Living-donor lobar lung transplantation for pulmonary hypertension: living on the edge? Free

‘Living on the Edge’ is the first studio album by Stéphane Pompougnac, a French psychotherapist and dental surgeon [1]. The expression is used to indicate someone is taking a risk above and beyond what most people would do, to have a lifestyle in which one tends to engage in dangerous or risky behaviour.

The majority of lung transplantation (LTx) worldwide is performed with lungs from deceased donors declared death on neurologic or circulatory criteria [2]. A very small proportion of patients though receive a lobe from a living donor, mainly in countries with a very low deceased donor conversion rate such as Japan [3]. The largest experience with living-donor lobar LTx has been reported by the groups at Okayama University and Kyoto University with remarkable results.

Compared to other diagnoses, patients with end-stage lung disease related to pulmonary arterial hypertension (PAH) form a difficult population with the highest post-transplant mortality [4]. It is believed that PAH patients need perfect lungs to accommodate the enhanced pulmonary blood flow resulting from an acute change in cardiopulmonary physiology with a decrease in right ventricular afterload and an increase in left ventricular preload during the first post-transplant days. Donor to recipient size matching based on donor height or total lung capacity is a parameter of special importance when choosing the best donor for PAH patients as their postoperative risk is reduced when transplanted with an oversized lung with a large pulmonary vascular bed [5].

In this issue of the journal, Kayawake et al. [6] from Kyoto University report their findings of a small, single-centre, non-randomized, retrospective study between 2008 and 2021 comparing post-transplant outcome in PAH patients between lung recipients from living-lobar donors (n = 12) versus cadaveric donors (n = 22). Although patients in the first group had worse preoperative conditions with more ventilator-dependency and less ambulation, higher preoperative mean pulmonary artery pressure and more single-LTxs (2/12), their outcome in terms of primary graft dysfunction (PGD), duration of mechanical ventilation, intensive care unit stay, hospital mortality and overall survival and chronic lung allograft dysfunction-free survival at 1 and 5 years was comparable between both groups. As hypothesized by the authors, these similar results despite their higher risk profile may be related to the perfect quality of the lobe from well-selected living donors as well as the shorter cold ischaemic times (157 [107–223] vs 557 [385–711] min, respectively; P < 0.001).

Some findings are remarkable and interesting to discuss. The prevalence of PGD-3 within 72 h in both groups was higher (66.7% and 77.3%, respectively; NS) as compared to the 30% prevalence usually reported after LTx in large series [7]. This complication correlated with the reported need for prolonged mechanical ventilation in both groups (24.5 [2–125] vs 18.5 [3–192] days, respectively; NS). No information, however, was given on the need for tracheostomy in these recipients.

What may have contributed to this high PGD-3 prevalence? First, PAH patients have a higher risk to develop cardiogenic oedema early after LTx. This results from transient ventricular diastolic dysfunction of the chronically deprived left heart [8]. Importantly, the Kyoto group did not apply a strategy for prophylactic post-transplant use of veno-arterial extracorporeal membrane oxygenation to bypass the lungs in the initial post-transplant period to overcome the need for prolonged sedation and ventilation in intensive care unit. Second, a significant number of their patients (8/12 and 10/22, respectively) were transplanted with the use of conventional cardiopulmonary bypass for intraoperative extracorporeal circulatory support. There is increasing evidence that PGD-3 prevalence is higher in patients transplanted on cardiopulmonary bypass compared to extracorporeal membrane oxygenation [9]. Finally, the choice for an undersized lobe from a living donor with a forced vital capacity <100% to >50% of the recipient, and thus, a smaller than ideal pulmonary vascular bed may have contributed to PGD development.

It is important to mention that, despite the higher PGD-3 incidence, short- and long-term recipient outcomes in this study remained excellent. Remarkably, 2 paediatric recipients in the living-lobar group underwent single-LTx. Double-lung or heart-LTx remains the preferred transplant type for PAH patients in the majority of LTx centres nowadays [4]. Nevertheless, some groups have reported good post-transplant outcome after single-LTx for PAH [10]. Our experience in Leuven with single-LTx for this indication is limited to 1 female recipient transplanted back in 1992. Early postoperative management in this patient was very difficult once she developed massive reperfusion oedema resulting in significant ventilation/perfusion mismatch early on and also later during her post-transplant course once a bronchial anastomotic complication occurred.

Living-donor LTx may lower the risk of both acute and chronic rejection by reducing the number of HLA mismatches between donor and (related) recipient. Yet, acute rejection was not addressed by the authors and CLAD prevalence unexpectedly did not differ from that observed in (unrelated) cadaveric lung recipients.

Despite the limitations inherent to the design of their study, Dr Date and his group at Kyoto University are to be congratulated with their impressive results in a difficult patient group with PAH. They have demonstrated that living-donor lobar LTx is a viable rescue option for young patients if further waiting for a suitable cadaveric donor is no longer achievable. For patients with pulmonary vascular disease, most centres worldwide, however, continue to prefer the use of full-sized, healthy lungs from a deceased donor for double-LTx.

Living on the edge? In their series, the authors reported 5 cases of morbidities greater than grade 3 according to the Clavien-Dindo classification in 4 living donors. Careful patient selection and meticulous surgery to lower the risk for postoperative death of the living donor is of utmost importance. We want the living donor to stay alive by all means!

Funding

Dirk Van Raemdonck and Geert M. Verleden are supported by the Broere Charitable Foundation. Laurens J. Ceulemans is supported by a named chair at the KU Leuven funded by Medtronic and a postdoc research fellowship funded by the University Hospitals Leuven (KOOR). Robin Vos is a senior clinical research fellow of the Fund for Scientific Research Flanders (FWO).

REFERENCES