Longer Life or More Life: Choose One Please

In the pre-2005, wait time-based system of lung allocation, chronic obstructive pulmonary disease (COPD) patients listed for lung transplant had a distinct advantage in the competition for donor organs because the system ironically favored those who could survive 2–3 y before receiving a transplant. The Lung Allocation Score system (LAS), implemented in 2005, refocused the system to directly address medical urgency to reduce the risk of dying while waiting for a lung donation.¹ Consequently, despite severely impaired lung function and dismal quality of life, transplant candidates with COPD became less likely recipients for donated lungs because of their relatively longer survival on the wait list.

The number of new patients added to the wait list, the number of donations, and the number of lung transplants performed have increased with time, reflecting the acceptance of transplant as a therapeutic option for advanced lung disease. At the same time, the number of wait list deaths and removals from the wait list without transplant (often a surrogate of impending death) have risen, a symptom and reminder that a seemingly perpetual shortage of donated organs remains the key factor limiting broader application of lung transplantation as a therapy.²

Many lung transplant candidates, especially those with COPD, can do well with one or two lungs, but single lung transplant potentially doubles the impact of a single organ donor. Nevertheless, most transplant surgeries being performed in the United States for COPD are double lung transplants, a practice pattern based on the belief that transplanting two lungs offers a survival benefit over transplanting one lung even for patients without an established requirement.^2,3 This practice has not been tested prospectively, and current data, which are subject to known and unknown biases, are open to conflicting interpretations.^2-9

To address this issue, Crawford et al.¹⁰ used the UNOS database to examine post-transplant survival for COPD patients receiving a single or double lung transplant in the LAS era (May, 2005-December, 2014), including COPD retransplants and extracorporeal membrane oxygenation-to-transplant patients.

Over the 9.5 y of the study, 265 (21%) of the COPD candidates on the wait list died before receiving a transplant. Based on data in the Organ Procurement and Transplant Network annual report, it is reasonable to estimate that an equal number of COPD candidates were removed from the wait list before transplant during the same time period.²

Among the 3554 COPD patients who were transplanted, 1358(38%) underwent single and 2196 (62%) underwent double lung transplant. There were important clinical differences between the single and double lung transplant groups. Those undergoing double lung transplant were more likely to be male and appeared to be more urgently ill with higher LAS at the time of transplant and higher rates of pretransplant ICU admission, mechanical ventilation, and extracorporeal membrane oxygenation. Those undergoing single lung transplant were more often female, older, with lower LAS at the time of transplant and tended to be transplanted at lower volume transplant centers.¹⁰

Crawford found no overall survival benefit for COPD patients who were transplanted compared with COPD patients listed for transplant, a finding consistent with previous studies and unchanged across the wait time and medical urgency-based allocation systems.¹⁰

Post-transplantation, the incidence of chronic lung allograft disease, aka CLAD, and time-to-onset of CLAD were similar between the single and double lung transplant groups. Five years after transplant, the cost of CLAD (graft loss or patient death) was slightly lower for double lung recipients (HR 0.83, CI 0.74–0.94), presumably due to a greater amount of residual functioning lung once CLAD ensues.¹⁰

Significant unadjusted survival differences between single and double lung recipients emerged by 3 y posttransplant. However, after risk adjustment, these differences nearly disappeared. There was no difference in the risk adjusted hazard for death between single and double lung recipients at 1 y (HR 0.89, CI 0.69–1.14) and 3 y (HR 0.90, CI 0.78–1.04). At 5 y post-transplant, there was a statistically significant but modest survival difference (HR 0.88, CI 0.78–0.99, p = 0.04). Despite statistical significance, the size of the survival difference is small and is unlikely to be discernible when working with individual patients in a clinical setting.¹⁰

Crawford’s findings comport with those of Schaffer et al., who, using a slightly smaller version of the same UNOS database in the LAS era (May,2005-December, 2012), found the same 5-y risk adjusted hazard ratio for death in COPD double lung recipients compared to those receiving single lungs (HR 0.89, CI 0.71–1.13, p = 0.23 [stratified log-rank test]). But, based on his results that did not reach statistical significance, Shaffer concluded there was no survival benefit for COPD patients receiving two lungs rather than one.¹¹

Crawford’s findings are also remarkably similar to those of Thabut et al., who analyzed International Society for Heart and Lung Transplantation Registry data for survival differences in COPD patients receiving one versus two lungs a decade earlier during the wait time-based organ allocation era. Thabut found a similar risk adjusted hazard for death among U.S. double lung recipients (HR 0.86, CI 0.78–0.95). He calculated that double lung transplants had an adjusted difference in 5 y survival between 4.0% and 6.3% or an absolute survival difference of about 3 mo on average, all other factors being equal.³

During Crawford’s study period, an estimated 500 COPD patients died or were removed from the wait list before receiving organs. Assuming the Crawford, Shaffer, and Thabut results are correct in identifying a small survival effect, then, had the number of COPD double lung transplants been reduced by 500 to transplant COPD patients removed from the wait list, approximately 125 life years would have been lost in the double lung group but approximately 2500 life years would have been gained among those removed from the wait list before transplant. This estimate assumes that patients dying on the wait list or removed from the list would respond to transplantation as well as those actually transplanted and that there are always two recipients waiting per donor. The enormity of the potential gain in overall life years derived from lung transplantation suggests that a preference for single lung transplantation for end-stage COPD in place of the current double lung practice must be considered. Providing a transplant option for patients who are removed from the wait list may well result in an overall survival benefit for transplantation for COPD–an outcome long sought, but repeatedly unfound.

The LAS system attempts to balance medical urgency and likelihood of post-transplant survival to ensure the best possible outcome for individual patients who compete for scarce donor organs.¹ The current allocation system and practice preference for double lung transplant in COPD does not prioritize or consider potential life years derived per donor. The current practice laudably recognizes that individual patients are important and that cumulative life years from a patient population are not transferable from patient to patient. In this case, however, the emphasis on individual recipient outcomes results in a dramatic suboptimal use of donated organs. Performing double lung transplants in COPD to optimize individual recipient outcomes nearly halves the potential number of life years gained per donor.¹² In an environment characterized by a perpetual donor lung shortage, Crawford’s findings highlight the need for better stewardship of donated organs by the transplant community.