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.