Prognostic significance of early pulmonary function changes after onset of chronic lung allograft dysfunction.

Background: Chronic lung allograft dysfunction (CLAD), including the phenotypes of bronchiolitis obliterans syndrome (BOS) and restrictive CLAD (R-CLAD), represents the leading cause of late death after lung transplantation. Little is known, however, regarding the natural history or prognostic significance of pulmonary function changes after the onset of these conditions. We examined changes in forced expiratory volume in 1 second (FEV) and forced vital capacity (FVC) over the first 18 months after CLAD.

Antibody depletion strategy for the treatment of suspected antibody-mediated rejection in lung transplant recipients: Does it work?

Background: Donor-specific antibodies (DSAs) after lung transplantation correlate with poor outcomes. The ideal treatment strategy for antibody-mediated rejection AMR is not defined. Our institution implemented an aggressive multimodality protocol for the treatment of suspected AMR.

Survival Benefit of Lung Transplantation in the Modern Era of Lung Allocation.

Rationale: Lung transplantation is an accepted and increasingly employed treatment for advanced lung diseases, but the anticipated survival benefit of lung transplantation is poorly understood.

Objectives: To determine whether and for which patients lung transplantation confers a survival benefit in the modern era of U.S.

Validation and Refinement of Chronic Lung Allograft Dysfunction Phenotypes in Bilateral and Single Lung Recipients.

Rationale: The clinical course of chronic lung allograft dysfunction (CLAD) is heterogeneous. Forced vital capacity (FVC) loss at onset, which may suggest a restrictive phenotype, was associated with worse survival for bilateral lung transplant recipients in one previously published single-center study.

Objectives: We sought to replicate the significance of FVC loss in an independent, retrospectively identified cohort of bilateral lung transplant recipients and to investigate extended application of this approach to single lung recipients.

Impact of forced vital capacity loss on survival after the onset of chronic lung allograft dysfunction.

Rationale: Emerging evidence suggests a restrictive phenotype of chronic lung allograft dysfunction (CLAD) exists; however, the optimal approach to its diagnosis and clinical significance is uncertain.

Objectives: To evaluate the hypothesis that spirometric indices more suggestive of a restrictive ventilatory defect, such as loss of FVC, identify patients with distinct clinical, radiographic, and pathologic features, including worse survival.

Methods: Retrospective, single-center analysis of 566 consecutive first bilateral lung recipients transplanted over a 12-year period.

Assessing the causal effect of organ transplantation on the distribution of residual lifetime.

Because the number of patients waiting for organ transplants exceeds the number of organs available, a better understanding of how transplantation affects the distribution of residual lifetime is needed to improve organ allocation. However, there has been little work to assess the survival benefit of transplantation from a causal perspective. Previous methods developed to estimate the causal effects of treatment in the presence of time-varying confounders have assumed that treatment assignment was independent across patients, which is not true for organ transplantation.

Implications for human leukocyte antigen antibodies after lung transplantation: a 10-year experience in 441 patients.

Background: Long-term survival after lung transplant is limited by the development of chronic and progressive airflow obstruction, a condition known as bronchiolitis obliterans syndrome (BOS). While prior studies strongly implicate cellular rejection as a strong risk factor for BOS, less is known about the clinical significance of human leukocyte antigen (HLA) antibodies and donor HLA-specific antibodies in long-term outcomes.

Methods: A single-center cohort of 441 lung transplant recipients, spanning a 10-year period, was prospectively screened for HLA antibodies after transplant using flow cytometry-based methods.

Impact of lung transplantation on recipient quality of life: a serial, prospective, multicenter analysis through the first posttransplant year.

Background: Quality of life (QOL) is an important but understudied outcome after lung transplantation. Previous cross-sectional, single-center studies suggest improved QOL, but few prior longitudinal multicenter data exist regarding the effect of transplantation on the patient’s QOL.

Methods: We hypothesized that lung transplantation confers a 1-year QOL benefit in both physical and psychologic well-being; we further hypothesized that the magnitude of benefit would vary by sex, native disease, age, or type of transplant operation.

Epithelial clara cell injury occurs in bronchiolitis obliterans syndrome after human lung transplantation.

Bronchiolitis obliterans syndrome (BOS) is a condition of progressive airflow obstruction that affects a majority of lung transplant recipients and limits long-term posttransplant survival. Although epithelial injury appears central to the development of BOS, little is known regarding the specific epithelial cell types that are affected in this condition. We hypothesized that BOS would involve preferential injury to the secretory Clara cells that function in innate defense and epithelial repair.

Spirometrically significant acute rejection increases the risk for BOS and death after lung transplantation.

Acute rejection (AR) is a common complication following lung transplantation and is an established risk factor for bronchiolitis obliterans syndrome (BOS). AR clinical presentation varies considerably and is sometimes associated with an acute decrease in forced expiratory volume in 1 s (FEV1). We hypothesized that lung transplant recipients who experience such spirometrically significant AR (SSAR), as defined by a ≥10% decline in FEV1 relative to the prior pulmonary function test, are subsequently at increased risk for BOS and worse overall survival.

Long-term efficacy and safety of 12 months of valganciclovir prophylaxis compared with 3 months after lung transplantation: a single-center, long-term follow-up analysis from a randomized, controlled cytomegalovirus prevention trial.

Background: The optimal approach to cytomegalovirus (CMV) prevention after lung transplantation is controversial. We recently completed a prospective, randomized, placebo-controlled study of CMV prevention in lung transplantation that demonstrated the short-term efficacy and safety of extending valganciclovir prophylaxis to 12 months vs 3 months of therapy. In the current analysis, we monitored a single-center subset of patients enrolled in the CMV prevention trial to determine if extended prophylaxis conferred a sustained long-term benefit and to assess its hematologic safety.

Survival after bronchiolitis obliterans syndrome among bilateral lung transplant recipients.

Rationale: Despite the importance of bronchiolitis obliterans syndrome (BOS) in lung transplantation, little is known regarding the factors that influence survival after the onset of this condition, particularly among bilateral transplant recipients.

Objectives: To identify factors that influence survival after the onset of BOS among bilateral lung transplant recipients.

Methods: The effect of demographic or clinical factors, occurring before BOS, upon survival after the onset of BOS was studied in 95 bilateral lung transplant recipient using Cox proportional hazards models.

Cytomegalovirus pneumonitis is a risk for bronchiolitis obliterans syndrome in lung transplantation.

Rationale: Cytomegalovirus pneumonitis is one of the most prevalent opportunistic infections after lung transplantation. Early studies reported that cytomegalovirus pneumonitis was a risk factor for chronic allograft dysfunction. More recently, in the era of routine prophylaxis and ganciclovir treatment, the adverse impact of treated cytomegalovirus pneumonitis on bronchiolitis obliterans syndrome has been challenged.