Τίτλος:
Early increase of VEGF-A is associated with resolution of ventilator-associated pneumonia: Clinical and experimental evidence
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Background and objective: The role of vascular endothelial growth factor (VEGF)-A in the resolution of ventilator-associated pneumonia (VAP) was investigated in clinical and mouse pneumonia models. Methods: VEGF-A was measured for seven consecutive days by an immunosorbent assay in sera of 82 patients with VAP and changes from baseline were correlated with the resolution of VAP. Experimental animals were challenged intratracheally with Pseudomonas aeruginosa. Mouse bronchoalveolar lavage (BAL) samples and segments of lung tissue were obtained at 24, 48 and 124 h after bacterial challenge. Levels of VEGF-A, tumour Necrosis Factor alpha (TNF-α), interleukin (IL)-1β, interferon-gamma (IFNγ) and myeloperoxidase (MPO) activity were measured in these samples. Results: VAP resolved in 36.1% of patients with a less than 45% increase of VEGF-A on day 5 compared to 65.2% of patients with a more than 45% increase (P = 0.014). This was also accompanied by an earlier resolution of VAP (log-rank: 7.99; P = 0.005) and it was not pathogen-specific. The increase of VEGF-A was an independent variable associated with VAP resolution in forward logistic regression analysis where Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores were included as independent variables. VEGF-A in mouse BAL and lung tissue increased significantly at 124 h but not with the other mediators. In mice pre-treated with bevacizumab, VEGF-A concentrations decreased while TNF-α and MPO significantly increased. Conclusion: In patients, an association between increased levels of circulating VEGF-A and VAP resolution was observed. The mouse study suggests that elevated VEGF-A levels may be associated with lung inflammation resolution. Clinical trial registration: NCT00297674 at www.clinicaltrials.gov. © 2018 Asian Pacific Society of Respirology
Συγγραφείς:
Strouvalis, I.
Routsi, C.
Adamopoulou, M.
Raftogiannis, M.
Renieris, G.
Orfanos, S.E.
Kotanidou, A.
Sabracos, L.
Giamarellos-Bourboulis, E.J.
Εκδότης:
Blackwell Publishing Inc.
Λέξεις-κλειδιά:
bevacizumab; clarithromycin; colistimethate; gamma interferon; interleukin 1beta; myeloperoxidase; placebo; serum albumin; tumor necrosis factor; vasculotropin A; antiinfective agent; biological marker; clarithromycin; gamma interferon; IFNG protein, mouse; IL1B protein, mouse; interleukin 1beta; peroxidase; tumor necrosis factor; vascular endothelial growth factor A, mouse; vasculotropin A; VEGFA protein, human, animal experiment; animal model; animal tissue; APACHE; Article; bacterial overgrowth; blood sampling; controlled study; double blind procedure; enzyme activity; experimental mouse; follow up; human; immunoadsorption; independent variable; logistic regression analysis; lung lavage; lung parenchyma; major clinical study; mouse; neutrophil chemotaxis; nonhuman; priority journal; protein blood level; Pseudomonas pneumonia; randomized controlled trial; receiver operating characteristic; sensitivity and specificity; Sequential Organ Failure Assessment Score; ventilator associated pneumonia; animal; bacterial pneumonia; blood; bronchoalveolar lavage fluid; chemistry; metabolism; microbiology; prospective study; Pseudomonas aeruginosa; Pseudomonas infection; time factor; ventilator associated pneumonia, Animals; Anti-Bacterial Agents; APACHE; Biomarkers; Bronchoalveolar Lavage Fluid; Clarithromycin; Double-Blind Method; Humans; Interferon-gamma; Interleukin-1beta; Mice; Peroxidase; Pneumonia, Bacterial; Pneumonia, Ventilator-Associated; Prospective Studies; Pseudomonas aeruginosa; Pseudomonas Infections; Time Factors; Tumor Necrosis Factor-alpha; Vascular Endothelial Growth Factor A
