Simona Soresi

De novo donor HLA-specific antibodies predict development of bronchiolitis obliterans syndrome after lung transplantation

BACKGROUND Bronchiolitis obliterans syndrome (BOS) is the major cause of late graft failure after lung transplantation. The objective was to determine whether de novo donor human leukocyte antigen (HLA)-specific antibodies (DSA) are associated with the development of BOS or patient survival. Data were analyzed from 188 lung transplant recipients with a follow-up period up to 8 years. METHODS HLA antibody monitoring was performed at 3-month intervals post-transplant at routine outpatient clinic attendances and during the investigation of any acute deterioration. HLA antibody data were available for 148 patients; 66 (45%) had produced HLA antibodies after transplant, of which 38 (26%) were DSA and 28 (19%) non-donor-specific HLA antibodies. RESULTS De novo DSA was associated with development of BOS Stage 1 (BOS1; hazard ratio [HR] = 2.302, p = 0.0015), BOS2 (HR = 3.627, p < 0.0001) and BOS3 (HR = 5.736, p < 0.0001). De novo persistent DSA correlated strongly with shorter time to onset of BOS3 (HR = 6.506, p = 0.0001). There was a significant reduction in patient survival associated with de novo DSA (HR = 1.886, p = 0.047). In multivariable analyses, de novo DSA was an independent predictor for development of all stages of BOS as well as an independent predictor of poor patient survival. CONCLUSIONS De novo DSA is a major risk factor for progression to BOS and shorter patient survival. Treatments to remove antibodies or limit antibody-mediated damage could be considered when DSA are first detected. However, a randomized, controlled trial of treatment options would enable a clearer understanding of the benefits, if any, of antibody-removal therapies.

Pre-transplant donor HLA-specific antibodies: characteristics causing detrimental effects on survival after lung transplantation.

BACKGROUND The impact of Luminex-detected HLA antibodies on outcomes after lung transplantation is unclear. Herein we have undertaken a retrospective study of pre-transplant sera from 425 lung transplants performed between 1991 and 2003. METHODS Pre-transplant sera, originally screened by complement-dependent cytotoxicity (CDC) assays, were retrospectively tested for the presence of HLA-specific antibodies using HLA-coated Luminex beads and C4d deposition on Luminex beads. The results were correlated with graft survival at 1 year. RESULTS Twenty-seven patients were retrospectively identified as having been transplanted against donor-specific HLA antibodies (DSA) and 36 patients against non-donor-specific HLA antibodies (NDSA). DSA-positive patients had 1-year survival of 51.9% compared with 77.8% for NDSA and 71.8% for antibody-negative patients (p = 0.029). One-year survival of patients with complement-fixing DSA was 12.5% compared with 62.5% for non-complement-fixing DSA, 75.8% for non-complement-fixing NDSA and 71.8% for antibody-negative patients (p < 0.0001). DSA-positive patients with mean fluorescence intensity (MFI) >5,000 had 1-year survival of 33.3% compared with 71.4% for MFI 2,000 to 5000 and 62.5% for MFI <2,000 (p = 0.0046). Multivariable analysis revealed DSA to be an independent predictor of poor patient survival within 1 year (p = 0.0010, hazard ratio [HR] = 3.569) as well as complement-fixing DSA (p < 0.0001, HR = 11.083) and DSA with MFI >5,000 (p = 0.0001, HR = 5.512). CONCLUSIONS Pre-formed DSA, particularly complement-fixing DSA, and high MFI are associated with poor survival within the first year after lung transplantation. Risk stratification according to complement fixation or MFI levels may allow for increased transplantation in sensitized patients.

Long-term results after lung transplantation using organs from circulatory death donors: a propensity score-matched analysis †

OBJECTIVES Due to organ shortage in lung transplantation (LTx), donation after circulatory death (DCD) has been implemented in several countries, contributing to an increasing number of organs transplanted. We sought to assess long-term outcomes after LTx with organs procured following circulatory death in comparison with those obtained from donors after brain death (DBD). METHODS Between January 2007 and November 2013, 302 LTxs were performed in our institution, whereby 60 (19.9%) organs were retrieved from DCD donors. We performed propensity score matching (DCD:DBD = 1:2) based on preoperative donor and recipient factors that were significantly different in univariate analysis. RESULTS After propensity matching, there were no statistically significant differences between the groups in terms of demographics and preoperative donor and recipient characteristics. There were no significant differences regarding intraoperative variables and total ischaemic time. Patients from the DCD group had significantly higher incidence of primary graft dysfunction grade 3 at the end of the procedure (P = 0.014), and significantly lower pO2/FiO2 ratio during the first 24 h after the procedure (P = 0.018). There was a trend towards higher incidence of the need for postoperative extracorporeal life support in the DCD group. Other postoperative characteristics were comparable. While the overall cumulative survival was not significantly different, the DCD group had significantly poorer results in terms of bronchiolitis obliterans syndrome (BOS)-free survival in the long-term follow-up. CONCLUSIONS Long-term results after LTx with organs procured following DCD are in general comparable with those obtained after DBD LTx. However, patients transplanted using organs from DCD donors have a predisposition for development of BOS in the longer follow-up.

When the Battle is Lost and Won: Delayed Chest Closure After Bilateral Lung Transplantation

In this article we summarize benefits of delayed chest closure strategy in lung transplantation, addressing indications, different surgical techniques, and additional perioperative treatment. Delayed chest closure seems to be a valuable and safe strategy in managing patients with various conditions after lung transplantation, such as instable hemodynamics, need for high respiratory pressures, coagulopathy, and size mismatch. Therefore, this approach should be considered in lung transplant centers to give patients time to recover before the chest is closed.

Utilization of the organ care system for bilateral lung transplantation: preliminary results of a comparative study

OBJECTIVES Lung transplantation (LTx) remains the gold standard for patients with end-stage lung disease. However, due to donor organ shortage and brain stem death-related lung injury, only a small proportion of lungs are used increasing the mortality rate on the waiting list. A portable normothermic continuous ex vivo perfusion using the organ care system (OCS) represents one of the tools to increase the pool of donor organs and to improve the function of marginal lungs. We sought to assess mid-term outcomes after LTx using OCS and to compare outcomes including overall survival and freedom from bronchiolitis obliterans syndrome (BOS) with those after conventional preservation. METHODS Included were 322 consecutive LTx performed at Harefield Hospital between January 2007 and December 2014. Recipients were divided into two groups depending on the organ storage strategy: the majority of patients (n = 308) were transplanted using lungs after cold storage (cold storage group), whereas 14 organs were preserved using OCS (OCS group). The primary end-points were overall survival and freedom from BOS after LTx. The secondary end-points were perioperative clinical characteristics and adverse events. RESULTS There were no statistically significant differences in terms of most baseline donor and recipient characteristics. The percentage of heavy smokers among donors [8 (2.9%) vs 6 (42.9%), P < 0.001] and the median number of pack-years smoked by donors [14 (7;24) vs 25 (24;30), P = 0.026] were statistically higher in the OCS group. Patients from the OCS group had significantly better postoperative FEV1 at 3 [69 (54;86) vs 93 (87;89), P < 0.001] and 6 [77 (60;90) vs 94 (84;100), P = 0.006] months. There were no statistically significant differences in terms of cumulative survival and freedom from BOS between the two groups. CONCLUSIONS Results after LTx using OCS are acceptable with excellent survival, and superior early outcome in terms of postoperative lung function despite higher risk in the OCS group. Further larger prospective trials are warranted to confirm our preliminary results and to elaborate long-term outcomes.

The role of cardiopulmonary bypass in lung transplantation

The risk–benefit for utilizing cardio‐pulmonary bypass (CPB) in lung transplantation (LTx) remains debatable. This study compares outcomes after LTx utilizing different CPB strategies – elective CPB vs. off‐pump vs. off‐pump with unplanned conversion to CPB.

Contemporary review of the organ care system in lung transplantation: potential advantages of a portable ex-vivo lung perfusion system

ABSTRACT Introduction: Lung transplantation remains the definite treatment for various end-stage lung diseases. Cold flush perfusion, the standard method for organ procurement has severe limitations. Organ Care System (OCS; TransMedics, Inc., Andover, USA) is an approved method to preserve hearts for transplantation that allows for greatly reduced cold ischemic time. Consequently, the use of an adapted OCS lung as a portable full ex-vivo lung perfusion system in lung transplantation is currently under close evaluation. Areas covered: The aim of this article is to review the advantages and the role of the OCS in the field of lung transplantation by reviewing the latest literature and evaluating this novel procurement technique in the context of conventional methods like cold flush and regular ex-vivo lung perfusion. Expert commentary: The use of OCS in the field of lung transplantation has great potential for improved patients outcomes and is justified in cases with (i) marginal donor lungs, (ii) foreseeable long time of transportation (iii) high-risk recipient or donor /recipient profiles, particularly in the setting of an overall increasing need for suitable donor organs. Results from two major multi-centre prospective studies are pending to objectively assess the possible advantages of this portable ex-vivo lung perfusion system.

Lung transplantation in chronic obstructive pulmonary disease: long‐term survival, freedom from bronchiolitis obliterans syndrome, and factors influencing outcome

Lung transplantation (LTx) remains the definitive treatment for end‐stage lung failure, whereas chronic obstructive pulmonary disease (COPD) represents one of the main diagnoses leading to the indication for a transplant. We sought to assess long‐term outcomes after LTx in patients diagnosed with COPD and analyze factors influencing outcome in this frequent patient cohort.

Influence of history of cannabis smoking in selected donors on the outcomes of lung transplantation

OBJECTIVES Cannabis is the most commonly abused illicit drug and the smokers are at the risk of lung infections, bullous emphysema and lung cancer. However, no evidence about the outcomes of lung transplantation (LTx) utilizing the lungs from such donors is available in the literature. METHODS We retrospectively analysed lung ‘organ offers’ and LTx at our centre between January 2007 and November 2013. The outcomes of LTx utilizing lungs from donors with a history of cannabis smoking were compared with the outcomes of those with no such history using unadjusted model as well as propensity score matching. RESULTS A total of 302 LTxs were performed during this period and were grouped depending on the history of cannabis smoking in donors—‘cannabis’ (n = 19) and control group (n = 283). All the donors in ‘cannabis’ group were tobacco smokers compared with 43% in the control group. Preoperative characteristics in recipients in both groups were comparable. Intraoperative and post-LTx variables including 1- and 3-year survivals were comparable in both groups. CONCLUSIONS The history of donor cannabis smoking does not appear to affect early and mid-term outcomes after LTx and potentially improve the donor pool. As it does not seem to negatively affect the outcomes after LTx, it should not be per se considered a contraindication for lung donation.

Moving Back to the Future: Use of Organ Care System Lung for Lobectomy Before Lobar Lung Transplantation

Background Lung transplantation remains the gold standard treatment for patients with end-stage lung disease. Lobar lung transplantation allows for transplantation of size-mismatch donor lungs in small recipients; however, donor lung volume reduction represents a challenging surgical technique. In this paper we present our initial experience with bilateral lobectomy in donor lungs before lobar lung transplantation using normothermic perfusion on the Organ Care System (OCS) Lung. Material/Methods Specifics of the surgical technique for donor lung instrumentation on the OCS, lobar dissection on the OCS, and right and left donor lobectomies are presented in detail. Results Potential advantages of the use of the OCS for lobectomy for lobar lung transplantation are described in this section. Donor lung volume reduction utilizing OCS appeared to be easier and safer compared to the conventional cold storage technique, due to continuous perfusion of the lungs with blood and well-distended vessels that offer the feel of live lobectomy. Moreover, the OCS represents a platform for donor organ assessment and optimization of its function before transplantation. Conclusions Donor lung volume reduction was safe and feasible utilizing the OCS, which could be a useful tool for volume reduction in cases of size mismatch. Further research is needed to evaluate early and long-term results after lobar lung transplantation using the OCS in clinical studies.