Clinical and molecular features of virus-induced acute exacerbations of chronic obstructive pulmonary diseas

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.

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