| 1. |
- Auråen, Henrik, et al.
(författare)
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Effect of Donor Age on Outcome of Lung Transplantation Stratified by Recipient Diagnosis : A Nordic Multicenter Study
- 2019
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Ingår i: Transplantation. - 1534-6080. ; 103:4, s. 807-814
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Organs from older donors are increasingly used in lung transplantation, and studies have demonstrated that this could be safe in selected recipients. However, which recipient groups that have the largest benefit of older organs are unclear. This multicenter study reviews all bilateral lung transplantations (BLTx) from donors 55 years or older stratified by recipient diagnosis and compares outcomes with transplantations from younger donors. METHODS: All BLTx recipients (excluding retransplantation) at 5 Scandiatransplant centers between 2000 and 2013 were included (n = 913). Recipients were stratified to diagnosis groups including cystic fibrosis (CF), chronic obstructive pulmonary disease (COPD), interstitial lung disease (ILD), and "other." Intensive care unit (ICU) length of stay (LOS) and survival were assessed. RESULTS: Overall, there was no difference in survival among patients transplanted from donors 55 years or older compared with younger donors. However, in CF recipients, donor age 55 years or older was associated with inferior survival (P = 0.014), and this remained significant in a multivariate model (hazard ratio, 5.0; 95% confidence interval, 1.8-14.1; P = 0.002). There was no significant effect of donor age on survival in recipients with COPD, ILD, or in the "other" group in multivariate models. Utilization of older donors was associated with increased ICU LOS for recipients with CF and ILD, but not in the COPD or "other" group. CONCLUSIONS: The BLTx recipients with CF had inferior survival and longer ICU LOS when receiving organs from donors 55 years or older. Recipients with COPD, ILD, or in the "other" group did not have inferior survival in multivariate models.
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| 2. |
- Auråen, Henrik, et al.
(författare)
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Urgent lung allocation system in the Scandiatransplant countries
- 2018
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Ingår i: Journal of Heart and Lung Transplantation. - 1053-2498. ; 37:12, s. 1403-1409
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 3. |
- Gullestad, Lars, et al.
(författare)
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Long-term outcomes of thoracic transplant recipients following conversion to everolimus with reduced calcineurin inhibitor in a multicenter, open-label, randomized trial
- 2016
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Ingår i: Transplant International. - : Wiley-Blackwell Publishing Inc.. - 0934-0874 .- 1432-2277. ; 29:7, s. 819-829
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Tidskriftsartikel (refereegranskat)abstract
- The NOCTET study randomized 282 patients ≥1 year after heart or lung transplantation to continue conventional calcineurin inhibitor (CNI) therapy or to start everolimus with reduced-exposure CNI. Last follow-up, at ≥5 years postrandomization (mean: 5.6 years) was attended by 72/140 everolimus patients (51.4%) and 91/142 controls (64.1%). Mean measured GFR remained stable in the everolimus group from randomization (51.3 ml/min) to last visit (51.4 ml/min) but decreased in controls (from 50.5 ml/min to 45.3 ml/min) and was significantly higher with everolimus at last follow-up (P = 0.004). The least squares mean (SE) change from randomization was -1.5 (1.7)ml/min with everolimus versus -7.2 (1.7)ml/min for controls (difference: 5.7 [95% CI 1.7; 9.6]ml/min; P = 0.006). The difference was accounted for by heart transplant patients (difference: 6.9 [95% 2.3; 11.5]ml/min; P = 0.004). Lung transplant patients showed no between-group difference at last follow-up. Rates of rejection, death, and major cardiac events were similar between groups, as was graft function. Pneumonia was more frequent with everolimus (18.3% vs. 6.4%). In conclusion, introducing everolimus in maintenance heart transplant patients, with reduced CNI, achieves a significant improvement in renal function which is maintained for at least 5 years, but an early renal benefit in lung transplant patients was lost. Long-term immunosuppressive efficacy was maintained.
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| 4. |
- Müller, Catharina, et al.
(författare)
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Protein signatures of remodeled airways in transplanted lungs with Bronchiolitis Obliterans Syndrome obtained using laser capture microdissection
- 2021
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Ingår i: American Journal of Pathology. - : Elsevier BV. - 1525-2191 .- 0002-9440. ; 191:8, s. 1398-1411
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Tidskriftsartikel (refereegranskat)abstract
- Bronchiolitis obliterans syndrome (BOS), a common form of chronic lung allograft dysfunction, is the major limitation to long-term survival after lung transplantation. The histological correlate is progressive, fibrotic occlusion of small airways, obliterative bronchiolitis lesions, ultimately leading to organ failure. The molecular composition of these lesions is unknown. By laser-capture microdissection and optimized sample preparation protocols for mass spectrometry the protein composition of the lesions in explanted lungs from four end-stage BOS patients were analysed. Immunohistochemistry and immunofluorescence were used to determine the spatial distribution of commonly identified proteins on the tissue level, protein signatures for in total 14 OB-lesions were established. A set of 39 proteins identified in more than 75% of lesions included distinct structural proteins (collagen type IV and VI) and cellular components (actins, vimentin, tryptase). Each respective lesion exhibited a unique composition of proteins (on average n=66 proteins), thereby mirroring the morphological variation of the lesions. Antibody-based staining confirmed these MS-based findings. The 14 analyzed OB-lesions showed variations in their protein content, but also common features. This study provides molecular and morphological insights into the development of chronic rejection after lung transplantation. The protein patterns in the lesions were correlated to pathways of extracellular matrix organization, tissue development and wound healing processes.
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| 5. |
- Eguíluz-Gracia, Ibon, et al.
(författare)
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Long-Term persistence of human donor alveolar macrophages in lung transplant recipients
- 2016
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Ingår i: Thorax. - : BMJ. - 0040-6376 .- 1468-3296. ; 71:11, s. 1006-1011
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Tidskriftsartikel (refereegranskat)abstract
- Background Alveolar macrophages (AMFs) are critical regulators of lung function, and may participate in graft rejection following lung transplantation. Recent studies in experimental animals suggest that most AMFs are self-maintaining cells of embryonic origin, but knowledge about the ontogeny and life span of human AMFs is scarce. Methods To follow the origin and longevity of AMFs in patients with lung transplantation for more than 100â €..weeks, we obtained transbronchial biopsies from 10 gender-mismatched patients with lung transplantation. These were subjected to combined in situ hybridisation for X/Y chromosomes and immunofluorescence staining for macrophage markers. Moreover, development of AMFs in humanised mice reconstituted with CD34+ umbilical cord-derived cells was assessed. Results The number of donor-derived AMFs was unchanged during the 2â €..year post-Transplantation period. A fraction of the AMFs proliferated locally, demonstrating that at least a subset of human AMFs have the capacity to self-renew. Lungs of humanised mice were found to abundantly contain populations of human AMFs expressing markers compatible with a monocyte origin. Moreover, in patients with lung transplantation we found that recipient monocytes seeded the alveoli early after transplantation, and showed subsequent phenotypical changes consistent with differentiation into proliferating mature AMFs. This resulted in a stable mixed chimerism between donor and recipient AMFs throughout the 2-year period. Conclusions The finding that human AMFs are maintained in the lung parenchyma for several years indicates that pulmonary macrophage transplantation can be a feasible therapeutic option for patients with diseases caused by dysfunctional AMFs. Moreover, in a lung transplantation setting, long-Term persistence of donor AMFs may be important for the development of chronic graft rejection.
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| 6. |
- Müller, Catharina, et al.
(författare)
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Early extracellular matrix changes are associated with later development of bronchiolitis obliterans syndrome after lung transplantation
- 2017
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Ingår i: BMJ Open Respiratory Research. - : BMJ. - 2052-4439. ; 4:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Chronic lung allograft dysfunction in the form of bronchiolitis obliterans syndrome (BOS) is the main cause of death beyond 1-year post-lung transplantation. The disease-initiating triggers as well as the molecular changes leading to fibrotic alterations in the transplanted lung are largely unknown. The aim of this study was to identify potential early changes in the extracellular matrix (ECM) in different compartments of the transplanted lung prior to the development of BOS.METHODS: Transbronchial biopsies from a cohort of 58 lung transplantation patients at the Copenhagen University hospital between 2005 and 2006, with or without development of BOS in a 5-year follow-up, were obtained 3 and 12 months after transplantation. Biopsies were assessed for total collagen, collagen type IV and biglycan in the alveolar and small airway compartments using Masson's Trichrome staining and immunohistochemistry.RESULTS: A time-specific and compartment-specific pattern of ECM changes was detected. Alveolar total collagen (p=0.0190) and small airway biglycan (p=0.0199) increased between 3 and 12 months after transplantation in patients developing BOS, while collagen type IV (p=0.0124) increased in patients without BOS. Patients with early-onset BOS mirrored this increase. Patients developing grade 3 BOS showed distinct ECM changes already at 3 months. Patients with BOS with treated acute rejections displayed reduced alveolar total collagen (p=0.0501) and small airway biglycan (p=0.0485) at 3 months.CONCLUSIONS: Patients with future BOS displayed distinct ECM changes compared with patients without BOS. Our data indicate an involvement of alveolar and small airway compartments in post-transplantation changes in the development of BOS.
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