Effects of Prophylactic Use of Sirolimus on Bronchiolitis Obliterans Syndrome Development in Lung Transplant Recipients

Sacher, Vikas Y.; Fertel, Debra; Srivastava, Karan; Panos, Anthony L.; Nguyen, D.; Baxter, Tammy M.; Shafazand, Shirin; Pham, Si M.

doi:10.1016/j.athoracsur.2013.07.072

Cited by 23 publications

(24 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previously, a randomized open-label trial by Bhorade et al 6 compared sirolimus therapy initiated 3 months after transplant with azathioprine therapy and found no significant differences in 3-year survival, whereas a cohort study by Sacher et al 14 found that sirolimus therapy initiated 1 year after transplant was associated with significantly better survival than mycophenolate mofetil, and the improvement was sustained for the follow-up period of 10 years. The different study durations may partly explain the discrepant findings because short-term mortality is relatively low and commonly unrelated to immunosuppressive efficacy or adverse effects, so immunosuppression-related survival differences may only manifest later.…”

Section: Discussionmentioning

confidence: 99%

Survival Associated With Sirolimus Plus Tacrolimus Maintenance Without Induction Therapy Compared With Standard Immunosuppression After Lung Transplant

et al. 2019

View full text Add to dashboard Cite

Key Points Question Which immunosuppressive strategy is associated with the highest survival in lung transplantation? Findings In this cohort study of US recipients of lung transplants, sirolimus plus tacrolimus was associated with significantly better conditional survival from 1 year after transplant compared with mycophenolate mofetil plus tacrolimus (median survival, 8.9 vs 7.1 years after transplant). The highest conditional survival was observed in patients receiving sirolimus plus tacrolimus with no induction therapy (median survival, 10.7 years), which was significantly better than survival for those receiving mycophenolate mofetil plus tacrolimus with induction therapy (median survival, 7.4 years). Meaning Sirolimus plus tacrolimus was associated with improved patient survival compared with mycophenolate mofetil plus tacrolimus, and using no induction therapy with sirolimus plus tacrolimus was associated with the highest survival.

show abstract

Section: Discussionmentioning

confidence: 99%

Survival Associated With Sirolimus Plus Tacrolimus Maintenance Without Induction Therapy Compared With Standard Immunosuppression After Lung Transplant

et al. 2019

View full text Add to dashboard Cite

show abstract

“…While Schliesser et al demonstrated that TGF-β1 led to increasing of CD25(+)Foxp3(+)-expressing Tregs (33), which are well-known inhibitory regulatory cells to immune response and results in allograft tolerance and long-term graft survival. Lung transplantation patients were normally treated with immunosuppressive agents, such as Sirolimus, cyclosporine A, Tacrolimus or azathioprine for successful outcomes (2, 34). Based on these findings, we proposed that the total level of TGF-β1 could not be used as a biomarker to monitor the process of BO development post lung transplantation, but the B220 + IGM + IgG - TGF-β1 + cells can be served as a useful cellular marker for prognosis and treatment of BO.…”

Section: Discussionmentioning

confidence: 99%

Rapamycin prevents bronchiolitis obliterans through increasing infiltration of regulatory B cells in a murine tracheal transplantation model

Zhao

Gillen

Meher

et al. 2016

The Journal of Thoracic and Cardiovascular Surgery

View full text Add to dashboard Cite

Objective B lymphocytes are generally considered to be activators of the immune response, However recent findings have shown that a subtype of B-lymphocytes, regulatory B lymphocytes (Bregs) play a role in attenuating the immune response. Bronchiolitis obliterans (BO) remains the major limitation to modern day lung transplantation. Bregs role in BO has not been elucidated. We hypothesized that Bregs play a role in the attenuation of BO. Methods A standard heterotopic tracheal transplant model (HTT) model we performed. Tracheas from Balb/c were transplanted into C57BL/6 recipients. Rapamycin treatment and DMSO control groups each treated for the first 14 days after the transplant. Tracheas were collected on Days 7, 14, and 28 post-transplantation. Luminal obliteration was evaluated by HE staining and picrosirius red staining. Immune cell infiltration and characteristics, secretion of IL-10 and TGF-β1 were accessed by immunohistochemistry. Cytokines and TGF-β1 were measured using luminex assay. Results The results revealed that intraperitoneal injection of rapamycin for 14 days after tracheal transplantation significantly reduced luminal obliteration on days 28 when compared with DMSO control group (97.78% ±3.63% Vs 3.02% ±2.14%, P<0.001). Rapamycin treatment markedly induced Breg (B220+IgM+IgG- IL-10+TGF- β1+) cells when compared with DMSO controls. Rapamycin treatment inhibited IL-1β, -6, -13 and -17 at day 7 and 14. Furthermore, rapamycin also greatly increased IL-10 and TGF-β1 production in B cells and Treg infiltration on day 28. Conclusions mTOR inhibition decreases BO development via inhibition of pro-inflammatory cytokines and increasing Breg cell infiltration, which subsequently produce anti-inflammatory cytokines and upregulate Treg cells.

show abstract

“…Sacher et al on the other hand showed a lower incidence of CR and improved overall survival in patients treated with sirolimus compared to patients treated with MMF (53). However, sirolimus was also associated with significant adverse effects including venous thromboembolism and impaired bronchial anastomosis healing (52)(53)(54).…”

Section: Mammalian Target Of Rapamycin (Mtor) Inhibitors: Everolimusmentioning

confidence: 99%

Prevention of chronic rejection after lung transplantation

et al. 2017

View full text Add to dashboard Cite

show abstract

Effects of Prophylactic Use of Sirolimus on Bronchiolitis Obliterans Syndrome Development in Lung Transplant Recipients

Cited by 23 publications

References 27 publications

Survival Associated With Sirolimus Plus Tacrolimus Maintenance Without Induction Therapy Compared With Standard Immunosuppression After Lung Transplant

Survival Associated With Sirolimus Plus Tacrolimus Maintenance Without Induction Therapy Compared With Standard Immunosuppression After Lung Transplant

Rapamycin prevents bronchiolitis obliterans through increasing infiltration of regulatory B cells in a murine tracheal transplantation model

Prevention of chronic rejection after lung transplantation

Contact Info

Product

Resources

About