Abstract
Objectives
Although the long-term prognosis after lung transplantation has improved recently, primary graft dysfunction (PGD) remains the major cause of early mortality. The aim of this study was to elucidate trends in PGD incidence and short-term mortality following lung transplantation in the contemporary era.
Methods
We analyzed a single-center database of lung transplantations performed across three periods (Era 1: 2009–2013, Era 2: 2014–2017, and Era 3: 2018–2021). PGD was graded according to the 2016 International Society for Heart and Lung Transplantation definition, and PGD grade 3 within T0–T72 was used as the primary outcome. Trends in PGD incidence, factors associated with PGD, and early mortality rates after lung transplantation were identified.
Results
This study included 856 lung transplants: 277 in Era 1, 296 in Era 2, and 283 in Era 3. PGD grade 3 incidence decreased significantly over time: 35.9% (99 cases) in Era 1, 26.4% (78 cases) in Era 2, and 18.4% (52 cases) in Era 3 (P<0.001). During the study period, the lung allocation score (LAS) and intraoperative cardiopulmonary bypass (CPB) use decreased, whereas the use of intraoperative nitric oxide and extracorporeal membrane oxygenation increased. Logistic multivariate modeling identified era, recipient sex (male), underlying disease, race, and blood transfusion as factors associated with PGD. No significant difference was observed in 30-day hospital mortality across the three eras (2.9%, 1.4%, and 1.4% for Era 1, Era 2, and Era 3, respectively; P=0.313).
Conclusion
This study demonstrated a significant reduction in PGD incidence over time, which coincided with a decrease in LAS and intraoperative CPB use. However, no significant changes were observed in short-term mortality after lung transplantation.
Keywords: Lung transplantation, Primary graft dysfunction, Early mortality, Lung allocation score, Trend
Introduction
Over the past four decades, lung transplantation has evolved into a well-established treatment option for patients with end-stage pulmonary disease. The number of lung transplantations performed has increased steadily from 11,000 in the 1990s to 34,000 between 2010 and 2018.1 According to the International Society for Heart and Lung Transplantation (ISHLT) registry, notable changes in donor and recipient characteristics have been observed across different eras (1992–2000, 2001–2009, and 2010–2018).1 The median recipient age increased consistently from 50 years during the 1992–2000 era to 57 years during the 2010–2018 era. In addition, the proportion of male recipients increased in the most recent era, whereas the prevalence of recipients with a history of smoking declined over time. Despite significant improvements in long-term survival among adult lung transplant recipients between 2000 and 2017, attributed to advancements in immunosuppression and surgical techniques,1, 2, 3, 4 it remains unclear whether recent changes in donor and recipient characteristics have influenced short-term outcomes compared to earlier eras.
The primary aim of this study was to examine trends in donor and recipient characteristics, as well as short-term outcomes, including the incidence of primary graft dysfunction (PGD) and 30-day mortality over time. The secondary aim was to identify factors associated with PGD development.
Material and methods
Data collection and study population
We conducted a retrospective cohort study using a prospectively maintained single-center database of lung transplant donors and recipients at our institution between January 2009 and December 2021. During the study period, 4 multi-organ transplants, 28 re-transplants, 43 single lung transplants, and 2 transplants from donation after circulatory death donors were excluded to maintain a homogeneous cohort of primary bilateral lung transplant recipients. The patients were classified into three eras: Era 1 (2009–2013), Era 2 (2014–2017), and Era 3 (2018–2021). The eras were defined to ensure numerical balance between the groups. The Washington University School of Medicine Institutional Review Board for Human Studies approved the study protocol (ID #202203073). The Institutional Review Board waived the requirement for individual written consent for the publication of the study data because of the retrospective nature of the study.
Definition
PGD was graded according to the 2016 ISHLT definition.5 The PGD grade was assessed at 0, 24, 48, and 72 h post-transplantation, with the highest grade within the first 72 h considered the outcome of interest.
Statistical analysis
Donor and recipient characteristics, along with operative variables, were summarized using descriptive statistics. Categorical variables are presented as counts (%), and continuous variables are expressed as mean ± standard deviation for normally distributed variables or as median (quartile 1 to quartile 3) for highly skewed data. Comparisons between the groups were conducted using Fisher’s exact test for categorical variables and analysis of variance for continuous variables. The Kaplan—Meier method was used to estimate survival probabilities from the date of lung transplantation to the endpoints of death or censoring.
Univariate logistic regression was performed to identify the risk factors for PGD, and variables with a p-value of <0.05 were included in the multivariate model. Odds ratios (ORs) and 95% confidence intervals (CIs) were evaluated for logistic regression analysis. Temporal trends in PGD incidence were assessed using the Cochran—Armitage trend test. All statistical analyses were performed using SPSS (version 28.0; SPSS Inc.) and JMP Pro 17 (SAS Institute).
Results
A total of 856 lung transplantations were included in the study and categorized according to era as follows: Era 1 (n=277), Era 2 (n=296), and Era 3 (n=283). PGD incidence significantly decreased over time (35.9% in Era 1, 26.4% in Era 2, and 18.4% in Era 3; Cochran—Armitage test, p<0.001; Figure 1A, B). Donor characteristics, including age, sex, smoking history, and best PaO2, did not differ significantly between the eras (Table 1). However, there was a significant decrease in the proportion of white donors (73.3% in Era 1, 74.0% in Era 2, and 67.1% in Era 3) and stroke as the cause of death (37.9% in Era 1, 29.7% in Era 2, and 26.5% in Era 3). Recipient characteristics, including sex, ethnicity, smoking history, and cytomegalovirus mismatch, were consistent across eras. Nonetheless, recipient age increased significantly over time: 56.0 in Era 1, 59.5 in Era 2, and 61.0 years in Era 3 (p<0.001), as did the proportion of recipients with restrictive lung disease (46.2% in Era 1, 54.1% in Era 2, and 54.8% in Era 3). In contrast, the lung allocation score (LAS) decreased (40.4% in Era 1, 39.3% in Era 2, and 37.9% in Era 3; p<0.001), whereas the ischemic time increased significantly (269 min in Era 1, 246 min in Era 2, and 309 min in Era 3; p<0.001). Operative trends also changed over time, with a significant increase in the use of extracorporeal membrane oxygenation (ECMO; Cochran—Armitage test, p<0.001; Figure 2A), and a decrease in the use of cardiopulmonary bypass (CPB; Cochran—Armitage test, p<0.001; Figure 2B). An increase in the use of nitric oxide (NO; Cochran—Armitage test; p<0.001, Figure 2C) was also noted. Despite these changes, neither 30-day hospital mortality nor 1-year mortality differed significantly among the eras. Thirty-day hospital mortality was 2.9% in Era 1, 1.4% in Era 2, and 1.4% in Era 3 (p=0.313; Table 2), and 1-year mortality was 11.6%, 9.5%, and 14.5% in Eras 1, 2, and 3, respectively (p=0.225).
Figure 1.
(A) Incidence of PGD grade 3 within 72 h after transplantation stratified by years. (B) Incidence of PGD grade 3 within 72 h after transplantation was 35.9%, 26.4%, and 18.4% in Era 1, Era 2, and Era 3, respectively. Abbreviation: PGD, primary graft dysfunction.
Table 1.
Baseline Characteristics of Donors and Recipients
| Variables | Era 1 (n=277) | Era 2 (n=296) | Era 3 (n=283) | P Value |
|---|---|---|---|---|
| Donor | ||||
| Age (years) | 35 (24–50) | 34 (23–49) | 34 (23–48) | 0.830 |
| Male | 174 (62.8) | 170 (57.4) | 183 (64.7) | 0.177 |
| Ethnicity | 0.012 | |||
| White | 203 (73.3) | 219 (74.0) | 190 (67.1) | |
| Black | 63 (22.7) | 59 (19.9) | 61 (21.6) | |
| Others | 11 (4.0) | 18 (6.1) | 32 (11.3) | |
| Cause of death | 0.037 | |||
| Stroke | 105 (37.9) | 88 (29.7) | 75 (26.5) | |
| Head trauma | 115 (41.5) | 125 (42.2) | 123 (43.5) | |
| Anoxia | 47 (17.0) | 75 (25.3) | 73 (25.8) | |
| Others | 10 (3.6) | 8 (2.7) | 12 (4.2) | |
| Creatinine (mg/dL) | 1.0 (0.8–1.2) | 1.0 (0.8–1.3) | 1.1 (0.9–1.6) | <0.001 |
| Cigarette use | 30 (10.9) | 41 (13.9) | 21 (7.6) | 0.051 |
| Best PaO2 (mmHg) | 506 (461–559) | 524 (473–561) | 511 (470–565) | 0.131 |
| Non-local donor | 120 (43.3) | 122 (41.2) | 206 (72.8) | <0.001 |
| Recipient | ||||
| Age (years) | 56 (43–62) | 60 (49–66) | 61 (54–66) | <0.001 |
| Male | 160 (57.8) | 171 (57.8) | 180 (63.6) | 0.261 |
| Ethnicity | 0.664 | |||
| White | 258 (93.1) | 266 (89.9) | 258 (91.2) | |
| Black | 15 (5.4) | 22 (7.4) | 20 (7.1) | |
| Others | 4 (1.4) | 8 (2.7) | 5 (1.8) | |
| Indications for transplant | 0.005 | |||
| Obstructive lung disease | 88 (31.8) | 84 (28.4) | 91 (32.2) | |
| Pulmonary vascular disease | 6 (2.2) | 3 (1.0) | 12 (4.2) | |
| Cystic fibrosis | 53 (19.1) | 47 (15.9) | 23 (8.1) | |
| Restrictive lung disease | 128 (46.2) | 160 (54.1) | 155 (54.8) | |
| Others | 2 (0.7) | 2 (0.7) | 2 (0.7) | |
| Cigarette use | 146 (52.7) | 153 (51.7) | 168 (59.4) | 0.135 |
| Lung allocation score | 40 (34–53) | 39 (35–49) | 38 (34–46) | 0.011 |
| CMV mismatch | 116 (41.9) | 135 (45.6) | 130 (45.9) | 0.561 |
| PAH | 146 (66.7) | 172 (75.4) | 191 (78.3) | 0.014 |
| Preoperative MV | 24 (8.7) | 24 (8.1) | 11 (3.9) | 0.049 |
| Preoperative ECMO | 3 (1.1) | 6 (2.0) | 11 (3.9) | 0.082 |
| Lung downsizing | 27 (9.7) | 22 (7.4) | 18 (6.4) | 0.313 |
| Total ischemic time (min) | 269 (226–327) | 246 (199–306) | 309 (265–340) | <0.001 |
| Blood transfusion (unit) | 2 (0–3) | 2 (0–5) | 2 (0–5) | <0.001 |
| Intraoperative ECMO | 2 (0.7) | 5 (1.7) | 108 (38.2) | <0.001 |
| Intraoperative CPB | 135 (48.7) | 136 (45.9) | 38 (13.4) | <0.001 |
| Intraoperative NO | 183 (66.3) | 226 (76.4) | 261 (92.9) | <0.001 |
| Postoperative ECMO | 7 (2.5) | 13 (4.4) | 18 (6.4) | 0.088 |
Abbreviations: CMV, cytomegalovirus; CPB, cardiopulmonary bypass; ECMO, extracorporeal membrane oxygenation; MV, mechanical ventilation; NO, nitric oxide; PAH, pulmonary arterial hypertension; PaO2, partial pressure of oxygen
Figure 2.
(A) Trends in ECMO use by era. The percentage of intraoperative ECMO use was 0.7%, 1.7%, and 38.2% in Era 1, Era 2, and Era 3, respectively. (B) Trends in CPB use by era. The percentage of intraoperative CPB use was 48.7%, 45.9%, and 13.4% in Era 1, Era 2, and Era 3, respectively. (C) Trends in NO use by era. The percentage of intraoperative NO use was 66.3%, 76.4%, and 92.9% in Era 1, Era 2, and Era 3, respectively. Abbreviations: ECMO, extracorporeal membrane oxygenation; CPB, cardiopulmonary bypass; NO, nitric oxide.
Table 2.
Postoperative Outcomes in Recipients
| Variables | Era 1 (n=277) | Era 2 (n=296) | Era 3 (n=283) | P Value |
|---|---|---|---|---|
| Tracheostomy | 55 (19.9) | 74 (25.0) | 54 (19.1) | 0.167 |
| PGD grade ≧ 3 (T0-T72) | 99 (35.7) | 78 (26.4) | 52 (18.4) | <0.001 |
| 30-day hospital mortality | 8 (2.9) | 4 (1.4) | 4 (1.4) | 0.313 |
| Length of hospital stay (days) | 15 (11–23) | 16 (12–28) | 17 (12–31) | 0.006 |
PGD, primary graft dysfunction
Logistic multivariate modeling identified several factors that were significantly associated with PGD. The era of transplantation was a significant factor (p<0.001), with a lower risk of PGD observed in Era 2 than in Era 1 (odds ratio [OR], 0.509; confidence interval [CI], 0.338–0.766; p=0.001) and in Era 3 than in Era 1 (OR, 0.385; CI, 0.238–0.620; p<0.001). Male recipients demonstrated a reduced risk of developing PGD (OR, 0.630; CI, 0.442–0.897; p=0.011). Underlying disease was also associated with PGD risk, with pulmonary vascular disease showing a higher risk than obstructive lung disease (OR, 3.872; CI, 1.406–10.666; p=0.009). Restrictive lung disease was also associated with an increased PGD risk compared with obstructive lung disease (OR, 2.487; CI, 1.553–3.983; p<0.001). Race was also a significant factor (p=0.012), with black recipients having a higher risk of developing PGD than white recipients (OR, 2.033; CI, 1.082–3.82; p=0.027). The operative factors associated with PGD included the use of CPB (OR, 1.480; CI, 1.002–2.185; p=0.049) and blood transfusion (OR, 1.106; CI, 1.058–1.157; p<0.001) (Table 3).
Table 3.
Univariate and Multivariate Logistic Regression Analyses of Risk Factors for PGD
| Variables | Univariate Analysis | P Value | Multivariate Analysis | P Value |
|---|---|---|---|---|
| OR (95% CI) | OR (95% CI) | |||
| Era 1 (2009–2013) | Reference | Reference | ||
| Era 2 (2014–2017) | 0.640 (0.448–0.914) | 0.014 | 0.509 (0.338–0.766) | 0.001 |
| Era 3 (2018–2021) | 0.404 (0.274–0.596) | <0.001 | 0.385 (0.238–0.620) | <0.001 |
| Donor age | 1.006 (0.997–1.016) | 0.203 | ||
| Donor male | 1.006 (0.737–1.373) | 0.972 | ||
| Donor ethnicity | ||||
| White | Reference | |||
| Black | 0.934 (0.641–1.361) | 0.723 | ||
| Others | 1.069 (0.593–1.926) | 0.825 | ||
| Cause of death | ||||
| Stroke | Reference | |||
| Head trauma | 1.068 (0.749–1.522) | 0.716 | ||
| Anoxia | 0.964 (0.635–1.465) | 0.864 | ||
| Others | 0.436 (0.147–1.295) | 0.135 | ||
| Donor cigarette use | 1.149 (0.713–1.851) | 0.569 | ||
| Best PaO2 | 0.999 (0.997–1.002) | 0.592 | ||
| Distant donor | 1.059 (0.782–1.453) | 0.710 | ||
| Recipient age | 0.998 (0.997–0.999) | 0.032 | 0.989 (0.972–1.006) | 0.213 |
| Recipient male | 0.643 (0.474–0.873) | <0.001 | 0.630 (0.442–0.897) | 0.011 |
| Ethnicity | ||||
| White | Reference | Reference | ||
| Black | 2.628 (1.525–4.528) | <0.001 | 2.033 (1.082–3.820) | 0.027 |
| Others | 0.626 (0.178–2.200) | 0.465 | 0.252 (0.059–1.082) | 0.064 |
| Indications for transplant | ||||
| Obstructive lung disease | Reference | Reference | ||
| Pulmonary vascular disease | 4.762 (1.902–11.922) | <0.001 | 3.872 (1.406–10.666) | 0.009 |
| Cystic fibrosis | 1.690 (0.997–2.864) | 0.051 | 0.915 (0.488–1.869) | 0.808 |
| Restrictive lung disease | 2.531 (1.722–3.721) | <0.001 | 2.487 (1.553–3.983) | <0.001 |
| Others | 5.238 (1.022–26.841) | 0.047 | 1.416 (0.209–9.596) | 0.721 |
| Recipient cigarette use | 0.807 (0.595–1.092) | 0.165 | ||
| Lung allocation score | 1.028 (1.019–1.036) | <0.001 | 1.006 (0.994–1.018) | 0.341 |
| CMV mismatch | 1.009 (0.744–1.368) | 0.954 | ||
| PAH | 1.117 (0.758–1.645) | 0.576 | ||
| Preoperative MV | 2.980 (1.738–5.109) | <0.001 | 1.894 (0.941–3.814) | 0.074 |
| Preoperative ECMO | 2.283 (0.934–5.585) | 0.070 | ||
| Lung downsizing | 1.088 (0.625–1.893) | 0.076 | ||
| Total ischemic time | 1.003 (1.000–1.005) | 0.030 | 1.002 (0.999–1.004) | 0.237 |
| Blood transfusion | 1.122 (1.079–1.167) | <0.001 | 1.106 (1.058–1.157) | <0.001 |
| Intraoperative ECMO | 0.827 (0.521–1.311) | 0.418 | ||
| Intraoperative CPB | 3.054 (2.234–4.176) | <0.001 | 1.480 (1.002–2.185) | 0.049 |
| Intraoperative NO | 1.009 (0.697–1.459) | 0.963 |
Abbreviations: CI, confidence interval; CMV, cytomegalovirus; CPB, cardiopulmonary bypass; ECMO, extracorporeal membrane oxygenation; MV, mechanical ventilation; NO, nitric oxide; OR, odds ratio; PAH, pulmonary arterial hypertension; PaO2, partial pressure of oxygen.
Discussion
In this study, we report an improvement in PGD incidence after lung transplantation in recent eras (2014–2017 and 2018–2021) compared with that in the early era (2009–2013). Over the study period, we observed several changes in the donor and recipient demographic characteristics. Specifically, there was an increase in head trauma as the donor cause of death, recipient age, and prevalence of restrictive lung disease, whereas LAS and intraoperative use of CPB decreased. These changes occurred in parallel with an observed improvement in PGD incidence. Our multivariate analysis showed that lung transplants performed in the recent era were independently associated with a significantly lower risk of PGD, regardless of other contributing risk factors. Although transplant era remained independently associated with PGD in multivariable analysis, era likely serves as a proxy for multiple concurrent changes in recipient characteristics and perioperative management over time rather than a single causal exposure. Accordingly, the association between era and PGD should be interpreted cautiously and viewed as reflecting cumulative temporal improvements in practice and case-mix.
In a prospective multicenter cohort study conducted between 2011 and 2018, Cantu et al. reported an overall incidence of PGD grade 3 of 25.7%, with a significant increase from 14.3% in 2011 to 38.2% in 2018.6 They also demonstrated that the median LAS significantly increased from 38.0 to 47.7 over the same period, and that a higher LAS was associated with an increased incidence of PGD. The same group previously reported a PGD incidence of 16.8% in a cohort enrolled between 2002 and 2010.7 The authors speculated that this increasing trend in PGD grade 3 incidence may be attributed to the growing proportion of sicker patients on the transplant waitlist, characterized by a combination of restrictive lung disease, pulmonary hypertension, and obesity.6 In contrast, our study demonstrated a decreasing trend in PGD incidence and LAS in recent years. Although the exact reason for the downward trend in LAS over time remains unclear, it may have contributed to the observed improvement in PGD outcomes in this study.
The intraoperative use of CPB has been identified as an independent risk factor for PGD.7, 8, 9 This association may be attributed to hemodynamic instability observed during transplantation, which is linked to an increased risk of PGD. A recent multicenter international study reported that patients undergoing lung transplantation with CPB had a higher risk of PGD grade 3 than those managed with veno-arterial (VA) ECMO or off-pump procedures.10 VA-ECMO is increasingly being preferred at high-volume centers as an alternative to CPB for intraoperative cardiopulmonary support,11 particularly during double-lung transplantation. At our institution, VA-ECMO has been routinely selected as the primary method for cardiopulmonary support, replacing CPB since 2018. A meta-analysis further demonstrated that VA-ECMO support was associated with reduced PGD incidence, bleeding complications, and renal failure compared with conventional CPB.11
PGD is a leading cause of short-term morbidity and mortality after lung transplantation, with a reported mortality rate of up to 40%.12, 13 Although no statistically significant improvement was observed in short-term prognosis across the eras, our study demonstrated a downward trend in 30-day hospital mortality in the two most recent eras compared to that in the early era. This trend may be partly explained by the relatively small number of patients in our cohort who died within 30 days of lung transplantation during the study period.
Despite the observed reduction in severe PGD incidence over time, the length of hospital stay modestly increased across eras. This apparent discrepancy likely reflects changes in recipient case-mix rather than worsening early graft function. In particular, recipients in the more recent eras were older and more frequently transplanted for restrictive lung disease and pulmonary hypertension, clinical profiles that are often associated with prolonged postoperative recovery even in the absence of severe PGD. In addition, advances in perioperative management—including increased use of intraoperative ECMO and nitric oxide—may have improved early survival among higher-risk recipients who previously might have experienced early mortality. As a result, these patients may survive the immediate postoperative period but require longer hospitalization for recovery and rehabilitation. Finally, institutional changes in postoperative care pathways, discharge planning, and rehabilitation practices over time may also have contributed to longer hospital stays in more recent eras. Taken together, the increasing length of stay likely reflects evolving recipient complexity and improved survival rather than a deterioration in early allograft outcomes.
This study had some limitations. First, this was a retrospective, single-center, observational study, which may have limited the generalizability of the findings. Second, we did not account for the experience level of lung transplant surgeons or specific technical aspects of the surgical procedures, both of which could have influenced the outcomes. Finally, there may have been other potential risk factors of PGD that were not included in our analysis, which could have affected the results.
Conclusions
We observed a decreasing trend in severe PGD (PGD grade 3), defined as the highest PGD grade within the first 72 h after transplantation (T0-T72), incidence following lung transplantation. This improvement in PGD incidence in recent years is likely multifactorial; however, the reduction in recipients’ LAS and decreased use of CPB may have contributed significantly to this decline.
Funding statement
none.
Declaration of Competing Interest
The authors 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
none.
Author contributions statement
T.Y. and T.T. contributed to the study conception and design, data acquisition, statistical analysis, drafting of the manuscript, critical revision, and final approval of the final version. All authors participated in critical revision and approved the final manuscript.
Meeting presentation
none.
References
- 1.Chambers D.C., Perch M., Zuckermann A., et al. International Society for Heart and Lung Transplantation. The International Thoracic Organ Transplant Registry of the International Society for Heart and Lung Transplantation: Thirty-eighth adult lung transplantation report - 2021; Focus on recipient characteristics. J Heart Lung Transplant. 2021;40:1060–1072. doi: 10.1016/j.healun.2021.07.021. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Chambers D.C., Cherikh W.S., Harhay M.O., et al. International Society for Heart and Lung Transplantation. The International Thoracic Organ Transplant Registry of the International Society for Heart and Lung Transplantation: Thirty-sixth adult lung and heart-lung transplantation Report-2019; Focus theme: Donor and recipient size match. J Heart Lung Transplant. 2019;38:1042–1055. doi: 10.1016/j.healun.2019.08.001. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Chambers D.C., Cherikh W.S., Goldfarb S.B., et al. International Society for Heart and Lung Transplantation. The International Thoracic Organ Transplant Registry of the International Society for Heart and Lung Transplantation: Thirty-fifth adult lung and heart-lung transplant report-2018; Focus theme: Multiorgan transplantation. J Heart Lung Transplant. 2018;37:1169–1183. doi: 10.1016/j.healun.2018.07.020. [DOI] [PubMed] [Google Scholar]
- 4.Chambers D.C., Yusen R.D., Cherikh W.S., et al. International Society for Heart and Lung Transplantation. The Registry of the International Society for Heart and Lung Transplantation: Thirty-fourth Adult Lung and Heart-Lung Transplantation Report-2017; Focus Theme: Allograft ischemic time. J Heart Lung Transplant. 2017;36:1047–1059. doi: 10.1016/j.healun.2017.07.016. [DOI] [PubMed] [Google Scholar]
- 5.Snell G.I., Yusen R.D., Weill D., et al. Report of the ISHLT Working Group on Primary Lung Graft Dysfunction, part I: Definition and grading-A 2016 Consensus Group statement of the International Society for Heart and Lung Transplantation. J Heart Lung Transplant. 2017;36:1097–1103. doi: 10.1016/j.healun.2017.07.021. [DOI] [PubMed] [Google Scholar]
- 6.Cantu E., Diamond J.M., Cevasco M., et al. Contemporary trends in PGD incidence, outcomes, and therapies. J Heart Lung Transplant. 2022;41:1839–1849. doi: 10.1016/j.healun.2022.08.013. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Diamond J.M., Lee J.C., Kawut S.M., et al. Lung Transplant Outcomes Group Clinical risk factors for primary graft dysfunction after lung transplantation. Am J Respir Crit Care Med. 2013;187:527–534. doi: 10.1164/rccm.201210-1865OC. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Diamond J.M., Arcasoy S., Kennedy C.C., et al. Report of the International Society for Heart and Lung Transplantation Working Group on Primary Lung Graft Dysfunction, part II: Epidemiology, risk factors, and outcomes-A 2016 Consensus Group statement of the International Society for Heart and Lung Transplantation. J Heart Lung Transplant. 2017;36:1104–1113. doi: 10.1016/j.healun.2017.07.020. [DOI] [PubMed] [Google Scholar]
- 9.Liu Y., Liu Y., Su L., Jiang S.J. Recipient-related clinical risk factors for primary graft dysfunction after lung transplantation: a systematic review and meta-analysis. PLoS One. 2014;9 doi: 10.1371/journal.pone.0092773. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Loor G., Huddleston S., Hartwig M., et al. Effect of mode of intraoperative support on primary graft dysfunction after lung transplant. J Thorac Cardiovasc Surg. 2022;164:1351–1361. doi: 10.1016/j.jtcvs.2021.10.076. [DOI] [PubMed] [Google Scholar]
- 11.Magouliotis D.E., Tasiopoulou V.S., Svokos A.A., Svokos K.A., Zacharoulis D. Extracorporeal membrane oxygenation versus cardiopulmonary bypass during lung transplantation: a meta-analysis. Gen Thorac Cardiovasc Surg. 2018;66:38–47. doi: 10.1007/s11748-017-0836-3. [DOI] [PubMed] [Google Scholar]
- 12.Lee J.C., Christie J.D., Keshavjee S. Primary graft dysfunction: definition, risk factors, short- and long-term outcomes. Semin Respir Crit Care Med. 2010;31:161–171. doi: 10.1055/s-0030-1249111. [DOI] [PubMed] [Google Scholar]
- 13.Christie J.D., Bellamy S., Ware L.B., et al. Construct validity of the definition of primary graft dysfunction after lung transplantation. J Heart Lung Transplant. 2010;29:1231–1239. doi: 10.1016/j.healun.2010.05.013. [DOI] [PMC free article] [PubMed] [Google Scholar]