Effects of adjunct treatments on end-organ damage and histological injury severity in acute respiratory distress syndrome and multiorgan failure caused by smoke inhalation injury and burns. Issue 8 (December 2019)

• Record Type: Journal Article
• Authors: Choi, Jae Hyek; Necsoiu, Corina; Wendorff, Daniel; Jordan, Bryan; Dixon, Alexander; Roberts, Teryn R.; Beely, Brendan M.; Cancio, Leopoldo C.; Batchinsky, Andriy I.
• Is Part Of: Burns. Volume 45:Issue 8(2019)
• Page Start: 1765
• Page End: 1774
• Publication Date: 2019-12
• Subjects: Acute respiratory distress syndrome -- Multi organ failure -- Burns -- Mesenchymal stem cells -- Extracorporeal life support -- Smoke inhalation injury; Burns and scalds -- Periodicals; 617.11
• DOI: 10.1016/j.burns.2019.07.020
• Languages: English
• ISSNs: 0305-4179

Abstract

Highlights: Treatment after SII and burn with MSCs were effective in mitigating ARDS. Autologous MSC showed greater benefit than Allogeneic MSC. ECLS also showed therapeutic benefit, although not as robust as MSC treatment. Abstract: Background: We investigated effects of mesenchymal stem cells (MSC) or low-flow extracorporeal life support (ECLS) as adjunctive treatments for acute respiratory distress syndrome (ARDS) due to inhalation injury and burns. We hypothesized that these interventions decrease histological end-organ damage. Methods: Anesthetized female swine underwent smoke inhalation injury and 40% TBSA burns, then critical care for 72 h. The following groups were studied: CTR (no injury, n = 4), ICTR (injured untreated, n = 10), Allo (injured treated with allogenic MSC, n = 10), Auto (injured treated with autologous MSC, n = 10), Hemo (injured and treated with the Hemolung low flow ECLS system, n = 9), and Nova (injured and treated with the NovaLung low flow ECLS system, n = 8). Histology scores from lung, kidneys, liver, and jejunum were calculated. Data are presented as means ± SEM. Results: Survival at 72 h was 100% in CTR; 40% in ICTR; 50% in Allo; 90% in Auto; 33% in Hemo; 63% in Nova. ARDS developed in 0/10 CTR; 10/10 ICTR; 8/9 Hemo; 5/8 Nova; 9/10 Allo; 6/10 Auto. Diffuse alveolar damage (DAD) was present in all injured groups. MSC groups had significantly lower DAD scores than ICTR animals (Allo 26.6 ± 3.4 and Auto 18.9 ± 1.5 vs. ICTR 46.8 ± 2.1, p < 0.001). MSC groups also had lower DAD scores than ECLS animals (Allo vs. Nova, p < 0.05, Allo vs. Hemo p < 0.001, Auto vs. Nova p < 0.001, Auto vs. Hemo, p < 0.001). Kidney injury ICTR ( p < 0.05) and Hemo ( p < 0.01) were higher than in CTR. By logistic regression, a PaO2 -to-FiO2 ratio (PFR) < 300 was a function of the DAD score: logit (PFR < 300) = 0.84 + 0.072*DAD Score, odds ratio 1.074 (1.007, 1.147, p < 0.05) with a ROC AUC of 0.76, p < 0.001. Conclusion: Treatment with Auto MSC followed by Allo and then Nova were most effective in mitigating ARDS and MOF severity in this model. Further studies will elucidate the role of combination therapies of MSC and ECLS as comprehensive treatments for ARDS and MOF.