values are statistically significant (p <0.05). Adjusted factors included respondent of questionnaire, age, sex, and family history of atopy. * 0.01 ≤ p <0.05; ** 0.001 ≤ p <0.01; # p <0.001 in chi-square test.

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Table 6 Associations of the studied diseases as related to current dietary habits Rhinitis symptoms, in last year Allergic rhinitis, ever Rhinitis symptoms, ever Items a Prevalence, % AOR,95%CIb Prevalence, % AOR,95%CIb Prevalence, % AOR,95%CIb 1. Averaged frequency of currently eating fast food per month 0 time 13.9 Reference 54.2 Reference 43.7 Reference 1 time 12.4 0.93, 0.81-1.05 53.6 0.98, 0.90-1.07 42.8 1.00, 0.91-1.08 ≥ 2 times 10.9# 0.81, 0.69-0.94 54.7 1.05, 0.96-1.16 41.0 0.95, 0.86-1.05 2. Foods that the child currently eats often (Yes vs. No) (1) Flour or sweet foods Cookies 13.1 vs. 11.6 1.16, 1.03-1.31 55.2 vs. 52.6** 1.13, 1.04-1.22 43.6 vs. 41.3* 1.11, 1.03-1.20 Bread 13.0 vs. 11.9 1.07, 0.95-1.20 55.6 vs. 52.4# 1.12, 1.03-1.20 44.1 vs. 40.8# 1.11, 1.03-1.20 Candy 11.4 vs. 14.2# 0.79, 0.71-0.89 53.5 vs. 55.4* 0.95, 0.88-1.02 42.4 vs. 43.3 0.98, 0.91-1.06 Ice cream 9.2 vs. 14.1# 0.66, 0.58-0.76 52.8 vs. 55.0* 0.97, 0.89-1.05 39.5 vs. 44.2# 0.87, 0.80-0.95 Chocolate 11.7 vs. 13.3# 0.90, 0.80-1.00 54.9 vs. 54.9 1.06, 0.98-1.14 43.1 vs. 42.5 1.04, 0.97-1.12 Sweet cake 13.6 vs. 12.5 1.11, 0.90-1.37 59.2 vs. 53.9** 1.20, 1.04-1.38 43.7 vs. 42.7 1.04, 0.90-1.20 (2) Other foods Frozen foods 15.1 vs. 12.2** 1.13, 0.96-1.34 62.0 vs. 53.3# 1.36, 1.21-1.53 50.2 vs. 41.8# 1.34, 1.19-1.50 Canned foods 7.6 vs. 12.7** 0.61, 0.40-0.92 55.4 vs. 54.3 1.07, 0.86-1.34 42.7 vs. 42.8 1.02, 0.82-1.28 Organ meat 13.7 vs. 12.4 1.05, 0.88-1.25 60.6 vs. 53.5# 1.32, 1.17-1.49 47.9 vs. 42.2# 1.23, 1.09-1.39 Pickled 8.8 vs. 12.8** 0.65, 0.49-0.86 54.9 vs. 54.3 1.06, 0.90-1.24 41.5 vs. 42.8 0.97, 0.82-1.14 vegetables Jam 14.0 vs. 12.4 1.05, 0.86-1.29 60.7 vs. 53.8# 1.33, 1.16-1.52 46.4 vs. 42.5* 1.14, 1.00-1.31 Smoked meat 12.3 vs. 12.6 0.96, 0.64-1.46 59.6 vs. 54.2 1.19, 0.91-1.56 49.4 vs. 42.6* 1.22, 0.93-1.60 Pepper/other 9.5 vs. 12.6 0.78, 0.50-1.21 54.7 vs. 54.3 0.96, 0.74-1.25 38.6 vs. 42.9 0.78, 0.59-1.03 spices (3) Beverage Juice 11.1 vs. 14.3# 0.75, 0.67-0.85 54.1 vs. 54.6 0.99, 0.92-1.07 42.0 vs. 43.7* 0.94, 0.87-1.01 Soft drinks 10.6 vs. 13.2# 0.78, 0.68-0.90 53.0 vs. 54.7 0.95, 0.87-1.03 40.3 vs. 43.5** 0.90, 0.83-0.99 Tea or coffee 6.9 vs. 12.7* 0.61, 0.33-1.12 54.0 vs. 54.3 1.06, 0.79-1.44 38.1 vs. 42.8 0.90, 0.66-1.24 (4) Fast food Chips 9.3 vs. 14.4# 0.69, 0.61-0.78 52.2 vs. 55.5# 0.90, 0.83-0.97 39.3 vs. 44.7# 0.85, 0.79-0.92 Fried chicken 9.8 vs. 12.9# 0.74, 0.61-0.90 56.2 vs. 54.1 1.12,1.00 -1.26 42.8 vs. 42.8 1.06, 0.95-1.19 French fries 9.7 vs. 13.5# 0.76, 0.66-0.88 53.4 vs. 54.6* 0.98, 0.90-1.06 39.7 vs. 43.8# 0.89, 0.81-0.97 Hamburger 8.6 vs. 13.0# 0.67, 0.54-0.84 53.6 vs. 54.4 1.00, 0.88-1.13 38.8 vs. 43.2** 0.89, 0.79-1.02 Instant noodle 8.4 vs. 12.9# 0.69, 0.53-0.87 51.9 vs. 54.5 0.90, 0.78-1.03 37.3 vs. 43.3# 0.81, 0.70-0.93 Pop corn 7.7 vs. 13.0# 0.65, 0.50-0.83 52.5 vs. 54.5 0.97, 0.85-1.12 36.4 vs. 43.3# 0.80, 0.69-0.92 a Prevalences of the disease/symptoms before and after “vs.” are corresponding to the options for different items. The latter options are references in the logistic regression analyses except for the specific indication. b AOR: adjusted odds ratio; CI: confidence interval. Adjusted factors included respondent of questionnaire, age, sex, and

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Table 7 Dose-response relationship between some selected factors and the prevalence of the studied diseases Allergic rhinitis, ever Rhinitis symptoms, ever Rhinitis symptoms, in last year Items Prevalence, Prevalence, Prevalence, a a AOR, 95%CI AOR, 95%CI AOR, 95%CIa n (%) n (%) n (%) (1) Duration of exclusive breastfeedingb > 6 months 139 (8.2) Reference 821 (47.8) Reference 602 (35.3) Reference 3-6 months 526 (12.7) 1.49, 1.21-1.84 2271 (54.0) 1.24, 1.10-1.39 1762 (42.3) 1.28, 1.13-1.45 < 3 months 552 (14.9) 1.71, 1.39-2.10 2136 (56.9) 1.34, 1.18-1.51 1732 (46.3) 1.43, 1.26-1.62 Never 165 (14.2)# 1.71, 1.32-2.22 640 (54.7) # 1.23, 1.05-1.44 511 (43.9) # 1.38, 1.18-1.62 c (2) Total number (n) of periods when new furniture was bought n=0 564 (11.3) Reference 2526 (50.3) Reference 1964 (39.2) Reference n=1 348 (13.0) 1.02, 0.87-1.19 1406 (52.3) 1.03, 0.94-1.14 1134 (42.4) 1.08, 0.98-1.19 n=2 141 (13.8) 1.02, 0.83-1.27 560 (54.2) 1.09, 0.95-1.26 451 (44.0) 1.11, 0.97-1.29 n≥3 82 (12.1)* 0.95,0.73-1.24 391 (57.5) # 1.27, 1.08-1.51 300 (44.5) # 1.19, 1.00-1.41 (3) Total number (n) of periods when the residence was renovatedc n=0 844 (11.7) Reference 3767 (51.8) Reference 2945 (40.6) Reference n=1 242 (13.6) 1.06, 0.90-1.25 964 (53.8) 1.06, 0.95-1.18 778 (43.6) 1.09, 0.98-1.22 n≥2 34 (13.5) 0.90, 0.61-1.32 145 (58.0) 1.10, 0.84-1.44 113 (46.3)* 1.07, 0.81-1.40 (4) Total number (n) of dampness indicators in the current residence d n=0 146 (9.1) Reference 736 (45.7) Reference 540 (33.7) Reference n=1 298 (11.5) 1.14, 0.91-1.43 1347 (51.5) 1.23, 1.08-1.41 1049 (40.3) 1.29, 1.12-1.48 n=2 277 (13.9) 1.31, 1.04-1.65 1130 (56.1) 1.38, 1.20-1.59 922 (46.2) 1.52, 1.32-1.76 n≥3 267 (15.1) # 1.35, 1.07-1.71 1077 (60.1) # 1.65, 1.42-1.90 884 (49.6) # 1.74, 1.50-2.02 (5) Total number (n) of dampness indicators in the early residence at the child’s birthe n=0 492 (10.1) Reference 2413 (49.0) Reference 1805 (37.0) Reference n=1 703 (13.4) 1.20, 1.06-1.37 2924 (55.3) 1.19, 1.10-1.29 2377 (45.3) 1.30, 1.19-1.41 n≥2 250 (16.6) # 1.48, 1.24-1.77 945 (62.3) 1.60, 1.41-1.81 746 (49.4) # 1.50, 1.33-1.70 f (6) Total number (n) of pets in the current residence n=0 1233 (12.1) Reference 5481 (53.4) Reference 4254 (41.8) Reference n=1 347(14.9) 1.14, 0.99-1.31 1331 (56.6) 1.10, 1.00-1.21 1073 (45.8) 1.12, 1.02-1.23 n≥2 25 (8.4) # 0.59, 0.38-0.90 161 (53.3)* 0.93, 0.73-1.18 130 (43.5)** 1.00, 0.78-1.29 f (7) Total number (n) of pets in the early residence at the child’s birth n=0 1376 (12.3) Reference 6057(53.6) Reference 4725 (42.2) Reference n=1 208 (15.0) 1.17, 0.99-1.39 804 (57.6) 1.13, 1.00-1.27 637 (45.9) 1.10, 0.98-1.24 n≥2 16 (8.2)** 0.59, 0.34-1.00 98 (50.0)** 0.81, 0.60-1.10 80 (40.8)* 0.88, 0.65-1.20 (8) Total number (n) of smokers in the current residence g n=0 695 (12.7) Reference 3004 (54.2) Reference 2352 (42.9) Reference n=1 696 (12.7) 1.03, 0.92-1.17 2980 (53.4) 0.98, 0.91-1.06 2338 (42.2) 0.99, 0.91-1.07 n≥2 193 (12.2) 1.00, 0.83-1.20 870 (54.8) 1.02, 0.91-1.15 685 (43.3) 1.04, 0.92-1.17 a AOR: Adjusted odds ratio; CI: Confidence Interval. Adjusted factors included the respondent of the questionnaire, age, sex, and family history of atopy. b Definition of exclusive breastfeeding was presented in

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Table S11. c The periods included one year before pregnancy, during pregnancy, during 0-1 year-old, and during ≥ 1 year-old. d The dampness indicators included water damage, damp clothing and/or bedding, mouldy odor, mould spots, damp stains, and windows pane condensation. e The dampness indicators included mouldy odor, mould spots or damp stains, and windows pane condensation. f Included cat, dog, bird, rabbit (hamster), fish (chelonian), and others. g Included father, mother, grandfather, grandmother, siblings, and others. * 0.01 ≤ p <0.05; ** 0.001 ≤ p <0.01; # p <0.001 in chi-square test.

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Table 8 Multiplicative interaction effect of some selected factors on the prevalence of the studied diseases Adjusted odds ratio (p-value)a

Items

TNFc

TRRd

TDI-CRe

TDI-ERf

TP-CRg

TP-ERh

TS-CRi

TS-ERj

(1) Doctor-diagnosed allergic rhinitis, ever EBFb

1.09 (0.066) 1.16 (0.089) 0.98 (0.572) 1.01 (0.886) 1.02 (0.983) 1.09 (0.358) 1.02 (0.693) 0.95 (0.454)

c

1.05 (0.500) 0.97 (0.462) 0.91 (0.071) 1.09 (0.236) 0.89 (0.205) 0.97 (0.615) 0.88 (0.081)

TNF

d

TRR

0.84 (0.024) 0.94 (0.555) 1.25 (0.064) 1.17 (0.261) 1.03 (0.752) 0.83 (0.181) e

0.94 (0.290) 1.04 (0.626) 1.03 (0.733) 1.09 (0.110) 0.98 (0.755)

f

TDI-ER

1.03 (0.764) 0.93 (0.509) 0.95 (0.388) 0.87 (0.116)

g

0.84 (0.106) 0.95 (0.516) 0.96 (0.742)

h

1.03 (0.814) 0.92 (0.558)

TP-CR

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TDI-CR

TP-ER

i

cr

TS-CR

(2) Rhinitis symptoms, ever

0.97 (0.788)

1.03 (0.302) 1.03 (0.578) 0.99 (0.620) 1.02 (0.114) 0.93 (0.164) 0.93 (0.208) 0.95 (0.109) 0.99 (0.792)

c

0.96 (0.399) 0.98 (0.528) 1.00 (0.929) 0.97 (0.510) 1.00 (0.942) 0.93 (0.031) 0.85 (0.001)

TNF

us

EBFb d

TRR

1.02 (0.718) 0.95 (0.441) 0.95 (0.575) 0.98 (0.838) 1.02 (0.714) 0.88 (0.155) e

0.98 (0.653) 1.03 (0.521) 1.03 (0.622) 1.04 (0.275) 0.98 (0.648)

an

TDI-CR

f

TDI-ER TP-CR

0.92 (0.182) 1.03 (0.709) 0.94 (0.159) 0.93 (0.184)

g

0.73 (<0.001) 0.97 (0.567) 0.99 (0.867)

h

TP-ER

0.93 (0.279) 1.00 (0.970)

M

i

TS-CR

(3) Rhinitis symptoms, in the last year

1.00 (0.974)

1.03 (0.402) 1.06 (0.306) 1.01 (0.816) 0.98 (0.615) 0.92 (0.112) 0.92 (0.176) 0.96 (0.262) 0.95 (0.269)

c

0.97 (0.485) 1.00 (0.855) 1.00 (0.963) 0.95 (0.263) 0.96 (0.489) 0.93 (0.027) 0.85 (0.001)

TNF

ed

EBFb d

TRR

1.04 (0.444) 0.92 (0.224) 0.90 (0.209) 0.95 (0.637) 1.03 (0.637) 0.87 (0.126) e

TDI-CR

0.95 (0.156) 1.03 (0.560) 1.07 (0.288) 0.99 (0.734) 1.07 (0.002)

TDI-ER TP-CR

g

h

TP-ER

i

TS-CR

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f

0.98 (0.731) 1.01 (0.875) 0.93 (0.075) 0.93 (0.184) 0.76 (<0.001) 0.96 (0.499) 0.96 (0.580) 0.95 (0.454) 1.00 (0.971) 0.99 (0.832)

Adjusted factors included the respondent of the questionnaire, age, sex, and family history of atopy.

b

Duration of exclusive breastfeeding (> 6 months vs. 3-6 months vs. < 3 months vs. Never).

c

Total number (n) of periods when new furniture was bought (n = 0 vs. n = 1 vs. n = 2 vs. n ≥ 3).

d

Total number (n) of periods when the residence was renovated (n = 0 vs. n = 1 vs. n ≥ 2).

e

Total number (n) of dampness indicators in the current residence (n = 0 vs. n = 1 vs. n = 2 vs. n ≥ 3).

f

Total number (n) of dampness indicators in the early residence at the child’s birth (n = 0 vs. n = 1 vs. n ≥ 2).

g

Total number (n) of pets in the current residence (n = 0 vs. n = 1 vs. n ≥ 2).

h

Total number (n) of pets in the early residence at the child’s birth (n = 0 vs. n = 1 vs. n ≥ 2).

Ac

a

i

Total number (n) of smokers in the current residence (n = 0 vs. n = 1 vs. n ≥ 2).

j

Whether parents smoked in the early residence at the child’s birth (yes vs. no).

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