A new study published in the March 3 issue of the Journal of the American Medical Association (JAMA) finds that a medical need-based donor lung allocation protocol has been associated with better graft survival than single-lung transplantation procedures in persons afflicted with idiopathic pulmonary fibrosis (IPF).
The research paper, entitled “Transplantation in Patients With Chronic Obstructive Pulmonary Disease and Idiopathic Pulmonary Fibrosis Since the Implementation of Lung Allocation Based on Medical Need“ (JAMA. 2015;313(9):936-948. doi:10.1001/jama.2015.1175) is coauthored by Justin M. Schaffer, MD, and Bruce A. Reitz MD of the Stanford Hospital and Clinics Department of Cardiothoracic Surgery at Stanford, California; Steve K. Singh, MD and Hari R. Mallidi, MD of the Michael E. DeBakey Division of Cardiothoracic Surgery at Baylor College of Medicine, and the Texas Heart Institute Center for Cardiac Support — both in Houston, Texas; and Roham T. Zamanian, MD, of the Vera Moulton Wall Center for Pulmonary Vascular Disease Department of Medicine Division at Stanford, California
The coauthors note that single- and double-lung transplantation outcomes had not been rigorously assessed since the allocation of donor lungs according to medical need as quantified by Lung Allocation Scoring, which began in 2005.
The study objective was to compare outcomes in single and double-lung transplant recipients over the decade since implementation of the Lung Allocation Score. For this exploratory analysis, participant adults with idiopathic pulmonary fibrosis (IPF) or chronic obstructive pulmonary disease (COPD) who received lung transplants in the United States between May 4, 2005 and December 31, 2012 were identified through the United Network for Organ Sharing thoracic registry, with follow-up to December 31, 2012.
An assessment of post-transplantation graft survival was assessed using Kaplan-Meier analysis, with propensity scores applied in order to control for treatment selection bias. The investigators then used a multivariable flexible parametric prognostic model to characterize the time-variance hazard associated with assessing single- vs double-lung transplantation outcomes.
Lead investigator Hari R. Mallidi, M.D., Chief of the Division of Transplant and Assist Devices at Baylor College of Medicine in Houston, and colleagues reviewed data pertaining to patients with IPF (of whom 2010 underwent single-lung and 2124 underwent double-lung transplants during the interval investigated) or COPD (of whom 1299 underwent single-lung and 1875 underwent double-lung transplantation during the same time period), with a median follow-up time of 23.5 months. Of the patients with IPF, 1380 (33.4%) died and 115 (2.8%) underwent retransplantation. Of the COPD subject cohort, 1138 (34.0%) died and 59 (1.9%) underwent retransplantation.
After potentially confounding factors were controlled for using propensity score analysis, it was determined that double-lung transplants were associated with better graft survival in patients with IPF (adjusted median survival, 65.2 months vs 50.4 months) but not in patients with COPD (adjusted median survival, 67.7 months vs 64.0 months).
Other variables associated with transplant failure included the patient’s age, excessively high or low body mass index, worse functional status, poor 6-minute walk test performance, pulmonary hypertension (in patients with COPD), and donor age. Variables associated with graft survival included the transplantation being done at a high-performing center and/or at a moderate or high volume transplant center, receiving a locally allocated organ, and donor-recipient race match (in patients with IPF).
The coauthors note that “The interaction between diagnosis (COPD or IPF) and treatment type (single- and double-lung transplantation) was significant, supporting the finding that the benefit of double-lung transplantation may differ by diagnosis. Likewise, prognostic models designed to account for the time-varying effect of double-lung transplantation (compared with single-lung transplantation) showed that double-lung transplantation was significantly associated with graft survival among patients with IPF but not among patients with COPD.”
The researchers conclude that this exploratory analysis of registry data since implementation of a medical need based lung allocation system reveals that double-lung transplantation has been associated with better graft survival than single-lung transplantation in patients with IPF. However, no survival difference was found between single- and double-lung transplant recipients in patients with chronic obstructive pulmonary disease (COPD).
Prior to 2005, allocation of lungs for transplant in the United States was based on first-come-first-serve seniority on the transplant waiting list after matching for ABO blood type. However, as a response to increasing wait times, the U.S. Department of Health and Human Services imposed development of an allocation system based on severity medical need in individual cases rather than wait time.
The resulting protocol, called the “Lung Allocation Score (LAS) organ allocation algorithm” — came into effect in May 2005. Under the revised system, a patient’s LAS is based on risk factors associated with either wait list or post-transplantation mortality. Application of the LAS brought with it a demographic shift in single- and double-lung transplant recipients, but whatever effect this may have had on post-transplantation outcomes had not previously been assessed, according to the article coauthors.
JAMA – Journal of the American Medical Association. Note: Materials
Baylor College Of Medicine