Clinical and pathogenetic features and polymorphic gene variants in various phenotypes of occupational bronchial asthma

Introduction. Currently, scientists consider occupational bronchial asthma as a phenotypically and genetically heterogeneous disease. The assessment of clinical data, features of immunopathogenesis and molecular genotyping opens up new opportunities in assessing the development, predicting the features of the course and a personalized approach to pharmacotherapy of occupational bronchial asthma, as well as in developing an individual strategy for its prevention.

The study aims to determine clinical, immunological and genetic markers of the risk of developing occupational bronchial asthma (OBA) under exposure to sensitizing substances based on the results of an assessment of polymorphic variants rs2069812 of the IL5 gene and polymorphic variants rs1837253 of the TSLP gene.

Materials and methods. The study included 170 patients with different OBA phenotypes and 50 people in the control group. The levels of cytokines IL-17, TNF-α, IFN-γ, VEGF, total IgE, C-reactive protein and fibronectin in blood serum were determined by solid-phase enzyme immunoassay using kits and reagents (Protein Contour LLC, Vector-Best, Diatex-E, DIA‑plus», «Pharmacologicia diagnostika», «eBioscience»). The authors have performed genotyping by polymerase chain reaction in real time using primers and probes developed using the PrimerQuest program (Integrated DNA Technologies, Inc.).

Results. For the first time, researchers established the features of clinical and immunological manifestations in allergic, non-allergic phenotypes of occupational bronchial asthma, as well as phenotypes of combination of occupational bronchial asthma with occupational chronic obstructive pulmonary disease and metabolic syndrome (MS), genetic markers of the risk of developing OBA when exposed to sensitizing substances were also identified: polymorphic variants rs2069812 of the IL-5 gene and polymorphic variants rs1837253 of the TSLP gene. This allows us to recommend the determination of these immunological parameters and genetic markers during in-depth periodic medical examinations in persons working under the influence of sensitizing and irritating substances for differential diagnosis in various phenotypes of occupational bronchial asthma.

Limitation. The study has regional (Samara region) and professional (in terms of detailing the working conditions in the studied comparison groups) limitations.

Conclusion. The revealed clinical, immunological and genotypic features in various phenotypes of occupational bronchial asthma, the established genotypic profiles of occupational bronchial asthma make it possible to optimize the approach to early diagnosis, prognosis, prevention and pharmacotherapy of this disease, as well as expand the list of immunological indicators and genetic studies used during preliminary and periodic medical examinations, in-depth examination of patients with occupational bronchial asthma in occupational disease clinics and occupational pathology centers, the use of new significant criteria for predicting the course of the disease.

Ethics. The study was carried out within the Framework of the complex topic of the Department of Occupational Diseases and Clinical Pharmacology named after Honored Scientist of the Russian Federation Professor V.V. Kosarev of Samara State Medical University «A systematic approach to early diagnosis, prevention and prediction of the impact of low-intensity production factors on the health of workers» (State registration number AAAA18-118122190069-6, date of statement registered on December 21, 2018). The study was approved by the local Ethics Committee of the Samara State Medical University of the Ministry of Health of the Russian Federation on 11/23/2021. Each participant of the study gave informed voluntary written consent to participate in the study and publish personal medical information in an impersonal form in the journal «Russian Journal of Occupational Health and industrial Ecology» («Meditsina truda i promyshlennaya ekologiya»).

Contribution:
Strizhakov L.A. — the concept and design of the study, writing the text, editing, approval of the final version of the article, responsibility for the integrity of all parts of the article;
Babanov S.A. — research concept and design, data collection and processing, text writing, editing, approval of the final version of the article, responsibility for the integrity of all parts of the article;
Lavrentieva N.E. — writing the text, editing, approval of the final version of the article, responsibility for the integrity of all parts of the article;
Baikova A.G. — data collection and processing, approval of the final version of the article, responsibility for the integrity of all parts of the article
Agarkova A.S. — writing the text, editing, approval of the final version of the article, responsibility for the integrity of all parts of the article;
Melentyev A.V. — writing the text, editing, approval of the final version of the article, responsibility for the integrity of all parts of the article.

Funding. The study had no funding.

Conflict of interests. The authors declare no conflict of interests.

Received: 12.03.2024 / Accepted: 09.06.2024 / Published: 20.08.2024

1. Vasil’eva O.S., Sorkina N.S. Professional bronchial asthma. In: Izmerov N.F., Chuchalin A.G. red. Occupational diseases of the respiratory system: national guidelines. M.: GEOTAR-Media; 2015: 338–363 (in Russian).

2. Spirin V.G., Velichkovskiy B.T., Vasil’eva O.S. Occupational bronchial asthma. V kn.: Spirin V.G., Velichkovskiy B.T., Vasil’eva O.S. Occupational hygiene and respiratory diseases in livestock and feed production workers. Saratov: Saratov. gos. agrar. un-t im. N.I. Vavilova; 2002: 111–124 (in Russian).

3. Mukhin N.A., Babanov S.A. red. Occupational diseases. A guide for doctors. M.: GEOTAR-Media; 2018 (in Russian).

4. Izmerov N.F. red. Occupational pathology. National Leadership. M.: GEOTAR-Media; 2011 (in Russian).

5. Babanov S.A., Budash D.S., Baykova A.G., Baraeva R.A. Periodic medical examinations and professional selection in industrial medicine. Zdorov’e naseleniya i sreda obitaniya. 2018; 5(302): 48–53 (in Russian).

6. Strizhakov L.A., Babanov S.A., Budash D.S., Lebedeva M.V., Baykova A.G., Vostroknutova M.Yu. et al. Immunological features and prognosis in modern forms of occupational lung diseases. Meditsina truda i promyshlennaya ekologiya. 2020; 60(2): 81–88 (in Russian).

7. Babanov S.A., Strizhakov L.A., Baykova A.G., Vostroknutova M.Yu., Agarkova A.S., Ostryakova N.A. et al. Occupational bronchial asthma (workplace asthma): diagnosis, examination of the connection of the disease with the profession, treatment. Vrach. 2021; 32(7): 17–24 (in Russian).

8. Nenasheva N.M. Phenotypes of bronchial asthma and the choice of therapy. Prakticheskaya pul’monologiya. 2014; 2: 2–11 (in Russian).

9. Henneberger P.K., Redlich C.A., Callahan D.B., Harber P., Lemiere C., Martin J. et al. An official American thoracic society statement: work-exacerbated asthma. American journal of respiratory and critical care medicine. 2011; 184(3): 368–378. https://doi.org/10.1164/rccm.812011ST

10. Kogevinas M., Zock J.P., Jarvis D., Kromhout H., Lillienberg L., Plana E., et al. Exposure to substances in the workplace and new-onset asthma: an international prospective population-based study (ECRHS-II). Lancet. 2007; 370(9584): 336–341. https://doi.org/10.1016/S0140-6736(07)61164-7

11. Lemiere C., Forget A., Dufour M.H., Boulet L.P., Blais L. Characteristics and medical resource use of asthmatic subjects with and without workrelated asthma. J Allergy Clin Immunol. 2007; 120(6): 1354–1359. https://doi.org/10.1016/j.jaci.2007.07.043

12. Maestrelli P., Saetta M., Mapp C., Fabri L.M. Mechanisms of occupational asthma. Clin. Exp. Allergy. 1997; 27(1): 47–54. https://doi.org/10.1111/j.1365-2222.1997.tb01826.x

13. Tilles S.A., Jerath Tatum A. Differential diagnosis of occupational asthma. Immunol. Allergy Clin. N. Am. 2003; 23: 167–176. https://doi.org/10.1016/s0889-8561(02)00089-9

14. Sastre J., Vandesplas O., Park H.S. Pathogenesis of occupational asthma. Eur. Respir. J. 2003; 22: 364–367. https://doi.org/10.1183/09031936.03.00045103

15. Silveira E., Taft C., Sundh V., Waern M., Palsson S., Steen B. Performance of the SF-36 health survey in screening for depressive and anxiety disorders in an elderly female Swedish population. Qual Life Res. 2005; 14(5): 1263–1274. https://doi.org/10.1007/s11136-004-7753-5

16. Schatz M., Hsu J.W., Zeiger R.S., Chen W., Dorenbaum A., Chipps B.E. et al. Phenotypes determined by cluster analysis in severe or intractable asthma. J. Allergy Clin. Immunol. 2014; 133(6): 1549–1556. https://doi.org/10.1016/j.jaci.2013.10.006