sirolimus and Emphysema

Renal failure induced by calcineurin-inhibitor agents is a common complication of lung transplantation. Sirolimus, a macrolide immunosuppressant with a distinct mechanism of action, may prevent renal failure but was found to have a high infectious and toxicity rate in the only relevant study conducted so far. The aim of the present prospective pilot study was to assess the benefit of sirolimus combined with low-dose calcineurin inhibitors in this patient population.. Sixteen lung transplant recipients with post-transplantation renal dysfunction were allocated to receive the standard immunosuppression regimen or a combination sirolimus/low-dose calcineurin-inhibitor regimen. Target trough levels of sirolimus were 4 to 8 ng/mL. Tacrolimus was tapered down to target trough levels of 4 to 8 ng/mL and cyclosporine to 80 to 120 ng/mL. Duration of follow-up was 18 months.. At the end of follow-up, the sirolimus group showed a significant improvement in creatinine clearance (42.6 mL/min vs. 32.5 mL/min, P= 0.05), whereas the control group showed a significant reduction (32.3 mL/min vs. 40.3 mL/min, P= 0.02). The difference between the groups was statistically significant (P < 0.0001). Acute rejection episodes occurred in 2 patients in the sirolimus group and 1 patient in the control group (P= NS). Pneumonia developed in 6 study patients and 4 controls; all responded to antibiotics.. Sirolimus combined with low-dose calcineurin inhibitors appears to be a safe and effective alternative immunosuppressive therapy to sirolimus alone in lung transplant recipients with renal failure. Graft function is preserved, and infection and drug toxicity rates are low.

Topics: Aged; Creatinine; Drug Therapy, Combination; Emphysema; Female; Graft Survival; Humans; Immunosuppressive Agents; Kidney Diseases; Lung Transplantation; Male; Middle Aged; Pilot Projects; Postoperative Complications; Sirolimus

To evaluate the function of the mammalian target of the rapamycin (mTOR) pathway in chronic obstructive pulmonary disease (COPD) patients with emphysema.. Observational study.. Department of Pulmonology, Mugla Training and Research Hospital, Turkey, from January to March 2022.. Thirty COPD patients and thirty healthy volunteers were included. Demographic data, pack-year of cigarette, spirometric values, and emphysema percentage (calculated with CT scan) were recorded. mTOR, raptor, and deptor were measured with ELISA method. Statistical significance was accepted as p<0.05.. The mean value of mTOR in the COPD group was 3.48±2.01 ng/ml and it was significantly higher than the control (1.51±0.44 ng/ml). The mTOR was positively correlated with MMRC, annual exacerbation rate, emphysema percentage, and pack/year of cigarette and negatively correlated with SpO2 and FEV1. The significant relationship was found with only emphysema (B=0.067, SE=0.020, 95% CI=0.027-0.107, p=0.002). The cut-off value of mTOR for COPD was found as 1.815 ng/ml (sensivity=77%).. Overexpression of mTOR and its signalling proteins have a significant role in emphysema development. Reduction of mTOR expression/activity might be helpful to control dyspnea severity, number of exacerbations, loss of FEV1, and progression of emphysema.. COPD, Emphysema, mTOR.

Topics: Emphysema; Forced Expiratory Volume; Humans; Intracellular Signaling Peptides and Proteins; Lung; Pulmonary Disease, Chronic Obstructive; Pulmonary Emphysema; Severity of Illness Index; Sirolimus; TOR Serine-Threonine Kinases

Topics: Basilar Artery; Brain Infarction; Cerebellum; Cerebral Arteries; Disease Progression; Emphysema; Female; Headache; Hemianopsia; Humans; Hypertension; Immunosuppressive Agents; Intracranial Hemorrhage, Hypertensive; Kidney Neoplasms; Lung Transplantation; Magnetic Resonance Imaging; Middle Aged; Occipital Lobe; Posterior Cerebral Artery; Sirolimus