Introduction. Inflammation in viral-induced acute exacerbations of chronic obstructive pulmonary disease (COPD) is not studied enough.The aim was to establish molecular pattern of inflammation in viral-induced acute exacerbations of chronic obstructive pulmonary disease (AECOPD) in comparison with bacterial AECOPD and to reveal associations with AECOPD phenotype and subsequent COPD progression.Materials and methods. Subjects hospitalized with acute exacerbations of COPD (AECOPD) of which 60 were viral, 60 were bacterial and 60 were viral-bacterial were recruited to single center prospective (52 weeks) cohort study. Control group – 30 healthy people. COPD were diagnosed previously during stable phase of the disease according to spirographic criteria. Viral AECOPD were confirmed by detection of RNA of influenza A and B, respiratory syncytial virus, rhinovirus or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in sputum or bronchoalveolar lavage fluid (BALF) using reverse transcription-polymerase chain reaction (RT-PCR). Bacterial AECOPD were confirmed by sputum/BALF neutrophilia or elevated blood procalcitonin levels or by detecting bacteria by standard culture method. Plasma concentrations of cytokines, fibrotic markers, enzymes were measured by enzyme-linked immunosorbent assay, plasma fibrinogen – by Clauss method. Complex lung function investigation, Dopplerechocardiography, subsequent AECOPD assessment were done. Kruskal-Wallis and chi-square test were used to compare groups, Cox regression and linear regression – to explore relationships.Results. Viral AECOPD were characterized by highest plasma concentrations of Eosinophilic cationic protein (62,3 (52,4; 71,0) ng/ml)), interleukin-5 (IL-5) (11,3 (8,4; 15,9) pg/ml), fibroblast growth factor-2 (FGF-2) (10,4 (6,2; 14,9) pg/ml), transforming growth factor-β1 (TGF-β1) (922,4 (875,7; 953,8) pg/ml), hyaluronic acid (185,4 (172,8; 196,3) ng/ml), amino-terminal propeptide of type III procollagen (PIIINP) (249,2 (225,1; 263,7) ng/ml), matrix metalloproteinase-1 (MMP-1) (235,2 (208,6; 254,9) pg/ml). Levels of IL-5 during AE COPD was the predictor of FEV1, bronchodilation coefficient, subsequent exacerbations at remote period, fibrinogen was associated with FEV1, PIIINP and FGF-2 with DLco, PaO2, mean pulmonary artery pressure (mPAP), exacerbations, MMP-1 – with mPAP.Conclusions. In virus-induced AECOPD inflammation pattern differed from those in bacterial one and associated with AECOPD phenotype and COPD phenotype at the stable phase.
Aim. To establish symptoms, lung function and to evaluate subsequent exacerbations of chronic obstructive pulmonary disease (COPD) during a year after virus-induced COPD exacerbations. Materials and methods. Patients hospitalized with viral (n=60), bacterial (n=60) and viral-bacterial (n=60) COPD exacerbations were enrolled to single-center prospective observational study. COPD was diagnosed according spirography criteria. Viral infection was established in bronchoalveolar lavage fluid or sputum by real-time reverse transcription-polymerase chain reaction for RNA of influenza A and B virus, rhinovirus, respiratory syncytial virus and SARS-CoV-2. Symptoms, lung function, COPD exacerbations were assessed. Patients were investigated at the hospitalization onset and then 4 and 52 weeks following the discharge from the hospital. Results. After 52 weeks in viral and viral-bacterial COPD exacerbations groups the rate of forced expiratory volume in one second (FEV1) decline were maximal 71 (68; 73) ml/year and 69 (67; 72) ml/year versus 59 (55; 62) ml/year after bacterial exacerbations. Low levels of diffusion lung capacity for carbon monoxide (DLco/Va) 52.5% (45.1%; 55.8%), 50.2% (44.9%; 56.0%) and 75.3% (72.2%; 80.1%) respectively, of 6-minute walk distance; p0.001 in relation to bacterial exacerbations. In Cox proportional hazards regression analyses viral and viral-bacterial exacerbations were associated with increased risk of subsequent COPD exacerbations by 2.4 times independent of exacerbations rate before index event and FEV1. In linear regression models the relationships between airflow limitation and respiratory syncytial virus, rhinovirus and influenza virus infection, between low DLco/Va and rhinovirus, influenza virus and SARS-CoV-2 infection. Conclusion. COPD after virus-induced exacerbations were characterized by progression of airflow limitation, low DLco/Va, low 6-minute walking test distance, subsequent COPD exacerbations risk.
RATIONALE. Respiratory viruses are proven triggers for chronic obstructive pulmonary disease (COPD) exacerbations. Biomechanisms and phenotype of virus-induced exacerbations of COPD in conditions of industrial aerosol exposure is not studied enough. The objective of this study was to evaluate cellular, molecular and clinical features of occupational COPD exacerbations triggered by viral infection.METHODS. Subjects with COPD (GOLD 2011 criteria) were enrolled in a single center observational study at the onset of an exacerbation (GOLD definition). Overall, 230 exacerbations were captured from 209 subjects of which viral-induced occupational COPD exacerbations (n=60), bacterial (n=58) and non-infection (n=55) occupational COPD exacerbations, viral-induced COPD exacerbations in tobacco smokers (n=57). Occupational COPD causality were silica dust (30.5%), organic solvents (25.7%), welding fumes (26.3%), metal fumes (17.5%). Rhinovirus, respiratory syncytial virus, influenza virus in induced sputum were assessed by polymerase chain reaction. Bacteria were detected by routine culture method. Sputum concentrations of fibrotic markers, cytokines, growth factors, matrix metalloproteinases, eotaxin, neutrophil elastase were measured by ELISA. Sputum cytology assessment, spirometry, diffusion lung capacity of carbon monoxide (DL CO ), measurement of partial oxygen tension in arterial blood (PaO 2 ) was done. Relationships were assessed by multiple linear regression. Model were adjusted for age, gender, forced expiratory volume in one second (FEV1). Significance level 0.05.RESULTS. Virus-induced exacerbations in occupational COPD patients were characterized by prolonged hospital stay (median (IQR) was 14 (10; 16) days versus 10 (8; 11) days for bacterial, 8 (6; 10) days for non-infection and 7 (6; 10) days for viral exacerbations in tobacco smokers, p=0,010), need for respiratory support -in 13 (21.7%) exacerbations versus 7 (12.1%), 9 (16.4%) and 6 (10.5%) cases, p=0.002. DL CO and PaO 2 were significantly lower in studied group. DL CO was 27±2.5% versus 42±4.7%, 38±3.1% and 50±6.4%, p=0.004, PaO 2 was 58±6.13 mmHg versus, 71±4.2 mmHg, 64±5.7 mmHg and 75±2.39 mmHg, p=0.007. In virus-induced COPD exacerbations, as anticipated, an eosinophilic inflammation was seen. A greatest levels of sputum eotaxin, fibroblast growth factor 2, hyaluronic acid, procollagen III N-terminal propeptide (PIIINP), desmosine, matrix metalloproteinase 9 and the least level of sputum neutrophil elastase was seen in this group. In linear regression model sputum eotaxin (B=2.1), hyaluronic acid (B=1.5), PIIINP (B=1.7), DL CO (B=-1.5) and length of service (B=1.2) were associated with virus-induced exacerbations of occupational COPD. CONCLUSION. Viral exacerbations of occupational COPD are distinct phenotype, characterized by inflammation pattern, longer hospital length of stay, low DL CO , hypoxemia, high rate of need for respiratory support.
Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are associated with disease progression and increased risk of death. We need to better understand the phenotypes of AECOPD to improve treatment strategies. The main triggers of COPD exacerbations are viral and bacterial infections.The aim is to characterize the viral, bacterial, and viral-bacterial phenotypes of acute exacerbations in patients with COPD caused by industrial aerosol exposure or tobacco smoke.Methods. 180 subjects with established moderate and severe COPD who met the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria, 2020 – 2021, and were hospitalized with AECOPD, were enrolled in this prospective observational study. The virus-induced, bacteria-induced, and virus-bacteria-induced AECOPD strata (n = 60 each) were formed. Each stratum included 30 patients with occupational COPD and 30 patients with COPD caused by tobacco smoke. Virus-induced AECOPDs were diagnosed by PCR of bronchoalveolar fluid. Length of hospital stay, symptoms, lung function, mean pulmonary artery pressure (mPAP), and type of inflammation were assessed. Cox proportional hazard regression was used to examine the relationships.Results. The length of hospital stay was highest in patients with virus-induced and virus-bacteria-induced exacerbations of occupational COPD, being equal to (Me, IQR) 16.5 (14 – 18) and 18 (16 – 20) days. The virus-induced exacerbations in occupational COPD and in COPD caused by tobacco smoke featured the highest bronchodilation coefficient, 10.9 (9.8 – 11,5)% and 9.2 (8.3 – 10.3)%, respectively, decrease in the diffusing capacity of the lungs (DLCO/Va) by 42 (40 – 45)% and 49 (47 – 52)%, increase in mPAP by 44 (39 – 45) и 33 (29 – 38) mmHg, and eosinophilic inflammation with blood eosinophil count of 425 (385 –527) and 350 (310 – 391) cells per μl (р > 0.01). Virus-bacteria-induced AECOPD in occupational COPD and in COPD caused by smoke were characterized by decrease in FEV1 by 40.2 (36.6 – 42.2)% and 31.0 (28.1 – 33.6%), decrease in DLCO/Va by 48 (44 – 50)% and 37 (35 – 41)%, increase in mPA by 43 (38 – 46) and 50 (45 – 54) mmHg, and eosinophilic-neutrophilic inflammation in 63.3 and 66.6% of patients. The mid-range FEV1, highest DLCO/Va, and neutrophilic inflammation were seen in patients with bacteria-induced AECOPD.Conclusion. Exacerbations of occupational COPD are characterized by more severe functional impairment and inflammation with high eosinophil count when these exacerbations have viral origin.
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