Before May 2005, the allocation of lungs for transplantation in the United States was based on waiting time, which resulted in early listing of patients, long waiting times, and high mortality among patients with an immediate life-threatening illness. The LAS was developed to address these issues by prioritizing patients on the basis of medical urgency and expected outcome. Using national transplant data from UNOS, we found that the LAS has been successful in improving the likelihood of transplantation and decreasing the risk of death for the majority of patients on the waiting list without negatively affecting 1-year post-transplant mortality. Our data indicate, however, that the relative impact of these changes varied substantially between diagnoses. Compared with other diagnoses, transplantation for IPAH remains low, whereas mortality on the waiting list for IPAH is equal or higher.
The fact that the LAS has improved the time to transplantation for all diagnoses is not particularly surprising. Under the previous wait-based system, patients were listed early in the course of their disease, thereby inflating the waiting list with patients for whom transplant was not an immediate consideration. By removing waiting time from the equation, the LAS has drastically reduced the number of patients on the waiting list, effectively shortening time to transplantation for all diagnoses (17
). Earlier studies that have attempted to evaluate the impact of the LAS are limited in size, but they suggest that under the new system transplant priority has increased for patients with IPF and decreased for patients with COPD (8
). Our results support these findings in that we observed a significant increase in transplantation for IPF, relative to other diagnoses, accompanied by a significant decrease in death on the waiting list. A similar pattern of benefit was observed among patients with CF.
Our results build upon existing data by providing additional insight into those patients with IPAH, a significantly understudied population in lung transplantation. We found that the proportion of patients listed for IPAH dropped significantly compared with IPF, COPD, and CF. Despite this, the likelihood of transplantation for IPAH improved from the pre-LAS to post-LAS period. Although this may seem counterintuitive, it reflects an overall reduction in waiting time and a decrease in the total number of patients on the waiting list after implementation of the LAS. In our analysis, we considered likelihood of transplant, given that a patient was listed, and found that transplantation for IPAH did not improve relative to other diagnoses (as was observed in the case of IPF). Furthermore, implementation of the LAS did not reduce mortality on the waiting list for patients with IPAH, despite reductions in mortality observed for IPF, COPD, and CF.
One potential explanation may be that patients with IPAH are less likely to receive transplants because of differences in the available donor pool. For example, patients with IPAH are typically listed for bilateral lung transplant whereas patients with IPF and COPD commonly compete for both single and bilateral lungs. To address this, we controlled for lung transplant type in our analyses. In addition, we also controlled for demographic differences including age, sex, race, height, weight, blood type, and CMV status. Despite taking these factors into account, we still found that patients with IPAH were less likely to receive transplants than patients with IPF and CF, and more likely to die while on the waiting list than patients with COPD and CF. We obtained similar results when we restricted our analyses to the subgroup of patients listed for bilateral lung transplant only.
Another potential explanation for our findings may be differences in LAS at listing. Among those listed in the post-LAS period, we found that patients with IPAH had lower scores than patients with IPF and CF, which explains in part the lower likelihood of transplantation. Despite having lower LAS at listing, patients with IPAH demonstrated higher mortality on the waiting list when taking the lower likelihood of transplantation into account as a competing risk. Emerging data from other studies have lead to speculation that the LAS may underestimate the risk of death in patients with IPAH (18
). The LAS relies on diagnosis-specific estimating equations for IPF, COPD, CF, and IPAH developed using historical data collected by UNOS (7
). Clinical data most relevant to patients with IPAH (i.e., measures of right ventricular function) were not systematically collected at the time and therefore do not inform the LAS. Hemodynamic variables currently included in the LAS, such as pulmonary capillary wedge pressure, provide little predictive information for patients with IPAH. In contrast, mean right atrial pressure and cardiac index, which are known to be strong predictors of mortality in the pulmonary hypertension (1
), are not utilized by the estimating equations for IPAH. Serum biomarkers, such as BNP, that correlate well with right ventricular function (19
), may also be important but are not taken into account.
Notably, we found that the observed differences in transplantation and waiting list mortality for IPAH were only partly mediated by differences in LAS itself. Such results suggest that factors other than the LAS at listing are also likely to be involved. In fact, factors determined at the time of organ matching often have a larger impact on determining who ultimately receives a lung transplant. For example, organ size matching, immunologic compatibility, and geographic proximity to the donor hospital are all factors that frequently play an important role. It remains possible there may be something inherent about the lower likelihood of transplantation in IPAH that was not captured in the data used for our analyses.
Other limitations must also be taken into consideration. As previously mentioned, it should be recognized that the changes in listing practices and referral patterns could have contributed to our findings. Because UNOS data contains only information for those on the waiting list, no conclusions can be drawn about patients who may not have been listed as a result of the change in allocation system. Furthermore, secular trends, such as advances in surgical techniques, perioperative management, and immunosuppressive therapy, may have influenced our results. In the case of IPAH, recent advances in pulmonary hypertension therapy could explain, in part, the lower likelihood of transplantation (if newer treatments reduce medical urgency), but does not account for the higher mortality of IPAH while on the waiting list. A more likely explanation may be that, with the accrued waiting time out of the equation and new therapies available, patients with IPAH are listed later in the course of their disease only after medical therapy has already failed. Such patients have often entered into a rapid phase of deterioration, thereby inflating their risk of death while on the waiting list relative to other diagnoses.
In conclusion, our results indicate that although the LAS has been successful in improving the efficiency of lung allocation for the majority of patients, lung allocation remains an ongoing challenge especially for underrepresented diagnoses such as IPAH. Further research is needed to understand why patients with IPAH continue to be at a high risk of death while on the waiting list despite the recently implemented LAS. How data currently collected by UNOS will be used to revise the original predictive models used by the LAS remains to be seen. Modifications of the LAS that include additional information, such as measures of right ventricular function, may help to improve transplant priority for patients with IPAH.