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• W2056511391 abstract "PurposeCalcineurin inhibitors are considered the backbone of lung transplant immunosuppression regimens. When used de novo, tacrolimus has been shown to be associated with fewer acute rejection episodes compared to cyclosporine. However, conflicting evidence exists regarding the superiority of tacrolimus or cyclosporine in preventing bronchiolitis obliterans syndrome (BOS). Furthermore, the effect of these drugs on fibroproliferation ultimately leading to BOS remains to be investigated.MethodsThe effect of tacrolimus and cyclosporine on collagen synthetic function of mesenchymal cells isolated from patients with BOS was investigated by western blot analysis. Furthermore, we investigate if conversion to cyclosporine at later time point post-lung transplantation can effect development of BOS. Patients transplanted between 2005-2012 at our institution were reviewed. Patients who were converted to cyclosporine greater 180 days post-transplant and had no evidence of BOS were compared to patients who continued on tacrolimus therapy. All patients received an antiproliferative agent and prednisone. Time to BOS was analyzed by Kaplan Meier.ResultsBOS mesenchymal cells treated with cyclosporine (5µm) demonstrated 76% decrease in baseline collagen protein expression (n=8, p = 0.0017). In comparison, BOS mesenchymal cells treated with tacrolimus (5µM) demonstrated no significant decline in collagen (n=6, p = 0.48). 17 of 200 (8.5%) patients transplanted between 2005-2012 were switched to cyclosporine post-transplant for a variety of reasons. Median time to conversion was 377 days (159-1968 days). Cyclosporine group was compared to 124 tacrolimus patients. Cyclosporine patients had a trend towards increased BOS free survival as compared to tacrolimus group (p value= 0.07 log rank test).ConclusionCyclosporine has a superior anti-fibrotic action on mesenchymal cells, and patients who were converted to it later than 180 days post-transplant have a lower rate of BOS. These findings bring forward the need to design future clinical studies investigating the utility and optimal timing of conversion to cyclosporine offsetting the risk of acute rejection. PurposeCalcineurin inhibitors are considered the backbone of lung transplant immunosuppression regimens. When used de novo, tacrolimus has been shown to be associated with fewer acute rejection episodes compared to cyclosporine. However, conflicting evidence exists regarding the superiority of tacrolimus or cyclosporine in preventing bronchiolitis obliterans syndrome (BOS). Furthermore, the effect of these drugs on fibroproliferation ultimately leading to BOS remains to be investigated. Calcineurin inhibitors are considered the backbone of lung transplant immunosuppression regimens. When used de novo, tacrolimus has been shown to be associated with fewer acute rejection episodes compared to cyclosporine. However, conflicting evidence exists regarding the superiority of tacrolimus or cyclosporine in preventing bronchiolitis obliterans syndrome (BOS). Furthermore, the effect of these drugs on fibroproliferation ultimately leading to BOS remains to be investigated. MethodsThe effect of tacrolimus and cyclosporine on collagen synthetic function of mesenchymal cells isolated from patients with BOS was investigated by western blot analysis. Furthermore, we investigate if conversion to cyclosporine at later time point post-lung transplantation can effect development of BOS. Patients transplanted between 2005-2012 at our institution were reviewed. Patients who were converted to cyclosporine greater 180 days post-transplant and had no evidence of BOS were compared to patients who continued on tacrolimus therapy. All patients received an antiproliferative agent and prednisone. Time to BOS was analyzed by Kaplan Meier. The effect of tacrolimus and cyclosporine on collagen synthetic function of mesenchymal cells isolated from patients with BOS was investigated by western blot analysis. Furthermore, we investigate if conversion to cyclosporine at later time point post-lung transplantation can effect development of BOS. Patients transplanted between 2005-2012 at our institution were reviewed. Patients who were converted to cyclosporine greater 180 days post-transplant and had no evidence of BOS were compared to patients who continued on tacrolimus therapy. All patients received an antiproliferative agent and prednisone. Time to BOS was analyzed by Kaplan Meier. ResultsBOS mesenchymal cells treated with cyclosporine (5µm) demonstrated 76% decrease in baseline collagen protein expression (n=8, p = 0.0017). In comparison, BOS mesenchymal cells treated with tacrolimus (5µM) demonstrated no significant decline in collagen (n=6, p = 0.48). 17 of 200 (8.5%) patients transplanted between 2005-2012 were switched to cyclosporine post-transplant for a variety of reasons. Median time to conversion was 377 days (159-1968 days). Cyclosporine group was compared to 124 tacrolimus patients. Cyclosporine patients had a trend towards increased BOS free survival as compared to tacrolimus group (p value= 0.07 log rank test). BOS mesenchymal cells treated with cyclosporine (5µm) demonstrated 76% decrease in baseline collagen protein expression (n=8, p = 0.0017). In comparison, BOS mesenchymal cells treated with tacrolimus (5µM) demonstrated no significant decline in collagen (n=6, p = 0.48). 17 of 200 (8.5%) patients transplanted between 2005-2012 were switched to cyclosporine post-transplant for a variety of reasons. Median time to conversion was 377 days (159-1968 days). Cyclosporine group was compared to 124 tacrolimus patients. Cyclosporine patients had a trend towards increased BOS free survival as compared to tacrolimus group (p value= 0.07 log rank test). ConclusionCyclosporine has a superior anti-fibrotic action on mesenchymal cells, and patients who were converted to it later than 180 days post-transplant have a lower rate of BOS. These findings bring forward the need to design future clinical studies investigating the utility and optimal timing of conversion to cyclosporine offsetting the risk of acute rejection. Cyclosporine has a superior anti-fibrotic action on mesenchymal cells, and patients who were converted to it later than 180 days post-transplant have a lower rate of BOS. These findings bring forward the need to design future clinical studies investigating the utility and optimal timing of conversion to cyclosporine offsetting the risk of acute rejection." @default.
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• W2056511391 date "2014-04-01" @default.
• W2056511391 modified "2023-09-27" @default.
• W2056511391 title "Halting BOS in Lung Transplant: Is Cyclosporine Conversion the Answer?" @default.
• W2056511391 doi "https://doi.org/10.1016/j.healun.2014.01.787" @default.
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