Cellular and molecular features of occupational-related chronic obstructive pulmonary disease (OCOPD) in combination with malignant neoplasm

Introduction. The development of malignant neoplasms (MNs) in people who have worked in contact with industrial aerosols is a complex mechanism associated with exposure to carcinogens and chronic occupational respiratory diseases, including chronic obstructive pulmonary disease (COPD). The heterogeneity of occupational-related chronic obstructive pulmonary disease suggests differences in the predisposition to oncogenesis.

The study aims to determine the clinical, functional, and cellular-molecular characteristics of OCOPD in combination with malignant neoplasm (MN).

Materials and methods. Design: a single-center, one-step comparative study. The main group consisted of patients with OCOPD, which occurs as a result of exposure to silicon-containing dust in combination with malignant neoplasms. The comparison group consisted of patients with OCOPD without malignant neoplasms, patients with COPD in tobacco smokers with malignant neoplasms and without MN (in each group n=30 people, the comparison groups were selected by the pseudorandom method, the parameters for comparison were age, duration of respiratory symptoms). The authors evaluated the symptoms, lung function, fibrobronchoscopy, brush biopsy of the bronchial mucosa with cytological and immunohistochemical examination, as well as the study of blood molecular factors by solid-phase enzyme immunoassay. Statistical data processing included standard methods of descriptive statistics, group comparison — the Kruskall–Wallis test, and relationship analysis — logistic regression.

Results. Occupational-related COPD, in combination with malignant neoplasm, was characterized by a decrease in lung diffusion capacity — Me (Q2–Q3) by 39 (35–42)% in the comparison groups 51 (48–55)%, 60 (56–63)% and 58 (55–62)% — frequent exacerbations, small-cell type of inflammation, severity bronchial atrophy, increased Ki-67 expression by epithelial cells — 35 (30–44)% ; in comparison groups 10 (8–12)%, 17 (14–18)% and 15 (13–19)%, serum concentrations of procollagen type 3 N-terminal propeptide (PIIINP) — 162.3 (155.4–173.5) pg/ml, in the comparison groups — 95.0 (83.7–98.1) pg/ml, 31.9 (25.6–35.2) pg/ml and 28.3 (24.8–34.6) pg/ml, 8-hydroxy-2-deoxyguanosine (8 OHdG), D-dimer. In a multifactorial analysis, the most significant independent factors associated with squamous cell carcinoma in OCOPD were work experience (OR 1.9, 95% CI 1.5–2.4, p=0.001), Ki-67 expression by epithelial cells (OR 1.5, 95% CI 1.1–6.2, p=0.001), D-dimer (OR 1.4, 95% CI 1.03–2.7, p=0.003). Work experience (OR 1.7, 95% CI 1.4–5.9, p=0.001), PIIINP concentration in blood (OR 1.6, 95% CI 1.3–1.9, p=0.001), 8 OHdG (OR 1.3, 95% CI 1.04–4.9, p=0.005) were associated with adenocarcinoma.

Limitations. Limitations of the study relate to the recruitment and examination of patients at a single center. Environmental factors assessments included only assessments of working conditions and smoking status.

Conclusion. Under the conditions of exposure to silicon-containing dust, occupational-related chronic obstructive pulmonary disease in combination with malignant neoplasms is characterized by a decrease in the diffusional ability of the lungs, the frequency of exacerbations, small cell inflammation, the severity of bronchial atrophy, increased expression of Ki-67, serum concentrations of PIIINP, 8 OHdG and D-dimer.

Ethics. The study was conducted in compliance with the Ethical principles set out in the Helsinki Declaration of the World Medical Association and in accordance with the ethical standards and regulations stipulated in the Bulletin of the Higher Attestation Commission of the Ministry of Education of the Russian Federation No. 3 of 2002. The study was approved by the Ethics Committee of the Federal State Budgetary Educational Institution of Higher Medical Education of the Ministry of Health of the Russian Federation, Protocol No. 121 dated 11/21/2019.

Contribution:
Shpagina L.A. — research concept and design, data collection and interpretation, text writing;
Shpagin I.S. — research concept and design, data collection and interpretation, text writing;
Kondyurina E.G. — data collection and interpretation;
Zelenskaya V.V. — data collection and interpretation;
Kotova O.S. — collecting and interpreting data, writing text;
Karmanovskaya S.A. — data collection and interpretation;
Kuznetsova G.V. — data collection and interpretation;
Kamneva N.V. — data collection and interpretation;
Smarzh T.M. — data collection and interpretation;
Lushnikova V.D. — data collection and interpretation;
Zemlyukova M.I. — data collection and interpretation.

Funding. The study had no funding.

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

Received: 05.02.2025 / Accepted: 17.02.2025 / Published: 05.03.2025

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