BPA & childhood asthma
14th Jun, 2022

BPA and childhood asthma

 

According to a new meta-analysis, prenatal exposure to Bisphenol A (BPA) is associated with an increased risk of asthma and wheezing in school-aged girls (1).

Global paediatric asthma prevalence has increased significantly over the last 40 years, and asthma is now the most reported non-communicable disease among children worldwide (2). Several factors including diet, lifestyle, genetics, and environmental factors (microbial exposure, exposure to passive smoking and air pollution) are believed to underlie this trend (3,4). More recently, there is increasing evidence that early-life chemical exposures may significantly impact the development of the immune system and increase the risk of asthma and allergies in children (5,6,7).

BPA, a common endocrine-disrupting chemical, has gained attention recently for its ubiquitous exposure and potential health effects, including carcinogenesis, neurogenesis, reproductive effects and immunotoxicity (8,9). It is produced in large quantities (>7 million tons per year worldwide) and is used in the manufacture of polycarbonate plastics (e.g. toys, water bottles, dental sealants) or epoxy resins (coating the insides of cans for beverages and food) (1). The European Chemicals Agency (ECHA) included BPA on its list of substances of "very high concern" in 2017 (10). Consequently, some countries have limited its use, leading manufacturers to replace BPA with other bisphenols with suspected similar toxicity (11).

Although BPA in infant feeding bottles has been banned or voluntarily phased out in some countries, it is still used in plastic toys and other items used by infants and young children, and international biomonitoring studies confirm that >90% of children in the United States, Europe, Asia, and Australia are exposed to BPA (12). In addition, children typically have elevated exposures and higher serum concentrations of BPA than adults due to their low metabolic capacity, higher intestinal absorption, lower body size to surface area and food/water intake ratios, object-to-mouth activities, and maternal exposure through placenta and breastfeeding (12,13,14,15,16).

The early life stages (from conception to age two years) are critical windows of growth and development, and prenatal BPA exposure has been shown to affect offspring immune function in experimental studies (13,14). Due to the presence of oestrogen receptors in immunomodulatory cells, BPA has been shown to influence immune responses by acting as a xenoestrogen  to promote T-helper type 2 cell responses, with increased cytokines (interleukin (IL)-4, −5, and −13), and immunoglobin (Ig) E production (15,16,17,18,19). These responses are characteristic of allergic asthma. Animal models have also shown that BPA can affect pulmonary function and cause airway inflammation (20). However, epidemiological data regarding associations between prenatal BPA exposure and asthma are limited.

The current meta-analysis included eight studies, analysing urine samples taken during pregnancy from 3,007 women from six European countries (Spain, France, Greece, Norway, the Netherlands, and the United Kingdom) collected between 1999 and 2010, and questionnaire and spirometry data on the respiratory health of their offspring collected between 7- and 11-years age.

Analysis of the urine samples revealed a high prevalence of BPA, found in 90% of the samples. The substitute bisphenols, bisphenol F (BPF) and bisphenol S (BPS), were less prevalent and were only detected in 27% and 49% of samples, respectively. This finding was probably due to the study being conducted before these chemicals became widely available.

This study revealed an association in girls between concentrations of BPA in maternal urine during pregnancy and an increased risk of asthma and wheezing at school age. Among girls, each doubling in BPA concentration during pregnancy was associated with a 13% increased risk of having current asthma, and a 14% increased risk of wheeze.

However, no association was observed between prenatal BPA exposure and lung function in school-aged boys or girls. Furthermore, there was no association between BPA exposure and asthma or wheezing in boys, or BBF and BPS exposure and respiratory health in boys and girls.

Previous studies have demonstrated an association between changing oestrogen levels (endogenous and xenoestrogen s) and asthma (21,22,23,24). The sexual dimorphism of asthma is especially observed in periods of hormonal imbalance such as puberty, pregnancy, and menopause (21). Given the endocrine-disrupting capacity of bisphenols, and their ability to alter key hormone-signalling pathways, they may be able to induce changes in sex hormones and immune function, which may partly explain the sex-specific results found in this study.

The meta-analysis includes cross-sectional studies, and the findings are limited to single samples to measure BPA exposure and therefore are not capable of establishing a causal relationship between BPA and childhood asthma or wheeze. Regardless, the meta-analysis builds on existing evidence linking prenatal or early childhood BPA exposure to respiratory symptoms and other health conditions. Further research is needed to assess temporal variabilities in bisphenol exposure concerning health outcomes and provide data to improve chemical regulation.

Furthermore, the findings highlight the need for minimising BPA exposure to reduce adverse health risks. Tips for reducing BPA exposure include avoiding plastic containers with numbers 3 and 7, avoiding tetra pack liquids, eating less canned food, and choosing ceramic, stainless steel, or glass re-usable containers where possible, especially for hot food and liquids.

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References
1Abellan A, Mensink-Bout SM, Garcia-Esteban R, Beneito A, Chatzi L, Duarte-Salles T, Fernandez MF, Garcia-Aymerich J, Granum B, Iñiguez C, Jaddoe VW. In utero exposure to bisphenols and asthma, wheeze, and lung function in school-age children: a prospective meta-analysis of 8 European birth cohorts. Environment International. 2022 Apr 1;162:107178.
2Dooley AA, Pillai DK. Paediatric obesity-related asthma: Disease burden and effects on pulmonary physiology. Paediatric respiratory reviews. 2021 Mar 1;37:15-7.
3Noutsios GT, Floros J. Childhood asthma: causes, risks, and protective factors; a role of innate immunity. Swiss medical weekly. 2014 Dec 15(51).
4Miller RL, Lawrence J. Understanding root causes of asthma. Perinatal environmental exposures and epigenetic regulation. Annals of the American Thoracic Society. 2018 Apr;15(Supplement 2):S103-8.
5Qi C, Xu CJ, Koppelman GH. The role of epigenetics in the development of childhood asthma. Expert review of clinical immunology. 2019 Dec 2;15(12):1287-302.
6DeWitt JC, Patisaul HB. Endocrine disruptors and the developing immune system. Current Opinion in Toxicology. 2018 Aug 1;10:31-6.
7Popescu M, Feldman TB, Chitnis T. Interplay Between Endocrine Disruptors and Immunity: Implications for Diseases of Autoreactive Etiology. Frontiers in pharmacology. 2021 Mar 23;12:165.
8Ma Y, Liu H, Wu J, Yuan L, Wang Y, Du X, Wang R, Marwa PW, Petlulu P, Chen X, Zhang H. The adverse health effects of bisphenol A and related toxicity mechanisms. Environmental research. 2019 Sep 1;176:108575.
9Kapustka K, Ziegmann G, Klimecka-Tatar D, Ostrega M. Identification of health risks from harmful chemical agents-review concerning bisphenol A in workplace. Production Engineering Archives. 2020;26.
10Beausoleil C, Emond C, Cravedi JP, Antignac JP, Applanat M, Appenzeller BR, Beaudouin R, Belzunces LP, Canivenc-Lavier MC, Chevalier N, Chevrier C. Regulatory identification of BPA as an endocrine disruptor: Context and methodology. Molecular and cellular endocrinology. 2018 Nov 5;475:4-9.
11Bousoumah R, Leso V, Iavicoli I, Huuskonen P, Viegas S, Porras SP, Santonen T, Frery N, Robert A, Ndaw S. Biomonitoring of occupational exposure to bisphenol A, bisphenol S and bisphenol F: A systematic review. Science of the Total Environment. 2021 Aug 20;783:146905.
12Healy BF, English KR, Jagals P, Sly PD. Bisphenol A exposure pathways in early childhood: Reviewing the need for improved risk assessment models. Journal of exposure science & environmental epidemiology. 2015 Nov;25(6):544-56.
13Ghassabian, A., Vandenberg, L., Kannan, K., & Trasande, L. (2022). Endocrine-Disrupting Chemicals and Child Health. Annual Review of Pharmacology and Toxicology, 62, 573–594.
14Lite, C., Raja, G. L., Juliet, M., Sridhar, V. V., Subhashree, K. D., Kumar, P., Chakraborty, P., & Arockiaraj, J. (2022). In utero exposure to endocrine-disrupting chemicals, maternal factors and alterations in the epigenetic landscape underlying later-life health effects. Environmental Toxicology and Pharmacology, 89(November 2021), 103779.
15Mehlsen A, Høllund L, Boye H, Frederiksen H, Andersson AM, Bruun S, Husby S, Jensen TK, Timmermann CA. Pregnancy exposure to bisphenol A and duration of breastfeeding. Environmental research. 2022 Apr 15;206:112471.
16Lee J, Choi K, Park J, Moon HB, Choi G, Lee JJ, Suh E, Kim HJ, Eun SH, Kim GH, Cho GJ. Bisphenol A distribution in serum, urine, placenta, breast milk, and umbilical cord serum in a birth panel of mother–neonate pairs. Science of the total environment. 2018 Jun 1;626:1494-501.
17Lee MH, Chung SW, Kang BY, Park J, Lee CH, Hwang SY, Kim TS. Enhanced interleukin‐4 production in CD4+ T cells and elevated immunoglobulin E levels in antigen‐primed mice by bisphenol A and nonylphenol, endocrine disruptors: involvement of nuclear factor‐AT and Ca2+. Immunology. 2003 May;109(1):76-86.
18Yan H, Takamoto M, Sugane K. Exposure to bisphenol A prenatally or in adulthood promotes TH2 cytokine production associated with reduction of CD4+ CD25+ regulatory T cells. Environmental health perspectives. 2008 Apr;116(4):514-9.
19Sawai C, Anderson K, Walser-Kuntz D. Effect of bisphenol A on murine immune function: modulation of interferon-gamma, IgG2a, and disease symptoms in NZB X NZW F1 mice. Environmental Health Perspectives. 2003 Dec;111(16):1883-7.
20Midoro-Horiuti T, Tiwari R, Watson CS, Goldblum RM. Maternal bisphenol a exposure promotes the development of experimental asthma in mouse pups. Environmental health perspectives. 2010 Feb;118(2):273-7.
21Shah R, Newcomb DC. Sex bias in asthma prevalence and pathogenesis. Frontiers in immunology. 2018:2997.
22Naeem A, Silveyra P. Sex differences in paediatric and adult asthma. European Medical Journal (Chelmsford, England). 2019 Jun;4(2):27.
23Lauzon‐Joset JF, Mincham KT, Abad AP, Short BP, Holt PG, Strickland DH, Leffler J. Oestrogen amplifies pre‐existing atopy‐associated Th2 bias in an experimental asthma model. Clinical & Experimental Allergy. 2020 Mar;50(3):391-400.
24Barbagelata E, Cilloniz C, Nicolini A, Moretti AM. Sex differences in asthma and immunological response: an overview. Ital J Gender-Specific Med. 2019;5:68-73.