Discussion
Lung transplantation is now a well-accepted treatment option for the management of a wide range of chronic end-stage lung disorders, including IPF. The primary goal of lung transplantation is to provide a survival benefit for patients who are failing medical therapy or for whom there is no effective medical treatment. However, there are far fewer available donor organs than patients that would potentially benefit from the lung transplantation procedure. In 2011, approximately 886 IPF patients in the US underwent lung transplantation. Using a prevalence of 14–43 per 100,000 and a US adult population of approximately 311 million in 2011, less than 1% of the estimated 42,000–130,000 US IPF patients had received a lung transplant during 2011. Not all IPF patients would be eligible for or willing to undergo transplantation, thus this probably overestimates the proportion not receiving a transplant. Nonetheless, there remains a large gap between those eligible and those receiving a transplant. Therefore, it is important that the available resources are optimally used, so that the patients selected for transplantation have the best chances for favorable long-term outcomes. There is no cure for IPF and current guidelines for the selection of lung transplant candidates recommend that appropriate IPF patients should be referred for transplantation as early as possible.
In this review we summarized lung transplantation outcomes in IPF patients using recent evidence. The published data and publically available data from the OPTN and ISHLT demonstrate that approximately 50% of IPF patients are alive at five years' post-transplantation. IPF patients continue to have poorer survival compared to lung transplant patients with other underlying diagnoses. IPF patients also have a higher wait-list mortality compared to other diagnoses. The high proportion of IPF patients dying prior to receipt of a lung transplant and the low survival time among those who do die, support the benefits of lung transplantation as a treatment for IPF patients as well as the high unmet need in this patient population. However, there is the potential for a survivor treatment selection bias in the comparison of wait list vs. post-transplant survival — IPF patients who receive lung transplants have to live long enough to receive a donor lung, so if they are compared to the non-transplant group they may appear to have better survival. There has been a significant increase in the proportion of IPF patients receiving BLT vs. SLT. Data tend to suggest that BLT is associated with improved long-term survival compared to SLT. However, the apparent improved long-term survival may be due to the SLT patients being at higher risk for poor survival rather than effects of the BLT per se. Given the shortage of donor lungs available, it is important to understand whether there is a subgroup of IPF patients for whom BLT does offer a true survival advantage and whether it would be beneficial to reserve bilateral transplants for those patients. Data specifically comparing survival among IPF patients who received a lung transplant pre- vs. post-LAS are limited. However, implementation of the LAS has resulted in an increase in lung transplants due to IPF, and has resulted in shorter wait times when compared to patients in the pre-LAS period (due to patients being listed later since wait time is no longer a primary factor in determining allocation, and due to the fact that IPF patients are selected for transplants based on their LAS). The ISHLT data show that longer 1 year survival is associated with more recent transplant year; this could be an effect of the LAS system but may also be due to other factors such as improvements in medical care and immunosuppression drug regimens. Other than mortality data, there are few reported data on post- or peri-transplant outcomes among IPF patients. The data reported in the papers included in this review suggest that transplantation for IPF is associated with considerable resource allocation beyond the actual transplantation procedure; this includes substantial ICU length of stay as well as necessity for adjunct interventions such as tracheostomy and use of inhaled nitric oxide and prolonged mechanical ventilation.
To our knowledge, this is the first systematic and most extensive review of the available evidence on lung transplantation outcomes in IPF patients, evaluating the published literature over more than two decades. The systematic methodology employed for this effort and the extensive nature of the outcomes assessed (i.e., wait list and post-transplant survival; pre- vs. post-LAS survival; BLT vs. SLT survival; post-transplant morbidity) are strengths of this review. A substantial amount of the reviewed evidence was derived from OPTN or ISHLT data. While the availability if the OPTN and ISHLT data contributes extensively to the understanding of post-transplant survival, detailed post-transplant outcomes are not collected. A limitation of the data summarized in this review is the lack of actual confirmation of IPF in most of the studies.