CLINICAL AND FUNCTIONAL, CELLULAR AND MOLECULAR CHARACTERISTICS OF OCCUPATIONAL CHRONIC OBSTRUCTIVE PULMONARY DISEASE DEPENDING ON THE COMPOSITION OF UNINTENTIONAL NANOPARTICLES
Authors:   Novosibirsk State Medical University, Novosibirsk, Russia, Shpagina L.A. , Zenkova M.A. ,   Institute of Chemical Biology and Fundamental Medicine SB RAS, Novosibirsk, Russia, Shpagin I.S. ,   Novosibirsk State Medical University, Novosibirsk, Russia, Anikina E.V. ,   Novosibirsk State Medical University, Novosibirsk, Russia, Kotova O.S. ,   Novosibirsk State Medical University, Novosibirsk, Russia, Logashenko E.B. ,   Institute of Chemical Biology and Fundamental Medicine SB RAS, Novosibirsk, Russia
Published: December 2022

Introduction. Occupational chronic obstructive pulmonary disease (OCOPD) is characterized by steadily progressive persistent bronchial obstruction and emphysema, which leads to disability and reduced life expectancy of patients. Industrial aerosols are one of the main occupational health risks. According to Federal State Statistics Service, 4.5% of all workers are exposed to aerosols of predominantly fibrogenic action, 7.7% – to a chemical factor. At present, the determination of the physicochemical properties of nanoparticles and the study of their effect on the phenotype of occupational bronchopulmonary pathology are still insufficiently studied. Aim of the research. To identify clinical, functional, cellular and molecular features of the phenotype of occupational chronic obstructive pulmonary disease under exposure to aerosols with unintentional nanoparticles of various compositions. Materials and methods. A single-center cohort study was performed. Patients with OCOPD (GOLD 2011-2021 criteria) who worked under conditions of exposure to aerosols containing unintentional nanoparticles were included (n = 70). Comparison group – COPD due to tobacco smoking (n = 70), control – conditionally healthy (n = 70). The groups are comparable in terms of demographic indicators, duration of the disease. Nanoparticles in the air of the working area were determined by inductively coupled plasma atomic emission spectrometry (ICP-AES) and scanning electron microscopy. At the workplaces, in 36 persons, the mass concentration of metal nanoparticles was the highest, in 34 persons – that of silica nanoparticles. Spirography, body plethysmography, assessment of the diffusing capacity of the lungs (DLco/Va) for carbon monoxide (DLco/Va), cytological examination of induced sputum were performed. Markers of cellular inflammation and fibrosis were studied: interleukin-1β (IL1-β), interleukin-5 (IL-5), C-reactive protein (CRP), fibroblast growth factor-2 (FGF-2), transforming growth factor-β1 (TGF-β1), procollagen type 3 N-terminal propeptide (PIIINP), matrix metalloproteinase-1 (MMP-1), matrix metalloproteinase-9 (MMP-9), soluble vascular cell adhesion molecule-1 (sVCAM 1) and distribution subpopulations of blood monocytes by flow cytometry. Correlations were determined by the method of linear regression. Results. The clinical and functional peculiar characteristics of COPD when exposed to aerosols with metal nanoparticles are: the greatest severity of dyspnea according to mMRC scale 2.35 ± 0.120 points, dry cough with paroxysms 75.0%, low quality of life 70.8 ± 5.68 points, ventilation function of the lungs with the greatest severity of bronchial obstruction (Raw 0.66 kPa s/l, FEV1 36%) and static pulmonary hyperinflation (functional residual capacity (FRC) 192%, residual volume of the lungs (PRV) 187%), maximum pulmonary hypertension (37 mm Hg), the lowest values of DLco 36%. The cellular and molecular composition in OCOPD from exposure to metal nanoparticles is characterized by: eosinophilic type of inflammation 47.2%, the highest level of classical monocytes 95.4%, high expression of CCR5 21.56%, elevated serum concentrations of PIIINP 156.7 ± 15.23 ng/mL, IL-5 2.1 ± 0.42 pg/mL and MMP-9 346.2 ± 31.74 pg/mL. In COPD due to expose to industrial aerosols containing silica nanoparticles, the disease is characterized by the least severity of dyspnea mMRC 1.64 ± 0.118 points, the presence of a pronounced dry cough 61.7%, a significant decrease in DLco/Va (47%) with the least severity of bronchial obstruction (Raw 0.51 kPa s/l, FEV1 56%) and pulmonary hyperinflation. The cellular and molecular features of COPD from exposure to silica nanoparticles include: paucigranulocytic type of inflammation 44.1%, the lar¬gest proportion of non-classical CD14DimCD16+ monocytes – 21.1%, a significant level of CCR2 expression 11.10%, elevated serum concentrations of PIIINP 92, 1 ± 9.32ng/mL, FGF-2 16.1 ± 3.51pg/mL and sVCAM-1 46.1 ± 9.15 pg/mL. Reliable correlations between the mass concentrations of metal nanoparticles and classical monocytes (B = 1.6), silicon nanoparticles and nonclassical monocytes (B = 1.2) were determined. At the same time, classic monocytes were significant predictors of DLco (B = –1.7), functional residual lung capacity (B = 1.3), mean pulmonary artery pressure (B = –1.6), inflammation with eosinophilia (B = 1.2), non-classical monocytes – DLco (B = –1.4), paucigranulocytic inflammation (B = 1.3), p < 0.015. In the linear regression model, the mass concentration of metal nanoparticles is associated with the N-terminal propeptide of type 3 procollagen, interleukin-5, and matrix metalloproteinase-9. Serum PIIINP concentrations were associated with carbon monoxide diffusing capacity (DLco), IL-5 – with eosinophilic airway inflammation, and MMP-9 – with residual volume of lungs/total lung capacity (RV/TLC) ratio. The mass concentration of silica nanoparticles was associated with PIIINP, FGF-2 and sVCAM-1. In turn, the N-terminal propeptide of procollagen type 3 was associated with DLco, mean pulmonary artery pressure (MPAP); fibroblast growth factor-2 – with DLco, and sVCAM-1 – with MPAP (p < 0.01). Conclusion. Under conditions of exposure to industrial aerosol, various phenotypes of chronic obstructive pulmonary disease are formed depending on the composition of unintentional nanoparticles.