Age- and Sex-Specific Features of Biomarkers of Exposure and Adverse Health Effects in Children with Respiratory Diseases and Comorbidities Associated with a Combined Exposure to Airborne Chemicals

Introduction: Nowadays, the use of a system of exposure and effect biomarkers is highly relevant in assessing public health disorders associated with chemical exposure. The study of age and sex-specific biomarkers in risk-sensitive populations with certain types of functional disorders and diseases related to airborne chemical exposures helps improve the effectiveness of scientific and methodological support for activities of the bodies and organizations of the Russian Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing (Rospotrebnadzor) in establishing causes and identifying circumstances for the occurrence and spread of non-communicable diseases related to chemical pollution of the environment.
Objective: To establish and age- and sex-specific biomarkers of exposure and its adverse health effects in children with respiratory diseases and comorbid conditions exposed to a combination of airborne chemicals.
Materials and methods: The object of the research was the system of biomarkers of exposure to six substances and negative effects (eight indicators), substantiated in biomedical studies conducted by the Federal Scientific Center for Medical and Preventive Health Risk Management Technologies in 2021–2022 to establish adverse health effects of a combined exposure to multiple airborne chemicals emitted by metallurgical plants in children aged 4–7 years; the classifying criteria included sex, age, target organs and systems, and adverse effects.
Results: The article gives a detailed description of age- and sex-dependent changes in biomarkers of exposure and adverse health effects in children. It also provides substantiation that the best (most informative) age for studying the levels of markers of exposure and effect in children with respiratory diseases and associated comorbidities is 4–5 years for boys and 6–7 years for girls. General patterns of changes in the levels of biomarkers in response to chronic exposure to airborne chemicals include an increase in the level of chemicals in biological fluids above the reference values, a growth of the spectrum, severity, and prevalence of changes relative to the physiological norm of biochemical parameters, and expansion of the spectrum of adverse health effects.
Conclusions: Our findings can serve as a criteria basis for priority setting in order to objectify and improve the accuracy of hygienic assessments, increase the efficiency of predictive techniques of diagnosis, predict and prevent health risks in the populations sensitive to airborne industrial chemicals.

1. Human Biomonitoring: Facts and Figures. Copenhagen: WHO Regional Office for Europe; 2015. (In Russ.) Accessed February 13, 2023. https://apps.who.int/iris/bitstream/handle/10665/164589/WHO-EURO-2015-3209-42967-60041-rus.pdf?sequence=3&isAllowed=y

2. Chuiko GM, Tomilina II, Kholmogorova NV. Methods of biodiagnostics in aquatic ecotoxicology. Toksikologicheskiy Vestnik. 2022;30(5):315-322. (In Russ.) doi: 10.47470/0869-7922-2022-30-5-315-322

3. Pollock T, Karthikeyan S, Walker M, Werry K, St-Amand A. Trends in environmental chemical concentrations in the Canadian population: Biomonitoring data from the Canadian Health Measures Survey 2007–2017. Environ Int. 2021;155:106678. doi: 10.1016/j.envint.2021.106678

4. Valcke M, Karthikeyan S, Walker M, Gagné M, Copes R, St-Amand A. Regional variations in human chemical exposures in Canada: A case study using biomonitoring data from the Canadian Health Measures Survey for the provinces of Quebec and Ontario. Int J Hyg Environ Health. 2020;225:113451. doi: 10.1016/j.ijheh.2020.113451

5. Chao YS, Wu CJ, Wu HC, et al. Opportunities and challenges from leading trends in a biomonitoring project: Canadian Health Measures Survey 2007–2017. Front Public Health. 2020;8:460. doi: 10.3389/fpubh.2020.00460

6. Faure S, Noisel N, Werry K, Karthikeyan S, Aylward LL, St-Amand A. Evaluation of human biomonitoring data in a health risk based context: An updated analysis of population level data from the Canadian Health Measures Survey. Int J Hyg Environ Health. 2020;223(1):267–280. doi: 10.1016/j.ijheh.2019.07.009

7. Biomonitoring-based indicators of exposure to chemical pollutants. Report of a meeting, Catania, Italy, April 19–20, 2012. WHO Regional Office for Europe; 2012. Accessed February 15, 2023. https://www.who.int/publications/m/item/biomonitoring-based-indicators-of-exposure-to-chemical-pollutants

8. Zaitseva NV, Zemlyanova MA, Chashchin VP, Gudkov AB. Scientific principles of use of biomarkers in medico-ecological studies (review). Ekologiya Cheloveka [Human Ecology]. 2019;(9):4-14. (In Russ.) doi: 10.33396/1728-0869-2019-9-4-14

9. Nguyen VK, Colacino J, Patel CJ, Sartor M, Jolliet O. Identification of occupations susceptible to high exposure and risk associated with multiple toxicants in an observational study: National Health and Nutrition Examination Survey 1999–2014. Exposome. 2022;2(1):osac004. doi: 10.1093/exposome/osac004

10. Zaitseva NV, Onishchenko GG, May IV, Shur PZ. Developing the methodology for health risk assessment within public management of sanitary-epidemiological welfare of the population. Health Risk Analysis. 2022;(3):4–20. (In Russ.) doi: 10.21668/health.risk/2022.3.01.eng

11. Onischenko GG. Health risk assessment and management as an effective tool to solve issues to ensure the health and epidemiological well-being of the Russian Federation population. Health Risk Analysis. 2013;(1):4-14. (In Russ.)

12. Suk WA. Invited perspective: Integrating data reveals benefits of remediation for children’s exposure to hazardous substances. Environ Health Perspect. 2022;130(3):31301. doi: 10.1289/ehp10594

13. Heacock ML, Amolegbe SM, Skalla LA, et al. Sharing SRP data to reduce environmentally associated disease and promote transdisciplinary research. Rev Environ Health. 2020;35(2):111–122. doi: 10.1515/reveh-2019-0089

14. Willey JB, Pollock T, Thomson EM, et al. Exposure load: Using biomonitoring data to quantify multi-chemical exposure burden in a population. Int J Hyg Environ Health. 2021;234:113704. doi: 10.1016/j.ijheh.2021.113704

15. Kholmatova KK, Kharkova OA, Grjibovski AM. Cohort studies in medicine and public health. Ekologiya Cheloveka [Human Ecology]. 2016;(4):56–64. (In Russ.) doi: 10.33396/1728-0869-2016-4-56-64

16. Bushnik T, Wong SL, Holloway AC, Thomson EM. Association of urinary polycyclic aromatic hydrocarbons and obesity in children aged 3–18: Canadian Health Measures Survey 2009–2015. J Dev Orig Health Dis. 2020;11(6):623–631. doi: 10.1017/S2040174419000825

17. Choi J, Knudsen LE, Mizrak S, Joas A. Identification of exposure to environmental chemicals in children and older adults using human biomonitoring data sorted by age: Results from a literature review. Int J Hyg Environ Health. 2017;220(2 Pt A):282–298. doi: 10.1016/j.ijheh.2016.12.006

18. Shin HH, Maquiling A, Thomson EM, Park IW, Stieb DM, Dehghani P. Sex-difference in air pollution-related acute circulatory and respiratory mortality and hospitalization. Sci Total Environ. 2022;806 (Pt 3):150515. doi: 10.1016/j.scitotenv.2021.150515

19. Arbuckle TE, Fraser WD, Fisher M, et al. Cohort profile: the maternal-infant research on environmental chemicals research platform. Paediatr Perinat Epidemiol. 2013;27(4):415–425. doi: 10.1111/ppe.12061

20. Matus PC, Oyarzún MG. Impact of particulate matter (PM 2,5) and children’s hospitalizations for respiratory diseases. A case cross-over study. Rev Chil Pediatr. 2019;90(2):166-174. (In Spanish.) doi: 10.32641/rchped.v90i2.750

21. Landrigan PJ, Goldman LR. Children’s vulnerability to toxic chemicals: a challenge and opportunity to strengthen health and environmental policy. Health Aff (Millwood). 2011;30(5):842–850. doi: 10.1377/hlthaff.2011.0151

22. Maklakova OA, Zaitseva NV, Kiryanov DA. Methodical aspects in assessing risks of comorbid pathology occurrence under exposure to chemical environmental factors. Health Risk Analysis. 2020;(4):55–62. doi: 10.21668/health.risk/2020.4.06.eng

23. Zemlyanova MA, Zaitseva NV, Koldibekova JV, Ustinova OYu, Kobjakova OA. Substantiation of marker indicators of diseases of the respiratory organs and the blood system in children with elevated blood levels of copper, nickel and chromium. Gigiena i Sanitariya. 2022;101(11):1347-1353. (In Russ.) doi: 10.47470/0016-9900-2022-101-11-1347-1353

24. Zeng X, Xu X, Qin Q, Ye K, Wu W, Huo X. Heavy metal exposure has adverse effects on the growth and development of preschool children. Environ Geochem Health. 2019;41(1):309–321. doi: 10.1007/s10653-018-0114-z

25. Lanin DV, Zaytseva NV, Zemlyanova MA, Dolgikh OV, Dianova DG. Characteristics of regulatory system in children exposed to the environmental chemical factors. Gigiena i Sanitariya. 2014;93(2):23-26. (In Russ.)

26. Chelombitko MA. Role of reactive oxygen species in inflammation: a minireview. Moscow University Biological Sciences Bulletin. 2018;73(4):199-202.

27. Sies H, Berndt C, Jones DP. Oxidative stress. Annu Rev Biochem. 2017;86:715–748. doi: 10.1146/annurev-biochem-061516-045037

28. Moldogazieva NT, Mokhosoev IM, Feldman NB, Lutsenko SV. ROS and RNS signalling: adaptive redox switches through oxidative/nitrosative protein modifications. Free Radic Res. 2018;52(5):507–543. doi: 10.1080/10715762.2018.1457217

29. Zaitseva NV, Zemlyanova MA, Lugeckiy KP, Kleyn SV. Scientific justification of the exposure and effect biomarkers in terms of proving health impact when identifying environmentally-determined unacceptable risk. Vestnik Permskogo Universiteta. Seriya: Biologiya. 2016;(4):374–378. (In Russ.)

30. Maklakova OA. Assessing risks of respiratory organs diseases and co-morbid pathology in children caused by ambient air contamination with technogenic chemicals (cohort study). Health Risk Analysis. 2019;(2):56–63. doi: 10.21668/health.risk/2019.2.06.eng