Local complement activation is associated with primary graft dysfunction after lung transplantation.

BACKGROUNDThe complement system plays a key role in host defense but is activated by ischemia/reperfusion injury (IRI). Primary graft dysfunction (PGD) is a form of acute lung injury occurring predominantly due to IRI, which worsens survival after lung transplantation (LTx). Local complement activation is associated with acute lung injury, but whether it is more reflective of allograft injury compared with systemic activation remains unclear. We proposed that local complement activation would help identify those who develop PGD after LTx. We also aimed to identify which complement activation pathways are associated with PGD.METHODSWe performed a multicenter cohort study at the University of Pennsylvania and Washington University School of Medicine. Bronchoalveolar lavage (BAL) and plasma specimens were obtained from recipients within 24 hours after LTx. PGD was scored based on the consensus definition. Complement activation products and components of each arm of the complement cascade were measured using ELISA.RESULTSIn both cohorts, sC4d and sC5b-9 levels were increased in BAL of subjects with PGD compared with those without PGD. Subjects with PGD also had higher C1q, C2, C4, and C4b, compared with subjects without PGD, suggesting classical and lectin pathway involvement. Ba levels were higher in subjects with PGD, suggesting alternative pathway activation. Among lectin pathway-specific components, MBL and FCN-3 had a moderate-to-strong correlation with the terminal complement complex in the BAL but not in the plasma.CONCLUSIONComplement activation fragments are detected in the BAL within 24 hours after LTx. Components of all 3 pathways are locally increased in subjects with PGD. Our findings create a precedent for investigating complement-targeted therapeutics to mitigate PGD.FUNDINGThis research was supported by the NIH, American Lung Association, Children's Discovery Institute, Robert Wood Johnson Foundation, Cystic Fibrosis Foundation, Barnes-Jewish Hospital Foundation, Danish Heart Foundation, Danish Research Foundation of Independent Research, Svend Andersen Research Foundation, and Novo Nordisk Research Foundation.

A single-center experience of 1500 lung transplant patients.

OBJECTIVE: Over the past 30 years, lung transplantation has emerged as the definitive treatment for end-stage lung disease. In 2005, the lung allocation score (LAS) was introduced to allocate organs according to disease severity. The number of transplants performed annually in the United States continues to increase as centers have become more comfortable expanding donor and recipient criteria and have become more facile with the perioperative and long-term management of these patients. We report a single-center experience with lung transplants, looking at patients before and after the introduction of LAS. METHODS: We retrospectively reviewed 1500 adult lung transplants at a single center performed between 1988 and 2016. Patients were separated into 2 groups, before and after the introduction of LAS: group 1 (April 1988 to April 2005; 792 patients) and group 2 (May 2005 to September 2016; 708 patients). RESULTS: Differences in demographic data were noted over these periods, reflecting changes in allocation of organs. Group 1 patient average age was 48 ± 13 years, and 404 subjects (51%) were male. Disease processes included emphysema (52%; 412), cystic fibrosis (18.2%; 144), pulmonary fibrosis (16.1%; 128) and pulmonary vascular disease (7.2%; 57). Double lung transplant (77.7%; 615) was performed more frequently than single lung transplant (22.3%; 177). Group 2 average age was 50 ± 14 years, and 430 subjects (59%) were male. Disease processes included pulmonary fibrosis (46%; 335), emphysema (25.8%; 188), cystic fibrosis (17.7%; 127) and pulmonary vascular disease (1.6%; 11). Double lung transplant (96.2%; 681) was performed more frequently than single lung transplant (3.8%; 27). Overall incidence of grade 3 primary graft dysfunction (PGD) in group 1 was significantly lower at 22.1% (175) than in group 2 at 31.6% (230) (P < .001). Nonetheless, overall hospital mortality was not statistically different between the 2 groups (4.4% vs 3.5%; P < .4). Most notably, survival at 1 year was statistically different at 646 (81.6%) for group 1 and 665 (91.4%) for group 2 (P < .02). CONCLUSIONS: Patient demographics over the study period have changed with an increased number of fibrotic patients transplanted. In addition, more aggressive strategies with donor/recipient selection appear to have resulted in a higher incidence of primary graft dysfunction. This does not, however, appear to affect patient survival on index hospitalization or at 1 year. In fact, we have observed a significant improvement in survival at 1 year in the more recent era. This observation suggests that continued expansion of possible donors and recipients, coupled with a more sophisticated understanding of primary graft dysfunction and long-term chronic rejection, can lead to increased transplant volume and prolonged survival.

Single-lung transplantation in the setting of aborted bilateral lung transplantation.

Background. The outcome of patients undergoing a single-lung transplant in the setting of an aborted bilateral lung transplant is unclear. Methods. A retrospective review of single lung transplants at an institutional program. Results. Of the 543 lung transplants performed over the last 10 years, 31 (5.7%) were single-lung transplants. Nineteen of 31 (61%) were planned single-lung transplants, while 12/31 (39%) were intraoperatively aborted, double lung transplants converted to single-lung transplants. The aborted and planned groups were similar in age, lung allocation score and NYHA status. The reasons for aborted double lung transplantation were cardiac/hemodynamic instability 4/12 (33%), difficult pneumonectomy 3/12 (25%), size mismatch 4/12(33%), and technical issues 1/12 (8%). The aborted group had higher CPB utilization (5/12 versus 1/19, P = .02), similar ischemic times (260 versus 234 min) and similar incidence of grade 3 primary graft dysfunction (6/12 versus 3/19, P = .13). ECMO was required for graft dysfunction in 2 patients in the aborted group. The one and two-year survival was 84% and 79% in the planned group and 62% and 52% in the aborted group, respectively. Conclusions. Patients undergoing single-lung transplantation in the setting of an aborted bilateral lung transplant may be at a higher risk of worse outcomes.

Lung transplantation and donation after cardiac death: a single center experience.

BACKGROUND: Lung donation after cardiac death (DCD) can enlarge the donor pool. Single-center reports have shown comparable outcomes after lung transplantation using conventional donors versus DCD in small numbers of patients. METHODS: We performed a retrospective review of DCD experience at a single lung transplant program using a prospective database. RESULTS: Between January 2003 and April 2008, 293 lung transplantations were performed, including 11 bilateral transplantations (3.7%) using DCD lungs. Similar criteria were used to assess donor quality. The hospital mortality for DCD recipients was 2 of 11 (18%) and overall mortality was 4 of 11 (36%) by 18 months of follow-up. Seven DCD patients (64%) are alive with a median follow-up of 32 months. The DCD group was comparable to the control group in age and ischemic times. The 4 deaths, when compared with 7 DCD survivors, had longer ischemic time (293 minutes versus 232 minutes) and a higher incidence of nonlocal donors (3 of 4 versus 1 of 7). CONCLUSIONS: At our center, early outcomes after DCD lung transplantations are somewhat inferior to those of series from other centers but approach national averages for conventional lung transplantation. Thus, DCD lung transplantation has the potential to increase the donor pool but must be offered cautiously.