Increased di-(2-ethylhexyl) phthalate exposure poses a differential risk for adult asthma clusters

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Abstract

Background

DEHP, a common plasticizer known for its hormone-disrupting properties, has been associated with asthma. However, a significant proportion of adult asthma cases are “non-atopic”, lacking a clear etiology.

Methods

In a case-control study conducted between 2011 and 2015, 365 individuals with current asthma and 235 healthy controls from Kaohsiung City were enrolled. The control group comprised individuals without asthma, Type 2 Diabetes Mellitus (T2DM), hypertension, or other respiratory/allergic conditions. The study leveraged asthma clusters (Clusters A to F) established in a prior investigation. Analysis involved the examination of urinary DEHP metabolites (MEHP and MEHHP), along with the assessment of oxidative stress, sphingolipid metabolites, and inflammatory biomarkers. Statistical analyses encompassed Spearman’s rank correlation coefficients, multiple logistic regression, and multinomial logistic regression.

Results

Asthma clusters (E, D, C, F, A) exhibited significantly higher ORs of MEHHP exposures compared to the control group. When considering asthma-related comorbidities (T2DM, hypertension, or both), patients without comorbidities demonstrated significantly higher ORs of the sum of primary and secondary metabolites (MEHP + MEHHP) and MEHHP compared to those with asthma comorbidities. A consistent positive correlation between urinary HEL and DEHP metabolites was observed, but a consistent negative correlation between DEHP metabolites and selected cytokines was identified.

Conclusion

The current study reveals a heightened risk of MEHHP and MEHP + MEHHP exposure in specific asthma subgroups, emphasizing its complex relationship with asthma. The observed negative correlation with cytokines suggests a new avenue for research, warranting robust evidence from epidemiological and animal studies.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12931-024-02764-8.

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Most cited references 32

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What are the sources of exposure to eight frequently used phthalic acid esters in Europeans?

Matthias Wormuth, Martin Scheringer, Meret Vollenweider … (2006)

Phthalic acid esters (phthalates) are used as plasticizers in numerous consumer products, commodities, and building materials. Consequently, phthalates are found in human residential and occupational environments in high concentrations, both in air and in dust. Phthalates are also ubiquitous food and environmental contaminants. An increasing number of studies sampling human urine reveal the ubiquitous phthalate exposure of consumers in industrialized countries. At the same time, recent toxicological studies have demonstrated the potential of the most important phthalates to disturb the human hormonal system and human sexual development and reproduction. Additionally, phthalates are suspected to trigger asthma and dermal diseases in children. To find the important sources of phthalates in Europeans, a scenario-based approach is applied here. Scenarios representing realistic exposure situations are generated to calculate the age-specific range in daily consumer exposure to eight phthalates. The scenarios demonstrate that exposure of infant and adult consumers is caused by different sources in many cases. Infant consumers experience significantly higher daily exposure to phthalates in relation to their body weight than older consumers. The use of consumer products and different indoor sources dominate the exposure to dimethyl, diethyl, benzylbutyl, diisononyl, and diisodecyl phthalates, whereas food has a major influence on the exposure to diisobutyl, dibutyl, and di-2-ethylhexyl phthalates. The scenario-based approach chosen in the present study provides a link between the knowledge on emission sources of phthalates and the concentrations of phthalate metabolites found in human urine.

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The Association between Asthma and Allergic Symptoms in Children and Phthalates in House Dust: A Nested Case–Control Study

Carl-Gustaf Bornehag, Jan Sundell, Charles Weschler … (2004)

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.

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Phthalates impact human health: Epidemiological evidences and plausible mechanism of action.

Kenji Takahashi, Eiji Masai, Robin C. Anderson … (2017)

Disregarding the rising alarm on the hazardous nature of various phthalates and their metabolites, ruthless usage of phthalates as plasticizer in plastics and as additives in innumerable consumer products continues due low their cost, attractive properties, and lack of suitable alternatives. Globally, in silico computational, in vitro mechanistic, in vivo preclinical and limited clinical or epidemiological human studies showed that over a dozen phthalates and their metabolites ingested passively by man from the general environment, foods, drinks, breathing air, and routine household products cause various dysfunctions. Thus, this review addresses the health hazards posed by phthalates on children and adolescents, epigenetic modulation, reproductive toxicity in women and men; insulin resistance and type II diabetes; overweight and obesity, skeletal anomalies, allergy and asthma, cancer, etc., coupled with the description of major phthalates and their general uses, phthalate exposure routes, biomonitoring and risk assessment, special account on endocrine disruption; and finally, a plausible molecular cross-talk with a unique mechanism of action. This clinically focused comprehensive review on the hazards of phthalates would benefit the general population, academia, scientists, clinicians, environmentalists, and law or policy makers to decide upon whether usage of phthalates to be continued swiftly without sufficient deceleration or regulated by law or to be phased out from earth forever.

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Author and article information

Contributors

Chih-Hsing Hung: pedhung@gmail.com

Chon-Lin Lee: a0780047@g-mail.nsysu.edu.tw

Ming-Shyan Huang: ed110209@edah.org.tw

Shau-Ku Huang: skhuang@nhri.edu.tw

Journal

Journal ID (nlm-ta): Respir Res

Journal ID (iso-abbrev): Respir Res

Title: Respiratory Research

Publisher: BioMed Central (London )

ISSN (Print): 1465-9921

ISSN (Electronic): 1465-993X

Publication date (Electronic): 23 March 2024

Publication date PMC-release: 23 March 2024

Publication date (Print): 2024

Volume: 25

Electronic Location Identifier: 139

Affiliations

[1 ]National Institute of Environmental Health Sciences, National Health Research Institutes, ( https://ror.org/02r6fpx29) No.35, Keyan Road, Zhunan, Miaoli County, 35053 Taiwan

[2 ]National Center for Geriatrics and Welfare Research, National Health Research Institutes, ( https://ror.org/02r6fpx29) Miaoli, Taiwan

[3 ]GRID grid.413804.a, Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, , Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, ; Kaohsiung, Taiwan

[4 ]Department of Public Health, Kaohsiung Medical University, ( https://ror.org/03gk81f96) Kaohsiung, Taiwan

[5 ]GRID grid.412019.f, ISNI 0000 0000 9476 5696, Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, , Kaohsiung Medical University Hospital, Kaohsiung Medical University, ; Kaohsiung, Taiwan

[6 ]Department of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, ( https://ror.org/03gk81f96) Kaohsiung, Taiwan

[7 ]National Institute of Cancer Research, National Health Research Institutes, ( https://ror.org/02r6fpx29) Tainan, Taiwan

[8 ]Department of Mathematics, Hong Kong Baptist University, ( https://ror.org/0145fw131) Hong Kong, China

[9 ]Division of Chest Medicine, Kaohsiung Veterans General Hospital, ( https://ror.org/04jedda80) Kaohsiung, Taiwan

[10 ]Chest Division, Department of Internal Medicine, Antai Medical Care Cooperation Antai Tian-Sheng Memorial Hospital, Ping-Tung, Taiwan

[11 ]Department of Internal Medicine, E-Da Cancer Hospital, I-Shou University, ( https://ror.org/04d7e4m76) Kaohsiung, Taiwan

[12 ]GRID grid.411447.3, ISNI 0000 0004 0637 1806, Division of Chest Medicine, Department of Internal Medicine, , E-Da Hospital, I-Shou University, ; Kaohsiung, Taiwan

[13 ]Department of Respiratory Therapy, College of Medicine, Kaohsiung Medical University, ( https://ror.org/03gk81f96) Kaohsiung, Taiwan

[14 ]Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University, ( https://ror.org/03gk81f96) Kaohsiung, Taiwan

[15 ]Department of Pediatrics, Kaohsiung Medical University Hospital and College of Medicine, Kaohsiung Medical University, ( https://ror.org/03gk81f96) Kaohsiung, Taiwan

[16 ]Department of Pediatrics, Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University, ( https://ror.org/03gk81f96) Kaohsiung, Taiwan

[17 ]Department of Marine Environment and Engineering, National Sun Yat-Sen University, ( https://ror.org/00mjawt10) Kaohsiung, Taiwan

[18 ]GRID grid.21107.35, ISNI 0000 0001 2171 9311, Johns Hopkins University School of Medicine, ; Baltimore, MD USA

[19 ]GRID grid.412019.f, ISNI 0000 0000 9476 5696, Department of Pediatrics, , Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University, ; Kaohsiung, Taiwan

Article

Publisher ID: 2764

DOI: 10.1186/s12931-024-02764-8

PMC ID: 10960985

PubMed ID: 38521900

SO-VID: 2b035093-1d39-4a19-80b0-aa88a0f5bd3a

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 16 October 2023

Date accepted : 10 March 2024

Funding

Funded by: National Health Research Institutes, Taiwan

Award ID: EOPP10-014, EOSP07-014 and NHRI-102A1-PDCO-03010201

Funded by: FundRef http://dx.doi.org/10.13039/100008903, Ministry of Health and Welfare;

Award ID: EODOH01

Funded by: FundRef http://dx.doi.org/10.13039/501100001868, National Science Council;

Award ID: NSC 102-2314-B-037-052

Funded by: FundRef http://dx.doi.org/10.13039/501100004663, Ministry of Science and Technology, Taiwan;

Award ID: MOST 103-2320-B-110-001

Funded by: FundRef http://dx.doi.org/10.13039/501100001869, Academia Sinica;

Award ID: BM-102021170

Custom metadata

ScienceOpen disciplines: Respiratory medicine

Keywords: dehp,hel,comorbidities,asthma phenotype,inflammatory markers

Data availability:

ScienceOpen disciplines: Respiratory medicine

Keywords: dehp, hel, comorbidities, asthma phenotype, inflammatory markers

Increased di-(2-ethylhexyl) phthalate exposure poses a differential risk for adult asthma clusters

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Abstract

Background

Methods

Results

Conclusion

Supplementary Information

Related collections

Inflamed lung in vitro co-culture models

Most cited references 32

What are the sources of exposure to eight frequently used phthalic acid esters in Europeans?

The Association between Asthma and Allergic Symptoms in Children and Phthalates in House Dust: A Nested Case–Control Study

Phthalates impact human health: Epidemiological evidences and plausible mechanism of action.

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