Advanced Lung Disease
The CF community is incredibly fortunate to have highly effective modulator therapy, however, there continues to be a role for care of PwCF and ALD. The French 3-year prognostic score for death or lung transplantation, previously verified by Canada, has also been verified using the US CFFPR and United Network for Organ Sharing (UNOS) data, thereby providing useful information to inform discussions with PwCF and ALD55.
Once PwCF have ALD, many varied treatment modalities are utilized, such as noninvasive ventilation (NIV). A review of NIV over 9 years (2011-2019) at one center, demonstrated increases in lung function, BMI, and 47% of the patients survived/made it to transplant during the 9 years studied56. Pre transplant characteristics of PwCF with ALD can affect post-transplant outcomes, therefore understanding these factors is important to allocate the rare resources. Data from UNOS on 3881 patients, over age 18, who were transplanted between 1992-2016 was assessed to evaluate pre transplant factors57. Post-transplant survival was higher for those ≥30 years old (9.47 years vs. 5.21 years in 18-29 years of age). Private insurance was also associated with increased survival. Using the Scientific Registry of Transplant Recipients, in 2573 patients (>18 years, 2005-2018), transplant centers with accreditation by the CF Foundation had a greater survival (7.8 vs 4.4 years) and a 33% reduction in graft failure despite no difference in Lung Allocation Scores or volume of transplantations58. Using data from a combination of UNOS and the CFF PR, adults with ALD who had a BMI ≤17 kg/m2 had lower likelihood of referral, listing for transplantation, and a higher risk of death without transplantation, although regional variation did exist59. These epidemiologic evaluations provide clinicians with strong evidence to continue to work to optimize health while referring for transplantation to achieve the most optimal long-term outcome.
Once patients are critically ill, many centers use mechanical ventilation and/or ECMO as a bridge to transplantation. UNOS data from 2015 – 2020, in patients 12 years of age and older, showed that of the 1064 patients requiring ECMO, 13% had CF60. There was no difference in likelihood to receive lung transplantation while on ECMO for PwCF compared to those with obstructive lung disease, or interstitial lung disease. A separate analysis of UNOS, evaluated 68 patients in a younger cohort (under 20 years of age), over 2004 – 2019, and found 42.7% of those requiring ECMO as a bridge to transplantation, had CF61. In this younger cohort, use of ECMO as a bridge had 2-3 times odds of mortality prior to discharge compared to those on a ventilator. Furthermore, pulmonary hypertension and black race were independent predictors of mortality. Once discharged, however, no difference was seen in 1- or 5-year mortality or re-transplantation rates. Overall, the mortality rate with ECMO has decreased due to improvements in ECMO care, from 75% in 2010, to 33% in 2018. In one center’s comparison of invasive ventilation versus ventilation plus ECMO as bridges to transplantation, no differences were seen for mortality prior to discharge, or at 1, or 5 years, however, those on ECMO had longer length of stay62. The information related to ECMO is encouraging as there have been improvements in care leading to decreases in mortality and therefore increasing the potential benefit of using ECMO as a bridge to transplantation.
Outcomes for transplantation vary, with some requiring re-transplantation. Using UNOS data from 2005 – 2020, 52% of 534 adults who underwent a repeat double lung transplant had CF63. Re- transplantation was associated with more renal and cardiac disease, increased rates of reintubation, longer times on ventilator post-transplant, longer length of stay, and decreased 5-year survival compared to initial double lung transplantation.
Differences in outcomes have also been seen between the US and Canada, such that between 2005 and 2016, PwCF and ALD in the US had an equal chance of death or transplantation, while those in Canada were two times more likely to receive a transplant than die64. Lung transplantation rate was lower in the US. A separate analysis over the same time found that differences in death without transplantation and post-transplant survival explained about 30% of the survival gap between the two countries65. Overall, lung transplantation has come a long way in care and outcomes, and through continued understanding of variations, care teams can work to provide optimal systems to ensure best possible outcomes.