A review of lung transplant donor acceptability criteria

Orens, Jonathan B.; Boehler, Annette; Perrot, Marc de; Estenne, Marc; Glanville, Allan R.; Keshavjee, Shaf; Kotloff, Robert M.; Morton, J.; Studer, Sean M.; Raemdonck, Dirk Van; Waddel, Thomas; Snell, Gregory I

doi:10.1016/s1053-2498(03)00096-2

Cited by 326 publications

(214 citation statements)

References 89 publications

(127 reference statements)

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“…The internationally accepted selection criteria of the 'optimal donor' are primarily opinion based rather than evidence based, and their accuracy in determining the physiological status of the donor lung and predicting post-operative lung function is not optimal. 18 Fisher et al 19 have shown that current clinical donor lung assessment criteria are poor predictors of existing inflammation or infection in the donor lung, suggesting that many donor lungs deemed unusable may be unnecessarily excluded. Ware et al 20 evaluated 29 pairs of unusable lungs by physiological, microbiological and histological methods, and concluded that as many as 40% of these lungs would have been potentially suitable for transplantation.…”

Section: Assessment Of Donor Lung Usabilitymentioning

confidence: 99%

An observational study of Donor Ex Vivo Lung Perfusion in UK lung transplantation: DEVELOP-UK

Fisher

Andreasson

Chrysos

et al. 2016

Health Technol Assess

110

115

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BackgroundMany patients awaiting lung transplantation die before a donor organ becomes available. Ex vivo lung perfusion (EVLP) allows initially unusable donor lungs to be assessed and reconditioned for clinical use.ObjectiveThe objective of the Donor Ex Vivo Lung Perfusion in UK lung transplantation study was to evaluate the clinical effectiveness and cost-effectiveness of EVLP in increasing UK lung transplant activity.DesignA multicentre, unblinded, non-randomised, non-inferiority observational study to compare transplant outcomes between EVLP-assessed and standard donor lungs.SettingMulticentre study involving all five UK officially designated NHS adult lung transplant centres.ParticipantsPatients aged ≥ 18 years with advanced lung disease accepted onto the lung transplant waiting list.InterventionThe study intervention was EVLP assessment of donor lungs before determining suitability for transplantation.Main outcome measuresThe primary outcome measure was survival during the first 12 months following lung transplantation. Secondary outcome measures were patient-centred outcomes that are influenced by the effectiveness of lung transplantation and that contribute to the health-care costs.ResultsLungs from 53 donors unsuitable for standard transplant were assessed with EVLP, of which 18 (34%) were subsequently transplanted. A total of 184 participants received standard donor lungs. Owing to the early closure of the study, a non-inferiority analysis was not conducted. The Kaplan–Meier estimate of survival at 12 months was 0.67 [95% confidence interval (CI) 0.40 to 0.83] for the EVLP arm and 0.80 (95% CI 0.74 to 0.85) for the standard arm. The hazard ratio for overall 12-month survival in the EVLP arm relative to the standard arm was 1.96 (95% CI 0.83 to 4.67). Patients in the EVLP arm required ventilation for a longer period and stayed longer in an intensive therapy unit (ITU) than patients in the standard arm, but duration of overall hospital stay was similar in both groups. There was a higher rate of very early grade 3 primary graft dysfunction (PGD) in the EVLP arm, but rates of PGD did not differ between groups after 72 hours. The requirement for extracorporeal membrane oxygenation (ECMO) support was higher in the EVLP arm (7/18, 38.8%) than in the standard arm (6/184, 3.2%). There were no major differences in rates of chest radiograph abnormalities, infection, lung function or rejection by 12 months. The cost of EVLP transplants is approximately £35,000 higher than the cost of standard transplants, as a result of the cost of the EVLP procedure, and the increased ECMO use and ITU stay. Predictors of cost were quality of life on joining the waiting list, type of transplant and number of lungs transplanted. An exploratory model comparing a NHS lung transplant service that includes EVLP and standard lung transplants with one including only standard lung transplants resulted in an incremental cost-effectiveness ratio of £73,000. Interviews showed that patients had a good understanding of the need for, and the processes of, EVLP. If EVLP can increase the number of usable donor lungs and reduce waiting, it is likely to be acceptable to those waiting for lung transplantation. Study limitations include small numbers in the EVLP arm, limiting analysis to descriptive statistics and the EVLP protocol change during the study.ConclusionsOverall, one-third of donor lungs subjected to EVLP were deemed suitable for transplant. Estimated survival over 12 months was lower than in the standard group, but the data were also consistent with no difference in survival between groups. Patients receiving these additional transplants experience a higher rate of early graft injury and need for unplanned ECMO support, at increased cost. The small number of participants in the EVLP arm because of early study termination limits the robustness of these conclusions. The reason for the increased PGD rates, high ECMO requirement and possible differences in lung injury between EVLP protocols needs evaluation.Trial registrationCurrent Controlled Trials ISRCTN44922411.FundingThis project was funded by the NIHR Health Technology Assessment programme and will be published in full inHealth Technology Assessment; Vol. 20, No. 85. See the NIHR Journals Library website for further project information.

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Section: Assessment Of Donor Lung Usabilitymentioning

confidence: 99%

An observational study of Donor Ex Vivo Lung Perfusion in UK lung transplantation: DEVELOP-UK

Fisher

Andreasson

Chrysos

et al. 2016

Health Technol Assess

110

115

View full text Add to dashboard Cite

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“…The current International Society for Heart and Lung Transplantation (ISHLT) criteria outlining an ideal donor are based on strict criteria established during the development of lung transplantation (Table 2). Although this has helped establish safe clinical lung transplantation, this combination of stringent donor criteria coupled with an increased susceptibility of donor lungs to injury leads to a conservative and low utilization rate (Orens et al 2003).…”

Section: Donor Selectionmentioning

confidence: 99%

Overview of Clinical Lung Transplantation

Yeung

Keshavjee

2014

Cold Spring Harbor Perspectives in Medicine

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Since the first successful lung transplant 30 years ago, lung transplantation has rapidly become an established standard of care to treat end-stage lung disease in selected patients. Advances in lung preservation, surgical technique, and immunosuppression regimens have resulted in the routine performance of lung transplantation around the world for an increasing number of patients, with wider indications. Despite this, donor shortages and chronic lung allograft dysfunction continue to prevent lung transplantation from reaching its full potential. With research into the underlying mechanisms of acute and chronic lung graft dysfunction and advances in personalized diagnostic and therapeutic approaches to both the donor lung and the lung transplant recipient, there is increasing confidence that we will improve short-and long-term outcomes in the near future.

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“…Indeed, lung specimens from donors gives the unique opportunity to analyse a large amount of lung tissue in relatively healthy individuals; nonetheless, there are still potential biases. In particular, since smoking history is not an exclusion criterion for selection of lung donors [34], it is possible that some of the donors were smokers. Moreover, some of them would have been ventilated before lung transplantation.…”

Section: Discussionmentioning

confidence: 99%

Transforming growth factor- type II receptor in pulmonary arteries of patients with very severe COPD

Beghè¹,

Bazzan²,

Baraldo³

et al. 2006

European Respiratory Journal

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A mild-to-moderate increase in pulmonary arterial pressure is often associated with severe chronic obstructive pulmonary disease (COPD). Transforming growth factor (TGF)-b is a cytokine involved in the maintenance of integrity of vasculature. The aim of the study was to investigate whether the TGF-b pathway might be involved in the development of pulmonary hypertension associated with COPD.Surgical specimens from 14 patients undergoing lung transplantation for very severe COPD (forced expiratory volume in one second 17¡2% of the predicted value) and from seven donors were examined. The expression of TGF-b1 and TGF-b type II receptor (TGF-bRII), cell proliferation index and structural changes in pulmonary arteries were quantified immunohistochemically.In severe COPD patients, increased expression of TGF-bRII was observed in both the tunica media and intima, which was associated with a normal proliferation index in both layers. Conversely, significant thickening of the tunica intima, which was not present in the tunica media, was observed, suggesting that mechanisms other than cell proliferation may be involved in intimal thickening.In conclusion, in the pulmonary arteries of patients with severe chronic obstructive pulmonary disease, there is upregulation of transforming growth factor-b type II receptor expression associated with a normal proliferation index. These findings suggest the activation of an antiproliferative pathway, which might explain the relatively low degree of pulmonary hypertension observed in these subjects.

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A review of lung transplant donor acceptability criteria

Cited by 326 publications

References 89 publications

An observational study of Donor Ex Vivo Lung Perfusion in UK lung transplantation: DEVELOP-UK

An observational study of Donor Ex Vivo Lung Perfusion in UK lung transplantation: DEVELOP-UK

Overview of Clinical Lung Transplantation

Transforming growth factor- type II receptor in pulmonary arteries of patients with very severe COPD

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