Abstract
Organ procurement organizations (OPOs) vary in willingness to pursue and utilize non-ideal donor lungs; implications of these practices for lung transplant (LTx) recipients remain unclear. We examined associations between OPO-level behavior toward non-ideal donors and post-LTx outcomes. Adult lung donors and corresponding adult first-time LTx recipients in the 2008-2019 UNOS registry were included. Non-ideal donors had any of age>50, smoking history ≥20 pack-years, PaO2/FiO2 ratio ≤350, donation after circulatory death, or increased risk status. OPOs were classified as least, moderately, or most aggressive based on non-ideal donor pursuit, consent attainment, lung recovery, and transplantation. Post-transplant outcomes were compared among aggressiveness strata. Of 22,795 recipients, 6,229 (27.3%), 8,256 (36.2%), and 8,310 (36.5%) received lungs from least, moderately, and most aggressive OPOs, respectively. Moderately aggressive OPOs had the highest recipient rates of pre-discharge acute rejection, grade 3 primary graft dysfunction, postoperative extracorporeal membrane oxygenation, and longest lengths of stay. After adjustment, moderately and most aggressive OPOs had similar risks of recipient mortality as least aggressive OPOs. The most and least aggressive OPOs achieve similar patient survival and short-term post-LTx outcomes. Aggressive pursuit and utilization of non-ideal donor lungs by less aggressive OPOs would likely expand the donor pool, without compromising recipient outcomes.
Keywords: organ procurement organization, lung transplantation, extended-criteria donor, patient survival
INTRODUCTION
The demand for suitable donor lungs continues to outpace its supply as disproportionate growth of the lung transplant waitlist and a dismal 22% rate of donor lung utilization offset a trend of increasing lung transplantation (LTx) in the United States.1,2 This imbalance has historically been perpetuated by conservative donor selection guidelines, which define “ideal” lung donors as those who are young, with no smoking history, clear chest x-ray and bronchoscopy, and minimal organ ischemic time.3 However, few donors meet these criteria, and use of “extended-criteria” or “non-ideal,” but acceptable donor lungs represents a critical means by which to expand the donor pool for LTx. Increasingly, available evidence supports the use of more liberal lung donor selection criteria that include donors with older age, smoking history, US Public Health Service increased risk for disease (IRD) transmission classification, donation after circulatory death (DCD) status, and suboptimal PaO2/FiO2 (P/F) ratios, demonstrating acceptable post-transplant outcomes and decreased waitlist mortality with use of these donor lungs.4-13 Nonetheless, non-ideal, but acceptable donor lungs remain underutilized, and ongoing investigation is necessary to identify opportunities to safely increase their use.
Wider pursuit of non-ideal lung donors by organ procurement organizations (OPOs) may represent one avenue by which to increase donor lung availability and utilization. In the US, OPOs are responsible for evaluating donor referrals, obtaining consent for organ donation, overseeing donor management, and facilitating organ procurement and distribution; as such, the donation process is critically dependent upon OPOs as facilitators of donor identification, organ optimization, and eventual transplantation.14-16 For many years, OPO-level practices have been poorly understood as the transplant community lacks a national system that captures and reports OPO-level data, and existing evaluation metrics fail to objectively and transparently reflect OPO performance, particularly toward non-ideal donor groups.14,17,18 In a recent investigation, our group found that OPOs vary widely in willingness to pursue and utilize non-ideal donor lungs, suggesting that interventions to standardize practices across OPOs and non-ideal donor groups may represent an important modifiable means to expand the donor pool for LTx.19
Before encouraging OPOs to more aggressively pursue and utilize non-ideal donor lungs, it is important to understand the implications of current OPO-level practices for LTx candidates and recipients. Therefore, we sought to characterize the association between OPO-level behavior toward non-ideal donors and outcomes after LTx. We hypothesized that aggressive non-ideal donor pursuit and utilization by OPOs does not compromise post-transplant outcomes, and may safely support provision of LTx to a greater proportion of patients on the waitlist.
METHODS
Data source
We conducted a retrospective cohort analysis using United Network for Organ Sharing (UNOS) Standard Analysis and Research data. The data reported here have been supplied by UNOS as the contractor for the Organ Procurement and Transplantation Network (OPTN). The interpretation and reporting of these data are the responsibility of the authors and in no way should be seen as an official policy of or interpretation by the OPTN or the US Government. This study was deemed exempt by our Institutional Review Board.
Study population
Adult (age≥18) donors who donated at least one organ for transplantation and corresponding adult patients who underwent first-time isolated LTx between January 1, 2008 and December 31, 2019 were included. Donors who were missing a documented date of death, had organs recovered outside the US, were missing an OPO identifier, and those missing lung disposition were excluded. Recipients with a prior history of LTx, those undergoing multi-organ transplantation, and those missing post-transplant survival time were excluded.
Assessment and classification of OPO-level aggressiveness
OPO-level aggressiveness was assessed as previously described.19 Briefly, unique donors were the units of analysis. The final disposition for each donor was determined based on which of the left, right, or bilateral lungs progressed farthest in the donation process (Figure 1), since both single and bilateral LTx are considered successful donor utilization. Non-ideal lung donors were defined by any of age>50 years, smoking history ≥20 pack-years, P/F ratio ≤350, DCD, or IRD status as previously described.19 Non-ideal donors could have multiple non-ideal characteristics, but only one was required to meet criteria. Only 1% of P/F ratios were missing from our data; donors who were missing this parameter were considered to have P/F ratio >350.
Figure 1. Schematic representation of the donation process and study design.
OPOs were evaluated based on rates of non-ideal donor pursuit, consent attainment, lung recovery, and lung transplantation. Donor pursuit was defined as an OPO requesting consent for lung donation. The rate of non-ideal donor pursuit was defined as the proportion of non-ideal donors at each OPO from whom consent for lung donation was requested; higher numbers correspond to increasingly aggressive OPO-level behavior toward non-ideal donors (Table S1). Rates of consent attainment, lung recovery, and transplantation each built upon the previous donation process stage as outlined in Table S1 and Figure 1.
To assess overall OPO-level aggressiveness across the donation process, multivariable logistic regression was used to assign each OPO adjusted odds ratios (ORs) for non-ideal donor pursuit, consent attainment, lung recovery, and transplantation. Adjusted ORs for each donation process stage were ranked with each OPO receiving a score from 1-58 with higher scores corresponding to increased aggressiveness (Figure S1). Final OPO scores could range from 4-232 based on the sum of scores across the four steps of the donation process (donor pursuit, consent attainment, lung recovery, transplantation).
The distribution of individual OPO composite scores is shown in Figure 2. OPOs were assigned to three tiers of increasing aggressiveness:
Figure 2. Distribution of individual organ procurement organization (OPO) performance scores.
Higher scores correspond to overall increased aggressiveness toward non-ideal lung donors. Three tiers of increasing aggressiveness were defined based on the distribution of individual OPO performance scores: least aggressive (<25th percentile, score < 92.5), moderately aggressive (25-75th percentile, 92.5 < score < 139.75), most aggressive (>75th percentile, 139.75 < score).
Least aggressive (<25th percentile): score < 92.5
Moderately aggressive (25-75th percentile): 92.5 < score < 139.75
Most aggressive (>75th percentile): 139.75 < score
OPOs in each tier were characterized based on size (average annual lung donor volume during the study period) and rates of non-ideal donor pursuit, consent attainment, lung recovery, and transplantation.
Association between OPO-level aggressiveness and recipient post-transplant outcomes
Unique LTx recipients were matched to corresponding lung donors and stratified by OPO-level aggressiveness. Post-transplant outcomes including patient survival, rates of grade 3 primary graft dysfunction (PGD3) at 72 hours, need for extracorporeal membrane oxygenation (ECMO) support at 72 hours, acute rejection prior to discharge, and post-transplant hospital length of stay were compared among aggressiveness strata. PGD3 at 72 hours post-transplant was defined as a P/F ratio <200 or need for ECMO support based on a modification of the 2016 International Society for Heart and Lung Transplantation consensus report definition.20,21 Patients not requiring mechanical ventilation at 72 hours post-transplant were classified as not having PGD3.
Statistical analysis
In the first part of our analysis, donor race, sex, and OPO were included as covariates in models of donor pursuit, consent attainment, lung recovery, and transplantation to adjust for case-mix heterogeneity across OPOs. OPO-specific ORs for aggressiveness ranking were determined using a fixed effects model with an interaction between OPO and a binary indicator for presence of at least one non-ideal donor characteristic to determine how the effect of non-ideal donor characteristic on donor pursuit, consent attainment, lung recovery, and transplantation varied by OPO.19
In the second part of our analysis, donor and recipient characteristics and recipient perioperative outcomes were compared among OPO-level aggressiveness strata using Wilcoxon rank-sum tests for continuous variables and Chi-squared or Fisher’s exact tests for categorical variables. Unadjusted patient survival was estimated using the Kaplan-Meier method and compared among aggressiveness strata using the log-rank test.
Adjusted patient survival was modeled using multivariable Cox regression. Due to violation of the proportional hazard assumption, time-varying covariates were used to model survival up to one-year and beyond one-year post-transplant separately. Covariates were selected a priori based on clinical relevance and availability within the dataset. As donor factors including demographics, medical history, and cause and mechanism of death are known to OPOs during the donation process and may thus influence decision-making and aggressiveness, only recipient factors were included in our model. Covariates in the Cox model of patient survival included recipient age, sex, race, body mass index (BMI), history of pulmonary hypertension, history of diabetes, diagnosis group, lung allocation score (LAS), need for pre-transplant ECMO support, transplant type (bilateral versus single), and transplant center annual LTx volume. Continuous variables were transformed using restricted cubic splines with three knots based on each variable’s distribution.
A two-sided p-value less than 0.05 was considered statistically significant. All analyses were performed using R version 3.5.1 (Vienna, Austria).
RESULTS
OPO characteristics
All 58 US OPOs were included, of which 15, 25, and 18 were classified as least, moderately, and most aggressive, respectively. As expected, the most and least aggressive OPOs had the highest and lowest respective rates of non-ideal donor pursuit, consent attainment, lung recovery, and transplantation. The most aggressive OPOs were larger than moderately and least aggressive OPOs, corresponding to the highest average annual lung donor volume during the study period (Table 1).
Table 1.
Organ procurement organization (OPO) characteristics stratified by aggressiveness.
| Characteristic | Least Aggressive OPOs (N = 15) |
Moderately Aggressive OPOs (N = 25) |
Most Aggressive OPOs (N = 18) |
|---|---|---|---|
| Average annual lung donor volumea | 144 (109) | 111 (60) | 161 (94) |
| Pursuit Rateb | 96.9% (4.5%) | 97.7% (2.7%) | 98.2% (2.4%) |
| Consent Attainment Rateb | 97.2% (2.0%) | 97.3% (2.0%) | 97.8% (1.8%) |
| Recovery for Transplantation Rateb | 13.0% (4.6%) | 14.7% (3.3%) | 15.0% (3.7%) |
| Transplant Rateb | 92.4% (9.4%) | 96.1% (2.3%) | 96.5% (3.6%) |
Including both ideal and non-ideal lung donors. Presented as the mean (standard deviation) among OPOs in each group.
Restricted to non-ideal lung donors. Presented as the mean (standard deviation) unadjusted rate among OPOs in each group.
Recipient and donor characteristics
A total of 22,795 adult first-time isolated LTx recipients and corresponding lung donors met inclusion criteria. Of those, 6,229 (27.3%), 8,256 (36.2%), and 8,310 (36.5%) were associated with least, moderately, and most aggressive OPOs, respectively. Recipients of donor lungs from most aggressive OPOs were most likely to be female, Hispanic, have diagnoses other than obstructive airway disease (group A), have undergone bilateral LTx, and be without history of pulmonary hypertension (Table 2). Recipients of donor lungs from most aggressive OPOs were also most likely to be on pre-transplant ECMO support, and had the highest LAS and longest waitlist time. Compared to recipients of donor lungs from least and most aggressive OPOs, recipients of donor lungs from moderately aggressive OPOs underwent LTx at transplant centers that performed significantly fewer LTx annually (Table 2).
Table 2.
Recipient characteristics stratified by organ procurement organization (OPO) aggressiveness.
| Least Aggressive OPOs (N = 6229) |
Moderately Aggressive OPOs (N = 8256) |
Most Aggressive OPOs (N = 8310) |
P- value |
|
|---|---|---|---|---|
| Recipient male sex | 3745 (60.1%) | 5090 (61.7%) | 4837 (58.2%) | <0.001 |
| Recipient age (years, median [IQR]) | 60.00 [52.00, 66.00] | 60.00 [52.00, 65.00] | 60.00 [51.00, 66.00] | 0.453 |
| Recipient body mass index (kg/m2, median [IQR]) | 25.52 [21.76, 28.84] | 25.71 [22.08, 29.04] | 25.53 [21.87, 28.71] | 0.003 |
| Recipient race/ethnicity | <0.001 | |||
| White | 5194 (83.4%) | 6792 (82.3%) | 6565 (79.0%) | |
| Black | 526 (8.4%) | 793 (9.6%) | 733 (8.8%) | |
| Hispanic | 333 (5.3%) | 500 (6.1%) | 764 (9.2%) | |
| Other | 176 (2.8%) | 171 (2.1%) | 248 (3.0%) | |
| Recipient history | ||||
| Diabetes | 1145 (18.4%) | 1617 (19.6%) | 1631 (19.6%) | 0.112 |
| Malignancy | 550 (8.8%) | 668 (8.1%) | 687 (8.3%) | 0.264 |
| Pulmonary hypertension | 3471 (58.6%) | 4485 (57.5%) | 4313 (55.4%) | 0.001 |
| Diagnosis group | 0.007 | |||
| A | 1886 (30.3%) | 2383 (28.9%) | 2280 (27.4%) | |
| B | 219 (3.5%) | 298 (3.6%) | 342 (4.1%) | |
| C | 670 (10.8%) | 890 (10.8%) | 942 (11.3%) | |
| D | 3454 (55.5%) | 4685 (56.7%) | 4746 (57.1%) | |
| Recipient creatinine (mg/dL, median [IQR]) | 0.80 [0.67, 0.97] | 0.80 [0.68, 1.00] | 0.80 [0.66, 0.97] | <0.001 |
| Recipient total bilirubin (mg/dL, median [IQR]) | 0.50 [0.30, 0.70] | 0.50 [0.30, 0.70] | 0.50 [0.30, 0.70] | 0.217 |
| Recipient ABO blood type | 0.147 | |||
| A | 2542 (40.8%) | 3291 (39.9%) | 3251 (39.1%) | |
| AB | 246 (3.9%) | 330 (4.0%) | 299 (3.6%) | |
| B | 669 (10.7%) | 958 (11.6%) | 936 (11.3%) | |
| O | 2772 (44.5%) | 3677 (44.5%) | 3824 (46.0%) | |
| Pre-transplant status | 0.074 | |||
| Intensive care unit | 675 (10.8%) | 1001 (12.1%) | 904 (10.9%) | |
| Hospitalized (non-ICU) | 581 (9.3%) | 774 (9.4%) | 784 (9.4%) | |
| Not hospitalized | 4973 (79.8%) | 6481 (78.5%) | 6622 (79.7%) | |
| Medical therapy | ||||
| IV antibiotics in 2 weeks before transplant | 664 (10.7%) | 864 (10.5%) | 829 (10.0%) | 0.365 |
| Ventilator support at transplant | 367 (5.9%) | 540 (6.5%) | 468 (5.6%) | 0.042 |
| ECMO support at transplant | 203 (3.3%) | 358 (4.3%) | 368 (4.4%) | 0.001 |
| Days on waitlist (median [IQR]) | 58.00 [17.00, 178.00] | 53.00 [16.00, 161.00] | 61.00 [18.00, 184.00] | <0.001 |
| Lung allocation score (median [IQR]) | 40.79 [34.88, 52.42] | 41.05 [35.07, 53.90] | 41.34 [35.44, 53.57] | 0.003 |
| Single organ lung transplant | 1885 (30.3%) | 2545 (30.8%) | 2264 (27.2%) | <0.001 |
| Donor-recipient pTLC ratio (median [IQR]) | 1.02 [0.89, 1.15] | 1.01 [0.88, 1.15] | 1.02 [0.89, 1.16] | 0.186 |
| Transplant center annual lung transplant volume (median [IQR]) | 44.67 [28.25, 63.50] | 38.92 [20.67, 78.42] | 44.50 [24.67, 68.86] | <0.001 |
Donor characteristics including age, sex, race, BMI, and cause of death were significantly different across OPO-level aggressiveness strata (Table 3). In addition, donors from moderately aggressive OPOs were most likely to have smoking history ≥20 pack-years and clinical pulmonary infection at donation, and had the lowest P/F ratios and longest lung allograft ischemic times (Table 3).
Table 3.
Donor characteristics stratified by organ procurement organization (OPO) aggressiveness.
| Least Aggressive OPOs (N = 6229) |
Moderately Aggressive OPOs (N = 8256) |
Most Aggressive OPOs (N = 8310) |
P-value | |
|---|---|---|---|---|
| Donor male sex | 3740 (60.0%) | 4920 (59.6%) | 5102 (61.4%) | 0.049 |
| Donor age (years, median [IQR]) | 32.00 [23.00, 46.00] | 33.00 [23.00, 46.00] | 33.00 [23.00, 47.00] | 0.005 |
| Donor body mass index (kg/m2, median [IQR]) | 25.18 [22.38, 28.89] | 25.41 [22.50, 29.06] | 25.51 [22.53, 29.16] | 0.015 |
| Donor race/ethnicity | <0.001 | |||
| White | 4235 (68.0%) | 5357 (64.9%) | 4446 (53.5%) | |
| Black | 1027 (16.5%) | 1668 (20.2%) | 1566 (18.8%) | |
| Hispanic | 658 (10.6%) | 969 (11.7%) | 1868 (22.5%) | |
| Other | 309 (5.0%) | 262 (3.2%) | 430 (5.2%) | |
| Donor history | ||||
| Cigarette use ≥20 pack-years | 529 (8.5%) | 735 (8.9%) | 628 (7.6%) | 0.006 |
| Cocaine use | 997 (16.0%) | 1184 (14.3%) | 1292 (15.5%) | 0.014 |
| Diabetes | 431 (6.9%) | 617 (7.5%) | 658 (7.9%) | 0.077 |
| Hypertension | 1426 (22.9%) | 1997 (24.2%) | 2035 (24.5%) | 0.067 |
| Cancer | 114 (1.8%) | 177 (2.1%) | 136 (1.6%) | 0.053 |
| Pulmonary infection | 3976 (63.8%) | 5405 (65.5%) | 4872 (58.6%) | <0.001 |
| Donor PaO2/FiO2 ratio (median [IQR]) | 441.00 [374.00, 502.00] | 433.00 [369.00, 492.00] | 440.00 [380.00, 498.10] | <0.001 |
| Donor creatinine (mg/dL, median [IQR]) | 1.00 [0.71, 1.40] | 0.98 [0.70, 1.40] | 1.00 [0.75, 1.43] | <0.001 |
| Donor total bilirubin (mg/dL, median [IQR]) | 0.70 [0.50, 1.10] | 0.70 [0.50, 1.10] | 0.70 [0.50, 1.10] | 0.046 |
| Donation after circulatory death donor | 199 (3.2%) | 266 (3.2%) | 220 (2.6%) | 0.056 |
| Donor cause of death | <0.001 | |||
| Anoxia | 1562 (25.1%) | 1772 (21.5%) | 1891 (22.8%) | |
| Cerebrovascular/stroke | 1785 (28.7%) | 2665 (32.3%) | 2758 (33.2%) | |
| Head trauma | 2687 (43.1%) | 3563 (43.2%) | 3448 (41.5%) | |
| CNS tumor | 39 (0.6%) | 59 (0.7%) | 36 (0.4%) | |
| Other | 156 (2.5%) | 197 (2.4%) | 177 (2.1%) | |
| Donor ABO blood type | 0.013 | |||
| A | 2355 (37.8%) | 2969 (36.0%) | 2940 (35.4%) | |
| AB | 139 (2.2%) | 195 (2.4%) | 163 (2.0%) | |
| B | 677 (10.9%) | 933 (11.3%) | 893 (10.7%) | |
| O | 3058 (49.1%) | 4159 (50.4%) | 4314 (51.9%) | |
| Lung allograft ischemic time (hours, median [IQR]) | 5.15 [4.08, 6.28] | 5.18 [4.12, 6.28] | 5.02 [4.05, 6.07] | <0.001 |
Short-term post-transplant outcomes
During the perioperative period, recipients of donor lungs from moderately aggressive OPOs were most likely to experience acute rejection prior to discharge (moderately vs least vs most aggressive: 9.2% vs 7.7% vs 7.8%, p=0.001), most likely to have PGD3 at 72 hours (22.2% vs 21.1% vs 19.6%, p=0.03), and most likely to require ECMO support at 72 hours post-transplant (7.6% vs 6.3% vs 6.1%, p=0.01). Recipients of donor lungs from moderately aggressive OPOs also had the longest post-transplant hospital lengths of stay (median 17 vs 16 vs 16 days, p<0.001) (Table 4).
Table 4.
Unadjusted short-term recipient outcomes stratified by organ procurement organization (OPO) aggressiveness.
| Least Aggressive OPOs (N = 6229) |
Moderately Aggressive OPOs (N = 8256) |
Most Aggressive OPOs (N = 8310) |
P-value | |
|---|---|---|---|---|
| Hospital length of stay (days, median [IQR]) | 16.00 [11.00, 27.00] | 17.00 [12.00, 29.00] | 16.00 [11.00, 26.00] | <0.001 |
| Acute rejection prior to discharge | 479 (7.7%) | 761 (9.2%) | 647 (7.8%) | 0.001 |
| Grade 3 primary graft dysfunction at 72 hours | 557 (21.1%) | 795 (22.2%) | 671 (19.6%) | 0.029 |
| ECMO at 72 hours post-transplant | 205 (6.3%) | 331 (7.6%) | 255 (6.1%) | 0.01 |
Post-transplant survival
On unadjusted survival analysis, recipients of donor lungs from moderately aggressive OPOs had the worst post-transplant survival (Figure 3, log-rank p=0.004). Specifically, 1-, 3-, and 5-year survival were approximately 87.8% (95% confidence interval [CI] 87.0-88.7%), 71.6% (95% CI 70.3-72.8%), and 58.6% (95% CI 57.2-60.2%), respectively among recipients of donor lungs from least aggressive OPOs; 87.1% (95% CI 86.4-87.8%), 70.4% (95% CI 69.3-71.5%), and 56.2% (95% CI 54.9-57.6%), respectively among recipients of donor lungs from moderately aggressive OPOs; and 88.3% (95% CI 87.6-89.0%), 71.7% (95% CI 70.7-72.8%), and 58.3% (95% CI 57.0-59.6%), respectively among recipients of donor lungs from most aggressive OPOs.
Figure 3. Kaplan-Meier survival analysis of adult first-time isolated lung transplant recipients stratified by organ procurement organization (OPO) aggressiveness.
After adjustment for recipient factors, OPO-level aggressiveness was not independently associated with patient survival during the first year post-transplant (moderately vs least aggressive: adjusted hazard ratio [HR] 1.02, 95% CI 0.93-1.13, p=0.676; most vs least aggressive: adjusted HR 0.95, 95% CI 0.85-1.05, p=0.351) or after the first year post-transplant (moderately vs least aggressive: adjusted HR 1.05, 95% CI 0.99-1.13, p=0.118; most vs least aggressive: adjusted HR 1.02, 95% CI 0.96-1.09, p=0.477) (Table 5).
Table 5.
Association between organ procurement organization (OPO) aggressiveness and post-transplant patient survival.
| 95% CI | 95% CI | |||||||
|---|---|---|---|---|---|---|---|---|
| OPO Aggressiveness |
Unadjusted Hazard Ratio |
Lower | Upper | P-value | Adjusted Hazard Ratio |
Lower | Upper | P-value |
| A. Up to one-year post-transplant. | ||||||||
| Least Aggressive | Ref | Ref | ||||||
| Moderately Aggressive | 1.06 | 0.96 | 1.16 | 0.245 | 1.02 | 0.93 | 1.13 | 0.676 |
| Most Aggressive | 0.95 | 0.86 | 1.04 | 0.277 | 0.95 | 0.86 | 1.05 | 0.351 |
| B. Beyond one-year post-transplant. | ||||||||
| Least Aggressive | Ref | Ref | ||||||
| Moderately Aggressive | 1.09 | 1.02 | 1.16 | 0.008 | 1.05 | 0.99 | 1.13 | 0.118 |
| Most Aggressive | 1.03 | 0.97 | 1.10 | 0.382 | 1.02 | 0.96 | 1.09 | 0.477 |
DISCUSSION
Efforts to standardize and optimize non-ideal lung donor pursuit among OPOs may represent one means to increase donor lung availability, provided that more aggressive OPO-level behavior does not compromise outcomes for LTx recipients. In this analysis of the UNOS registry, we examined the association between OPO-level aggressiveness toward non-ideal lung donors and recipient outcomes after LTx. We found that the most and least aggressive OPOs achieve similar patient survival and short-term outcomes after LTx. After controlling for recipient characteristics, OPO-level aggressiveness was not associated with patient survival, suggesting that more aggressive pursuit and utilization of non-ideal lung donors by less aggressive OPOs may represent a safe modifiable means to expand the donor pool for LTx.
Prior reports have examined how practice variation impacts LTx patients; however, these studies focused on transplant center behavior.22,23 Initially, Wey and colleagues found that high organ offer acceptance among LTx programs was associated with higher organ yield, increased local placement of transplanted lungs, decreased waitlist mortality, and increased LTx.22 Subsequently, Mulvihill and colleagues found that rates of organ offer acceptance for the highest priority patients vary markedly among LTx centers, and demonstrated a strong inverse relationship between center-level offer acceptance rates and waitlist mortality; higher rates of offer acceptance did not compromise post-transplant graft survival.23 Our group previously found that patterns of OPO- and center-level aggressiveness in LTx are closely related.19 More aggressive center-level behavior clearly offers favorable outcomes for LTx candidates and recipients,22,23 however implications of corresponding OPO-level practices remain unclear. In this study, we found that OPO-level aggressiveness toward non-ideal lung donors was not a significant predictor of patient survival after LTx. As the most aggressive OPOs also had the highest average annual lung donor volume during the study period, these findings suggest that more aggressive pursuit of non-ideal lung donors by less aggressive OPOs would simultaneously improve donor lung availability and support acceptable recipient outcomes. Transplant centers accept only a subset of lungs offered by OPOs.2,24 Our findings therefore support aggressive pursuit of all potential lung donors by OPOs to provide centers with many organ offers to consider to increase opportunities for safe and timely LTx.
Despite increasing evidence to support broader use of non-ideal donor lungs,8-11,13 careful consideration of recipient characteristics is warranted in this setting. Use of non-ideal donor lungs for high-acuity patients, such as those with older age, high LAS, interstitial lung disease or pulmonary hypertension, and those bridged to LTx with invasive ventilation may compromise post-transplant survival, necessitating thoughtful recipient selection and matching of allograft quality to recipient acuity.25-27 In our study, recipients of donor lungs from the most aggressive OPOs had the highest LAS, were most likely to have restrictive lung disease (group D), and were most likely to require pre-transplant ECMO support; on unadjusted analysis, however, these patients achieved similar survival and short-term outcomes compared to recipients of donor lungs from less aggressive OPOs. While OPOs are responsible for executing match runs for offered organs, assessment of the medical suitability of a particular organ for an intended recipient falls within the purview of the transplant center acting on that recipient’s behalf.15,23,28 In this context, our findings of acceptable outcomes among recipients of donor lungs from the most aggressive OPOs may reflect targeted donor/recipient matching by transplant centers, as OPOs remain comparatively removed from potential recipients throughout the donation process. Regardless, these findings further emphasize that OPOs should pursue all potential lung donors, and allow centers to evaluate every possible offer to determine the risk-benefit ratio for each potential recipient.
Typically, post-transplant outcomes are infrequently discussed in relation to OPO performance, though some within the transplant community advocate alignment of OPO and transplant center assessments to better direct their interdependent efforts toward a common goal of maximizing organ availability and utilization to facilitate safe and timely transplantation for the greatest number of patients.17 Indeed, the current framework, in which OPOs are evaluated using donation and transplantation rate metrics, whereas transplant centers are evaluated based on post-transplant patient and graft survival, may perpetuate underutilization of non-ideal donor lungs, as variable center-level offer acceptance practices may be amplified in this setting, potentially deterring OPOs from pursuing non-ideal donors that are more expensive and may yield fewer organs that are accepted by transplant centers.29,30 Implementation of revised OPO performance metrics that encourage optimal OPO-specific practices may represent the first necessary measure to increase non-ideal donor lung availability.19 However, our findings may begin to reassure transplant centers that more aggressive OPO-level behavior does not compromise recipient outcomes, facilitate broader utilization of non-ideal donor lungs, and reciprocally motivate more aggressive pursuit of these donors by reducing organ discards for which OPOs are penalized under the current evaluation paradigm.
Our study provides promising preliminary evidence to support more aggressive pursuit of non-ideal lung donors by less aggressive OPOs; however, further investigation is required to identify specific practice modifications that may facilitate achievement of this goal. In particular, understanding donor management strategies employed by the most aggressive OPOs may elucidate avenues through which less aggressive OPOs can improve non-ideal donor lung yield, without compromising outcomes. In a prospective study of 8 OPOs, Patel and colleagues found that achievement of at least 7 of 9 donor management goals during the management of non-ideal donors was associated with transplantation of 3 or more organs per donor and increased donor lung utilization.31 Intensive lung donor management protocols that emphasize protective ventilation strategies, lung recruitment maneuvers, fluid restriction, and diuresis may likewise increase rates of lung recovery and transplantation without adversely affecting rates of PGD3, duration of postoperative mechanical ventilation, intensive care unit or hospital length of stay, and post-transplant survival.24,32-35 As OPO-level donor management protocols are neither standardized nor published, we are unable to comment on how such practices may have contributed to higher rates of PGD3, early rejection, need for post-transplant ECMO, and prolonged length of stay among recipients of donor lungs from moderately aggressive OPOs in our study. It is conceivable that lower annual LTx volume among centers associated with these OPOs contributed to worse short-term outcomes in this group.21,36 Regardless, identification of OPO best practices is required to understand the relative contributions of OPO- and center-level practices and identify areas for improvement to optimize non-ideal donor lung quality, availability, and utilization moving forward.
There are several limitations in our study. Retrospective reviews using large national databases have the inherent limitation of unmeasured confounders that cannot be accounted for within the analysis. Several key confounders include OPO-specific definitions of “acceptable” donor, differences in OPOs’ reporting of donor pursuit, and transplant center offer acceptance practices.19 In addition to OPO-specific donor management strategies, we were unable to account for the duration and nature of care provided by donor hospital teams prior to OPO involvement, both of which likely affect donor lung quality, utilization, and outcomes. Some OPOs care for organ donors in centralized donor recovery facilities; however, available data preclude identification of donors managed in these settings. Use of such facilities may shorten donor hospital-level care, increase procurement efficiency, and reduce organ acquisition costs.37,38 OPOs with access to these specialized resources may thus be better able to not only streamline and optimize donor management, but also to offset potential financial barriers to non-ideal donor pursuit. Future studies should investigate how use of donor recovery facilities affects OPO-level aggressiveness to understand how centralization of OPO-level practices may augment pursuit and utilization of non-ideal donor lungs and implications for LTx recipients. Outside the US, donor identification and referral are often performed by intensive care and/or transplant specialists.39,40 While the OPO structure may be unique to the US, the need for designated responsible healthcare providers to aggressively pursue all potential donors for multi-organ donation is pervasive amidst global organ shortage. Future work comparing international transplant systems would be of interest to elucidate the most productive organ donation and transplantation practices; nevertheless, our findings should offer promising preliminary evidence to encourage aggressive assessment, pursuit, and utilization of all donor lungs by both transplant center and OPO personnel or their equivalents within diverse transplant systems worldwide. Finally, examining OPO-level practices over an 11-year period meant that our analysis included data before and after national lung allocation policy was revised to replace donation service area with a 250-nautical mile radius around the donor hospital as the first unit of lung allocation.41 This change may facilitate collaboration between OPOs and non-local transplant centers, and may thus alter OPO-level aggressiveness and associated outcomes, as OPOs adjust their practices to align with variable center-level behavior, and non-ideal donor lungs are offered to centers with variable expertise in non-ideal donor/recipient matching and post-transplant management. Further investigation is warranted to understand how this new allocation policy affected OPO-level aggressiveness and recipient outcomes to aid ongoing efforts to facilitate broad and equitable access to LTx.
CONCLUSIONS
In this national analysis of OPO-level aggressiveness toward non-ideal lung donors, we found that the most and least aggressive OPOs achieve similar patient survival and short-term outcomes after LTx. The most aggressive OPOs also maintain the highest average annual lung donor volume, suggesting that more aggressive pursuit and utilization of non-ideal lung donors by less aggressive OPOs would likely expand the donor pool for LTx, without compromising recipient outcomes. Our findings highlight the need for further investigation to identify OPO best practices that may safely facilitate standardization and optimization of non-ideal lung donor pursuit and utilization in an era of persistent organ shortage.
Supplementary Material
Conflicts of Interest and Sources of Funding:
The authors have no conflicts of interest to disclose. This work was supported by the National Institutes of Health (NIH) under award numbers 5T32CA093245 (VR) and 5T32HL069749 (OKJ), and the National Center for Advancing Translational Sciences (NCATS) of the NIH under award number TL1TR002555 (SEH, AYC). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or NCATS.
ABBREVIATIONS:
- BMI
body mass index
- CI
confidence interval
- DCD
donation after circulatory death
- ECMO
extracorporeal membrane oxygenation
- HR
hazard ratio
- IQR
interquartile range
- IRD
increased risk for disease transmission
- LAS
lung allocation score
- LTx
lung transplantation
- OPO
organ procurement organization
- OPTN
Organ Procurement and Transplantation Network
- OR
odds ratio
- P/F
PaO2/FiO2
- PGD3
grade 3 primary graft dysfunction
- UNOS
United Network for Organ Sharing
Footnotes
Data Statement:
Data available from the United Network for Organ Sharing.
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