Double lung transplantation (dLTx) is associated with a better postoperative functional capacity when compared with sLTx.(6, 7) However, a clear survival benefit conferred by dLTx has not unequivocally been documented.(7, 8) Can we therefore offer dLTx to all recipients? Or should we rather perform sLTx whenever possible in face of severe organ shortage and associated waiting list mortality?
Single center studies and registry-based studies have reported periprocedural and long-term outcomes after sLTX and dLTx. However, no prospective randomized trials have ever been performed to clearly document the individual merit of both procedures. Nevertheless 75% of lung transplantations are nowadays performed as dLTx.(9)
Pulmonary fibrosis is as restrictive pulmonary disease is frequently associated with secondary pulmonary hypertension. SLTx for pulmonary fibrosis will therefore lead to preferred ventilation of the graft and preferred perfusion of the graft resulting in an optimal ventilation perfusion match. Accordingly sLTX was considered to be an optimal procedure for fibrosis.(10) Meyers reported the first larger cohort of recipients with pulmonary fibrosis and did not observe a survival difference for sLTx vs. dLTx.(11) In a more recent analysis with pooled data from the United Network for Organ Sharing (UNOS) database a better graft survival was documented with dLTx for recipients with pulmonary fibrosis.(12) In contrast a current study based on pooled data of the Scientific Registry of Transplant Recipients employed propensity score matching to compare sLTX and dLTx. Long-term-survival up to ten years was similar in both groups (n = 466 in each group). A trend towards reduced rate of posttransplant renal failure and reduced hospital length of stay was observed in sLTx-recipients. (13)
SLTX for patients with COPD / emphysema is usually technically simple and rarely requires cardiopulmonary bypass. However, air trapping in the native lung may cause mediastinal shift and impaired ventilation-perfusion match. Thus volume reduction of the contralateral lung has been suggested to overcome this clinical dilemma.(10) If used with this precautions sLTx may lead to satisfactory long-term results, particularly for the elderly recipient. Thabut used the ISHLT database to analyse recipients between 1987 and 2007 worldwide. He documented a survival benefit of dLTx for recipients < 60 years.(14) The study by Schaffer et al. mentioned above, which employed the UNOS database, did not find a survival difference between sLTx and dLTx for COPD-patients.(12)
The LAS-system was implemented in the USA in 2005 and in 2011 in Germany. With this allocation model decreasing mortality on the waiting list was observed in both countries.(1, 15). While in Germany up to every fifth patient died on the waiting list before the advent of the LAS-system, mortality was reduced since then by 25%.(1) Nevertheless death on the waiting list is still an issue. A recent analysis based on the UNOS database documented that in only 43% of donors for sLTx, both lungs were used.(16) Thus centers should rethink their individual donor profiles. While an earlier analysis shed a critical light on lung splitting and sLTx (17), a very recent editorial by Ramos identified a decreased risk for death on the waiting list when patients with COPD or fibrosis were listed for sLTx without a compromised posttransplant outcome.(9)
Lung twinning, i.e. two sLTx from one lung donor, was first reported by Haydock in a multi-center-study.(18) This strategy may help to overcome donor lung shortage, but exposes the second donor lung to prolonged ischemic time since both single lung transplantation may only rarely be performed at the same time in different operating rooms by different teams in the same transplant center. Prolonged cold ischemia may in turn lead to ischemia/reperfusion injury. Improvements in lung preservation, surgical technique and perioperative care have helped to reduce the reduce the incidence of ischemia/reperfusion induced primary graft failure from 30–15% or less. Nevertheless ischemia/reperfusion injury remains a significant cause of early morbidity and mortality after lung transplantation.
Does the lung twinning concept turn the second twin (i.e. the low-risk patient with lower LAS) into a high-risk patient due to increased risk of ischemia/reperfusion injury? Sommers analyzed differences between lung twin pairs in the Pittsburgh transplant program and observed impaired early graft function associated with left-single-lung-recipients, pulmonary hypertension and cardiopulmonary bypass.(19) In contrast, Glanville documented that prolonged ischemia for the second lung did not induce early graft dysfunction.(20) Snell reported the largest single-center-experience of lung twinning with 38 pairs of recipients.(21) This Australian group did not observe different outcomes between first and second twins. However this group reported an inferior intermediate outcome of left-single-lung-recipients - primarily related to increased mortality from airway complications.(21) These observations were supported by Smits from Eurotransplant, who analyzed the outcome of 90 lung twin pairs operated in 16 European centers.(5) In this analysis more fatal complications were observed in recipients receiving a left-sided sLTx. Outcome was particularly worse if the retrieval center was different from the transplanting center (1-year-survival: right sLTx 92% / left sLTx 62%, p = 0.04).
Our results with lung twinning support the findings of prior studies that lung twinning can be performed safely despite of prolonged ischemic time for the second lung. Survival of our twin cohort was similar when compared with all standard sLTx, which had been performed in the same era. Our data document that also challenging transplantations in high-LAS patients (n = 6) or ECMO (n = 3) may be performed in this context without survival difference between first twin (high-risk-patient) and second twin (low-risk patient). Intermediate-term outcomes are comparable with outcomes in the ISHLT registry. Of interest, no survival difference was observed for left versus right sLTx in our patient cohort. Maybe this finding could be attributed to the fact that all retrievals were performed by our center and no airway complications were observed.
We conclude that stringent use of sLTX - i.e. (almost) always for pulmonary fibrosis and if suitable for COPD - may expand the donor pool and allows lung twinning. Such concept can lead to encouraging intermediate-term outcomes and may help to further reduce waiting list mortality in the LAS-era.
Table 1: Demographic data and postoperative outcome
Figure 1: Kaplan-Meyer survival analysis: whole cohort
Figure 2: Kaplan-Meyer survival analysis: first twin versus second twin
Figure 3: Kaplan-Meyer survival analysis: restrictive versus obstructive disease
Figure 4: Kaplan-Meyer survival analysis: left versus right single lung transplantation.
Table 1
Demographic data and postoperative outcome
Twin Pair No. | Age | Sex | Disease type | LAS | Allocation | sLTx type | Outcome | Best FEV1 (%) | CLAD Stage |
1 | 59 50 | f f | REST BOS | 55 43 | regular regular | left right | alive 107 mo died 4 d postop (sepsis) | 72 | 0 |
2 | 62 63 | f f | REST OBST | 49 36 | regular regular | left right | alive 84 mo died 6 mo postop (sepsis) | 72 | 0 |
3 | 56 53 | m m | REST REST | 90 34 | regular ext all | right left | died 11 mo postop (sepsis) alive 84 mo | 50 70 | 0 |
4 | 45 59 | m m | REST OBST | 88 38 | regular rescue | left right | died 70 mo postop (rejection) alive 75 mo | 79 58 | 0 1 |
5 | 63 50 | m m | REST OBST | 40 32 | regular regular | right left | alive 65 mo alive 65 mo | 90 53 | 0 3 |
6 | 52 61 | m m | REST OBST | 44 34 | regular ext all | left right | died 40 mo postop (stroke) alive 63 mo | 89 63 | 0 2 |
7 | 63 64 | m m | REST OBST | 67 32 | regular ext all | left right | alive 61 mo died 39 mo postop (sepsis) | 89 73 | 0 0 |
8 | 53 61 | m m | BOS REST | 43 38 | regular regular | right left | died 2 mo postop (sepsis) died 42 mo postop (lung cancer in native fibrosis lung) | 98 | 0 |
9 | 54 64 | f f | REST OBST | 61 33 | regular regular | left right | died 42 mo postop (pneumonia) alive 58 mo | 59 65 | 0 0 |
10 | 38 56 | m m | REST OBST | 92 34 | regular rescue | left right | alive 56 mo alive 56 mo | 65 61 | 0 0 |
11 | 55 56 | m m | REST REST | 38 34 | regular rescue | left right | died 48 mo postop (lung cancer in native fibrosis lung) died 6 mo postop (pulmonary embolism) | 52 57 | 0 0 |
12 | 61 66 | f f | OBST OBST | 34 31 | ext all rescue | left right | alive 53 mo died 47 mo postop (CLAD) | 54 62 | 0 3 |
13 | 61 64 | f f | OBST OBST | 33 34 | regular regular | left right | alive 39 mo alive 39 mo | 59 52 | 0 0 |
14 | 67 63 | m f | REST OBST | 46 40 | regular regular | left right | died 15 mo postop (COVID) alive 33 mo | 53 69 | 0 |
15 | 38 61 | f f | REST REST | 46 34 | regular regular | left right | alive 16 mo alive 16 mo | 60 73 | 0 0 |
16 | 62 57 | f f | REST OBST | 37 33 | ext all ext all | left right | died 5 mo postop (sepsis) alive 14 mo | 30 | 3 |
(REST: restrictive lung disease, OBST: obstructive lung disease, BOS: bronchiolitis obliterans syndrome, ext all: extended allocation, CLAD: chronic lung allograft dysfunction)