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

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 reac-tion (RT-PCR). Bacterial AECOPD were confirmed by sputum/BALF neutrophilia or elevated blood procalcitonin levels or by detect-ing 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, Doppler-echocardiography, 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 fac-tor-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, fibrin-ogen 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. © 2022, Remedium Group Ltd. All rights reserved.

Effectiveness of influenza and pneumococcal vaccines on chronic obstructive pulmonary disease exacerbations.

BACKGROUND AND OBJECTIVE: Single-study evidence of separate and combined effectiveness of influenza and pneumococcal vaccination in patients with chronic obstructive pulmonary disease (COPD) is limited. To fill this gap, we studied the effectiveness of trivalent seasonal influenza vaccine (TIV) and 23-valent pneumococcal polysaccharide vaccine (PPSV23), separately and together, at preventing adverse COPD outcomes. METHODS: Our study used a self-controlled, before-and-after cohort design to assess the effectiveness of TIV and PPSV23 in COPD patients. Patients were recruited from hospitals in Tangshan City, Hebei Province, China. Subjects self-selected into one of the three vaccination schedules: TIV group, PPSV23 group and TIV&PPSV23 group. We used a physician-completed, medical record-verified questionnaire to obtain data on acute exacerbations of COPD (AECOPD), pneumonia and related hospitalization. Vaccine effectiveness was determined by comparing COPD outcomes before and after vaccination, controlling for potential confounding using Cox regression. RESULTS: We recruited 474 COPD patients, of whom 109 received TIV, 69 received PPSV23 and 296 received TIV and PPSV23. Overall effectiveness for preventing AECOPD, pneumonia and related hospitalization were respectively 70%, 59% and 58% in the TIV group; 54%, 53% and 46% in the PPSV23 group; and 72%, 73% and 69% in the TIV&PPSV23 group. The vaccine effectiveness without COVID-19 non-pharmaceutical intervention period were 84%, 77% and 88% in the TIV group; 63%, 74% and 66% in the PPSV23 group; and 82%, 83% and 91% in the TIV&PPSV23 group. CONCLUSION: Influenza vaccination and PPSV23 vaccination, separately and together, can effectively reduce the risk of AECOPD, pneumonia and related hospitalization. Effectiveness for preventing AECOPD was the greatest.

Study of respiratory viruses and their coinfection with bacterial and fungal pathogens in acute exacerbation of chronic obstructive pulmonary diseases.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) develop acute exacerbations (AE), with varying natural history. The exacerbation is triggered by infection, leading to increased morbidity and mortality. The study on infectious aetiology of AECOPD is largely restricted to only viral or only bacterial aetiology. There are no studies from India that have investigated multiple viral, bacterial, and fungal associations from the same group of patients. This prospective study was conducted over 2 years to estimate the incidence and profile of viral infections in AECOPD patients, their coinfection with other bacterial and fungal agents, and association of the type and pattern of infective agent with the clinical severity. MATERIALS AND METHODS: Seventy-four AECOPD cases were included in the study. Multiplex polymerase chain reaction was performed from nasopharyngeal swab using Fast Track Diagnostics Respiratory Pathogens 21 Plus Kit. Ziehl-Neelsen (ZN) stain, Modified ZN, and potassium hydroxide (KOH) mount were performed for Mycobacteria, Nocardia, and fungal elements. Bacterial cultures and fungal cultures were done as per the standard techniques. Serum samples were tested for Mycoplasma and Chlamydia pneumoniae immunoglobulin M enzyme-linked immunosorbent assay. RESULTS: The number of AECOPD events involving only viral infection, only bacterial infection, bacterial-viral coinfection, and no infection were 43 (58.1%), 32 (43.2%), 20 (27%), and 19 (25.7%), respectively. Influenza A virus was the most common virus (22/43, 51%) identified. In 26 patients, monoviral infections were found, and in 17 patients, polyviral infections were identified, the most common pattern being influenza A and B virus, followed by human rhinovirus and human parainfluenza. The most common bacteria isolated were Pseudomonas aeruginosa (9/32,28%) followed by Acinetobacter baumanii and Klebsiella pneumoniae (7/32, 21%). Among the viral-bacterial coinfection, human coronavirus NL63 infection was always associated with a bacterial infection. CONCLUSION: This information on the various viral and bacterial etiologies of respiratory infections in AECOPD in this part of India will improve the understanding of the management of AECOPD using a timely institution of antivirals and reduce the overuse of antibiotics and the implementation of routine influenza vaccination.