Chronic obstructive pulmonary disease due to aerosols containing nanoparticles: inflammation and phenotype features

Introduction. Influence of incidental nanoparticles of industrial aerosols on occupational lung diseases development is not studied enough. As nanoparticles has properties to induce inflammation and fibrosis, it is hypothesized that they affect occupational chronic obstructive pulmonary disease (COPD) phenotype. The aim was to establish monocyte subsets, airway inflammation, clinical and functional features in occupational COPD due to aerosols containing nanoparticles exposure. Materials and methods. Study design was a single center prospective cohort observational. Subjects with occupational COPD (GOLD 2011-2021 criteria) exposed to aerosols containing nanoparticles (n=50) enrolled. Comparison group - COPD in tobacco smokers (n=50), control group - healthy people (n=50). Groups were matched by demographics and COPD duration. Nanoparticles at workplaces air were measured by inductively coupled plasma atomic emission spectrometry and by scanning electron microscopy. Of participants 26 were exposed to maximal concentrations of metal nanoparticles and 24 - of silica nanoparticles. Spirography, body pletysmography, lung diffusing capacity (DLco/Va), Doppler-ehocardiography, induced sputum cytology, COPD exacerbations assessment were done. Monocyte subsets were determined by flow cytometry. Linear regression model was used to explore relationships. Results. COPD due to aerosols containing metal nanoparticles was characterized by most severe airflow limitation, lung hyperinflation, pulmonary hypertension, most prominent decrease in DLco/Va, frequent and severe COPD exacerbations, eosinophilic inflammation. The largest proportion of «classical» CD14+CD16- monocytes subset, 96,4% (90,3%; 97,2%), high level of CCR5 expression were seen in this group. The features of COPD due to aerosols containing silica nanoparticles were substantial decrease in DLco/Va, the least airflow limitation, mild lung hyperinflation, rare COPD exacerbations, paucigranulocytic inflammation. The largest proportion of «non-classical» CD14DimCD16+ monocytes with high level of CCR2 expression revealed. Mass concentration of metal nanoparticles was associated with «classical» monocytes, (B=1,5), silica nanoparticles - with «non-classical» monocytes (B=1,4). On their turn, «classical» monocytes were associated with DLco (B=-1,6), functional residual volume (B=1,2), mean pulmonary artery pressure (B=-1,4), eosinophilic inflammation. «Non-classical» monocytes were associated with DLco (B=-1,5) and paucigranulocytic inflammation (B=1,2), p<0,015. Conclusions. Exposure of incidental nanoparticles was associated with circulated monocyte subsets, airway inflammation and occupaitonal CODP phenotype.

LUNG FUNCTION IN SUBJECTS WITH OCCUPATIONAL CHRONIC OBSTRUCTIVE PULMONARY DISEASE EXPOSED TO INDUSTRIAL AEROSOLS CONTAINING NANOPARTICLES

Despite decrease in industrial aerosol impact on workers’ health there are disproportionately high prevalence of occupational lung diseases. So, it is of interest to investigate the role of nanoparticles. Objective was to establish lung function features in subjects with occupational chronic obstructive pulmonary disease (COPD) exposed to aerosols containing nanoparticles. Methods. It was a cross-sectional observational study. Subjects with occupational COPD (GOLD 2011-2021 criteria) exposed to aerosols containing metal (n=26) or silica nanoparticles (n=24) enrolled. Comparison group – tobacco smokers with COPD (n=50). Nanoparticles at workplaces air were measured by inductively coupled plasma atomic emission spectrometry and by scanning electron microscopy. Groups were matched by gender, age, COPD duration. Results. Occupational COPD in conditions of metal nanoparticles exposure was characterized by severe airflow limitation – forced expiratory volume in one second (FEV1) was 38%(35%;42%), by prominent increase in lung volumes – functional residual capacity (FRC) was 192% (184%;203%) and by highest decrease in diffusing lung capacity for carbon monoxide (DLco/Va), 34% (31%;38%). In occupational COPD subjects exposed to silica nanoparticles mild airflow limitation, mild increase in lung volumes and substantial decrease in DLco/Va, were seen. In logistic regression model metal nanoparticles mass concentration was associated with DLco/Va, FRC, FEV1, Raw and silica nanoparticles mass concentration – with DLco and FEV1. Conclusion. Nanoparticles in industrial aerosols are associated with occupational COPD phenotype.

PREDICTORS OF PHYSICAL ACTIVITY IN PATIENTS WITH PROFESSIONAL COPD

Chronic obstructive pulmonary disease (COPD) is one of the leading causes of morbidity worldwide. In patients with COPD, the level of physical activity is reduced, which is associated with an increased risk of adverse outcomes of this disease. At the same time, the problem of physical activity in patients with occupational COPD has been little studied. There are a number of factors affecting the physical activity of patients with COPD, one of which is exercise tolerance. To evaluate it, special tests are used, one of which is the 6-minute walk test. The aim of the study was to compare the characteristics of exercise tolerance in patients with COPD and occupational COPD. We analyzed the case histories of patients with an established diagnosis of COPD undergoing inpatient treatment and pulmonary rehabilitation. Patients (n - 35) were divided into two groups. The first group - patients with generalized COPD (n -17), men from 55.0 ± 20.0 years. The second group is patients with occupational COPD (n-18), men from 55.0 ± 20.0 years. All patients underwent a 6-minute walk test. The analysis of the results has been carried out. On average, patients with occupational COPD walked a shorter distance in 6 minutes, although these differences were not significant. In the group of occupational COPD, a larger percentage of patients had a worse prognosis in the prevention of cardiovascular complications. The 6-minute walk test can be used in combination with other assessment methods at the stages of pulmonary rehabilitation in order to determine the prognosis, determine the tolerance of physical activity.

EVALUATION OF EFFECTIVENESS OF SPIRIVA RESPIMAT FOR PATIENTS WITH OCCUPATIONAL COPD

Spiriva respimat proved to be an effective and safe medication for medical treatment of patients who suffer from moderately severe occupational COPD. Spiriva respimat has advantages of glycopyrronium bromide: functional indices (FEV1 forced expiratory volume during the first second), clinical data (dyspnea), quality of patients’ life, frequency of exacerbations, the period before the first exacerbation happens, and patient compliance.

ACUTE EXACERBATIONS OF OCCUPATIONAL CHRONIC OBSTRUCTIVE PULMONARY DISEASE DUE TO INDUSTRIAL AEROSOLS CONTAINING

Phenotypes of exacerbations of occupational chronic obstructive pulmonary disease (COPD) due to aerosols containing nanoparticles is not studied enough. The objective was to establish rate, severity, cellular type of inflammation, clinical features of acute exacerbations of occupational COPD due to industrial aerosols containing nanoparticles exposure. Materials and methods. A prospective observational study of 50 subjects with occupational COPD (of which 26 due to aerosols, containing metal nanoparticles and 24 due to aerosols containing silica nanoparticles) and of 50 subjects with COPD due to tobacco smoke performed. Follow up period was 26 (24; 30) months. Groups were matched by age, gender, COPD duration. Groups of occupational COPD has the same smoking status. Nanoparticles and dust concentrations at workplaces air were measured by inductively coupled plasma atomic emission spectrometry and by scanning electron microscopy. COPD exacerbations rate and severity, cellular type of inflammation during exacerbations were investigated. Relationships were assessed by Cox proportional-hazards regression. Results. Occupational COPD due to aerosols containing metal nanoparticles exposure was characterized by high exacerbation rate. In comparison to occupational COPD due to aerosols containing silica nanoparticles exposure the hazard ratio (HR) was 4,59, 95% CI 1,35–15,63, in relation to COPD in tobacco smokers HR was 3,35, 95% CI1,22 – 9,21. The risk of exacerbations requiring hospitalization also was higher in this group, HR 4,35, 95% CI 1,10-12,3 and HR 3,90, 95% CI 1,33–11,42, respectively. In occupational COPD due to aerosols containing silica nanoparticles the exacerbation rate was the least. Metal nanoparticles mass concentration at the workplace air was associated with COPD exacerbations HR 1,031, 95% CI 1,012–1,11, exacerbations requiring hospitalization HR 1,028, 95% CI 1,010–1,092 and with eosinophilic inflammation during COPD exacerbation ОР 0,015, 95% CI 0,002 – 0,036. Silica nanoparticles mass concentration was associated with COPD exacerbations HR 0,025, 95% CI 0,003–0,094, exacerbations requiring hospitalization HR 0,021, 95% CI 0,009–0,105 and with neutrophilic inflammation during COPD exacerbation HR 1,019, 95% CI 1,008–1,057. Exacerbations of occupational COPD due to aerosols containing nanoparticles exposure had higher rate of respiratory support and excess length of hospital stay. Conclusion. Occupational COPD exacerbations are associated with chemical composition and mass concentration of nanoparticles in industrial aerosols

Oxidized low-density lipoproteins and its connection with dyslipidemia, inflammatory markers, and oxidative stress in patients with occupational chronic obstructive pulmonary disease

The role of low-density oxidized lipoproteins (OxLDL) in the pathogenesis of occupational chronic obstructive pulmonary disease (COPD) is not understood well enough.The study aims to determine the serum levels of oxidized low-density lipoproteins and their relationship with lipid profile, the level of oxidative stress and level C-reactive protein in patients with occupational chronic obstructive pulmonary disease.Methods. 116 patients diagnosed with occupational COPD and 25 patients with no respiratory diseases (comparison group) were examined. Serum levels of OxLDL was determined by solid phase enzyme-linked immunosorbent assay (ELISA) using the commercial reagent kit MDA-oxLDL from Biomedica Gruppe, Austria.Results. Circulating OxLDL was detected in serum in a significant proportion of patients with stable occupational COPD. In most of the patients, the concentration of OxLDL was within the values observed in the comparison group or exceeded them by no more than two times. In the minority of patients with occupational COPD (16.5%), the concentration of OxLDL was high and 4 – 10 times higher than its average value in the comparison group. It can be assumed that the revealed differences in the concentration of OxLDL are due to the different degree and intensity of oxidation of low-density lipoproteins. The relationships between OxLDL and lipid metabolism, oxidative stress (OS), the antioxidant capacity of serum (AOS), and serum levels of C-reactive protein were described.Conclusion. Serum OxLDL levels in patients with occupational COPD, the relationship between OxLDL and lipid metabolism, oxidative stress, and inflammation will provide an expanded view of the pathogenetic aspects of occupational COPD.

Molecular Markers in Occupational Chronic Obstructive Pulmonary Disease Comorbid with Heart Failure

Background.Comorbid heart failure (HF) is common in chronic obstructive pulmonary disease (COPD). Comorbid condition features are studied well in COPD due to tobacco smoke. There is a lack of data about mechanisms, clinical and functional specificity of occupational COPD and HF comorbidity. As occupational COPD and HF share common symptoms and sometimes lung function disorders, there is an unmet need in new markers of HF in occupational COPD.Aims to establish molecular markers associated with occupational COPD with HF comorbidity.Methods.Subjects with occupational COPD were enrolled in a single-center prospective cohort observational study. Comparison group COPD due to tobacco smoke. Then groups were stratified according to HF so the following subgroups were compared: occupational COPD with HF (n=63), occupational COPD without HF (n=52), COPD due to tobacco smoke with HF (n=41), COPD due to tobacco smoke without HF (n=74). Control group healthy people (n=115). Groups were matched by demographics, duration of COPD and HF. CODP was diagnosed according to GOLD 20112020 criteria, HF according to Russian Federal clinical guidelines. Occupational etiological factors were silica dust, organic solvents, metal fumes. Clinical and functional characteristics of CODP and HF were obtained. Serum levels of pulmonary and activation-regulated chemokine (PARC/CCL-18), protein S100, troponin, N terminal pro brain natriuretic peptide (NT-pro-BNP), von Willebrand factor, C-reactive protein were measured by enzyme linked immunosorbent assay, fibrinogen were measured by Clauss method, lactate dehydrogenase, creatine phosphokinase, alanine aminotransferase, aspartate aminotransferase were measured by standard biochemical method. Data are presented as median and interquartile range. Linear regression were used to explore relationships.Results.The molecular specificity of occupational COPD comorbid with HF were the largest increase in serum concentration of PARC-CCL18, NT-pro-BNP, protein S100, troponin, von Willebrand factor and fibrinogen. This factors were associated with length of service. For PARC-CCL18 В=1.1; for NT-pro-BNP В=0.9; for protein S100 В=1.3; for troponin В=0.8, for von Willebrand factor В=1.5 and for fibrinogen В=1.1. Molecular factors also were related to phenotype characteristics of COPD and HF. In multiply regression model the best predictors of comorbidity of CODP and HF were PARC-CCL18 (В=1.1; р=0.002), NT-pro-BNP (В=1.5; р=0.001), protein S100 (В=1.2; р=0.002), troponin (В=0.9; р=0.003). The model was adjusted for gender, age, duration of CODP and HF, FEV1.Conclusions.Occupational CODP comorbid with heart failure is the distinct phenotype. The perspective molecular markers of this phenotype are serum levels of PARC-CCL18, NT-pro-BNP, protein S100, troponin.

Never-smokers with occupational COPD have better exercise capacities and ventilatory efficiency than matched smokers with COPD

It is unknown whether or not never-smokers with chronic obstructive pulmonary disease (COPD) behave like their smoking counterparts during exercise. This is the first study showing that never-smokers with mild to moderate COPD [defined by a postbronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) < lower limit of normal] have preserved exercise capacities. They also have lower exertional dyspnea than patients with smoking-related COPD. This suggests that the two COPD groups should not be managed in the same way.

Predictors of hospitalizations for heart failure decompensation in patients with comorbid occupational chronic obstructive pulmonary disease

Background Heart failure decompensation requiring hospitalization is an important event, associated with mortality and investigating its predictors is topical problem. Chronic obstructive pulmonary disease (COPD) is a common comorbidity for heart failure. Both conditions share common molecular mechanisms such as systemic inflammation. COPD is heterogeneous and subpopulations with different inflammation patterns may interact with heart failure in different manner. Airway inflammation in occupational COPD may differs from COPD in tobacco smokers. Additionally cardiotoxicity of industrial chemicals influence heart failure features. Despite this biological plausibility, heart failure and occupational COPD comorbidity is not studied enough. Purpose To reveal predictors of hospitalizations for heart failure decompensation in patients with heart failure and occupational COPD comorbidity. Methods Occupational COPD patients (n=115) were investigated in a prospective cohort observational study. Comparison group – 115 tobacco smokers with COPD. Control group – 115 healthy persons. Controls were selected by propensity score matching, covariates were COPD duration, age and gender. Then COPD groups were stratified according to heart failure. Working conditions, echocardiography, spirometry, pulsoxymetry, 6-mitute walking test were done. Molecular markers of tissue damage – chemokine ligand 18 (CCL 18), lactate dehydrogenase, cardiac troponin T, N-terminal pro-B-type natriuretic peptide (NT pro-BNP), protein S100 beta, von Willebrand factor were measured in serum by ELISA. Follow up after initial assessment was 12 month. Predictors were determined by Cox proportional hazards regression with ROC analysis. Results Heart failure rate in occupational COPD patients were higher – 54.8% versus 36.5% in tobacco smokers with COPD, p&lt;0.05. Heart failure with preserved ejection fraction was predominant – 40.9%. Prevalence of biventricular heart failure was 38.3%, isolated right heart failure – 13%, left heart failure – 2.6%. Cumulative hospitalization rate in occupational COPD with heart failure group was higher than in comparison group, 17.5% and 9.5% respectively, p=0.01. In Cox proportional hazards regression model predictors of hospitalizations for heart failure decompensation during 12 months in this group were length of service (HR 1.22, 95% CI: 1.03–2.5), aromatic hydrocarbons concentration at workplaces air (HR 1.4, 95% CI: 1.15–1.96), serum protein S100 beta (HR 1.10, 95% CI: 1.02–1.87), SaO2 (HR 1.2, 95% CI: 1.06–2.13). Area under the ROC curve was 0.82. Conclusion Length of service, aromatic hydrocarbons concentration at workplaces air, serum protein S100 beta, SaO2 are considered to be independent risk factors of heart failure decompensation required hospitalization in patients with heart failure and occupational COPD comorbidity. Funding Acknowledgement Type of funding source: None