Household dampness-related exposures in relation to childhood asthma and rhinitis in China: A multicentre observational study

Contents lists available at ScienceDirect

Environment International

journal homepage: www.elsevier.com/locate/envint

Household dampness-related exposures in relation to childhood asthma and rhinitis in China: A multicentre observational study

Jiao Cai ^a,b , Baizhan Li ^a,b,⁎ , Wei Yu ^a,b , Han Wang ^a,b , Chenqiu Du ^a,b , Yinping Zhang ^c , Chen Huang ^d , Zhuohui Zhao ^e , Qihong Deng ^f , Xu Yang ^g , Xin Zhang ^h , Hua Qian ⁱ , Yuexia Sun ^j , Wei Liu ^c ,

Juan Wang ^a,k , Qin Yang ^a,b , Fanbin Zeng ^a,b , Dan Norbäck ^k , Jan Sundell ^j

a

Joint International Research Laboratory of Green Buildings and Built Environments (Ministry of Education), Chongqing University, Chongqing, China

b

National Centre for International Research of Low-carbon and Green Buildings (Ministry of Science and Technology), Chongqing University, Chongqing, China

c

School of Architecture, Tsinghua University, Beijing, China

d

School of Environment and Architecture, University of Shanghai for Science and Technology, Shanghai, China

e

School of Public Health, Key Lab of Public Health Safety of the Ministry of Education, Key Lab of Health Technology Assessment, National Health and Family Planning Commission of the People's Republic of China, Fudan University, Shanghai, China

f

School of Public Health, Central South University, Changsha, Hunan, China

g

College of Life Sciences, Central China Normal University, Wuhan, China

h

Research Center for Environmental Science and Engineering, Shanxi University, Taiyuan, China

i

School of Energy and Environment, Southeast University, Nanjing, China

j

School of Environmental Science and Engineering, Tianjin University, Tianjin, China

k

Department of Medical Sciences, Occupational and Environmental Medicine, Uppsala University, Uppsala SE-751, Sweden

A R T I C L E I N F O

Handling Editor: Xavier Querol Keywords:

Home Dampness Asthma Rhinitis Children China

A B S T R A C T

During 2010–2012, we conducted an observational study on household environment and health outcomes among 40,010 preschool children from seven cities of China. Here we examined associations of six dampness- related indicators (visible mold spots, visible damp stains, damp clothing and/or bedding, water damage, condensation on windowpane, moldy odor) in the current residence and three dampness-related indicators (visible mold spots, condensation on windowpane, moldy odor) in the early residence with childhood asthma and rhinitis. In the multi-level logistic regression analyses, visible mold spots and visible damp stains in the current residence were significantly associated with the increased odds of doctor-diagnosed asthma and allergic rhinitis during lifetime-ever (adjusted odd ratios (AORs) range: 1.18 –1.35). All dampness-related indicators were signi ficantly associated with increased odds of wheeze and rhinitis during lifetime-ever and in the past 12 months (AORs range: 1.16–2.64). The cumulative numbers of damp indicators had positively dose-response relationships with the increased odds of the studied diseases. These associations for wheeze and rhinitis were similar between northern children and southern children. Similar results were found in the sensitive analyses among children without a family history of allergies and among children without asthma and allergic rhinitis.

For 3 –6 years-old children in mainland of China in 2011, we speculated that about 90,000 (2.02%) children with asthma and about 59,000 (1.09%) children with allergic rhinitis could be attributable to exposing to visible mold spots in the current residence. Our results suggested that early and lifetime exposures to household dampness indicators are risk factors for childhood asthma and rhinitis.

1. Introduction

Asthma and rhinitis are common pediatric diseases and their pre- valences have rapidly increased in the past years in the developing countries (Asher et al., 2006; Yangzong et al., 2012; Zhang et al., 2013;

Zhao et al., 2010; Huang et al., 2015). In China, prevalence of asthma in

3 –6-year-olds preschool children has increased from 1.7% in 1990 to 9.8% in 2011 (Zhang et al., 2013). The prevalence of allergic rhinitis among children 13–14-year-olds in Guangzhou and Beijing has in- creased from 2.9% and 6.0% in 1994 to 11.0% and 20.0% in 2009, respectively (Asher et al., 2006; Zhao et al., 2010). As the time for the increases in prevalences of these diseases are short, and genes have not

https://doi.org/10.1016/j.envint.2019.03.013

Received 3 January 2019; Received in revised form 5 March 2019; Accepted 6 March 2019

⁎

Corresponding author at: Joint International Research Laboratory of Green Buildings and Built Environments (Ministry of Education), Chongqing University, Chongqing 400045, China.

E-mail address: baizhanli@cqu.edu.cn (B. Li).

Available online 14 March 2019

0160-4120/ © 2019 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/BY/4.0/).

T

changed, changed environmental exposures should be responsible for these increases (Greiner et al., 2011; Martinez and Vercelli, 2013; Papi et al., 2018). Numerous studies have showed that pediatric asthma and rhinitis were associated with environmental exposures, especially those exposures in the homes where children spent > 80% of their lifetime (Papi et al., 2018; von Mutius, 2002; Turner, 2012; Reynolds and Finlay, 2017; Kim et al., 2013; Liu et al., 2014; Laborde et al., 2015;

Heinrich, 2011; Wang et al., 2016; Brunekreef and Holgate, 2002; Fan et al., 2017; Sundell, 2017; Diette et al., 2007).

Household dampness, which were commonly showed by visible mold spots, visible damp stains, water damage, condensation on win- dowpane, and mold odor, and have been suggested to be signi ficantly associated with pediatric asthma and rhinitis in many developed and developing countries (Bornehag et al., 2004a, 2004b, 2005, 2011; Hu et al., 2014; Mendell et al., 2011, 2018; Fisk et al., 2007;

Gunnbjörnsdottir et al., 2003; Jaakkola et al., 2005, 2013; Peat et al., 1998; Quansah et al., 2012; Tischer et al., 2011; Wang et al., 2013; Sun and Sundell, 2013; Shorter et al., 2018; Choi et al., 2014; Tham et al., 2007). However, it is still not clear that whether a causal relationship exist between household dampness and childhood asthma and rhinitis (Bornehag et al., 2011; Mendell et al., 2018). Some studies also suggest that such associations could be confounded by the parents-reported bias in cross-sectional studies or retrospective cohort studies by using self- administered questionnaire (Sun et al., 2009; Sun and Sundell, 2013;

Larsson et al., 2011; Naydenov et al., 2008). Speci fically, Bornehag et al. conducted a study of Dampness in Buildings and Health (DBH) and tried to find that what “dampness” is causative for asthma and allergies in Sweden (Naydenov et al., 2008; Hägerhed-Engman et al., 2009). The conclusion was that “dampness” was strongly associated with the reported health outcomes in the questionnaire studies, but the association disappeared in the follow up-studies. Several studies have reported that household dampness were signi ficantly associated with the increased odds of childhood asthma and allergies in China (Liu et al., 2014; Sun and Sundell, 2013; Sun et al., 2018; Li et al., 2014).

The same analyses from di fferent cities involved in the China, Children, Homes, Health (CCHH) study also had the similar findings ( Wang et al., 2013, 2014, 2015a, 2015b, 2016; Hu et al., 2014; Deng et al., 2016;

Qian et al., 2016; Zhao et al., 2013; Lin et al., 2015; Norbäck et al., 2018; Zhang et al., 2018a, 2018b). However, these findings in China were mostly based on the study that were done in one city or in a speci fic climate area. None study compared associations of household dampness with childhood asthma and allergies in di fferent climate areas.

In the present study, we merged data from seven cities involved in the CCHH study and analyzed the associations and dose-response re- lationships of household dampness-related exposures in different life- time durations and the increased odds of childhood asthma and rhinitis in di fferent climate areas of China. The seven cities could be divided into two typical groups according to their ambient climates: (i) hot- moist in summer and cold-moist in winter (southern cities: Shanghai, Nanjing, Changsha, and Chongqing); (ii) hot-dry in summer and cold- dry in winter (northern cities: Urumqi, Taiyuan, and Beijing) (Fig. 1).

We hypothesized that household dampness-related exposures could have significant associations and dose-response relationships with the increased odds of childhood asthma and allergies, and that these as- sociations could be different among children with dampness-related exposures in different lifetime durations and among children from di fferent climate areas. Besides, to the best knowledge, none studies quantitatively estimated burdens of asthma and rhinitis attributable to household dampness-related exposures, we also estimated population attributable fractions and numbers of children with the studied diseases due to the representative dampness-related exposures.

2. Materials and methods

2.1. Study design and subjects

This study is a part of the China, Children, Homes, Health (CCHH) study, which was conducted in China involving seven large cities from October 2010 to April 2012 (Fig. 1). Based on the parent-administered data, the main purpose of the CCHH study is to explore the associations of household environment with lifetime-ever (from the child's birth to the survey) and current (in the last year before the survey) asthma and rhinitis in preschool children. In each city, we used a standard ques- tionnaire that was validated by a pilot study in Chongqing, China (Zhang et al., 2013). Herein questions for pediatric asthma, allergies, and related symptoms were modified from the International Study on Asthma and Allergies in Childhood (ISAAC) (Asher et al., 1995).

Questions for home characteristics, family life habits, and indoor en- vironment were updated from the study of Dampness in Building and Health (DBH) in Sweden (Bornehag et al., 2004a) with consideration of the speci fic life habits and building characteristics in China. The study and procedure were approved by the Ethical Committee in the School of Public Health, Fudan University (International Registered Number:

IRB00002408&FWA00002399). We obtained the consent from all in- volved parents or legal guardians of the studied children before the survey.

A multistage cluster sampling method was used to select the sur- veyed kindergartens. First, we coded all districts in each city and ran- domly selected 4–6 districts by lottery. Second, we coded all kinder- gartens in each selected district and randomly selected 10 –15 kindergartens by lottery. We determined the total numbers of the se- lected districts and kindergartens according to the population size in each city. We excluded those kindergartens in the rural areas that far from the urban center because the CCHH study focused on urban/

suburban household environment. All children from the selected kin- dergartens were invited to participate in the survey. A total of > 200 kindergartens and 59,337 children were surveyed and 42,666 ques- tionnaires were responded (response rate: 71.9%). In the present study, data from 40,010 children 3–6 years-old were selected (Fig. 1). Data from 1784 children in other ages were excluded because of the small sample sizes and data from 872 children were excluded for that chil- dren missed information on age. For analyses with respect to both current (during the survey) residences and current health outcomes, all 40,010 children were included as the basic database for the descriptive and regression analyses. For analyses regarding either early residences or lifetime-ever health outcomes, we selected 24,503 children (64.8%

of the 40,010 children) who lived in the same residences since birth as the basic database for the regression analyses, to avoid the influence of residence changing on the studied associations. Regarding to the valid one child policy during our questionnaire survey, and most families only had one child.

2.2. Household dampness-related exposures

In this study, we analyzed dampness-related indicators in the early and current residences. Herein, indicators for the current residence included visible mold spots, visible damp stains, damp clothing and/or bedding, water damage, condensation on windowpanes in winter, and mold odor; indicators for the early residence included visible mold spots, condensation on windowpanes in winter, and mold odor.

Questions for these dampness-related indicators were presented in the

supplemental Table S1. These questions were derived from those of the

DBH study in Sweden (Bornehag et al., 2004a). These questions also

used in the similar studies in the Texas study of America (Sun et al.,

2013) and in the Tianjin, China (Sun and Sundell, 2013). These studies

have con firmed that the indicators can reflect household dampness-

related exposures. Besides, the validity of these questions had been

validated thorough the comparison of the reported indicators in the

cross-sectional survey and on-site inspection in Shanghai, China (Cai et al., 2016). We defined that child had the dampness-related exposure if a “yes” answer was responded to the corresponding question. To show the dose-response relationships between home dampness ex- posures and the studied diseases, we cumulated the numbers (n) of household dampness-related indicators in the early residence (range:

n = 0–3) and in the current residence (range: n = 0–6). Besides, if both the early and current residences had any dampness-related indicators, we de fined that these children had “both early and current” dampness- related exposures. The same de finitions were applied to “never”, “only early”, and “only current” dampness-related exposures.

2.3. Health outcomes

We analyzed six health outcomes regarding childhood asthma and rhinitis. The de finitions of these outcomes were as follows: (1) lifetime- ever asthma: child ever had doctor-diagnosed asthma from the child's birth to the survey; (2) lifetime-ever wheeze: child ever had chest wheezing or whistling symptom from the child's birth to the survey; (3) lifetime-ever allergic rhinitis: child ever had doctor-diagnosed allergic rhinitis from the child's birth to the survey; (4) lifetime-ever rhinitis:

child ever had a problem about sneezing, or a runny, or a stu ffy nose without a cold or the flu from the child's birth to the survey; (5) past 12 months wheeze: child ever had chest wheezing or whistling symptom in the past year before the survey; (6) past 12 months rhinitis:

child ever had sneezing, or a runny nose or a stuffy nose without a cold or chest infection in the past year before the survey. We have presented questions for these health outcomes in the supplemental Table S2. We de fined that child had the outcome if a “yes” answer was responded to the corresponding question.

2.4. Covariates

According to the published articles from the CCHH study (Wang et al., 2016; Deng et al., 2016; Qian et al., 2016; Liu et al., 2013; Zhang et al., 2018a, 2018b; Norbäck et al., 2018) and other existed literature (von Mutius, 2002; Turner, 2012; Bornehag et al., 2005; Mendell et al., 2018; Jaakkola et al., 2013; Choi et al., 2014), we considered the fol- lowing factors as covariates in the present study. These factors included

the child's sex (girls vs. boys) and age (3-year-olds vs. 4-year-olds vs. 5- year-olds vs. 6-year-olds), residence-located area (urban vs. suburban/

rural district), residence ownership (owner vs. renter), family history of allergic diseases (yes vs. no), duration of breastfeeding (≤6 vs. > 6 months), household renovation during the early lifetime (yes vs. no), and indoor environmental tobacco smoke (ETS, yes vs. no). Herein, if a child's father, mother, grandparents, or siblings had asthma or other allergic problems, we considered that the child had family history of allergic diseases. If a child's residence was renovated within one year before pregnancy, during pregnancy, during 0 –1-year-old, or after 1- year-old, we considered that the child had household renovation during early lifetime. Questions for these covariates were presented in the Supplemental Table S3.

2.5. Statistical methods

Both STATA 11.0 (STATA Corp., Texas, USA) and SPSS 20.0 (IBM Ltd., USA) were applied to conduct the statistical analyses. In the spe- cific analysis, we selected the children with complete data for all re- quired variables in the analysis. Because some information on different items was missed, the total numbers of children in the subgroups could be not equal to the total sample sizes. Pearson's chi-square test was applied to compare the prevalence differences of the studied pediatric diseases in the di fferent subgroups, stratified by covariates and house- hold dampness-related exposures. For association analyses, two-level (city and child) logistic regression models were used to investigate the adjusted associations and dose-response relationships among household dampness-related exposures and asthma, wheeze, allergic rhinitis, and rhinitis symptoms. Adjusted odd ratios (AORs) with 95% confidence intervals (CIs) were used to show the target associations. A two-tailed p- value < 0.05 was considered as statistical signi ficance for all statistical analyses.

We conducted a sub-analysis, with stratifying children from the

southern cities (Chongqing, Changsha, Nanjing, and Shanghai) and

northern cities (Urumqi, Taiyuan, and Beijing) of China, and in-

vestigated the dose-response relationships between household damp-

ness and asthma, wheeze, allergic rhinitis, and rhinitis among southern

and northern children. Through these analyses, we explored di fferences

in the target associations between southern cities and northern cities of

Fig. 1. Location distributions and sample sizes (N) of the seven cities that participated in the study (Green: Northern cities; Blue: Southern cities). (For interpretation

of the references to colour in this figure legend, the reader is referred to the web version of this article.)

China.

Furthermore, some studies reported that parents with family history of allergy and whose children were diagnosed asthma or allergic rhi- nitis may subjectively tend to reporting more household dampness-re- lated problems than others (Hu et al., 2014; Larsson et al., 2011;

Hägerhed-Engman et al., 2009). To reduce impact of the potential re- ported bias on the target associations, we also conducted sensitive analyses among children without family history of allergic diseases and among children without both diagnosed asthma and allergic rhinitis.

Besides, our previous analyses have shown that these dampness- related exposures had statistically significant correlation among all surveyed children (Table S4, correlation coe fficient r: 0.074–0.558), and among children without changing residences since birth (Table S5, correlation coefficient r: 0.057–0.561). Herein, the largest correlation coefficient (0.561) appeared between visible mold spots and visible damp stains in the current residence among children without changing residences since birth (Table S5). Therefore, in the present study, among the studied diseases that had significant associations with household visible mold spots, we estimated their burdens attributable to household visible mold spots, to represent the impact of household dampness-related exposure on these diseases. Due to potential mis- classi fication, ORs that we calculated in the logistic regression analyses could overestimate the actual relative risks (RRs) and population at- tributable fractions (PAFs) of household visible mold spots for the studied diseases. We estimated RR and PAF with using OR by the fol- lowing equations (Ezzati et al., 2004):

= − + ×

RR OR

(1 Prevalence) Prevalence OR (1)

=

f N

N

e

(2)

= × −

+ × −

f

PAF f (RR 1)

1 (RR 1) (3)

Herein, N

is the number of children who were exposed to house- hold visible mold spots. N is the total number of the surveyed children.

Then the numbers (n) of infants with the studied diseases due to household visible mold spots were estimated by the following equation:

= × ×

n PAF Prevalence N

(4)

Herein, N

is the national total number of children aged 3–6- years-old in mainland of China in 2011 (the year when most children were surveyed in this study), and is about 591,040,000 according to the China Statistical Yearbook (The National Bureau of Statistics of the People's Republic of China, 2012). By the same equations, we used 95%

CIs of ORs to estimate the corresponding 95% CIs of the infant numbers (n) with the studied diseases due to household visible mold spots.

3. Results

3.1. Demographic information

Among 40,010 children (Table 1), 51.9% children were boys and 75.9% children lived in the urban district; 35.1% and 30.9% children were 4 years old and 5 years old, respectively. Herein 20.0% children had family history of allergic diseases and 48.3% children were breastfed ≤6 months; 64.2% children's families owned the current re- sidences; 58.9% children had ETS exposure and 32.5% children had household renovation during early lifetime. Among 24,503 children (Table S6) without changing residence since birth, 78.2% children lived in the urban district, 68.5% children's families owned the current re- sidences, and 29.3% children had household renovation during early lifetime. The proportions of other items among children without changing residence since birth were similar with all surveyed 40,010 children (Tables 1 and S6).

3.2. Prevalences of the studied diseases

Among all surveyed children, 7.5%, 27.1%, 9.0%, and 54.9% chil- dren were reported lifetime-ever asthma, wheeze, allergic rhinitis, and rhinitis, respectively. A total of 20.1% and 41.2% children were re- spectively reported wheeze and rhinitis in the last year before the survey (Table 1). Prevalences of these diseases were similar among all surveyed children without changing residence since birth (Table S6).

From the Pearson's chi-square test (Table S7 and Table S8), we found that prevalences of these diseases were significantly higher among boys, children with family history of allergic diseases, children from families who had the ownership of the current residences, children breastfed ≤6 months, and children from families who renovated the residences during early lifetime. Children in 6 years old showed the highest prevalence of lifetime-ever asthma, allergic rhinitis, rhinitis, whereas children in 3 years old had the highest prevalence of past Table 1

Demographic information, covariates, and disease prevalences for all surveyed children.

Items Proportion or prevalence, n (%)

Total 40,010 (100.0)

Sex

Boys 20,684 (51.9)

Girls 19,176 (48.1)

Age

3-year-olds 7079 (17.7)

4-year-olds 14,041 (35.1)

5-year-olds 12,352 (30.9)

6-year-olds 6526 (16.3)

Residence-located area

Urban district 29,432 (75.9)

Suburban/rural district 9349 (24.1)

Family history of allergic diseases

Yes 7725 (20.0)

No 30,866 (80.0)

Residence ownership

Owner 24,838 (64.2)

Renter 13,866 (35.8)

Breastfeeding duration

≤6 months 18,847 (48.3)

> 6 months 20,192 (51.7)

Household environmental tobacco smoke

Yes 22,295 (58.9)

No 15,581 (41.1)

Household renovation during early lifetime

Yes 12,993 (32.5)

No 27,017 (67.5)

Doctor-diagnosed asthma during lifetime-ever

Yes 2942 (7.5)

No 36,068 (92.5)

Wheeze during lifetime-ever

Yes 10,532 (27.1)

No 28,355 (72.9)

Doctor-diagnosed allergic rhinitis during lifetime-ever

Yes 3471 (9.0)

No 35,084 (91.0)

Rhinitis during lifetime-ever

Yes 21,346 (54.9)

No 17,505 (45.1)

Wheeze in the last year before survey

Yes 7847 (20.1)

No 31,150 (79.9)

Rhinitis in the last year before survey

Yes 16,018 (41.2)

No 22,847 (58.8)

12 months wheeze and rhinitis. Urban children indicated signi ficantly higher prevalence of asthma, allergic rhinitis, and rhinitis than sub- urban/rural children did. Compared to children without ETS exposure, children with ETS exposure had signi ficant higher prevalences of wheeze and rhinitis.

3.3. Status of the household dampness-related exposures

For household dampness in the current residence among all sur- veyed children (Table 2), 6.4% and 11.4% children respectively ex- posed to visible mold spots and visible damp stains. A total of 2.2% and 30.0% children reported frequently and sometimes damp clothing and/

or bedding, respectively. A total of 6.7% and 7.5% children reported water damage in the residence in the past year before survey and before the past year respectively. A total of 6.9% and 15.8% children respec- tively had > 25 cm and 5 –25 cm condensation on windowpane in winter. A total of 0.7% and 9.3% children respectively exposed to fre- quently and sometimes moldy odor. For household dampness in the early residence among all surveyed children (Table 2), 1.5% and 12.0%

exposed to visible mold spots frequently and sometimes, respectively. A total of 9.5% and 40.8% children exposed to condensation on win- dowpane in winter frequently and sometimes, respectively. A total of 0.5% and 7.7% children exposed to moldy odor frequently and some- times, respectively. The proportions of children with different damp- ness-related exposures among children without changing residence since birth (Table S9) were also similar with all surveyed children.

3.4. Associations of household dampness with the studied diseases

In the Pearson's chi-square test (Table S10), children in any damp- ness-related exposure had significantly higher prevalences of all studied diseases than children without the dampness-related exposure, and all p-values in the Pearson's chi-square test for the prevalence di fferences were smaller than 0.001. Compared to children who sometimes exposed to the damp indicators, children frequently exposed to the damp in- dicators generally had higher prevalences of the studied diseases.

In the multi-level logistic regression analyses (Table 3), exposures to visible mold spots, visible damp stains, and damp clothing and/or bedding were signi ficantly associated with the increased odds of life- time-ever asthma (AOR range: 1.15 –1.40). The increased odds of life- time-ever asthma also were significantly associated with water damage in the current residence before the past year, condensation on win- dowpane in winter > 25 cm, sometimes exposed to moldy odor in the current residence and in the early residence, sometimes exposed to visible mold spots in the early residence, and frequently found con- densation on windowpane in winter in the early residences (AOR range:

1.20–1.44). Visible mold spots, visible damp stains, condensation on windowpane in winter in the current and early residences were sig- ni ficantly associated with the increased odds of allergic rhinitis during lifetime-ever (AOR range: 1.18 –1.46). Frequently exposed to damp clothing and/or bedding, water damage in the current residence before the past year, frequently exposed to moldy odor in the current re- sidence, and sometimes exposed to visible mold spots in the early re- sidence were significantly associated with the increased odds of allergic rhinitis during lifetime-ever (AOR range: 1.15 –1.73). Besides, all stu- died dampness exposures had signi ficant associations with the in- creased odds of lifetime-ever and current wheeze and rhinitis (AOR range: 1.16–2.64). Compared to children with sometimes exposing to the studied damp indicators, children with frequently exposing to the studied damp indicators also had higher odds of wheeze and rhinitis during lifetime-ever and in the last year before the survey.

The cumulative numbers of damp exposures in the current residence had signi ficant and positive dose-response relationships with the in- creased odds of all studied diseases except for lifetime-ever asthma (Fig. 2 and Table S11). The cumulative numbers of damp exposures in the early residence also had signi ficantly dose-response relationships with the increased odds of all studied diseases. Compared to children who only had early household dampness-related exposures or only had current household dampness-related exposures, childhood who had dampness exposures in both early and current residences had higher odds of the studied diseases.

3.5. Sensitive analyses of the studied associations

In the sensitive analysis among children without family history of allergic diseases (Fig. 3 and Table S12), about half of the associations between household dampness indicators and doctor-diagnosed asthma and allergic rhinitis were signi ficant (AOR range: 1.25–2.19). Most of the studied associations regarding to wheeze during lifetime and in the past 12 months were significant (AOR range: 1.24–2.97). All of the studied associations regarding to rhinitis during lifetime and in the past 12 months were signi ficant (AOR range: 1.18–2.91). Besides, the dose- response relationships between the cumulative numbers of damp in- dicators in the current or early residence and all studied diseases (ex- cept for asthma) were signi ficant ( Fig. 3).

In the sensitive analysis among children without doctor-diagnosed asthma and allergic rhinitis (Fig. 4 and Table S13), except for associa- tions of frequently exposure to visible mold spots with wheeze during lifetime-ever and in the past 12 months, all analyzed associations be- tween household dampness-related indicators and the increased odds of wheeze and rhinitis during lifetime-ever and in the past 12 months were signi ficant (AOR range: 1.13–3.29). All dose-response relationships between the cumulative numbers of damp exposures in the current or Table 2

Status of damp exposures in the current and early residences for all surveyed children.

Items Sample size, n (%)

1. Dampness-related indicators in the current residence (1) Visible mold spots

Yes 2410 (6.4)

No 35,332 (93.6)

(2) Visible damp stains

Yes 4346 (11.4)

No 33,701 (88.6)

(3) Damp clothing and/or bedding

Yes, frequently 849 (2.2)

Yes, sometimes 11,554 (30.0)

No, never 26,174 (67.8)

(4) Water damage

Yes, in the past year 2568 (6.7)

Yes, before the past year 2849 (7.5)

No, never 32,669 (85.8)

(5) Condensation on windowpane in winter

Yes, > 25 cm 2195 (6.9)

Yes, 5–25 cm 4994 (15.8)

Yes, < 5 cm 8470 (26.7)

No, never 16,031 (50.6)

(6) Moldy odor

Yes, frequently 247 (0.7)

Yes, sometimes 3383 (9.3)

No, never 32,674 (90.0)

2. Dampness-related indicators in the early residence (1) Visible mold spots

Yes, frequently 589 (1.5)

Yes, sometimes 4656 (12.0)

No, never 33,445 (86.4)

(2) Condensation on windowpane in winter

Yes, frequently 3667 (9.5)

Yes, sometimes 15,726 (40.8)

No, never 19,137 (49.7)

(3) Moldy odor

Yes, frequently 181 (0.5)

Yes, sometimes 2834 (7.7)

No, never 33,598 (91.8)

Table 3 Adjusted ORs, 95% CIs for associations between diseases and damp exposures in the two-level (city-child) logistic regression analyses. Items Adjusted OR, 95% CI (p -value)

Lifetime-ever

Past 12 months

Asthma Wheeze Allergic rhinitis Rhinitis Wheeze Rhinitis 1. Dampness-related indicators in the current residence (1) Visible mold spots (reference: No) Yes 1.35, 1.13 –1.62 (0.001) 1.45, 1.29 –1.63 (< 0.001) 1.19, 1.01 –1.42 (0.046) 1.42, 1.27 –1.59 (< 0.001) 1.53, 1.38 –1.69 (< 0.001) 1.46, 1.33 –1.60 (< 0.001) (2) Visible damp stains (reference: No) Yes 1.35, 1.17 –1.56 (< 0.001) 1.44, 1.31 –1.58 (< 0.001) 1.18, 1.03 –1.35 (0.017) 1.50, 1.37 –1.64 (< 0.001) 1.49, 1.38 –1.62 (< 0.001) 1.39, 1.30 –1.49 (< 0.001) (3) Damp clothing and/or bedding (reference: No, never) Yes, frequently 1.40, 1.02 –1.92 (0.036) 1.41, 1.15 –1.73 (0.001) 1.38, 1.03 –1.84 (0.031) 1.66, 1.36 –2.03 (< 0.001) 1.41, 1.18 –1.68 (< 0.001) 1.66, 1.43 –1.94 (< 0.001) Yes, sometimes 1.15, 1.03 –1.29 (0.015) 1.40, 1.30 –1.50 (< 0.001) 1.00, 0.89 –1.11 (0.957) 1.36, 1.28 –1.45 (< 0.001) 1.44, 1.36 –1.53 (< 0.001) 1.31, 1.25 –1.38 (< 0.001) (4) Water damage (reference: No, never) Yes, in the past year 1.11, 0.91 –1.37 (0.304) 1.28, 1.14 –1.45 (< 0.001) 1.16, 0.97 –1.39 (0.110) 1.38, 1.23 –1.55 (< 0.001) 1.29, 1.16 –1.43 (< 0.001) 1.31, 1.20 –1.43 (< 0.001) Yes, before the past year 1.25, 1.04 –1.49 (0.015) 1.36, 1.22 –1.52 (< 0.001) 1.27, 1.08 –1.49 (0.004) 1.33, 1.19 –1.47 (< 0.001) 1.33, 1.21 –1.47 (< 0.001) 1.16, 1.06 –1.26 (0.001) (5) Condensation on windowpane in winter (reference: No, never) Yes, > 25 cm 1.43, 1.16 –1.76 (0.001) 1.47, 1.28 –1.69 (< 0.001) 1.46, 1.19 –1.78 (< 0.001) 1.35, 1.19 –1.53 (< 0.001) 1.55, 1.38 –1.74 (< 0.001) 1.51, 1.37 –1.67 (< 0.001) Yes, 5– 25 cm 0.98, 0.82 –1.16 (0.785) 1.33, 1.20 –1.47 (< 0.001) 1.24, 1.06 –1.44 (0.007) 1.18, 1.08 –1.29 (< 0.001) 1.36, 1.25 –1.48 (< 0.001) 1.38, 1.28 –1.48 (< 0.001) Yes, < 5 cm 1.08, 0.94 –1.24 (0.302) 1.32, 1.21 –1.43 (< 0.001) 1.24, 1.09 –1.41 (0.001) 1.22, 1.13 –1.31 (< 0.001) 1.39, 1.29 –1.49 (< 0.001) 1.28, 1.21 –1.36 (< 0.001) (6) Moldy odor (reference: No, never) Yes, frequently 1.53, 0.89 –2.61 (0.123) 2.27, 1.60 –3.22 (< 0.001) 1.73, 1.06 –2.80 (0.027) 1.93, 1.32 –2.82 (0.001) 2.23, 1.67 –2.97 (< 0.001) 1.60, 1.21 –2.11 (0.001) Yes, sometimes 1.33, 1.12 –1.58 (0.001) 1.58, 1.42 –1.76 (< 0.001) 1.07, 0.90 –1.27 (0.445) 1.61, 1.45 –1.78 (< 0.001) 1.65, 1.51 –1.80 (< 0.001) 1.43, 1.32 –1.54 (< 0.001) 2. Dampness-related indicators in the early residence

(1) Visible mold spots (reference: No, never) Yes, frequently 1.16, 0.75 –1.80 (0.495) 1.32, 1.01 –1.71 (0.039) 1.41, 0.96 –2.06 (0.080) 1.69, 1.31 –2.19 (< 0.001) 1.33, 1.00 –1.76 (0.048) 1.57, 1.23 –2.00 (< 0.001) Yes, sometimes 1.20, 1.03 –1.40 (0.019) 1.59, 1.45 –1.74 (< 0.001) 1.17, 1.02 –1.35 (0.028) 1.50, 1.37 –1.64 (< 0.001) 1.64, 1.49 –1.81 (< 0.001) 1.39, 1.27 –1.51 (< 0.001) (2) Condensation on windowpane in winter (reference: No, never) Yes, frequently 1.44, 1.21 –1.70 (< 0.001) 1.64, 1.47 –1.83 (< 0.001) 1.41, 1.20 –1.65 (< 0.001) 1.50, 1.35 –1.66 (< 0.001) 1.62, 1.44 –1.82 (< 0.001) 1.65, 1.50 –1.83 (< 0.001) Yes, sometimes 1.06, 0.95 –1.19 (0.321) 1.32, 1.23 –1.41 (< 0.001) 1.15, 1.04 –1.28 (0.009) 1.24, 1.17 –1.31 (< 0.001) 1.34, 1.25 –1.44 (< 0.001) 1.24, 1.17 –1.32 (< 0.001) (3) Moldy odor (reference: No, never) Yes, frequently 1.39, 0.69 –2.80 (0.352) 2.64, 1.67 –4.17 (< 0.001) 1.79, 0.98 –3.26 (0.058) 2.23, 1.33 –3.73 (0.002) 2.58, 1.63 –4.10 (< 0.001) 1.95, 1.23 –3.09 (< 0.001) Yes, sometimes 1.31, 1.08 –1.58 (0.006) 1.74, 1.55 –1.95 (< 0.001) 1.09, 0.90 –1.32 (0.377) 1.71, 1.52 –1.92 (< 0.001) 1.90, 1.68 –2.14 (< 0.001) 1.47, 1.31 –1.64 (< 0.001)

Adjusted for the child's sex, age, residence-located area, residence ownership, family history of allergic diseases, breastfeeding duration, hou sehold renovation during early lifetime and indoor environmental tobacco smoke (ETS);

For children who lived in the same residences since birth;

For all children except for dampness-related indicators in the early residence.

early residence and wheeze and rhinitis were also signi ficant ( Fig. 4).

In the sub-analyses with respect to northern children and southern children (Fig. 5, Table S14, and Table S15), most associations of the damp exposures in the current and early residence with the increased odds of pediatric wheeze and rhinitis during lifetime-ever and in the past 12 months were statistically signi ficant (AOR range: 1.19–4.25 for northern children; 1.14 –2.29 for southern children), whereas we found few significant associations of the damp exposures in the current and early residence with the increased odds of doctor-diagnosed asthma and allergic rhinitis during lifetime-ever (AOR range:1.44 –3.65 for northern children; 1.16–1.53 for southern children). The dose-response re- lationships between the cumulative numbers of damp indicators in the current residence and wheeze and rhinitis had no notable di fferences in southern cities and in northern cities (Fig. 5). However, the dose-re- sponse relationship between the cumulative numbers of damp in- dicators in the current residence and lifetime-ever asthma and allergic rhinitis in southern cities were stronger than in northern cities. We found the similar results regarding the early residence and regarding the cumulative damp-related indicators in the early residences and in the current residences (Table S14, Table S15). The dose-response re- lationship between the cumulative damp exposures in the early and current residence and lifetime-ever asthma in southern cities were stronger than in northern cities.

3.6. Disease burdens attributed to visible mold spots

Table 4 shows population attributable fraction and number to household visible mold spots in the current residence among 3 to 6 years-old children in 2011 in mainland of China. Specifically, about 90,000 (2.02%) children with lifetime-ever asthma, about 295,000 (1.89%) children with lifetime-ever wheeze, about 59,000 (1.09%) children with lifetime-ever allergic rhinitis, about 319,000 (0.98%) children with lifetime-ever rhinitis, about 2,291,000 (2.45%) children with wheeze in the last year, and > 354,000 (1.46%) children with rhinitis in the last year, could be attributable to exposing to visible mold spots in the current residence.

4. Discussion

4.1. Main findings

In this multicentre cross-sectional study, we found that different

kinds of the damp indicators in the current residence and in the early

residences had signi ficant associations with the increased odds of pe-

diatric asthma, wheeze, allergic rhinitis, and rhinitis. The cumulative

numbers of the damp indicators had significant dose-response re-

lationships with the increased odds of almost all studied diseases in the

overall analyses and in the sensitive analyses. Except for lifetime-ever

asthma and allergic rhinitis, these dose-response relationships had no

Fig. 2. Dose-response relationships between the cumulative numbers of damp indicators in the current and early residence and odds of the studied diseases in the

two-level (city-child) logistic regression analyses (reference: n = 0). AOR, adjusted odds ratio; CI, con fidence interval. The adjusted factors included the child's sex,

age, residence-located area, family history of allergic diseases, residence ownership, breastfeeding duration, household environmental tobacco smoke (ETS), and

household renovation during early lifetime. The supplemental Table S11 presented the detailed data for AORs and their 95% CIs.

substantial di fferences between northern children and southern chil- dren. Children who had early and current dampness-related indicators generally had higher odds of the studied diseases than children who only had early or current dampness-related exposures. Among 3 –6 years-old children in mainland of China in 2011, about 90,000 (2.02%) children with asthma and about 59,000 (1.09%) children with allergic rhinitis could be attributable to exposing to visible mold spots in the current residence.

4.2. Comparisons of our findings to the previous studies

Our findings with respect to associations of household dampness- related exposures with childhood asthma, wheeze, and rhinitis were consistent with many previous studies (Bornehag et al., 2004b, 2005, 2011; Hu et al., 2014; Mendell et al., 2011, 2018; Tischer et al., 2011;

Wang et al., 2013; Choi et al., 2014; Tham et al., 2007; Naydenov et al., 2008). Specifically, the DBH study in Sweden found that water leakage, floor moisture, visible mold spots, visible damp stains, and condensa- tion on windowpane in winter > 5 cm were significantly associated with pediatric asthma, wheeze, and rhinitis among children from 1 to 6 years old (Bornehag et al., 2004a, 2005). Bornehag and colleagues reviewed the related original studies conducted before 2004 and con- cluded that ORs for associations of home dampness exposures with childhood asthma and wheeze ranged from 1.4 to 2.2 (Bornehag et al., 2004b). This range of ORs is similar with the present study. A meta- analysis of eight European birth-cohort studies on associations between

household visible mold spots and childhood allergic disorders reported that household exposures to mold during early lifetime were associated with asthma in preschool children and were associated with allergic rhinitis in school-age children (Tischer et al., 2011). Mendell and col- leagues also conducted a series of reviews on the same topic in di fferent years, and found that household dampness-related exposures had con- sistent and significant associations with the development of asthma and rhinitis, and their related allergic symptoms (Mendell et al., 2011, 2018). In summary, these findings suggest that early and current household dampness exposures are risk factors for childhood asthma and rhinitis.

Besides, our findings regarding dose-response relationships of household dampness exposures and odds of the studied diseases were consistent with several previous studies (Hu et al., 2014; Fisk et al., 2007; Shorter et al., 2018; Hsu et al., 2010; Norbäck et al., 2013;

Weinmayr et al., 2013). Specifically, a field study of 97 children aged

4 –7-year-olds in Taiwan found that the severe growth of household

visible mold had signi ficant and positive dose-response relationships

with the total serum IgE concentrations of these children (Hsu et al.,

2010). The European Community Respiratory Health Survey (ECRHS)

indicated that household damp indicators (water damage and indoor

mold) had a dose-response effect on the new onset of asthma among

young adults from 12 European countries (Norbäck et al., 2013). A

case-control study for 150 children aged 1 –7-year-olds and with new-

onset wheeze in New Zealand found that household visible mold and

mold odor consistently and positively dose-depended the increased

Fig. 3. Dose-response relationships between the cumulative numbers of damp indicators in the current and early residence and odds of the studied diseases in the

two-level (city-child) logistic regression analyses (reference: n = 0), among children without family history of allergic diseases. AOR, adjusted odds ratio; CI,

confidence interval. The adjusted factors included the child's sex, age, residence-located area, residence ownership, breastfeeding duration, household environmental

tobacco smoke (ETS), and household renovation during early lifetime. The supplemental Table S12 presented the detailed data for AORs and their 95% CIs.

odds of new-onset wheeze (ORs ranged from 1.30 to 3.56) (Shorter et al., 2018). These consistent dose-response relationships in different studies seemingly suggest that household dampness-related exposures had causal relationships with childhood wheeze and rhinitis. Based on these dose-response relationships, the observation-based metrics for e ffect of household dampness on childhood respiratory health also could be developed (Mendell and Kumagai, 2017).

4.3. Regional differences of the studied associations

In China, the climate conditions between northern cities and southern cities had notable differences. The northern cities normally had a temperate monsoon climate with hot-rainy summer and cold-dry winters, whereas the southern cities normally had a subtropical mon- soon climate with hot-rainy summer and mild-humid winter. Generally, the southern cities had more rain and warmer than the northern cities.

These climate di fferences could lead differences in the indoor air climate (temperature and relative humidity) between northern cities and southern cities, thus could increase differences in the status of household dampness-related exposures which had strong associations with air temperature and relative humidity. As our analyses (Table S16 and Table S17) showed, the proportions of families who reported household dampness exposures were substantially higher in southern cities than northern cities.

However, a novel result we found in the present study was that, although household dampness-related exposures in northern cities and in southern cities had notable differences, the positive dose-response relationships of these indicators and odds of wheeze and rhinitis had no obvious di fferences between children from southern cities and children from northern cities of China. This finding was inconsistent with our hypothesis that these associations could be different among children from di fferent climate areas. It was supported by findings in several systematic reviews that evidences of household dampness-related ex- posures in the inducing asthma and allergic rhinitis and exacerbating their related symptoms were generally consistent in the studies from di fferent countries or regions ( Mendell et al., 2011, 2018; Fisk et al., 2007; Jaakkola et al., 2013; Tischer et al., 2011). These findings suggest that ambient climate could have little impact on associations of early and current household dampness-related exposures on childhood wheeze and rhinitis. However, due to the data limitation, we were not able to analyze the modification effect of different indicators for am- bient climate on these associations directly. More related studies were warranted.

Fig. 4. Dose-response relationships between the cumulative numbers of damp indicators in the current and early residence and odds of the studied diseases in the two-level (city-child) logistic regression analyses (reference: n = 0), among children without both doctor-diagnosed asthma and allergic rhinitis. AOR, adjusted odds ratio; CI, con fidence interval. The adjusted factors included the child's sex, age, residence-located area, family history of allergic diseases, re- sidence ownership, breastfeeding duration, household environmental tobacco smoke (ETS), and household renovation during early lifetime. The supple- mental Table S13 presented the detailed data for AORs and their 95% CIs.

Fig. 5. Dose-response relationships between the cu- mulative numbers of damp indicators in the current residence and odds of the studied diseases in the two- level (city-child) logistic regression analyses (re- ference: n = 0), stratified by northern cities and southern cities. AOR, adjusted odds ratio; CI, con- fidence interval; na, not available. The adjusted factors included the child's sex, age, residence-lo- cated area, family history of allergic diseases, re- sidence ownership, breastfeeding duration, house- hold environmental tobacco smoke (ETS), and household renovation during early lifetime. The supplemental Tables S14 and Table S15 presented the detailed data for AORs and their 95% CIs. The presented data in the figure were upper limits of 95%

CIs and the presented datum in the parenthesis was

AOR for the corresponding column.

4.4. Disease burdens for household dampness-related exposures

Another new contribution in the present study was that we quan- titatively estimated burdens (indicated by population attributable fractions and numbers) of childhood asthma, wheeze, and rhinitis at- tributable to current household visible mold spots, which had sig- nificant correlations with other dampness-related indicators and had significant associations with all the studied diseases in overall analyses (Table 4). Although the population attributable fractions were rela- tively small (ranged from 0.98% to 2.45%), the attributable numbers (ranged from 59,006 to 354,371) of children with the studied diseases due to household visible mold spots were large, with consideration of the huge population base in China. These analyses indicate that avoiding household dampness-related exposures could have substantial bene fits in reducing the numbers of children with asthma, wheeze, and rhinitis in China.

4.5. Limitations and strength

This study had some limitations. First, The ISAAC questionnaires about childhood health outcomes were used for 6 –7 years-old and 13–14 years-old children, whereas the surveyed children in the present study were 3 –6 years-old. The health data we collected by these ques- tionnaires could have deviation from the real situation, although the validation of these questionnaires has been confirmed in a previous study (Zhang et al., 2013). Second, some household dampness-related indicators, such as condensation on window pane and moldy odor, might have strong relationship with the season when the questionnaire survey was conducted. We did not consider the survey season during our analyses. These analyses also could have certain deviation from the real situation. Third, in the analyses with respect to dose-response re- lationship, we calculated dampness score with assuming that each in- dicator has the same importance. These processes had limitations, since our analyses (Table 3) shows that different dampness-related indicators could be associated with childhood asthma and rhinitis to different extent. Fourth, although several covariates were considered, there are perhaps other factors that could confound or modify the studied asso- ciations. These factors mainly include maternal medication and nutri- tion (Beckhaus et al., 2015), the child's dietary habits (Andrusaityte et al., 2017), as well as ambient air pollution (Liu et al., 2016; Kan et al., 2012). Fifth, as some previous studies reported (Larsson et al., 2011; Sun and Sundell, 2013), the significant associations could be confounded by the potential over-reporting of household dampness- related exposures that parents were aware of before our survey.

Namely, if parents had a sick child and considered that household damp indicators were risk factors for asthma and rhinitis, they might report more of these indicators, then ORs in our association analyses could be over-estimated.

However, parents' knowledge of e ffects of household damp in- dicators on childhood asthma and allergies could be limited in China. In Sweden, before the DBH study, a large information campaign with the

theme of risk factors for asthma and related allergies was conducted a few years ago (Larsson et al., 2011). None such campaign has ever happened in China. Therefore, our findings in the present study prob- ably were not confounded by the parents' reported bias. In the sensitive analyses among children with lower potential reported bias (children without family history of allergic diseases and children without both doctor-diagnosed asthma and allergic rhinitis), we also found that most of the target associations were significant and strong. These analyses and results could further con firm that household dampness-related exposures were strong risk factors for childhood asthma and related symptoms. While a follow-up study in China are highly warranted to conduct to further test these findings. Besides, our study had large sample size and high response rate. Our studied cities had different economic-development levels, ambient climates, and family lifestyles.

Findings in our study could have high representation of the status in China.

5. Conclusions

Current and early household dampness exposures, especially the continuous household dampness exposures (both current and early), are risk factors for childhood asthma, wheeze, and rhinitis in China.

Ambient climate (hot-moist in summer and cold-moist in winter vs. hot- dry in summer and cold-dry in winter) could have little impact on as- sociations of these exposures on childhood wheeze and rhinitis. To avoid household dampness-related exposures could be an available method to substantially prevent children getting asthma, wheeze, and rhinitis in China.

Acknowledgments

The research was financially supported by the National Key Research and Development Program of China (2017YFC0702700), the Natural Science Foundation of China (Grant no. 51561135002) and the 111 Project (Grant no. B13041). We sincerely appreciate all the tea- chers, children, parents, and others who were involved in the study.

Appendix A. Supplementary data

Supplementary data to this article can be found online at https://

doi.org/10.1016/j.envint.2019.03.013.

References

Andrusaityte, S., Grazuleviciene, R., Petraviciene, I., 2017. Effect of diet and maternal education on allergies among preschool children: a case-control study. Environ. Res.

159, 374–380.

Asher, M.I., Keil, U., Anderson, H.R., Beasley, R., Crane, J., Martinez, F., Mitchell, E.A., Pearce, N., Sibbald, B., Stewart, A.W., 1995. International study of asthma and al- lergies in childhood (ISAAC): rationale and methods. Eur. Respir. J. 8, 483–491.

Asher, M.I., Montefort, S., Björkstén, B., Lai, C.K., Strachan, D.P., Weiland, S.K., Williams, H., ISAAC Phase Three Study Group, 2006. Worldwide time trends in the prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and eczema in childhood: ISAAC Table 4

Population fraction of the studied diseases attributed to visible mold spots in the current residence in 3 –6-years-old children in mainland of China.

Disease Relative risk (95% CI)

Population attributable fraction (95%

CI)

Total number of children with disease

Attributable number for visible mold spots (95% CI)

Lifetime-ever

Asthma 1.32 (1.12–1.55) 2.02% (0.76%–3.50%) 4,491,904 90,563 (34,195–157,282)

Wheeze 1.30 (1.20–1.40) 1.89% (1.27%–2.54%) 15,603,456 295,624 (197,988–397,010)

Allergic rhinitis 1.17 (1.01–1.37) 1.09% (0.06%–2.35%) 5,437,568 59,006 (3157–127,778)

Rhinitis 1.15 (1.11–1.20) 0.98% (0.67%–1.28%) 32,625,408 318,940 (219,808–416,320)

Past 12 months

Wheeze 1.38 (1.28–1.48) 2.45% (1.81%–3.10%) 11,879,904 290,973 (214,466–368,115)

Rhinitis 1.23 (1.17–1.28) 1.46% (1.09%–1.81%) 24,350,848 354,371 (266,209–440,846)

a

According to adjusted odds ratio in the two-level logistic regression analyses (Table 4). CI, con fidence interval.

phases one and three repeat multicountry cross-sectional surveys. Lancet 368, 733–743.

Beckhaus, A.A., Garcia-Marcos, L., Forno, E., Pacheco-Gonzalez, R.M., Celedón, J.C., Castro-Rodriguez, J.A., 2015. Maternal nutrition during pregnancy and risk of asthma, wheeze, and atopic diseases during childhood: a systematic review and meta- analysis. Allergy 70, 1588–1604.

Bornehag, C.G., Sundell, J., Sigsgaard, T., 2004a. Dampness in buildings and health (DBH): report from an ongoing epidemiological investigation on the association be- tween indoor environmental factors and health effects among children in Sweden.

Indoor Air 14, 59–66.

Bornehag, C.G., Sundell, J., Bonini, S., Custovic, A., Malmberg, P., Skerfving, S., Sigsgaard, T., Verhoeff, A., 2004b. Dampness in buildings as a risk factor for health effects, EUROEXPO: a multidisciplinary review of the literature (1998–2000) on dampness and mite exposure in buildings and health effects. Indoor Air 14, 243–257.

Bornehag, C.G., Sundell, J., Hagerhad-Engman, L., Sigsggard, T., Janson, S., Aberg, N., DBH Study Group, 2005. “Dampness” at home and its association with airway, nose and skin symptoms among 10,851 preschool children in Sweden: a cross-sectional study. Indoor Air 15, 48–55.

Bornehag, C.G., Blomquist, G., Gyntelberg, F., Jarvholm, B., Malmberg, P., 2011.

Dampness in buildings and health. Indoor Air 11, 72–86.

Brunekreef, B., Holgate, S.T., 2002. Air pollution and health. Lancet 360, 1233–1242.

Cai, J., Liu, W., Huang, C., Wang, X.Y., Shen, L., Zou, Z.J., Hu, Y., Sun, C.J., Wei, X.Y., Chang, J., Zhao, Z.H., Sun, Y.X., Sundell, J., 2016. Validity of subjective ques- tionnaire in evaluating dwelling characteristics, home dampness, and indoor odors in Shanghai, China: cross-sectional survey and on-site inspection. Energ. Buildings 127, 1019–1027.

Choi, J., Chun, C., Sun, Y., Choi, Y., Kwon, S., Bornehag, C.G., Sundell, J., 2014.

Associations between building characteristics and children's allergic symptoms: a cross-sectional study on child's health and home in Seoul, South Korea. Build.

Environ. 75, 176–181.

Deng, Q., Lu, C., Ou, C., Chen, L., Yuan, H., 2016. Preconceptional, prenatal and postnatal exposure to outdoor and indoor environmental factors on allergic diseases/symptoms in preschool children. Chemosphere 152, 459–467.

Diette, G.B., Hansel, N.N., Buckley, T.J., Curtin-Brosnan, J., Eggleston, P.A., Matsui, E.C., McCormack, M.C., Williams, D.L., Breysse, P.N., 2007. Home indoor pollutant ex- posures among inner-city children with and without asthma. Environ. Health Perspect. 115, 1665–1669.

Ezzati, M., Lopez, A.D., Rodgers, A., Murray, C.J.L., 2004. Comparative quantification of health risks. World Health Organization, Geneva.

Fan, G., Xie, J., Yoshino, H., Yanagi, U., Hasegawa, K., Kagi, N., Liu, J., 2017.

Environmental conditions in homes with healthy and unhealthy schoolchildren in Beijing, China. Build. Environ. 112, 270–284.

Fisk, W.J., Lei-Gomez, Q., Mendell, M.J., 2007. Meta-analyses of the associations of re- spiratory health effects with dampness and mold in homes. Indoor Air 17, 284–296.

Greiner, A.N., Hellings, P.W., Rotiroti, G., Scadding, G.K., 2011. Allergic rhinitis. Lancet 378, 2112–2122.

Gunnbjörnsdottir, M.I., Norbäck, D., Plaschke, P., Norrman, E., Björnsson, E., Janson, C., 2003. The relationship between indicators of building dampness and respiratory health in young Swedish adults. Respir. Med. 97, 302–307.

Hägerhed-Engman, L., Bornehag, C.G., Sundell, J., 2009. Building characteristics asso- ciated with moisture related problems in 8,918 Swedish dwellings. Int. J. Environ.

Health Res. 19, 251–265.

Heinrich, J., 2011. Influence of indoor factors in dwellings on the development of childhood asthma. Int. J. Hyg. Environ. Health 214, 1–25.

Hsu, N.Y., Wang, J.Y., Su, H.J., 2010. A dose-dependent relationship between the severity of visible mold growth and IgE levels of pre-school-aged resident children in Taiwan.

Indoor Air 20, 392–398.

Hu, Y., Liu, W., Huang, C., Zou, Z.J., Zhao, Z.H., Shen, L., Sundell, J., 2014. Home dampness, childhood asthma, hay fever, and airway symptoms in Shanghai, China:

associations, dose–response relationships, and lifestyle's influences. Indoor Air 24, 450–463.

Huang, C., Liu, W., Hu, Y., Zou, Z., Zhao, Z., Shen, L., Weschler, L.B., Sundell, J., 2015.

Updated prevalences of asthma, allergy, and airway symptoms, and a systematic review of trends over time for childhood asthma in Shanghai, China. PLoS One 10, e0121577.

Jaakkola, J.J., Hwang, B.F., Jaakkola, N., 2005. Home dampness and molds, parental atopy, and asthma in childhood: a six-year population-based cohort study. Environ.

Health Perspect. 113, 357–361.

Jaakkola, M.S., Quansah, R., Hugg, T.T., Heikkinen, S.A., Jaakkola, J.J., 2013.

Association of indoor dampness and molds with rhinitis risk: a systematic review and meta-analysis. J. Allergy Clin. Immunol. 132, 1099–1110.

Kan, H.D., Chen, R.J., Tong, S.L., 2012. Ambient air pollution, climate change, and po- pulation health in China. Environ. Int. 42, 10–19.

Kim, K.H., Jahan, S.A., Kabir, E., 2013. A review on human health perspective of air pollution with respect to allergies and asthma. Environ. Int. 59, 41–52.

Laborde, A., Tomasina, F., Bianchi, F., Bruné, M.N., Buka, I., Comba, P., Corra, L., Cori, L., Duffert, C.M., Harari, R., Iavarone, I., McDiarmid, M.A., Gray, K.A., Sly, P.D., Soares, A., Suk, W.A., Landrigan, P.J., 2015. Children's health in Latin America: the influence of environmental exposures. Environ. Health Perspect. 123, 201–209.

Larsson, M., Hägerhed-Engman, L., Moniruzzaman, S., Janson, S., Sundell, J., Bornehag, C.G., 2011. Can we trust cross-sectional studies when studying the risk of moisture- related problems indoor for asthma in children? Int. J. Environ. Health Res. 21, 237–247.

Li, A., Sun, Y., Liu, Z., Xu, X., Sun, H., Sundell, J., 2014. The influence of home en- vironmental factors and life style on children's respiratory health in Xi'an. Chin. Sci.

Bull. 59, 2024–2030.

Lin, Z., Zhao, Z., Xu, H., Zhang, X., Wang, T., Kan, H., Norback, D., 2015. Home dampness signs in association with asthma and allergic diseases in 4618 preschool children in Urumqi, China-the influence of ventilation/cleaning habits. PLoS One 10, e0134359.

Liu, W., Huang, C., Hu, Y., Zou, Z., Sundell, J., 2013. Associations between indoor en- vironmental smoke and respiratory symptoms among preschool children in Shanghai, China. Chin. Sci. Bull. 58, 4211–4216.

Liu, F., Zhao, Y., Liu, Y.Q., Liu, Y., Sun, J., Huang, M.M., Liu, Y., Dong, G.H., 2014.

Asthma and asthma related symptoms in 23,326 Chinese children in relation to in- door and outdoor environmental factors: the Seven Northeastern Cities (SNEC) study.

Sci. Total Environ. 497–498, 10–17.

Liu, W., Huang, C., Hu, Y., Fu, Q., Zou, Z., Sun, C., Shen, L., Wang, X., Cai, J., Pan, J., Huang, Y., Chang, J., Sun, Y., Sundell, J., 2016. Associations of gestational and early life exposures to ambient air pollution with childhood respiratory diseases in Shanghai, China: a retrospective cohort study. Environ. Int. 92–93, 284–293.

Martinez, F.D., Vercelli, D., 2013. Asthma. Lancet 382, 1360–1372.

Mendell, M.J., Kumagai, K., 2017. Observation-based metrics for residential dampness and mold with dose-response relationships to health: a review. Indoor Air 27, 506–517.

Mendell, M.J., Mirer, A.G., Cheung, K., Tong, M., Douwes, J., 2011. Respiratory and al- lergic health effects of dampness, mold, and dampness-related agents: a review of the epidemiologic evidence. Environ. Health Perspect. 119, 748–756.

Mendell, M.J., Macher, J.M., Kumagai, K., 2018. Measured moisture in buildings and adverse health effects: a review. Indoor Air 28, 488–489.

Naydenov, K., Melikov, A., Markov, D., Stankov, P., Bornehag, C.G., Sundell, J., 2008. A comparison between occupants' and inspectors' reports on home dampness and their association with the health of children: the ALLHOME study. Build. Environ. 43, 1840–1849.

Norbäck, D., Zock, J.P., Plana, E., Heinrich, J., Svanes, C., Sunyer, J., Künzli, N., Villani, S., Olivieri, M., Soon, A., Jarvis, D., 2013. Mould and dampness in dwelling places, and onset of asthma: the population-based cohort ECRHS. Occup. Environ. Med. 70, 325–331.

Norbäck, D., Lu, C., Wang, J., Zhang, Y., Li, B., Zhao, Z., Huang, C., Zhang, X., Qian, H., Sun, Y., Sundell, J., Deng, Q., 2018. Asthma and rhinitis among Chinese children- indoor and outdoor air pollution and indicators of socioeconomic status (SES).

Environ. Int. 115, 1–8.

Papi, A., Brightling, C., Pedersen, S.E., Reddel, H.K., 2018. Asthma. Lancet 391, 783–800.

Peat, J.K., Dickerson, J., Li, J., 1998. Effects of damp and mould in the home on re- spiratory health: a review of the literature. Allergy 53, 120–128.

Qian, H., Zheng, X., Zhang, M., Weschler, L., Sundell, J., 2016. Associations between parents' perceived air quality in homes and health among children in Nanjing, China.

PLoS One 11, e0155742. https://doi.org/10.1371/journal.pone.0155742.

Quansah, R., Jaakkola, M.S., Hugg, T.T., Heikkinen, S.A.M., Jaakkola, J.J., 2012.

Residential dampness and molds and the risk of developing asthma: a systematic review and meta-analysis. PLoS One 7, e47526.

Reynolds, L.A., Finlay, B.B., 2017. Early life factors that affect allergy development. Nat.

Rev. Immunol. 17, 518–528.

Shorter, C., Crane, J., Pierse, N., Barnes, P., Kang, J., Wickens, K., Douwes, J., Stanley, T., Täubel, M., Hyvärinen, A., Howden-Chapman, P., 2018. Wellington region general practitioner research network. Indoor visible mold and mold odor are associated with new-onset childhood wheeze in a dose-dependent manner. Indoor Air 28, 6–15.

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., Zhang, Y., Sundell, J., Fan, Z., Bao, L., 2009. Dampness at dorm and its asso- ciations with allergy and airways infection among college students in China: a cross- sectional study. Indoor Air 19, 174–182.

Sun, Y., Hou, J., Kong, X., Zhang, Q., Wang, P., Weschler, L.B., Sundell, J., 2018.

“Dampness” and “dryness”: what is important for children's allergies? A cross-sec- tional study of 7366 children in northeast Chinese homes. Build. Environ. 139, 38–45.

Sundell, J., 2017. Reflections on the history of indoor air science, focusing on the last 50 years. Indoor Air 27, 708–724.

Tham, K.W., Zuraimi, M.S., Koh, D., Chew, F.T., Ooi, P.L., 2007. Associations between home dampness and presence of molds with asthma and allergic symptoms among young children in the tropics. Pediatr. Allergy Immunol. 18, 418–424.

The National Bureau of Statistics of the People's Republic of China, 2012. China Statistical Yearbook 2012. http://www.stats.gov.cn/tjsj/ndsj/2012/indexch.htm, Accessed date: 8 March 2019.

Tischer, C.G., Hohmann, C., Thiering, E., Herbarth, O., Müller, A., Henderson, J., Granell, R., Fantini, M.P., Luciano, L., Bergström, A., Kull, I., Link, E., von Berg, A., Kuehni, C.E., Strippoli, M.P.F., Gehring, U., Wijga, A., Eller, E., Bindslev-Jensen, C., Keil, T., Heinrich, J., as part of the ENRIECO consortium, 2011. Meta-analysis of mould and dampness exposure on asthma and allergy in eight European birth cohorts: an ENRIECO initiative. Allergy 66, 1570–1579.

Turner, S., 2012. Environmental exposures and respiratory outcomes in children.

Paediatr. Respir. Rev. 13, 252–257.

von Mutius, E., 2002. Environmental factors influencing the development and progression of pediatric asthma. J. Allergy Clin. Immunol. 109, S525–S532.

Wang, H., Li, B., Yang, Q., Yu, W., Wang, J., Liu, Y., Ou, Y., Sundell, J., 2013. 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, J., Li, B., Yu, W., Yang, Q., Wang, H., Huang, D., Sundell, J., Norbäck, D., 2014.

Rhinitis symptoms and asthma among parents of preschool children in relation to the home environment in Chongqing, China. PLoS One 9, e94731.

Wang, H., Li, B., Yu, W., Wang, J., Norbäck, D., 2015a. Early-life exposure to home

dampness associated with health effects among children in Chongqing, China. Build.

Environ. 94, 327–334.

Wang, L., Qu, F., Zhang, Y., Weschler, L.B., Sundell, J., 2015b. Home environment in relation to allergic rhinitis among preschool children in Beijing, China: a cross-sec- tional study. Build. Environ. 93, 54–63.

Wang, X., Liu, W., Hu, Y., Zou, Z.J., Shen, L., Huang, C., 2016. Home environment, lifestyles behaviors, and rhinitis in childhood. Int. J. Hyg. Environ. Health 219, 220–231.

Weinmayr, G., Gehring, U., Genuneit, J., Büuchele, G., Kleiner, A., Siebers, R., Wickens, K., Crane, J., Brunekreef, B., Strachan, D.P., the ISAAC Phase Two Study Group, 2013. Dampness and moulds in relation to respiratory and allergic symptoms in children: results from phase two of the international study of asthma and allergies in childhood (ISAAC phase two). Clin. Exp. Allergy 43, 762–774.

Yangzong, Y., Shi, Z., Nafstad, P., Häheim, L.L., Luobu, O., Bjertness, E., 2012. The prevalence of childhood asthma in China: a systematic review. BMC Public Health 12, 860–869.

Zhang, Y., Li, B., Huang, C., Yang, X., Qian, H., Deng, Q., Zhao, Z., Li, A., Zhao, J., Zhang, X., Qu, F., Hu, Y., Yang, Q., Wang, J., Zhang, M., Wang, F., Zheng, X., Lu, C., Liu, Z., Sun, Y., Mo, J., Zhao, Y., Liu, W., Wang, T., Norbäck, D., Bornehag, C.G., Sundell, J.,

2013. Ten cities cross-sectional questionnaire survey of children asthma and other allergies in China. Chin. Sci. Bull. 58, 4182–4189.

Zhang, X., Norbäck, D., Fan, Q., Bai, X., Li, T., Zhang, Y., Li, B., Zhao, Z., Huang, C., Deng, Q., Lu, C., Qian, H., Yang, X., Sun, Y., Sundell, J., Wang, J., 2018a. Dampness and mold in homes across China: associations with rhinitis, ocular, throat and dermal symptoms, headache and fatigue among adults. Indoor Air 1–13. https://doi.org/10.

1111/ina.12517.

Zhang, J., Sun, C., Liu, W., Zou, Z., Zhang, Y., Li, B., Zhao, Z., Deng, Q., Yang, X., Zhang, X., Qian, H., Sun, Y., Sundell, J., Huang, C., 2018b. Associations of household re- novation materials and periods with childhood asthma, in China: a retrospective cohort study. Environ. Int. 113, 240–248.

Zhao, J., Bai, J., Shen, K., Xiang, L., Huang, S., Chen, A., Huang, Y., Wang, J., Ye, R., 2010. Self-reported prevalence of childhood allergic diseases in three cities of China:

a multicenter study. BMC Public Health 10, 551.

Zhao, Z.H., Zhang, X., Liu, R.R., Norback, D., Wieslander, G., Chen, J., Sundell, J., 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 (34),

4245–4251.