Abstract
The molecular mechanisms and associations of mixed heavy metals (lead, mercury, and cadmium) on obstructive lung function (OLF) in males and females remain unknown. Here, we evaluated the interaction between the forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) ratio and three common heavy metals in males and females (n = 6221). Molecular processes involved in OLF development caused by mixed heavy metals were also identified to corroborate the earlier findings. In both males and females, as well as across the entire population, we found that serum cadmium levels were inversely related to the FEV1/FVC ratio. Interactions between serum cadmium and lead, as well as cadmium and mercury, were observed in relation to the FEV1/FVC ratio. Additionally, we observed negative correlations between the FEV1/FVC ratio and mixed serum cadmium, lead, and mercury in both men and women as well as in the overall population. Seven genes were identified as contributing to the etiology of OLF and targeted by combined heavy metals in silico analysis (CYP1A1, CRP, CXCL8, HMOX1, IL6, NOS2, and TNF). The primary relationships between these genes were co-expression interactions. The significant transcription factors and miRNAs associated with OLF and a combination of the examined heavy metals were identified as NFKB2, hsa-miR-155-5p, and hsa-miR-203a-3p. The main biological processes involved in the emergence of OLF induced by mixed heavy metals were listed as inflammatory and oxidative stress pathways, lung fibrosis, chronic obstructive pulmonary disease, as well as cytokine activity, monooxygenase activity, oxidoreductase activity, and interleukin-8 production. Threshold estimations and miRNA sponge patterns for heavy metal exposure levels associated with OLF were evaluated for both males and females. This study found that cadmium plays the most important role in the mixture of cadmium, lead, and mercury in the pathogenesis of OLF. Future studies are required to verify our findings and uncover the molecular mechanisms of long-term exposure to a variety of heavy metals, especially cadmium, in other populations, including children, adolescents, and the elderly.
Graphical abstract
Similar content being viewed by others
Data availability
Data are available on the official website of KNHANES (https://knhanes.kdca.go.kr).
References
Bagci, C., Bozkurt, A. I., Cakmak, E. A., Can, S., & Cengiz, B. (2004). Blood lead levels of the battery and exhaust workers and their pulmonary function tests. International Journal of Clinical Practice, 58(6), 568–572. https://doi.org/10.1111/j.1368-5031.2004.00002.x
Becker, K., Kaus, S., Krause, C., Lepom, P., Schulz, C., Seiwert, M., & Seifert, B. (2002). German Environmental Survey 1998 (GerES III): Environmental pollutants in blood of the German population. International Journal of Hygiene and Environmental Health, 205(4), 297–308. https://doi.org/10.1078/1438-4639-00155
Bobb, J. F., Valeri, L., Claus Henn, B., Christiani, D. C., Wright, R. O., Mazumdar, M., Godleski, J. J., & Coull, B. A. (2015). Bayesian kernel machine regression for estimating the health effects of multi-pollutant mixtures. Biostatistics, 16(3), 493–508.
Canada, H., (2010) Report on human biomonitoring of environmental chemicals in Canada. Results of the Canadian Health Measures Survey Cycle 1 (2007–2009). Health Canada Ottawa, Ontario.
Carone, M., Salerno, F. G., & Esquinas, A. M. (2016). Obstructive lung function decline and IPF: The dark face of the moon. Chronic Respiratory Disease, 13(2), 204–205. https://doi.org/10.1177/1479972316628534
Choi, J. Y., & Rhee, C. K. (2020). Diagnosis and treatment of early chronic obstructive lung disease (COPD). Journal of Clinical Medicine. https://doi.org/10.3390/jcm9113426
Croute, F., Beau, B., Arrabit, C., Gaubin, Y., Delmas, F., Murat, J. C., & Soleilhavoup, J. P. (2000). Pattern of stress protein expression in human lung cell-line A549 after short- or long-term exposure to cadmium. Environmental Health Perspectives, 108(1), 55–60. https://doi.org/10.1289/ehp.0010855
Dagenais, G. M. (1969). A threshold regression model. Econometrica: Journal of Econometric Society. https://doi.org/10.2307/1913530
De Smet, E. G., Van Eeckhoutte, H. P., Avila Cobos, F., Blomme, E., Verhamme, F. M., Provoost, S., Verleden, S. E., Venken, K., Maes, T., Joos, G. F., Mestdagh, P., Brusselle, G. G., & Bracke, K. R. (2020). The role of miR-155 in cigarette smoke-induced pulmonary inflammation and COPD. Mucosal Immunology, 13(3), 423–436. https://doi.org/10.1038/s41385-019-0241-6
Donaldson, G. C., Seemungal, T. A., Patel, I. S., Bhowmik, A., Wilkinson, T. M., Hurst, J. R., Maccallum, P. K., & Wedzicha, J. A. (2005). Airway and systemic inflammation and decline in lung function in patients with COPD. Chest, 128(4), 1995–2004. https://doi.org/10.1378/chest.128.4.1995
Duc, H. N., Oh, H., & Kim, M.-S. (2021a). The effect of mixture of heavy metals on obesity in individuals ≥50 years of age. Biological Trace Element Research. https://doi.org/10.1007/s12011-021-02972-z
Duc, H. N., Oh, H., & Kim, M. S. (2021b). Effects of antioxidant vitamins, curry consumption, and heavy metal levels on metabolic syndrome with comorbidities: A Korean community-based cross-sectional study. Antioxidants (basel, Switzerland). https://doi.org/10.3390/antiox10050808
Ekström, M., Schiöler, L., Grønseth, R., Johannessen, A., Svanes, C., Leynaert, B., Jarvis, D., Gislason, T., Demoly, P., Probst-Hensch, N., Pin, I., Corsico, A. G., Forsberg, B., Heinrich, J., Nowak, D., Raherison-Semjen, C., Dharmage, S. C., Trucco, G., Urrutia, I., … Torén, K. (2017). Absolute values of lung function explain the sex difference in breathlessness in the general population. European Respiratory Journal, 49(5), 1602047. https://doi.org/10.1183/13993003.02047-2016
Forti, E., Bulgheroni, A., Cetin, Y., Hartung, T., Jennings, P., Pfaller, W., & Prieto, P. (2010). Characterisation of cadmium chloride induced molecular and functional alterations in airway epithelial cells. Cellular Physiology and Biochemistry, 25(1), 159–168. https://doi.org/10.1159/000272060
Gam, K. B., Kwok, R. K., Engel, L. S., Curry, M. D., Stewart, P. A., Stenzel, M. R., McGrath, J. A., Jackson, W. B., 2nd., Jensen, R. L., Lichtveld, M. Y., Miller, A. K., & Sandler, D. P. (2018). Exposure to oil spill chemicals and lung function in deepwater horizon disaster response workers. Journal of Occupational and Environmental Medicine, 60(6), e312–e318. https://doi.org/10.1097/jom.0000000000001292
Gilowska, I. (2014). CXCL8 (interleukin 8)–the key inflammatory mediator in chronic obstructive pulmonary disease? Postepy Higieny I Medycyny Doswiadczalnej (online), 68, 842–850. https://doi.org/10.5604/17322693.1109219
Gong, Q., & Hart, B. A. (1997). Effect of thiols on cadmium-induced expression of metallothionein and other oxidant stress genes in rat lung epithelial cells. Toxicology, 119(3), 179–191. https://doi.org/10.1016/s0300-483x(96)03608-6
Graham, B. L., Steenbruggen, I., Miller, M. R., Barjaktarevic, I. Z., Cooper, B. G., Hall, G. L., Hallstrand, T. S., Kaminsky, D. A., McCarthy, K., McCormack, M. C., Oropez, C. E., Rosenfeld, M., Stanojevic, S., Swanney, M. P., & Thompson, B. R. (2019). Standardization of spirometry 2019 update. An official American thoracic society and European respiratory society technical statement. American Journal of Respiratory and Critical Care Medicine., 200(8), e70–e88. https://doi.org/10.1164/rccm.201908-1590ST
Han, C. H., & Chung, J. H. (2018). Association between hand grip strength and spirometric parameters: Korean National health and Nutrition Examination Survey (KNHANES). The Journal of Thoracic Disease., 10(11), 6002–6009.
Hays, S. M., Nordberg, M., Yager, J. W., & Aylward, L. L. (2008). Biomonitoring equivalents (BE) dossier for cadmium (Cd) (CAS No. 7440-43-9). Regulatory Toxicology and Pharmacology., 51(3 Suppl), 49–56. https://doi.org/10.1016/j.yrtph.2008.05.008
Henderson, J., Sherriff, A., Farrow, A., & Ayres, J. G. (2008). Household chemicals, persistent wheezing and lung function: Effect modification by atopy? European Respiratory Journal, 31(3), 547. https://doi.org/10.1183/09031936.00086807
Heo, J., Park, H. S., Hong, Y., Park, J., Hong, S.-H., Bang, C. Y., Lim, M.-N., & Kim, W. J. (2017). Serum heavy metals and lung function in a chronic obstructive pulmonary disease cohort. Toxicology and Environmental Health Sciences, 9(1), 30–35. https://doi.org/10.1007/s13530-017-0300-x
Jakubowski, M., Abramowska-Guzik, A., Szymczak, W., & Trzcinka-Ochocka, M. (2004). Influence of long-term occupational exposure to cadmium on lung function tests results. International Journal of Occupational Medicine and Environmental Health, 17(3), 361–368.
Jurdziak, M., Gać, P., Martynowicz, H., & Poręba, R. (2015). Function of respiratory system evaluated using selected spirometry parameters in persons occupationally exposed to lead without evident health problems. Environmental Toxicology and Pharmacology., 39(3), 1034–1040. https://doi.org/10.1016/j.etap.2015.03.009
Kalainayakan, S. P., FitzGerald, K. E., Konduri, P. C., Vidal, C., & Zhang, L. (2018). Essential roles of mitochondrial and heme function in lung cancer bioenergetics and tumorigenesis. Cell and Bioscience, 8(1), 56. https://doi.org/10.1186/s13578-018-0257-8
KMoHa, W. (2021). Korea National Health & Nutrition Examination Survey, Retrieved from, 20 Jan 2021, https://knhanes.cdc.go.kr/knhanes/eng/index.do
King, P. T. (2015). Inflammation in chronic obstructive pulmonary disease and its role in cardiovascular disease and lung cancer. Clinical and Translational Medicine, 4(1), 68. https://doi.org/10.1186/s40169-015-0068-z
Kirschvink, N., Martin, N., Fievez, L., Smith, N., Marlin, D., & Gustin, P. (2006). Airway inflammation in cadmium-exposed rats is associated with pulmonary oxidative stress and emphysema. Free Radical Research, 40(3), 241–250. https://doi.org/10.1080/10715760500494657
Kolsum, U., Roy, K., Starkey, C., Borrill, Z., Truman, N., Vestbo, J., & Singh, D. (2009). The repeatability of interleukin-6, tumor necrosis factor-alpha, and C-reactive protein in COPD patients over one year. International Journal of Chronic Obstructive Pulmonary Disease, 4, 149–156. https://doi.org/10.2147/copd.s5018
KoreaCDC, (2020) Korean National Health and Nutrition Examination Surveys, Retrieved from 21 May 2020, https://knhanes.kdca.go.kr/knhanes/main.do
Lampe Brad, J., Park Sung, K., Robins, T., Mukherjee, B., Litonjua Augusto, A., Amarasiriwardena, C., Weisskopf, M., Sparrow, D., & Hu, H. (2008). Association between 24-hour urinary cadmium and pulmonary function among community-exposed men: The VA normative aging study. Environmental Health Perspectives, 116(9), 1226–1230. https://doi.org/10.1289/ehp.11265
Leem, A. Y., Kim, S. K., Chang, J., Kang, Y. A., Kim, Y. S., Park, M. S., Kim, S. Y., Kim, E. Y., Chung, K. S., & Jung, J. Y. (2015). Relationship between blood levels of heavy metals and lung function based on the Korean National Health and Nutrition Examination Survey IV-V. International Journal of Chronic Obstructive Pulmonary Disease, 10, 1559–1570. https://doi.org/10.2147/copd.S86182
Lin, J., Chen, Y., Liu, L., Shen, A., & Zheng, W. (2018). MicroRNA-155-5p suppresses the migration and invasion of lung adenocarcinoma A549 cells by targeting Smad2. Oncology Letters, 16(2), 2444–2452. https://doi.org/10.3892/ol.2018.8889
Madrigal, J. M., Persky, V., Pappalardo, A., & Argos, M. (2018). Association of heavy metals with measures of pulmonary function in children and youth: Results from the National Health and Nutrition Examination Survey (NHANES). Environment International., 121, 871–878. https://doi.org/10.1016/j.envint.2018.09.045
Maestrelli, P., Páska, C., Saetta, M., Turato, G., Nowicki, Y., Monti, S., Formichi, B., Miniati, M., & Fabbri, L. M. (2003). Decreased haem oxygenase-1 and increased inducible nitric oxide synthase in the lung of severe COPD patients. European Respiratory Journal, 21(6), 971–976. https://doi.org/10.1183/09031936.03.00098203
Maria Maddalena, B., & James, O. B. (2004). Optimal predictive model selection. The Annals of Statistics, 32(3), 870–897. https://doi.org/10.1214/009053604000000238
Miller, M. D., & Marty, M. A. (2010). Impact of environmental chemicals on lung development. Environmental Health Perspectives, 118(8), 1155–1164.
Moitra, S., Blanc, P. D., & Sahu, S. (2013). Adverse respiratory effects associated with cadmium exposure in small-scale jewellery workshops in India. Thorax, 68(6), 565–570. https://doi.org/10.1136/thoraxjnl-2012-203029
Nguyen, H. D. (2022). Resveratrol, endocrine disrupting chemicals, neurodegenerative diseases and depression: genes, transcription factors, microRNAs, and sponges involved. Neurochemical Research. https://doi.org/10.1007/s11064-022-03787-7
Nguyen, H. D. (2023). Interactions between heavy metals and sleep duration among pre-and postmenopausal women: A current approach to molecular mechanisms involved. Environmental Pollution., 316, 120607. https://doi.org/10.1016/j.envpol.2022.120607
Nguyen, H. D., & Kim, M.-S. (2021a). Effects of heavy metal, vitamin, and curry consumption on metabolic syndrome during menopause: A Korean community-based cross-sectional study. Menopause, 28(8), 1. https://doi.org/10.1097/GME.0000000000001825
Nguyen, H. D., & Kim, M. S. (2021b). Effects of heavy metal, vitamin, and curry consumption on metabolic syndrome during menopause: A Korean community-based cross-sectional study. Menopause, 28(8), 949–959.
Nguyen, H. D., & Kim, M.-S. (2022a). Cadmium, lead, and mercury mixtures interact with non-alcoholic fatty liver diseases. Environmental Pollution., 309, 119780. https://doi.org/10.1016/j.envpol.2022.119780
Nguyen, H. D., & Kim, M.-S. (2022b). The effects of a mixture of cadmium, lead, and mercury on metabolic syndrome and its components, as well as cognitive impairment: Genes, MicroRNAs, transcription factors, and sponge relationships. Biological Trace Element Research. https://doi.org/10.1007/s12011-022-03343-y
Nguyen, H. D., & Kim, M.-S. (2022c). Effects of chemical mixtures on liver function biomarkers in the Korean adult population: Thresholds and molecular mechanisms for non-alcoholic fatty liver disease involved. Environmental Science and Pollution Research. https://doi.org/10.1007/s11356-022-21090-4
Nguyen, H. D., & Kim, M.-S. (2022d). Effects of heavy metals on cardiovascular diseases in pre and post-menopausal women: From big data to molecular mechanism involved. Environmental Science and Pollution Research. https://doi.org/10.1007/s11356-022-21208-8
Nguyen, H. D., & Kim, M.-S. (2022e). Exposure to a mixture of heavy metals induces cognitive impairment: Genes and microRNAs involved. Toxicology. https://doi.org/10.1016/j.tox.2022.153164
Nguyen, H. D., & Kim, M.-S. (2022f). The protective effects of curcumin on metabolic syndrome and its components: In-silico analysis for genes, transcription factors, and microRNAs involved. Archives of Biochemistry and Biophysics., 727, 109326. https://doi.org/10.1016/j.abb.2022.109326
Nguyen, H. D., & Kim, M.-S. (2022g). The role of mixed B vitamin intakes on cognitive performance: Modeling, genes and miRNAs involved. Journal of Psychiatric Research, 152, 38–56. https://doi.org/10.1016/j.jpsychires.2022.06.006
Nguyen, H. D., & Kim, M.-S. (2023). In silico identification of molecular mechanisms for stroke risk caused by heavy metals and their mixtures: Sponges and drugs involved. Neurotoxicology, 96, 222–239. https://doi.org/10.1016/j.neuro.2023.04.011
Nguyen, H. D., Oh, H., Hoang, N. H. M., Jo, W. H., & Kim, M. S. (2021a). Environmental science and pollution research role of heavy metal concentrations and vitamin intake from food in depression: A national cross-sectional study (2009–2017). Environmental Science and Pollution Research. https://doi.org/10.1007/s11356-021-15986-w
Nguyen, H. D., Oh, H., Hoang, N. H. M., & Kim, M.-S. (2021b). Association between heavy metals, high-sensitivity C-reaction protein and 10-year risk of cardiovascular diseases among adult Korean population. Science and Reports, 11(1), 14664. https://doi.org/10.1038/s41598-021-94158-9
Nguyen, H. D., Oh, H., Jo, W. H., Hoang, N. H. M., & Kim, M. S. (2021c). Mixtures modeling identifies heavy metals and pyrethroid insecticide metabolites associated with obesity. Environmental Science and Pollution Research International. https://doi.org/10.1007/s11356-021-16936-2
Nguyen, H. D., Oh, H., & Kim, M. S. (2021d). Effects of heavy metals on hypertension during menopause: A Korean community-based cross-sectional study. Menopause. https://doi.org/10.1097/gme.0000000000001865
Nguyen, H. D., Jo, W. H., Hoang, N. H. M., & Kim, M.-S. (2022a). In silico identification of the potential molecular mechanisms involved in protective effects of prolactin on motor and memory deficits induced by 1,2-Diacetylbenzene in young and old rats. Neurotoxicology, 93, 45–59. https://doi.org/10.1016/j.neuro.2022.09.002
Nguyen, H. D., Oh, H., & Kim, M.-S. (2022b). Effect of mixture of heavy metals on metabolic syndrome and its components in individuals ≥ 18 years of age: From big data to molecular mechanisms involved. Exposure and Health. https://doi.org/10.1007/s12403-022-00523-y
Nguyen, H. D., Oh, H., & Kim, M.-S. (2022c). An increased intake of thiamine diminishes the risk of metabolic syndrome in the Korean population with various comorbidities. Diabetes and Metabolic Syndrome: Clinical Research and Reviews, 16(3), 102443. https://doi.org/10.1016/j.dsx.2022.102443
Ohnhaus, E. E., & Bluhm, R. C. (1987). Induction of the monooxygenase enzyme system in human lung. European Journal of Clinical Investigation, 17(6), 488–492. https://doi.org/10.1111/j.1365-2362.1987.tb01146.x
Pan, Z., Guo, Y., Xiang, H., Hui, Y., Ju, H., Xu, S., & Li, L. (2020). Effects of lead, mercury, and cadmium co-exposure on children’s pulmonary function. Biological Trace Element Research, 194(1), 115–120. https://doi.org/10.1007/s12011-019-01772-w
Ranu, H., Wilde, M., & Madden, B. (2011). Pulmonary function tests. Ulster Medical Journal, 80(2), 84–90.
Rohlman, D., Dixon, H. M., Kincl, L., Larkin, A., Evoy, R., Barton, M., Phillips, A., Peterson, E., Scaffidi, C., Herbstman, J. B., Waters, K. M., & Anderson, K. A. (2019). Development of an environmental health tool linking chemical exposures, physical location and lung function. BMC Public Health, 19(1), 854. https://doi.org/10.1186/s12889-019-7217-z
Safiri, S., Carson-Chahhoud, K., Noori, M., Nejadghaderi, S. A., Sullman, M. J. M., Ahmadian Heris, J., Ansarin, K., Mansournia, M. A., Collins, G. S., Kolahi, A.-A., & Kaufman, J. S. (2022). Burden of chronic obstructive pulmonary disease and its attributable risk factors in 204 countries and territories, 1990–2019: Results from the Global Burden of Disease Study 2019. BMJ, 378, e069679. https://doi.org/10.1136/bmj-2021-069679
Schuliga, M. (2015). NF-kappaB signaling in chronic inflammatory airway disease. Biomolecules, 5(3), 1266–1283. https://doi.org/10.3390/biom5031266
Shi, L., Xin, Q., Chai, R., Liu, L., & Ma, Z. (2015). Ectopic expressed miR-203 contributes to chronic obstructive pulmonary disease via targeting TAK1 and PIK3CA. International Journal of Clinical and Experimental Pathology, 8(9), 10662–10670.
Torres-Castro, R., Vasconcello-Castillo, L., Alsina-Restoy, X., Solis-Navarro, L., Burgos, F., Puppo, H., & Vilaró, J. (2021). Respiratory function in patients post-infection by COVID-19: A systematic review and meta-analysis. Pulmonology, 27(4), 328–337. https://doi.org/10.1016/j.pulmoe.2020.10.013
van Nijnatten, J., Brandsma, C. A., Steiling, K., Hiemstra, P. S., Timens, W., van den Berge, M., & Faiz, A. (2022). High miR203a-3p and miR-375 expression in the airways of smokers with and without COPD. Science and Reports, 12(1), 5610. https://doi.org/10.1038/s41598-022-09093-0
Wang, C. D., Chen, N., Huang, L., Wang, J. R., Chen, Z. Y., Jiang, Y. M., He, Y. Z., & Ji, Y. L. (2015). Impact of CYP1A1 polymorphisms on susceptibility to chronic obstructive pulmonary disease: A meta-analysis. BioMed Research International, 2015, 942958. https://doi.org/10.1155/2015/942958
WHO. (2010). Ten chemicals of major public health concern, Retrieved from 17 February 2022, https://www.who.int/news-room/photo-story/photo-story-detail/10-chemicals-of-public-health-concern
WHO. (2019). Chronic obstructive pulmonary disease (COPD). Retrieved from 04 December 2022, https://www.who.int/news-room/fact-sheets/detail/chronic-obstructive-pulmonary-disease-(copd)
Wu, L., Cui, F., Ma, J., Huang, Z., Zhang, S., Xiao, Z., Li, J., Ding, X., & Niu, P. (2022). Associations of multiple metals with lung function in welders by four statistical models. Chemosphere, 298, 134202. https://doi.org/10.1016/j.chemosphere.2022.134202
Yu, D., Chen, T., Cai, Y., Zhao, Z., & Simmons, D. (2017). Association between pulmonary function and renal function: Findings from China and Australia. BMC Nephrology, 18(1), 143. https://doi.org/10.1186/s12882-017-0565-y
Yun, S., Nguyen, H. D., Park, J. S., Oh, C., & Kim, M. S. (2022). The association between the metabolic syndrome and iron status in pre- and postmenopausal women: Korean National Health and Nutrition Examination Survey (KNHANES) in 2012. British Journal of Nutrition, 127(4), 630–640. https://doi.org/10.1017/s0007114521001331
Zhang, Y., Dong, T., Hu, W., Wang, X., Xu, B., Lin, Z., Hofer, T., Stefanoff, P., Chen, Y., Wang, X., & Xia, Y. (2019). Association between exposure to a mixture of phenols, pesticides, and phthalates and obesity: Comparison of three statistical models. Environment International, 123, 325–336. https://doi.org/10.1016/j.envint.2018.11.076
Zhao, Y., Gao, S., Chou, I. N., Toselli, P., Stone, P., & Li, W. (2006). Inhibition of the expression of lysyl oxidase and its substrates in cadmium-resistant rat fetal lung fibroblasts. Toxicological Sciences, 90(2), 478–489. https://doi.org/10.1093/toxsci/kfj112
Zhu, H. Z., Fang, C. J., Guo, Y., Zhang, Q., Huang, L. M., Qiu, D., Chen, G. P., Pang, X. F., Hu, J. J., Sun, J. G., & Chen, Z. T. (2020). Detection of miR-155-5p and imaging lung cancer for early diagnosis: In vitro and in vivo study. Journal of Cancer Research and Clinical Oncology, 146(8), 1941–1951. https://doi.org/10.1007/s00432-020-03246-2
Acknowledgements
The authors are grateful to all research staff for their excellent contributions in data collection in the survey.
Funding
None.
Author information
Authors and Affiliations
Contributions
HDN: Conceptualization, Methodology, Formal analysis, Investigation, Resources, Data curation, Writing—original draft, Writing—review and editing, Visualization.
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Consent to participate
Before the examinations, all KNHANES participants received written informed permission, which was performed by the Korea Centers for Disease Control and Prevention's Health and Nutrition Examination Department. The KNHANES investigation commission authorized this study. These surveys were approved by the KNHANES inquiry commission (IRB Approval numbers: 2009-01CON-03-2C, 2010-02CON-21-C, 2011-02CON-06-C, 2012-01EXP-01-2C, 2013-07CON-03-4C, 2013-12EXP-03-5C). From 2016 to 2017, KNHANES was exempt from evaluation for research ethics under the Bioethics and Safety Act.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary Information
Below is the link to the electronic supplementary material.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Nguyen, H.D. Effects of mixed heavy metals on obstructive lung function: findings from epidemiological and toxicogenomic data. Environ Geochem Health 45, 8663–8683 (2023). https://doi.org/10.1007/s10653-023-01746-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10653-023-01746-x