M. Perch

Treatment of intractable interstitial lung injury with alemtuzumab after lung transplantation

A 44-year-old woman underwent left single-lung transplantation for end-stage emphysema due to α1-antitrypsin deficiency in January 2010. Cyclosporine, azathioprine, and prednisolone were administered for immunosuppression and antithymocyte globulin for induction therapy at the time of transplantation. Routine examination of a lung biopsy, 4 months after transplantation, showed nonspecific, diffuse interstitial inflammation with alveolar septal fibrosis. The patients clinical status and imaging studies, consistent with nonspecific interstitial pneumonitis, which was considered as signs of acute rejection, worsened within 2 weeks, despite high-dose steroids, change of calcineurin inhibitor, and plasmapheresis. Within a few days after a single, 10-mg, intravenous dose of alemtuzumab, the patients health improved markedly. She has remained stable for 4 months on a standard, ambulatory, posttransplant antirejection drug regimen. We have since successfully treated with alemtuzumab three additional patients who developed interstitial lung injury after lung transplantation, who are also summarized in this report.

ISHLT Consensus ReportsPrimary Lung Graft DysfunctionReport of the ISHLT Working Group on Primary Lung Graft Dysfunction, part I: Definition and grading—A 2016 Consensus Group statement of the International Society for Heart and Lung Transplantation

From the Allergy, Immunology and Respiratory Medicine, Alfred Hospital, Melbourne, Victoria, Australia; Division of Pulmonary and Critical Care Medicine, Washington University School of Medicine in St. Louis, St. Louis, Missouri; Institute for Advanced Organ Disease and Transplantation, Tampa General Hospital/University of South Florida, Tampa, Florida; Department of Surgery, Michigan State University, Ada, Michigan; Lung Transplant Program, University of Chicago, Chicago, Illinois; Lung Transplant Program, Harefield Hospital, Harefield, United Kingdom; Division of Pulmonary, Critical Care, and Sleep Medicine, University of Florida, Gainesville, Florida; Division of Pulmonary Medicine, Medical University of South Carolina, Charleston, South Carolina; Section of Lung Transplantation, Department of Cardiology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark; Section of Pulmonary and Critical Care, Department of Medicine, and Lung Transplant Program, University of Chicago, Chicago, Illinois; Department of Pulmonary, Allergy and Critical Care Medicine, Respiratory Institute, Cleveland Clinic, Cleveland, Ohio; National Pulmonary Hypertension Service (Newcastle), The Newcastle upon Tyne Hospitals NHS Foundation Trust, and Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom; Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; and the Department of Surgery, University of Pennsylvania, Philadelphia, Pennsylvania.

Early laparotomy after lung transplantation: Increased incidence for patients with α1-anti-trypsin deficiency

BACKGROUND Gastrointestinal complications after lung transplantation have been reported with incidence rates ranging from 3% to 51%, but the reasons are poorly understood. We aimed to investigate the correlations between pulmonary diseases leading to lung transplantation and early gastrointestinal complications requiring laparotomy after transplantation with outcomes for patients at increased risk. METHODS In this study we performed a retrospective analysis of data of patients who underwent lung transplantation at our institution from 2004 to 2012. The study period was limited to the first 90 days after transplantation. RESULTS Lung transplantation was performed in 258 patients, including 51 patients with α1-anti-trypsin deficiency (A1AD). Seventy-eight patients (30%) had an X-ray of the abdomen, and 23 patients (9%) required laparotomy during the first 90 days after transplantation. Patients with A1AD comprised 20% of the total recipients, 23% (18 of 78) of the patients who had an abdominal X-ray performed (p = 0.40), and 48% (11 of 23) of the patients who required laparotomy (p < 0.001). More than 1 of every 5 patients (11 of 51) with A1AD required laparotomy at a median 8 days after transplantation, and the estimated odds ratio for laparotomy for A1AD patients was 5.74 (CI 2.15 to 15.35). In the group of patients with A1AD who required laparotomy, the estimated hazard ratio for death was 1.62 (CI 0.57 to 4.62), the stay in the intensive care unit was prolonged, but no significant difference was observed for time on mechanical ventilation. Among pulmonary diseases and demographics of the patients, no other risk factors were identified for laparotomy. CONCLUSIONS A1AD was the only significant risk factor identified for gastrointestinal complications that required laparotomy within 3 months after lung transplantation. There was a trend toward a higher risk of death after laparotomy in patients with A1AD, and the length of stay in the intensive care unit was significantly prolonged, whereas the time on mechanical ventilation was unaffected.

Prognosis of patients with alpha1-antitrypsine deficiency on long-term oxygen therapy.

INTRODUCTION Data on patients with alpha1-antitrypsine deficiency (AATD) on long-term oxygen therapy (LTOT) is sparse. The aim of this study was to present the incidence of patients with AATD on LTOT, and compare their characteristics, comorbidities and prognosis (lung transplantation, termination of LTOT, and survival) with COPD patients without AATD. METHODS A National prospective study of all COPD patients who started LTOT for the first time in the period 01.11.1994 to 31.12.2010. RESULTS Among the 21,964 patients on LTOT, 234 patients had AATD. AATD patients were more often males and were on average about 17 years younger than patients without AATD. Cardio-vascular diseases and diabetes mellitus were significantly less prevalent among patients with AATD (60.4% versus 70.3% (P < 0.001) and 4.7% versus 12.2% (P < 0.001)), whereas osteoporosis was more frequent (28.5% versus 20.4%, p = 0.002. Eighty-nine (38.0%) AATD patients and 173 (0.8%) non-AATD patients were lung transplanted in the study period. Median survival was 8.7 years in AATD patients with lung transplantation, 3.3 years in AATD patients without lung transplantation, 6.3 years in non-AATD patients with lung transplantation, and 1.6 years in non-AATD without lung transplantation. Even after adjustment for gender, age, comorbidities, and the time between start of LTOT and lung transplantation, patients with AATD had a lower risk of death compared to non-AATD patients (Hazard ratio 0.73 (95% CI: 0.62-0.86; P < 0.001). CONCLUSIONS Compared with COPD without AATD, AATD patients are younger, more often males, have a lower prevalence of cardio-vascular diseases and diabetes mellitus, and higher prevalence of osteoporosis. Moreover, they have better prognosis, partly due to greater chance of receiving a lung transplantation.

Urgent lung allocation system in the Scandiatransplant countries

BACKGROUND Throughout the world, the scarcity of donor organs makes optimal allocation systems necessary. In the Scandiatransplant countries, organs for lung transplantation are allocated nationally. To ensure shorter wait time for critically ill patients, the Scandiatransplant urgent lung allocation system (ScULAS) was introduced in 2009, giving supranational priority to patients considered urgent. There were no pre-defined criteria for listing a patient as urgent, but each center was granted only 3 urgent calls per year. This study aims to explore the characteristics and outcome of patients listed as urgent, assess changes associated with the implementation of ScULAS, and describe how the system was utilized by the member centers. METHODS All patients listed for lung transplantation at the 5 Scandiatransplant centers 5 years before and after implementation of ScULAS were included. RESULTS After implementation, 8.3% of all listed patients received urgent status, of whom 81% were transplanted within 4 weeks. Patients listed as urgent were younger, more commonly had suppurative lung disease, and were more often on life support compared with patients without urgent status. For patients listed as urgent, post-transplant graft survival was inferior at 30 and 90 days. Although there were no pre-defined criteria for urgent listing, the system was not utilized at its maximum. CONCLUSIONS ScULAS rapidly allocated organs to patients considered urgent. These patients were younger and more often had suppurative lung disease. Patients with urgent status had inferior short-term outcome, plausibly due to the higher proportion on life support before transplantation.

Long-term survival in lung transplant recipients depending on icu length of stay: outcome in a series of 653 consecutive patients

Over the last two decades lung transplantation (LT) has become the treatment of choice for various end-stage lung diseases. It is well-known that the majority of patients who underwent LT experienced complications postoperatively. Postoperative mortality has decreased due to improved surgical techniques and intensive care. However, very little is known about the long-term outcome of lung transplant recipients with prolonged intensive care length of stay (ICU LOS).

Age-Related Decline in Lung Function in Patients Without CLAD After Double Lung Transplantation

This improvement was maintained at both 1 and 3 years post-conversion (p< 0.001). In regards to pulmonary function, FEV1 decreased from the time of sirolimus initiation to 3 years post-conversion (p= 0.042), mean decrease 0.23 L (95% CI, 0.01-0.46). However, early conversion to sirolimus (< 6 months post-transplant) resulted in a trend towards improved FEV1 at 3 years (+0.017 L in the early conversion group versus -0.44 L in the late conversion group, p= 0.052). The sirolimus discontinuation rate for reasons other than death was 17.8%. Conclusion: Sirolimus is a viable immunosuppressant option after lung transplant, which successfully allows for the reduction or withdrawal of the CNI, resulting in sustained improvement in renal function. The antifibrotic properties of sirolimus may allow it to slow the progression of BOS, especially when initiated within the first 6 months of transplant.

526 Chronic Allograft Dysfunction after Lung Transplantation. A Comparison of RAS vs. BOS

Chronic Allograft Dysfunction after Lung Transplantation. A Comparison of RAS vs. BOS C.H. Moller, M. Jorgensen, M. Perch, C.B. Andersen, J. Carlsen, D.A. Steinbruchel, M. Iversen. Cardiothoracic Surgery, Rigshospitalet, Copenhagen, Denmark; Nephrology, Rigshospitalet, Copenhagen, Denmark; Cardiology, Section for Lungtransplantation, Rigshospitalet, Copenhagen, Denmark; Pathology, Rigshospitalet, Copenhagen, Denmark.