Carl-Gustaf Bornehag

The association between asthma and allergic symptoms in children and phthalates in house dust : a nested case-control study

Global phthalate ester production has increased from very low levels at the end of World War II to approximately 3.5 million metric tons/year. The aim of the present study was to investigate potential associations between persistent allergic symptoms in children, which have increased markedly in developed countries over the past three decades, and the concentration of phthalates in dust collected from their homes. This investigation is a case–control study nested within a cohort of 10,852 children. From the cohort, we selected 198 cases with persistent allergic symptoms and 202 controls without allergic symptoms. A clinical and a technical team investigated each child and her or his environment. We found higher median concentrations of butyl benzyl phthalate (BBzP) in dust among cases than among controls (0.15 vs. 0.12 mg/g dust). Analyzing the case group by symptoms showed that BBzP was associated with rhinitis (p = 0.001) and eczema (p = 0.001), whereas di(2-ethylhexyl) phthalate (DEHP) was associated with asthma (p = 0.022). Furthermore, dose–response relationships for these associations are supported by trend analyses. This study shows that phthalates, within the range of what is normally found in indoor environments, are associated with allergic symptoms in children. We believe that the different associations of symptoms for the three major phthalates—BBzP, DEHP, and di-n-butyl phthalate—can be explained by a combination of chemical physical properties and toxicologic potential. Given the phthalate exposures of children worldwide, the results from this study of Swedish children have global implications.

Phthalates in indoor dust and their association with building characteristics

In a recent study of 198 Swedish children with persistent allergic symptoms and 202 controls without such symptoms, we reported associations between the symptoms and the concentrations of n-butyl benzyl phthalate (BBzP) and di(2-ethylhexyl) phthalate (DEHP) in dust taken from the childrens’ bedrooms. In the present study we examined associations between the concentrations of different phthalate esters in the dust from these bedrooms and various characteristics of the home. The study focused on BBzP and DEHP because these were the phthalates associated with health complaints. Associations have been examined using parametric and nonparametric tests as well as multiple logistic regression. For both BBzP and DEHP, we found associations between their dust concentrations and the amount of polyvinyl chloride (PVC) used as flooring and wall material in the home. Furthermore, high concentrations of BBzP (above median) were associated with self-reported water leakage in the home, and high concentrations of DEHP were associated with buildings constructed before 1960. Other associations, as well as absence of associations, are reported. Both BBzP and DEHP were found in buildings with neither PVC flooring nor wall covering, consistent with the numerous additional plasticized materials that are anticipated to be present in a typical home. The building characteristics examined in this study cannot serve as complete proxies for these quite varied sources. However, the associations reported here can help identify homes where phthalate concentrations are likely to be elevated and can aid in developing mitigation strategies.

The Association between Phthalates in Dust and Allergic Diseases among Bulgarian Children

Background Recent studies have identified associations between the concentration of phthalates in indoor dust and allergic symptoms in the airways, nose, and skin. Objectives Our goal was to investigate the associations between allergic symptoms in children and the concentration of phthalate esters in settled dust collected from children’s homes in Sofia and Burgas, Bulgaria. Methods Dust samples from the child’s bedroom were collected. A total of 102 children (2–7 years of age) had symptoms of wheezing, rhinitis, and/or eczema in preceding 12 months (cases), and 82 were nonsymptomatic (controls). The dust samples were analyzed for their content of dimethyl phthalate (DMP), diethyl phthalate (DEP), di-n-butyl phthalate (DnBP), butyl benzyl phthalate (BBzP), di(2-ethylhexyl) phthalate (DEHP), and di-n-octyl phthalate (DnOP). Results A higher concentration of DEHP was found in homes of case children than in those of controls (1.24 vs. 0.86 mg/g dust). The concentration of DEHP was significantly associated with wheezing in the preceding 12 months (p = 0.035) as reported by parents. We found a dose–response relationship between DEHP concentration and case status and between DEHP concentration and wheezing in the preceding 12 months. Conclusions This study shows an association between concentration of DEHP in indoor dust and wheezing among preschool children in Bulgaria.

Day care attendance and increased risk for respiratory and allergic symptoms in preschool age

Background:  The reported impact of day‐care attendance on respiratory and atopic symptoms has varied between studies from different countries. Regarding to the ‘hygiene‐hypothesis’, day‐care attendance may lead to less sensitization later in life, but the question still is whether day‐care attendance and subsequent exposure to more frequent early infections is a risk or a protection against future allergic disease or asthma (atopic and nonatopic).

Predicted risk of childhood allergy, asthma, and reported symptoms using measured phthalate exposure in dust and urine

UNLABELLED   The associated risk of phthalate exposure, both parent compounds in the home and their metabolites in urine, to childhood allergic and respiratory morbidity, after adjusting for exposures of indoor pollutants, especially bioaerosols, was comprehensively assessed. Levels of five phthalates in settled dust from the homes of 101 children (3-9 years old) were measured, along with their corresponding urinary metabolites. Other environmental risk factors, including indoor CO2, PM2.5, formaldehyde, 1,3-β-D-glucan, endotoxin, allergen and fungal levels, were concomitantly examined. Subjects health status was verified by pediatricians, and parents recorded observed daily symptoms of their children for the week that the home investigation visit took place. Significantly increased level of benzylbutyl phthalate, in settled dust, was associated with test case subjects (allergic or asthmatic children). Higher levels of dibutyl phthalate and its metabolites, mono-n-butyl phthalate, and mono-2-ethylhexyl phthalate were found to be the potential risk factors for the health outcomes of interest. Similarly, indoor fungal exposure remained a significant risk factor, especially for reported respiratory symptoms. The relative contribution from exposure to phthalates and indoor biocontaminants in childhood allergic and respiratory morbidity is, for the first time, quantitatively assessed and characterized. PRACTICAL IMPLICATIONS For asthmatic and allergic children living in subtropical and highly developed environments like homes in Taiwan, controlling environmental exposure of phthalates may be viewed as equally important as avoiding indoor microbial burdens, for the management of allergy-related diseases. It is also recognized that multidisciplinary efforts will be critical in realizing the true underlying mechanisms associated with these observations.

Prenatal Phthalate Exposures and Anogenital Distance in Swedish Boys

Background: Phthalates are used as plasticizers in soft polyvinyl chloride (PVC) and in a large number of consumer products. Because of reported health risks, diisononyl phthalate (DiNP) has been introduced as a replacement for di(2-ethylhexyl) phthalate (DEHP) in soft PVC. This raises concerns because animal data suggest that DiNP may have antiandrogenic properties similar to those of DEHP. The anogenital distance (AGD)—the distance from the anus to the genitals—has been used to assess reproductive toxicity. Objective: The objective of this study was to examine the associations between prenatal phthalate exposure and AGD in Swedish infants. Methods: AGD was measured in 196 boys at 21 months of age, and first-trimester urine was analyzed for 10 phthalate metabolites of DEP (diethyl phthalate), DBP (dibutyl phthalate), DEHP, BBzP (benzylbutyl phthalate), as well as DiNP and creatinine. Data on covariates were collected by questionnaires. Results: The most significant associations were found between the shorter of two AGD measures (anoscrotal distance; AGDas) and DiNP metabolites and strongest for oh-MMeOP [mono-(4-methyl-7-hydroxyloctyl) phthalate] and oxo-MMeOP [mono-(2-ethyl-5-oxohexyl) phthalate]. However, the AGDas reduction was small (4%) in relation to more than an interquartile range increase in DiNP exposure. Conclusions: These findings call into question the safety of substituting DiNP for DEHP in soft PVC, particularly because a shorter male AGD has been shown to relate to male genital birth defects in children and impaired reproductive function in adult males and the fact that human levels of DiNP are increasing globally. Citation: Bornehag CG, Carlstedt F, Jönsson BA, Lindh CH, Jensen TK, Bodin A, Jonsson C, Janson S, Swan SH. 2015. Prenatal phthalate exposures and anogenital distance in Swedish boys. Environ Health Perspect 123:101–107; http://dx.doi.org/10.1289/ehp.1408163

Pet‐keeping in early childhood and airway, nose and skin symptoms later in life

Background: It is discussed whether exposure to pets during childhood is a risk or a protective factor for sensitization and allergic symptoms. The aim of this study was to investigate the association between pet‐keeping at time of birth and allergic symptoms in airways, nose and skin among young children in Sweden.

Common household chemicals and the allergy risks in pre-school age children.

Background The risk of indoor exposure to volatile organic compounds (VOCs) on allergic airway diseases in children remains unknown. Objective We examined the residential concentrations of VOCs, emitted from building materials, paints, furniture, and other lifestyle practices and the risks of multiple allergic diseases as well as the IgE-sensitization in pre-school age children in Sweden. Methods In a case-control investigation (198 case children with asthma and allergy and 202 healthy controls), air samples were collected in the room where the child slept. The air samples were analyzed for the levels of eight classes of VOCs. Results A natural-log unit of summed propylene glycol and glycol ethers (PGEs) in bedroom air (equal to interquartile range, or 3.43 – 15.65 µg/m3) was associated with 1.5-fold greater likelihood of being a case (95% CI, 1.1 – 2.1), 1.5-fold greater likelihood of asthma (95% CI, 1.0 – 2.3), 2.8-fold greater likelihood of rhinitis (95% CI, 1.6 – 4.7), and 1.6-fold greater likelihood of eczema (95% CI, 1.1 – 2.3), accounting for gender, secondhand smoke, allergies in both parents, wet cleaning with chemical agents, construction period of the building, limonene, cat and dog allergens, butyl benzyl phthalate (BBzP), and di(2-ethylhexyl)phthalate (DEHP). When the analysis was restricted to the cases, the same unit concentration was associated with 1.8-fold greater likelihood of IgE-sensitization (95% CI, 1.1 – 2.8) compared to the non-IgE sensitized cases. No similar associations were found for the other classes of VOCs. Conclusion We propose a novel hypothesis that PGEs in indoor air exacerbate and/or induce the multiple allergic symptoms, asthma, rhinitis and eczema, as well as IgE sensitization respectively.

PVC flooring is related to human uptake of phthalates in infants

UNLABELLED Polyvinyl chloride (PVC) flooring material contains phthalates, and it has been shown that such materials are important sources for phthalates in indoor dust. Phthalates are suspected endocrine-disrupting chemicals (EDCs). Consecutive infants between 2 and 6 months old and their mothers were invited. A questionnaire about indoor environmental factors and family lifestyle was used. Urinary metabolites of the phthalates diethyl phthalate (DEP), dibutyl phthalate (DBP), butylbenzyl phthalate (BBzP), and dietylhexyl phthalate (DEHP) were measured in the urine of the children. Of 209 invited children, 110 (52%) participated. Urine samples were obtained from 83 of these. Urine levels of the BBzP metabolite monobenzyl phthalate (MBzP) was significantly higher in infants with PVC flooring in their bedrooms (P < 0.007) and related to the body area of the infant. Levels of the DEHP metabolites MEHHP (P < 0.01) and MEOHP (P < 0.04) were higher in the 2-month-old infants who were not exclusively breast-fed when compared with breast-fed children. The findings indicate that the use of soft PVC as flooring material may increase the human uptake of phthalates in infants. Urinary levels of phthalate metabolites during early life are associated with the use of PVC flooring in the bedroom, body area, and the use of infant formula. PRACTICAL IMPLICATIONS This study shows that the uptake of phthalates is not only related to oral uptake from, for example, food but also to environmental factors such as building materials. This new information should be considered when designing indoor environment, especially for children.

PVC--as flooring material--and its association with incident asthma in a Swedish child cohort study.

UNLABELLED The Dampness in Buildings and Health study (DBH) started in the year 2000 in Värmland, Sweden, with a baseline questionnaire sent to all children (n = 14,077) aged 1-6. Five years later, a follow-up questionnaire was sent to the children who were 1-3 years at baseline. A total of 4779 children participated in both the baseline and the follow-up studies and constitute the study population in this cohort study. The aim of this study was to examine the association between exposure to PVC-flooring in the childs and parents bedroom in homes of children aged 1-3 and the incidence of asthma, rhinitis, and eczema during the following 5-year period. Adjusted analyses showed that the incidence of asthma among children was associated with PVC-flooring in the childs bedroom (AOR 1.52; 95% CI 0.99-2.35) and in the parents bedroom (1.46; 0.96-2.23). The found risks were on borderline of significance and should therefore be interpreted with caution. There was further a positive relationship between the number of rooms with PVC-flooring and the cumulative incidence of asthma. PVC-flooring was found to be a stronger risk factor for incident asthma in multifamily homes when compared with single-family houses and in smoking families compared with non-smoking families and in women. PRACTICAL IMPLICATIONS These longitudinal data from the DBH study found an association between the presence of PVC-flooring in the home and incident asthma in children. However, earlier results from the DBH study have shown that PVC-flooring is one important source for phthalates in indoor dust, and exposure to such phthalates was found to be associated with asthma and allergy among children. This emphasizes the need for prospective studies that focus on the importance of prenatal and neonatal exposure to phthalates in the development of asthma and allergy in children.