Abstract
Introduction
We aimed to evaluate if known racial, ethnic, and sex disparities in lung transplant waitlist outcomes with the Lung Allocation Score (LAS) persist with implementation of the Composite Allocation Score (CAS).
Methods
We performed a retrospective cohort study of the Scientific Registry of Transplant Recipients (SRTR) database, examining waitlist outcomes of all adult patients listed for lung transplantation in the United States from January 2018 to March 2024, comparing patients listed in the LAS (1/1/2018–9/9/2022) or CAS (3/9/23–3/24/24) eras.
Results
Black candidates had a lower likelihood of transplantation (LAS sHR: 0.85, 95% CI: 0.79–0.91, p<0.001; CAS sHR: 0.81, 0.71–0.93, p=0.002) compared to White candidates in both eras, and a greater likelihood of waitlist removal (sHR: 2.31, 1.35–3.95, p=0.003) in the CAS era. Female candidates had lower rates of transplantation compared to male candidates in both eras (LAS sHR: 0.75, 0.71–0.80, p<0.001; CAS sHR: 0.88, 0.79–0.98, p=0.017). There were no significant differences in extracorporeal membrane oxygenation (ECMO) or mechanical ventilation while listed between race/ethnicity in the CAS era. Female candidates had lower odds of ECMO in both eras (LAS OR: 0.74, CI: 0.58–0.95, p=0.019; CAS OR: 0.53, 0.30–0.96, p=0.037). Black candidates had a greater hazard of waitlist removal due to “other” reasons compared to White candidates in both eras (LAS sHR: 1.75, 1.27–2.42, p<0.001; CAS sHR: 2.06, 1.17–3.61, p=0.013).
Conclusion
Disparities in lung transplant waitlist outcomes are improved but persist in the CAS era. These disparities warrant further investigation into ways to provide more equitable access to lung transplantation.
Keywords: Lung transplantation, Race, Ethnicity, Sex, Disparities
Introduction
Racial, ethnic, and sex disparities in access to and outcomes after lung transplantation are known to exist.1 The Lung Allocation Score (LAS), implemented in May 2005, aimed to make lung transplantation more equitable and eliminate biases by prioritizing waitlist urgency and likelihood of survival post-transplant. However, multiple studies have demonstrated persistent disparities in the LAS era despite improvements in access to transplantation among racial minorities, with females continuing to have longer waitlist times, racial minorities continuing to have increased likelihood of waitlist deaths or removals, and Hispanic candidates having higher risk of waitlist removal for being too sick.2, 3, 4, 5, 6
In March 2023, the lung transplant allocation system in the United States changed to the Composite Allocation Score (CAS), a continuous distribution score which aimed to improve lung transplant equity by eliminating fixed geographic boundaries in allocation and accounting for biologic disadvantages in access, thus theoretically mitigating the social and biological factors that have been identified as contributory to historical racial, ethnic, and sex disparities.3, 4, 7 In the CAS era, all lung transplant candidates are assigned a score out of 100 based on predicted waitlist mortality, predicted survival after transplant, biological limitations, donor locality, and whether the recipient is pediatric or an organ donor, with higher scores indicating greater waitlist priority.8 Waitlisting rates of candidates with the highest calculated waitlist mortality have increased over time, with more patients requiring extracorporeal membrane oxygenation (ECMO) or mechanical ventilation as a bridge to transplantation.9, 10, 11, 12 The impact of CAS implementation on the known disparities in waitlist outcomes, access to ECMO or mechanical ventilation while listed, and waitlist removal reasons, have yet to be examined.13
We primarily aimed to examine whether sex, racial, and ethnic disparities in waitlist outcomes for lung transplant have persisted or improved in the CAS era in comparison to the LAS era with secondary aims of evaluating differences in ECMO or mechanical ventilation while listed and waitlist removal reasons.
Methods
Data description
This analysis used data from the Scientific Registry of Transplant Recipients (SRTR). The SRTR data system includes data on all donors, wait-listed candidates, and transplant recipients in the U.S., submitted by the members of the Organ Procurement and Transplantation Network (OPTN). The Health Resources and Services Administration (HRSA), U.S. Department of Health and Human Services provides oversight to the activities of the OPTN and SRTR contractors. This study was performed in compliance with the International Society for Heart and Lung Transplantation ethics. We used the standard analysis files from the SRTR as of March 2025. We identified subjects listed for transplantation between January 1st, 2018, and March 24th, 2024. The exclusion criteria included pediatric candidates, multiorgan listings, subjects with no post-listing follow-up (listed after March 24th, 2024), re-transplantations, and subjects with a follow-up period that overlapped allocation eras (Figure 1).
Figure 1.
Exclusion Criteria.
Variable definitions
The LAS era includes all listings from January 1st, 2018, to September 9th, 2022, and the CAS era includes all listings from March 9th, 2023, to March 24th, 2024, to ensure a consistent maximal follow-up time between cohorts. Primary outcomes were time from listing to transplant, waitlist death, or waitlist removal for reasons other than death or transplant (“too sick or health deterioration” (code 13) or “other” (code 9)); the candidate censoring cohort date (March 24th, 2024) was used for censoring and follow-up was truncated at 6 months. Secondary outcomes were ECMO while listed, mechanical ventilation while listed, waitlist removal reasons, and LAS/CAS scores.
Missing data
Data were missing for the following variables: diagnosis group (0.01%), BMI at listing (0.27%), height (0.24%), education (2.72%), and insurance (<0.01%). Multiple imputation was used to handle the missing data.
Statistical analysis
Continuous variables were summarized using medians and interquartile range and compared between the LAS and CAS eras using Wilcoxon rank sum tests. Categorical variables were summarized using frequencies and percentages and compared using Pearson’s chi-squared tests.
We used multivariate imputation by chained equations to impute five datasets with complete data using the MICE package.14 The multiple imputation included sex, age at listing, race/ethnicity, height, blood type O, education level, insurance type, diagnosis group, and transplant center volume per year. All models were fit on each of the five imputed datasets, and parameter estimates were pooled.
We evaluated the association between candidate sex and race/ethnicity with time to event (transplant, removal, and death) using Fine-Gray competing risk models. We stratified by era and sex. We compared subdistribution hazard ratios (sHRs) across strata (era, sex). When analyzing transplantation, we examined whether there were interactions between race/ethnicity and era, sex and era, and race/ethnicity, sex, and era. We were unable to assess interactions when analyzing waitlist deaths or removals due to the low number of events. Bonferroni’s adjustment for multiple comparisons was used when examining associations within interactions. We evaluated the association between ECMO or mechanical ventilation while listed and race/ethnicity and sex using logistic regression and compared odds ratios across eras. We also examined the associations between ECMO or mechanical ventilation and time to waitlist removal using Fine-Gray competing risk models. We stratified by era and compared sHRs across strata. We also evaluated the association between race/ethnicity and waitlist removal using Fine-Gray competing risk models. We stratified by era and compared sHRs across strata. Finally, we performed a sub-group analysis looking at the association between LAS/CAS score and race/ethnicity for transplanted candidates. We performed a log-transformation on the LAS/CAS score to achieve normality and performed multivariable linear regression. Beta coefficients were back-transformed for interpretation. We stratified by era and compared Beta coefficients across eras. As a sensitivity analysis we fit cause-specific competing risks models for all the time-to-event models listed above and compared the estimates with the Fine-Gray competing risk models.
All tests were two-tailed and performed at a significance level of 0.05. Analyses were performed using R software v.4.4.1, using the ggsurvfit, tidycmprsk, and survival packages.15, 16., 17., 18. Tables and Figure 1 were constructed using the gtsummary and flowchart packages.19, 20.
Results
Cohort characteristics
We included 16,521 adult patients listed for lung transplant, of which 3371 (25.6%) were listed during the CAS era. There were significant differences in age at listing, race/ethnicity, diagnosis group, BMI at listing, insurance, and center average listing volume per year across eras (Table 1).
Table 1.
Candidate Characteristics
| Characteristic | CAS N = 3371a | LAS N = 13,150a | p-valueb |
|---|---|---|---|
| Age at Listing | <0.001 | ||
| 18−40 | 226 (6.7%) | 1186 (9.0%) | <0.001 |
| 40−50 | 271 (8.0%) | 1133 (8.6%) | 0.20 |
| 50−60 | 725 (22%) | 3093 (24%) | <0.001 |
| 60−70 | 1663 (49%) | 6088 (46%) | <0.001 |
| >70 | 486 (14%) | 1650 (13%) | <0/001 |
| Sex | 0.064 | ||
| Male | 1938 (57%) | 7791 (59%) | 0.40 |
| Female | 1433 (43%) | 5359 (41%) | 0.40 |
| Race/Ethnicity | <0.001 | ||
| Non-Hispanic, White | 2321 (69%) | 9591 (73%) | <0.001 |
| Hispanic of any race | 500 (15%) | 1631 (12%) | <0.001 |
| Non-Hispanic, Other | 203 (6.0%) | 581 (4.4%) | <0.001 |
| Non-Hispanic, Black | 347 (10%) | 1347 (10%) | 0.20 |
| Diagnosis Group | <0.001 | ||
| Restrictive Lung Disease | 2427 (72%) | 8965 (68%) | <0.001 |
| Obstructive Lung Disease | 681 (20%) | 2713 (21%) | 0.60 |
| Pulmonary Vascular Disease | 217 (6.4%) | 860 (6.5%) | 0.074 |
| Infectious Lung Disease | 46 (1.4%) | 610 (4.6%) | <0.001 |
| Missing | 0 | 2 | |
| BMI at Listing (kg/m2) | 0.036 | ||
| <18.5 | 121 (3.6%) | 514 (3.9%) | 0.074 |
| 18.5−25 | 1032 (31%) | 4050 (31%) | 0.70 |
| 25−30 | 1267 (38%) | 5131 (39%) | 0.041 |
| 30−35 | 888 (26%) | 3137 (24%) | 0.001 |
| >35 | 60 (1.8%) | 276 (2.1%) | 0.50 |
| Missing | 3 | 42 | |
| Blood Type O | >0.99 | ||
| No | 1776 (53%) | 6928 (53%) | 0.70 |
| Yes | 1595 (47%) | 6222 (47%) | 0.70 |
| Height (cm) | 170 (162, 178) | 170 (163, 178) | 0.12 |
| Missing | 3 | 37 | |
| Education | 0.12 | ||
| High School or Less | 1352 (42%) | 5181 (40%) | 0.30 |
| Some College | 810 (25%) | 3437 (27%) | <0.001 |
| College or More | 1065 (33%) | 4194 (33%) | 0.40 |
| Missing | 144 | 338 | |
| Insurance | 0.001 | ||
| Medicare | 1582 (47%) | 5742 (44%) | <0.001 |
| Private | 1336 (40%) | 5674 (43%) | <0.001 |
| Medicaid/CHIP | 306 (9.1%) | 1221 (9.3%) | 0.30 |
| Other | 147 (4.4%) | 512 (3.9%) | 0.50 |
| Missing | 0 | 1 | |
| Center Average Listing Volume per Year | 46 (31, 66) | 52 (33, 70) | <0.001 |
n (%); Median (Q1, Q3)
Pearson's Chi-squared test; Wilcoxon rank sum test
Waitlist outcomes by race/ethnicity and sex
Transplantation
Unadjusted cumulative incidences of transplantation varied significantly among races/ethnicities and sexes in both eras (Supplemental Figures 1 and 2). On adjusted analysis, Black candidates had a 15% lower rates of transplantation than White candidates in the LAS era (sHR: 0.85, 95% CI: 0.79–0.91, p<0.001) and 19% lower rates in the CAS era (sHR: 0.81, CI: 0.71–0.93, p=0.002) (Table 2). In the LAS era, Other race candidates had a 16% lower rates of transplantation (sHR: 0.84, CI: 0.76–0.93, p<0.001) and Hispanic candidates had 8% lower rates of transplantation (sHR: 0.92, CI: 0.86–0.98, p=0.011) compared to White candidates, whereas Hispanic candidates had a 15% greater rates of transplantation in the CAS era (sHR 1.15, CI: 1.03–1.29, p=0.012) (Table 2). Female candidates had a 25% lower rates of transplantation compared to male candidates in the LAS era (sHR: 0.75, CI: 0.71–0.80, p<0.001) and 12% lower rates in the CAS era (sHR: 0.88, CI: 0.79–0.98, p=0.017; Table 2).
Table 2.
Waitlist Outcomes by Era
| LAS |
CAS |
|||||
|---|---|---|---|---|---|---|
| Characteristic | sHRa | 95% CI | p-valueb | sHRa | 95% CI | p-valueb |
| Deceased Donor Transplantation | ||||||
| Candidate Race/Ethnicity | ||||||
| Non-Hispanic, White | — | — | — | — | ||
| Hispanic of any race | 0.92 | 0.86, 0.98 | 0.011 | 1.15 | 1.03, 1.29 | 0.012 |
| Non-Hispanic, Other | 0.84 | 0.76, 0.93 | <0.001 | 1.05 | 0.89, 1.23 | 0.56 |
| Non-Hispanic, Black | 0.85 | 0.79, 0.91 | <0.001 | 0.81 | 0.71, 0.93 | 0.002 |
| Candidate Sex | ||||||
| Male | — | — | — | — | ||
| Female | 0.75 | 0.71, 0.80 | <0.001 | 0.88 | 0.79, 0.98 | 0.017 |
| Waitlist Death | ||||||
| Candidate Race/Ethnicity | ||||||
| Non-Hispanic, White | — | — | — | — | ||
| Hispanic of any race | 1.04 | 0.81, 1.33 | 0.76 | 0.82 | 0.43, 1.55 | 0.53 |
| Non-Hispanic, Other | 1.45 | 1.05, 2.00 | 0.024 | 1.04 | 0.45, 2.37 | 0.93 |
| Non-Hispanic, Black | 1.09 | 0.83, 1.44 | 0.53 | 0.53 | 0.22, 1.28 | 0.16 |
| Candidate Sex | ||||||
| Male | — | — | — | — | ||
| Female | 1.05 | 0.86, 1.27 | 0.65 | 1.03 | 0.57, 1.84 | 0.93 |
| Waitlist Removal | ||||||
| Candidate Race/Ethnicity | ||||||
| Non-Hispanic, White | — | — | — | — | ||
| Hispanic of any race | 1.13 | 0.88, 1.46 | 0.32 | 0.72 | 0.38, 1.36 | 0.30 |
| Non-Hispanic, Other | 1.23 | 0.86, 1.76 | 0.27 | 0.63 | 0.22, 1.81 | 0.39 |
| Non-Hispanic, Black | 1.13 | 0.87, 1.48 | 0.36 | 2.31 | 1.35, 3.95 | 0.003 |
| Candidate Sex | ||||||
| Male | — | — | — | — | ||
| Female | 0.96 | 0.78, 1.18 | 0.69 | 0.60 | 0.33, 1.11 | 0.10 |
sHR = Subdistribution Hazard Ratio
Variables included in the model: sex, age at listing, race/ethnicity, height, blood type O and lung diagnosis group
Waitlist death
Unadjusted cumulative incidences of waitlist deaths significantly differed among races/ethnicities only in the LAS era, whereas significant differences between sexes existed in both eras (Supplemental Figures 1 and 2). On adjusted analysis, hazard of waitlist deaths did not differ among race/ethnicity or sex in either era, except Other race candidates in the LAS era with 45% greater hazard compared to White candidates (sHR: 1.45, CI: 1.05–2.00, p=0.024) (Table 2, Table 3).
Table 3.
Waitlist Outcomes by Era and Sex
| LAS |
CAS |
|||||||
|---|---|---|---|---|---|---|---|---|
| Male |
Female |
Male |
Female |
|||||
| Characteristicb | sHRa (95% CI) | p-value | sHRa (95% CI) | p-value | sHRa (95% CI) | p-value | sHRa (95% CI) | p-value |
| Deceased Donor Transplant | ||||||||
| Candidate Race/Ethnicity | ||||||||
| Non-Hispanic, White | - | - | - | - | - | - | - | - |
| Hispanic of any race | 0.94 (0.87 – 1.02) | 0.14 | 0.85 (0.76 – 0.96) | 0.007 | 1.10 (0.95 – 1.29) | 0.21 | 1.22 (1.04 – 1.44) | 0.016 |
| Non-Hispanic, Other | 0.87 (0.77 – 0.98) | 0.024 | 0.78 (0.65 – 0.93) | 0.006 | 1.03 (0.84 – 1.27) | 0.75 | 1.09 (0.84 – 1.41) | 0.53 |
| Non-Hispanic, Black | 0.88 (0.80 – 0.96) | 0.005 | 0.81 (0.73 – 0.90) | <0.001 | 0.83 (0.67 – 1.02) | 0.074 | 0.82 (0.68 – 0.98) | 0.028 |
| Waitlist Death | ||||||||
| Candidate Race/Ethnicity | ||||||||
| Non-Hispanic, White | - | - | - | - | - | - | - | - |
| Hispanic of any race | 1.29 (0.92 – 1.81) | 0.15 | 0.85 (0.59 – 1.22) | 0.38 | 1.25 (0.49 – 3.18) | 0.63 | 0.56 (0.23 – 1.39) | 0.21 |
| Non-Hispanic, Other | 1.60 (1.03 – 2.47) | 0.037 | 1.29 (0.79 – 2.08) | 0.30 | 1.66 (0.54 – 5.04) | 0.36 | 0.67 (0.18 – 2.52) | 0.54 |
| Non-Hispanic, Black | 1.26 (0.82 – 1.92) | 0.30 | 1.00 (0.70 – 1.44) | 0.99 | 1.11 (0.32 – 3.85) | 0.86 | 0.33 (0.10 – 1.14) | 0.078 |
| Waitlist Removal | ||||||||
| Candidate Race/Ethnicity | ||||||||
| Non-Hispanic, White | - | - | - | - | - | - | - | - |
| Hispanic of any race | 1.33 (0.95 – 1.87) | 0.095 | 0.97 (0.66 – 1.40) | 0.85 | 1.16 (0.55 – 2.46) | 0.70 | 0.35 (0.10 – 1.27) | 0.11 |
| Non-Hispanic, Other | 1.13 (0.66 – 1.93) | 0.65 | 1.35 (0.83 – 2.22) | 0.23 | 0.66 (0.15 – 2.88) | 0.57 | 0.59 (0.13 – 2.71) | 0.48 |
| Non-Hispanic, Black | 1.11 (0.73 – 1.70) | 0.62 | 1.13 (0.79 – 1.61) | 0.51 | 3.00 (1.35 – 6.66) | 0.008 | 1.73 (0.81 – 3.67) | 0.15 |
sHR = Subdistribution Hazard Ratio
Variables included in the model: sex, age at listing, race/ethnicity, height, blood type O and lung diagnosis group
Waitlist removal
In both eras, there was a significant difference in the unadjusted cumulative incidence of waitlist removal among race/ethnicity, whereas there was only a significant difference in the unadjusted cumulative incidence of waitlist removal and sex in the LAS era (Supplementary Figure 1, Table 3, Figure 3). On adjusted analysis, hazard of waitlist removal did not differ among race/ethnicity or sex in either era, except Black candidates in the CAS era with 131% greater hazard compared to White candidates (sHR: 2.31, CI: 1.35–3.95, p=0.003) (Table 2). There was little change between sHRs and cause-specific hazard ratios with a few exceptions (Supplementary Tables 1–4).
Interaction of waitlist outcomes by race/ethnicity and sex
Waitlist outcomes significantly differed among race/ethnicity and sex in intersectionality in both eras (Table 3). Black females had a 19% lower rate of transplantation compared to White female candidates (sHR: 0.81, CI: 0.73–0.90, p<0.001) in the LAS era and 18% lower rate of transplantation in the CAS era (sHR: 0.82, CI: 0.68–0.98, p=0.028). Black males had a 12% lower rate of transplantation compared to White male candidates only in the LAS era (sHR: 0.88, CI: 0.80–0.96, p=0.005) but a 200% greater hazard of waitlist removal only in the CAS era (sHR: 3.00, CI: 1.35–6.66, p=0.008). Other race females had a 28% lower rate of transplantation (sHR: 0.78, CI: 0.65–0.93, p=0.006) compared to White female candidates only in the LAS era, and Other race males had a 13% lower rate of transplantation (sHR: 0.87, CI: 0.77–0.98, p=0.024) and 60% greater hazard of waitlist death (sHR: 1.60, CI: 1.03–2.47, p=0.037) compared to White male candidates only in the LAS era. Hispanic females had a 15% lower rate of transplantation compared to White female candidates in the LAS era (sHR 0.85, CI: 0.76–0.96, p=0.007) but a 22% greater rate of transplantation in the CAS era (sHR:1.22, CI: 1.04–1.44, p=0.016). Interactions between race/ethnicity, sex, and eras are listed in Supplementary Table 5.
ECMO and mechanical ventilation while listed
ECMO during listing differed significantly by race/ethnicity in the LAS era and by sex in the CAS era (Supplemental Table 6). In the LAS era, Black candidates had 26% lower odds of being on ECMO (OR: 0.74, CI: 0.56–0.98, p=0.035), Other race candidates had 49% greater odds (OR: 1.49, CI: 1.07–2.07, p=0.018), and Hispanic candidates had 43% greater odds (OR: 1.43, CI: 1.14–1.81, p=0.002) compared to White candidates (Table 4). Female candidates had 26% lower odds of being on ECMO compared to male candidates in the LAS era (OR: 0.74, CI: 0.58–0.95, p=0.019) and 47% lower odds in the CAS era (OR: 0.53, CI: 0.30–0.96, p=0.037).
Table 4.
ECMO and Mechanical Ventilation by Allocation Era
| LAS |
CAS |
|||||
|---|---|---|---|---|---|---|
| Characteristic | ORa,b | 95% CI | p-value | ORa,b | 95% CI | p-value |
| ECMO | ||||||
| Candidate Race/Ethnicity | ||||||
| Non-Hispanic, White | — | — | — | — | ||
| Hispanic of any race | 1.43 | 1.14, 1.81 | 0.002 | 1.07 | 0.62, 1.83 | 0.81 |
| Non-Hispanic, Other | 1.49 | 1.07, 2.07 | 0.018 | 1.00 | 0.46, 2.19 | >0.99 |
| Non-Hispanic, Black | 0.74 | 0.56, 0.98 | 0.035 | 1.10 | 0.59, 2.02 | 0.77 |
| Candidate Sex | ||||||
| Male | — | — | — | — | ||
| Female | 0.74 | 0.58, 0.95 | 0.019 | 0.53 | 0.30, 0.96 | 0.037 |
| Mechanical Ventilation | ||||||
| Candidate Race/Ethnicity | ||||||
| Non-Hispanic, White | — | — | — | — | ||
| Hispanic of any race | 1.43 | 1.10, 1.86 | 0.008 | 0.93 | 0.48, 1.80 | 0.83 |
| Non-Hispanic, Other | 1.92 | 1.36, 2.72 | <0.001 | 0.63 | 0.22, 1.83 | 0.40 |
| Non-Hispanic, Black | 0.71 | 0.51, 0.99 | 0.045 | 0.59 | 0.24, 1.45 | 0.25 |
| Candidate Sex | ||||||
| Male | — | — | — | — | ||
| Female | 0.70 | 0.53, 0.92 | 0.011 | 0.50 | 0.25, 1.03 | 0.061 |
Variables included in the model: sex, age at listing, race/ethnicity, blood type O, education level, height, lung transplant center volume per year and lung diagnosis group
OR = Odds Ratio
Mechanical ventilation during listing significantly differed by race/ethnicity in the LAS era and sex in both eras (Supplemental Table 7). In the LAS era, Black candidates had 29% lower odds of mechanical ventilation (OR: 0.71, CI: 0.51–0.99, p=0.045), Other race candidates had 92% greater odds (OR: 1.92, CI: 1.36–2.72, p<0.001), and Hispanic candidates had 43% greater odds (OR: 1.43, CI: 1.10–1.86, p=0.008) compared to White candidates (Table 4). Female candidates had 30% lower odds of mechanical ventilation compared to male candidates (OR: 0.70, CI: 0.53–0.92, p=0.011). In the CAS era, there were no significant differences between race/ethnicity and sex in odds of mechanical ventilation.
Waitlist removals
Candidates on ECMO had a 186% greater hazard of waitlist removal than candidates without ECMO in the LAS era (sHR: 2.86, CI: 12.17–3.77, p<0.001) and 177% greater risk in the CAS era (sHR: 2.77, CI: 1.33–5.77, P=0.007) (Table 6). Mechanically ventilated candidates had a 231% greater hazard of waitlist removal compared to non-ventilated candidates only in the LAS era (sHR: 3.31, CI: 2.48–4.40, p<0.001).
Table 6.
Association between ECMO/Mechanical Ventilation and Waitlist Removal
| LAS |
CAS |
|||||
|---|---|---|---|---|---|---|
| Characteristicb | sHRa | 95% CI | Characteristicb | sHRa | 95% CI | Characteristicb |
| ECMO while Listed | ECMO while Listed | ECMO while Listed | ||||
| No | — | — | No | — | — | No |
| Yes | 2.86 | 2.17, 3.77 | Yes | 2.86 | 2.17, 3.77 | Yes |
| Mechanical Ventilation while Listed | Mechanical Ventilation while Listed | Mechanical Ventilation while Listed | ||||
| No | — | — | No | — | — | No |
| Yes | 3.31 | 2.48, 4.40 | Yes | 3.31 | 2.48, 4.40 | Yes |
asHR = Subdistribution Hazard Ratio
Variables included in the model: sex, age at listing, race/ethnicity, diagnosis group, height, type O blood
Waitlist removal reasons by race/ethnicity and sex
In the LAS era, Other race candidates had a 92% greater hazard of waitlist removal due to being too sick (sHR: 1.92, CI: 1.28–2.88, p=0.002) and Hispanic candidates had a 53% greater hazard of waitlist removal (sHR: 1.53, CI: 1.15–2.05, p=0.004) due to being too sick compared to White candidates (Table 5). Female candidates had a 62% lower hazard of waitlist removal due to being too sick compared to male candidates in the CAS era (sHR: 0.38, CI: 0.17–0.85, p=0.02). Black candidates had a 52% greater hazard of waitlist removal due to “other” reasons compared to White candidates in the LAS era (sHR: 1.52, CI: 1.01–2.29, p=0.044) and a 236% greater hazard in the CAS era (sHR: 3.36, CI: 1.66–6.79, p=0.001).
Table 5.
Association between Race/Ethnicity and Sex with Waitlist Removal Reason
| LAS |
CAS |
|||||
|---|---|---|---|---|---|---|
| Characteristicb | sHRa | 95% CI | Characteristicb | sHRa | 95% CI | Characteristicb |
| Too Sick | ||||||
| Candidate Race/Ethnicity | Candidate Race/Ethnicity | Candidate Race/Ethnicity | ||||
| Non-Hispanic, White | — | — | Non-Hispanic, White | — | — | Non-Hispanic, White |
| Hispanic of any race | 1.53 | 1.15, 2.05 | Hispanic of any race | 1.53 | 1.15, 2.05 | Hispanic of any race |
| Non-Hispanic, Other | 1.92 | 1.28, 2.88 | Non-Hispanic, Other | 1.92 | 1.28, 2.88 | Non-Hispanic, Other |
| Non-Hispanic, Black | 1.14 | 0.80, 1.63 | Non-Hispanic, Black | 1.14 | 0.80, 1.63 | Non-Hispanic, Black |
| Candidate Sex | Candidate Sex | Candidate Sex | ||||
| Male | — | — | Male | — | — | Male |
| Female | 0.95 | 0.74, 1.22 | Female | 0.95 | 0.74, 1.22 | Female |
| Other | ||||||
| Candidate Race/Ethnicity | Candidate Race/Ethnicity | Candidate Race/Ethnicity | ||||
| Non-Hispanic, White | — | — | Non-Hispanic, White | — | — | Non-Hispanic, White |
| Hispanic of any race | 1.01 | 0.64, 1.59 | Hispanic of any race | 1.01 | 0.64, 1.59 | Hispanic of any race |
| Non-Hispanic, Other | 0.82 | 0.38, 1.76 | Non-Hispanic, Other | 0.82 | 0.38, 1.76 | Non-Hispanic, Other |
| Non-Hispanic, Black | 1.52 | 1.01, 2.29 | Non-Hispanic, Black | 1.52 | 1.01, 2.29 | Non-Hispanic, Black |
| Candidate Sex | Candidate Sex | Candidate Sex | ||||
| Male | — | — | Male | — | — | Male |
| Female | 1.25 | 0.85, 1.83 | Female | 1.25 | 0.85, 1.83 | Female |
asHR = Adjusted Subdistribution Hazard Ratio
Variables included in the model: sex, age at listing, race/ethnicity, height, and type O blood
LAS/CAS scores
Black candidates had a 3% higher LAS score than White candidates (p=0.003) (Table 7). Other race candidates had a 6% higher LAS score (p<0.001) and 3% higher CAS score (p=0.038) than White candidates. Hispanic candidates had a 7% higher LAS score (p<0.001) compared to White candidates.
Table 7.
Association between LAS/CAS Scores and Race/Ethnicity and Sex
| LAS |
CAS |
|||||
|---|---|---|---|---|---|---|
| Characteristica | exp (β) | 95% CI | Characteristica | exp (β) | 95% CI | Characteristica |
| Race/Ethnicity | Race/Ethnicity | Race/Ethnicity | ||||
| Non-Hispanic, White | — | — | Non-Hispanic, White | — | — | Non-Hispanic, White |
| Hispanic of any race | 1.07 | 1.05, 1.09 | Hispanic of any race | 1.07 | 1.05, 1.09 | Hispanic of any race |
| Non-Hispanic, Other | 1.06 | 1.03, 1.09 | Non-Hispanic, Other | 1.06 | 1.03, 1.09 | Non-Hispanic, Other |
| Non-Hispanic, Black | 1.03 | 1.01, 1.06 | Non-Hispanic, Black | 1.03 | 1.01, 1.06 | Non-Hispanic, Black |
| Sex | Sex | Sex | ||||
| Male | — | — | Male | — | — | Male |
| Female | 0.99 | 0.98, 1.00 | Female | 0.99 | 0.98, 1.00 | Female |
Variables included in the model: sex, age at listing, race/ethnicity, diagnosis group, height, type O blood, education, insurance, and center average listing volume
Discussion
This study shows that racial, ethnic, and sex disparities in outcomes after lung transplant listing are decreased, but not eliminated, in the CAS era. Black and Hispanic candidates continued to be disadvantaged with lower transplantation rates, which is unchanged from the LAS era, and Black candidates have a higher risk of waitlist removal, particularly for “other” reasons, which is new in the CAS era.5 Conversely, Other race candidates appear to have fewer disparities in access to transplantation, waitlist death, and waitlist removal in the CAS era, despite continuing to have higher LAS/CAS scores than White candidates. Female candidates continued to be less likely to receive a lung transplant compared to males in the CAS era but did not appear to be at higher risk of waitlist death or removal. Racial/ethnic and sex disparities in ECMO and mechanical ventilation while listed were reduced in the CAS era compared to the LAS era.
Reasons for known racial, ethnic, and sex disparities in lung transplantation have been attributed to social determinants of health and sex-specific differences, such as shorter female recipients and increased rates of HLA sensitization.1, 3 Racial/ethnic minorities may have lower socioeconomic status and more comorbidities, thus increasing their pre- and post-transplant morbidity and mortality.4 Selection bias has also been thought to contribute to the underrepresentation of racial/ethnic minorities, with hypothesized disparities in timing of transplant referral and evaluation.5, 6 Implicit bias may impact scope of discussions had with transplant candidates or their medical decision makers, as demonstrated in work illustrating differences in critical care clinician empathy and disclosure of medical information to White and Black caregivers.21 Implicit bias may also impact organ offer decision-making, given data demonstrating lower rates of heart allograft acceptance for Black recipients compared to White recipients despite adjusting for multiple donor and recipient variables.22
CAS was created to reduce geographic disparities and promote more equitable access to transplantation by prioritizing the sickest patients and those most likely to benefit from a transplant, while accounting for biological differences impacting a candidate’s donor pool.7, 8, 23 Despite our limited follow-up period, our results already demonstrate a shift in the demographics of patients listed for lung transplantation in the CAS era with more minority racial/ethnic candidates, suggesting improvements in more equitable listing for lung transplantation. Criticisms of the CAS have already been raised regarding blood type disparities, with lower rates of transplantation for blood type O candidates, which led to a policy change in September 2023.24 Our adjusted analyses demonstrate that racial/ethnic and sex disparities persist even when adjusting for the known disparities in blood type.
Given that the blood type O policy modification decreased disparities in transplantation, we recommend further CAS policy modifications to include a race/ethnicity and sex scoring category to adjust for the persistent disadvantages in transplantation and waitlist removals among Black candidates and transplantation disadvantages among female candidates.24 While LAS scores were significantly higher among all racial/ethnic minority candidates than White candidates, only Other race candidates continued to have significantly higher CAS scores. Further investigation into Other race candidates with disaggregated data may be warranted. Additionally, availability of more nuanced data in the SRTR regarding waitlist removal reasons may also shed more light into these “other” reasons for waitlist removals that are significantly predominant among Black candidates to provide more insight into how to mitigate associated disparities.
Limitations of this study include short-term data in the CAS era given the follow-up time since CAS implementation with differing effect sizes. Though our study could not evaluate post-transplant survival rates, this remains an area for further study. As in any study utilizing the SRTR database, there are potential limitations in data collection and reporting, including lack of granularity to clinical information and missing data. Racial groups were limited to White, Black, and Other race to ensure a sufficient sample size, but aggregated racial/ethnic data has been demonstrated to hide significant differences in health outcomes when examined in disaggregate.25, 26 Future studies could benefit from evaluating allocation algorithm priorities for organs by race/ethnicities and disaggregating the Other race group to identify potential disparities and improve equity in lung transplantation. Lastly, we were unable to assess the ABO modification in the CAS period separately in this study.
Conclusion
In conclusion, race, ethnic, and sex disparities in lung transplantation waitlist outcomes have improved but persist in the CAS era. Future work should further investigate reasons for Black waitlist disparities, particularly as it relates to other reasons for waitlist removals, and future allocation systems should continue to work towards improving these disparities through continued policy modifications.
Financial Disclosure Statement
R. Lopez reports research funding from Gift of Life Foundation and One Legacy; serves on a Technical Expert Panel for OPO performance measurement sponsored by the Association for Organ Procurement Organizations. J.D. Schold reports consultancy for eGenesis, Novartis, Veloxis, the Organ Donation Advocacy Group, and Sanofi Corporation; research funding from Department of Defense, Gift of Life Foundation, Kidney Transplant Collaborative, NIH/NIDDK, NIH/NHLBI, the Donor Alliance Foundation, Kamada, Inc., and One Legacy Foundation; honoraria from eGenesis and Sanofi Inc.; advisory or leadership roles as Data Safety Monitoring Board Member for Bristol Myers Squibb; member of the UNOS Policy Oversight Committee; Chair of UNOS Data Advisory Committee; and ex-officio member of the SRTR Review Committee and speakers bureau for Sanofi. A.L. Gray reports consultancy and advisory roles for TFF Pharmaceuticals and Kamada Pharmaceuticals.
The other authors have no financial conflicts of interest.
Declaration of Competing Interest
The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Rocio Lopez, MS, MPH reports a relationship with Gift of Life Foundation that includes: funding grants. Rocio Lopez, MS, MPH reports a relationship with One Legacy that includes: funding grants. Rocio Lopez, MS, MPH reports a relationship with Association for Organ Procurement Organizations that includes: board membership. Jesse D. Schold, PhD reports a relationship with eGenesis that includes: consulting or advisory. Jesse D. Schold, PhD reports a relationship with Novartis Inc that includes: consulting or advisory. Jesse D. Schold, PhD reports a relationship with Veloxis that includes: consulting or advisory. Jesse D. Schold, PhD reports a relationship with Organ Donation Advocacy Group that includes: consulting or advisory. Jesse D. Schold, PhD reports a relationship with Sanofi Corporation that includes: consulting or advisory. Jesse D. Schold, PhD reports a relationship with US Department of Defense that includes: funding grants. Jesse D. Schold, PhD reports a relationship with Kidney Transplant Collaborative that includes: funding grants. Jesse D. Schold, PhD reports a relationship with National Institutes of Health that includes: funding grants. Jesse D. Schold, PhD reports a relationship with Donor Alliance Foundation that includes: funding grants. Jesse D. Schold, PhD reports a relationship with Kamada, Inc. that includes: funding grants. Jesse D. Schold, PhD reports a relationship with Gift of Life Foundation that includes: funding grants. Jesse D. Schold, PhD reports a relationship with One Legacy Foundation that includes: funding grants. Jesse D. Schold, PhD reports a relationship with Bristol Myers Squibb Co that includes: board membership. Jesse D. Schold, PhD reports a relationship with United Network for Organ Sharing that includes: board membership. Jesse D. Schold, PhD reports a relationship with Sanofi Inc that includes: board membership. Alice L. Gray, MD reports a relationship with TFF Pharmaceuticals Inc that includes: board membership, consulting or advisory, and travel reimbursement. Alice L. Gray, MD reports a relationship with Kamada Pharmaceuticals that includes: board membership and consulting or advisory. Alice L. Gray, MD reports a relationship with CareDx Inc that includes: speaking and lecture fees and travel reimbursement. Jordan R.H. Hoffman, MD, MPH reports a relationship with Donor Alliance Inc that includes: board membership. Jesse D. Schold, PhD reports a relationship with Centers for Medicare and Medicaid Services that includes: travel reimbursement. Jesse D. Schold, PhD reports a relationship with American Society of Transplantation that includes: travel reimbursement. Jesse D. Schold, PhD reports a relationship with NextCure Inc that includes: board membership. Jesse D. Schold, PhD reports a relationship with CSL Behring that includes: board membership. Rocio Lopez, MS, MPH reports a relationship with National Institutes of Health that includes: funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Acknowledgments
The data reported here have been supplied by the Hennepin Healthcare Research Institute (HHRI) as the contractor for the Scientific Registry of Transplant Recipients (SRTR). The interpretation and reporting of these data are the responsibility of the author(s) and in no way should be seen as an official policy of or interpretation by the SRTR or the U.S. Government.
Footnotes
Supplemental data associated with this article can be found in the online version at doi:10.1016/j.jhlto.2025.100441.
Appendix A. Supplemental material
Supplemental material
.
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