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Background: Pulmonary blood flow can be assessed on ventilation-perfusion (VQ) scan with relative lung perfusion, with a 55% to 45% (or 10%) right-to-left differential considered normal. We hypothesized that wide perfusion differential on routine VQ studies at 3 mo posttransplant would be associated with an increased risk of death or retransplantation, chronic lung allograft (CLAD), and baseline lung allograft dysfunction., Methods: We conducted a retrospective cohort study on all patients who underwent double-lung transplant in our program between 2005 and 2016, identifying patients with a wide perfusion differential of >10% on a 3-mo VQ scan. We used Kaplan-Meier estimates and proportional hazards models to assess the association between perfusion differential and time to death or retransplant and time to CLAD onset. We used correlation and linear regression to assess the relationship with lung function at time of scan and with baseline lung allograft dysfunction., Results: Of 340 patients who met inclusion criteria, 169 (49%) had a relative perfusion differential of ≥ 10% on a 3-mo VQ scan. Patients with increased perfusion differential had increased risk of death or retransplantation ( P  = 0.011) and CLAD onset ( P  = 0.012) after adjustment for other radiographic/endoscopic abnormalities. Increased perfusion differential was associated with lower lung function at time of scan., Conclusions: Wide lung perfusion differential was common after lung transplant in our cohort and associated with increased risk of death, poor lung function, and CLAD onset. The nature of this abnormality and its use as a predictor of future risk warrant further investigation., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Donor-specific antibodies (DSAs) have been associated with antibody-mediated rejection, chronic lung allograft dysfunction (CLAD), and increased mortality in lung transplant recipients. Our center performs transplants in the presence of DSA, and we sought to evaluate the safety of this practice with respect to graft loss, CLAD onset, and primary graft dysfunction (PGD)., Methods: We reviewed recipients transplanted from 2010 to 2017, classifying them as DSA positive (DSA + ) or negative. We used Kaplan-Meier estimation to test the association between DSA status and time to death or retransplant and time to CLAD onset. We further tested associations with severe PGD and rejection in the first year using logistic regression and Fisher exact testing., Results: Three hundred thirteen patients met inclusion criteria, 30 (10%) of whom were DSA + . DSA + patients were more likely to be female, bridged to transplant, and receive induction therapy. There was no association between DSA status and time to death or retransplant (log rank P  = 0.581) nor death-censored time to CLAD onset (log rank P  = 0.278), but DSA + patients were at increased risk of severe PGD (odds ratio 2.88; 95% confidence interval, 1.10-7.29; P  = 0.031) and more frequent antibody-mediated rejection in the first posttransplant year., Conclusions: Crossing DSA at time of lung transplant was not associated with an increased risk of death or CLAD in our cohort, but patients developed severe PGD and antibody-mediated rejection more frequently. However, these risks are likely manageable when balanced against the benefits of expanded access for sensitized candidates., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

The introduction of generic immunosuppressant medications may present an opportunity for cost savings in solid organ transplantation if equivalent clinical outcomes to the branded counterparts can be achieved. An interprofessional working group of the Canadian Society of Transplantation was established to develop recommendations on the use of generic immunosuppression in solid organ transplant recipients (SOTR) based on a review of the available data. Under current Health Canada licensing requirements, a demonstration of bioequivalence with the branded formulation in healthy volunteers allows for bridging of clinical data. Cyclosporine, tacrolimus, and sirolimus are designated as "critical dose drugs" and are held to stricter criteria. However, whether this provides sufficient guarantee of therapeutic equivalence in SOTR remains controversial, and failure to maintain an appropriate balance of immunosuppression may have serious consequences, including rejection, graft loss, and death. Published evidence supporting therapeutic equivalence of generic formulations in SOTR is lacking. Moreover, in the setting of multiple generic formulations the potential for uncontrolled product switching is a major concern, since generic preparations are not required to demonstrate bioequivalence with each other. Although close monitoring is recommended with any change in formulation, drug product switches are likely to occur without prescriber knowledge and may pose a significant patient safety risk. The advent of generic immunosuppression will require new practices including more frequent therapeutic drug and clinical monitoring, and increased patient education. The additional workload placed on transplant centers without additional funding will create challenges and could ultimately jeopardize patient outcomes. Until more robust clinical data are available and adequate regulatory safeguards are instituted, caution in the use of generic immunosuppressive drugs in solid organ transplantation is warranted.

Background: Cytomegalovirus (CMV) is an important infection in lung transplant recipients. Center-to-center variation in preventive and treatment strategies is unknown., Methods: An electronic survey was sent to 102 lung transplant programs registered with the International Society of Heart and Lung Transplantation and United Network for Organ Sharing., Results: Fifty-nine (58%) programs responded to the survey. For CMV prevention (D+/R-), 56 of the 59 (94.9%) programs used prophylaxis and two (3.4%) of them used preemptive therapy. For R+ patients, 86.4% used prophylaxis and 13.6% used preemptive strategy. Duration of prophylaxis was extremely variable ranging from 3 months to indefinite. Adjunctive prophylactic strategies included routine viral monitoring (51% D+/R-; 44% R+) and CMV immunoglobulin (32% D+/R-; 14% R+). The medication used for prophylaxis was valganciclovir with approximately half starting with intravenous ganciclovir. 9 of the 59 (15.2%) centers reported using specific CMV prophylaxis in D-/R- patients. Methods for viral monitoring included peripheral blood polymerase chain reaction, antigenemia, bronchoalveolar lavage viral culture, and bronchoalveolar lavage polymerase chain reaction. For treatment of CMV viremia, valganciclovir or intravenous ganciclovir were used. A total of 47.5% of centers routinely decreased immunosuppression at the time of viremia. Secondary antiviral prophylaxis was used routinely by 36 of the 59 (61%) centers., Conclusions: Although prophylaxis is the most commonly used preventive strategy, significant variation exists in the way it is implemented. Specifically, duration of prophylaxis is extremely variable. Uniform international guidelines would be of value in this population.