The use of double-lung transplants has been controversial because, of course, transplanting both lungs when it is not needed wastes a scarce resource. Historically, however, much of the literature has suggested that double-lung transplant outcomes are better, particularly in patients with IPF and COPD, perhaps because of underlying bronchiectasis or the improved functional reserve that comes with two lungs vs one. Many of these studies derived their data from the UNOS (United Network for Organ Sharing) or Lung Transplant Registry, and many of the earlier studies exploring this question were completed before we had the lung allocation score.
Previously, length of time on a waiting list was the main driver in terms of whether a patient received a lung transplant or not, and patients with IPF got a 6-month credit on the waiting list. More recently, the system for lung allocation has moved to one that is very similar to the system used for liver transplants, where the goal is to try to balance the risk for death while waiting for a lung transplant, against the benefit of receiving a lung transplant, to optimize outcomes for everyone in the pool.
Even after applying this lung allocation score, many patients with IPF or COPD receive bilateral lung transplants; however, many also get single transplants. The question is, what is the best way to allocate these scarce resources?
These investigators went to the UNOS registry to look at outcomes of patients after lung transplant as a function of whether they had IPF or COPD and whether they received a single- or double-lung transplant. They specifically compiled cases during the era of the lung allocation score, where some effort to balance risk and benefit has been integrated into the allocation of these scarce resources.
These authors looked at outcomes in about 4100 patients with IPF and 3100 patients with COPD. In an unadjusted analysis, the overall outcomes were good compared with historical outcomes, with median survivals above 50% at 5 years, regardless of whether patients received a single-lung transplant or a double-lung transplant, and of whether they had COPD or IPF.
When they looked specifically at patients with IPF, the unadjusted analysis found a survival advantage associated with double-lung transplant vs single-lung transplant. The Kaplan-Meier curves remained separated from the moment of transplantation forward. They also conducted an adjusted analysis that was propensity score–matched, to try to “pseudorandomize” the data to take into account the probability of getting one kind of transplant vs another. In addition, they looked at various important confounders such as the presence of pulmonary artery hypertension. This adjusted analysis showed a clear survival benefit associated with the double-lung transplant in patients with IPF: approximately 65-month survival vs about 50 months in IPF patients who received a single-lung transplant. That is a 15-month benefit and was statistically significant.
In the patients with COPD, the story is a bit more nuanced. The unadjusted analysis showed a benefit of double-lung transplant vs single-lung transplant in the population with COPD. However, the adjusted analysis—a careful, very nuanced statistical examination—found that the net benefit of a double- vs single-lung transplant was reduced to only 4 months. This was no longer statistically significant—not even close. It was also clear that there was a major interaction between double- and single-lung transplants, type of underlying disease (IPF or COPD), and eventual outcome.
These data are quite thought-provoking. It is a large analysis conducted during the lung allocation score era, and the investigators were very careful with their statistical modeling.
I believe that these results should begin to change our lung transplant practices. We need to derive better ways to sort out who needs a single-lung or a double-lung transplant. In patients with IPF, these data suggest clearly that the double-lung transplant is probably the right way to go. For patients with COPD vs historical controls, we do not have good data to show that there is necessarily any survival benefit associated with lung transplantation. For COPD, we need to step back and reevaluate the double- vs single-lung question, and perhaps use datasets similar to this to ascertain which patients benefit from a double- vs a single-lung transplant instead of simply saying that all patients with COPD are the same. Perhaps we should come up with scoring tools that are validated in external and other datasets across the globe to finally say which COPD patients, if any, benefit from double-lung transplant over single-lung transplant.