RESUMEN
Lung transplantation aims to improve health-related quality of life (HRQL) and survival. While lung function improvements are associated with these outcomes, the association between physical functioning and these outcomes is less clear. We investigated the association between changes in patient-reported physical functioning and HRQL, chronic lung allograft dysfunction (CLAD), and survival after lung transplantation. This single-center prospective cohort study analyzed 220 lung transplant recipients who completed the 15-item Lung Transplant Valued Life Activities (LT-VLA) before and repeatedly after transplant. HRQL was assessed using generic, respiratory disease-specific, and utility measures. Associations between 0.3-point changes (the minimally important difference) in LT-VLA as a time-varying predictor on HRQL, CLAD, and mortality were tested using linear regression and Cox proportional hazard models. Models were adjusted for demographics, disease diagnosis, and post-operative lung function as a time-varying covariate. Participants were 45% female and 75% White, with a mean age of 56 (±12) years. Each 0.3-point improvement in LT-VLA was associated with substantially improved HRQL across all measures (adjusted p-values <0.01). Each 0.3-point improvement in LT-VLA was associated with a 13% reduced hazard of CLAD (adjusted HR: 0.87, 95% CI: 0.76-0.99, p=0.03) and a 19% reduced hazard of mortality (adjusted HR: 0.81, 95% CI: 0.67-0.95, p=0.01). Improvements in patient-reported physical functioning after lung transplantation are associated with improved HRQL and reduced risk of CLAD and death, independent of allograft function. The simplicity of the LT-VLA suggests it could be a valuable monitoring or outcome measure in both clinical and research settings.
RESUMEN
BACKGROUND: Limited data and guidelines exist for using nirmatrelvir/ritonavir in solid organ transplant recipients stabilized on tacrolimus for the treatment of mild-to-moderate coronavirus disease. Concern exists regarding the impact of utilizing a 5-d course of nirmatrelvir/ritonavir with calcineurin inhibitors because of significant drug-drug interactions between ritonavir, a potent cytochrome P450 3A inhibitor, and other cytochrome P450 3A substrates, such as tacrolimus. METHODS: We report the successful use of nirmatrelvir/ritonavir in 12 outpatient lung transplant recipients with confirmed severe acute respiratory syndrome coronavirus 2 infection stabilized on tacrolimus immunosuppression. All patients stopped tacrolimus and started nirmatrelvir/ritonavir 10 to 14 h after the last dose of tacrolimus. Tacrolimus was withheld and then reinitiated at a modified dose 48 h following the completion of nirmatrelvir/ritonavir therapy. Tacrolimus trough levels were checked during nirmatrelvir/ritonavir therapy and tacrolimus reinitiation. RESULTS: Ten (10/12) patients were able to resume their original tacrolimus dose within 4 d of completing nirmatrelvir/ritonavir therapy and maintain therapeutic levels of tacrolimus. No patients experienced tacrolimus toxicity or acute rejection during the 30-d postcompletion of nirmatrelvir/ritonavir therapy. CONCLUSIONS: In this cohort of lung transplant recipients on tacrolimus, we demonstrated that nirmatrelvir/ritonavir can be safely used with close monitoring of tacrolimus levels and appropriate dose adjustments of tacrolimus. Further confirmatory studies are needed to determine the appropriate use of therapeutic drug monitoring and tacrolimus dose following completion of nirmatrelvir/ritonavir in the solid organ transplant population.