The Registry of the International Society for Heart and Lung Transplantation: Thirty-second Official Adult Lung and Heart-Lung Transplantation Report—2015; Focus Theme: Early Graft Failure

Abstract

This section of the 32nd official International Society for Heart and Lung Transplantation (ISHLT) Registry Report of 2015 summarizes data from 51,440 adult lung and 3,820 adult heart-lung transplants that occurred through June 30, 2014. This publication reports data for donor and recipient characteristics, transplant events, and recipient treatments and outcomes. This Registry Report focuses on an overall theme of recipient early graft failure. The Registry’s online full slide set1The International Society for Heart and Lung Transplantation. ISHLT Registries. Available at: www.ishlt.org/registries/Google Scholar provides more detail, additional analyses, and other information not included in this publication. National and multinational organ/data exchange organizations and individual centers submitted data to the ISHLT Registry. Since the Registry’s inception, 242 lung transplant centers and 174 heart-lung transplant centers have reported data. The Registry Web site provides spreadsheets that show data elements collected in the Registry.1The International Society for Heart and Lung Transplantation. ISHLT Registries. Available at: www.ishlt.org/registries/Google Scholar The online slide set provides PowerPoint (Microsoft Corp) slides of figures and tables that support this manuscript, additional slides, and slide sets from previous annual reports.1The International Society for Heart and Lung Transplantation. ISHLT Registries. Available at: www.ishlt.org/registries/Google Scholar This report refers to specific online eSlides when we discuss particular data but do not show it in full due to space limitations. The eSlide numbers in the lung transplant section refer to the adult lung slides, and eSlide numbers in the heart-lung transplant section refer to the online adult heart-lung slides. Regarding primary indications for lung transplantation, we used the term chronic obstructive pulmonary disease (COPD) for cases of COPD that were not associated with α1-anti-trypsin deficiency (A1ATD), and we used the term A1ATD for cases of A1ATD associated with COPD. We substituted the term interstitial lung disease (ILD) for data entered as idiopathic pulmonary fibrosis (IPF). For cystic fibrosis (CF), presumably associated with bronchiectasis, we used the term CF. For the indication of bronchiolitis obliterans syndrome (BOS), this report used a reported indication of obliterative bronchiolitis (OB) or BOS. Late deaths coded as “graft failure” may have represented lung rejection or BOS; without specific reporting of the event, we did not count them as having experienced BOS. This report used standard statistical methodology for analyses and reporting. For assessing time-to-event rates (e.g., survival), we used the Kaplan-Meier method. Survival graphs (i.e., time-to-event graphs) were truncated when the number of analyzable individuals was fewer than 10. Follow-up of surviving recipients was censored at the time last reported to be alive (e.g., most recent annual follow-up) or at the time of retransplantation. Median time-to-event estimated the point at which 50% of all recipients experienced the outcome event (e.g., death). Conditional analyses included only those transplant recipients who met the required criterion (e.g., survival past 1 year post-transplant). We used the log-rank test to compare survival curves among groups. To prevent some spuriously statistically significant findings, we adjusted pairwise tests for multiple comparisons with Scheffé or Bonferroni methods. For multivariable time-to-event analyses, we used Cox proportional hazards regression. These analyses used the censoring approaches described above. Cox models only included transplant recipients for whom data were available for most of the risk factors in the final model. The non-conditional models used the latest data available at the time of the transplant. In contrast, the conditional analyses also adjusted for post-transplant factors. We used restricted cubic splines to fit continuous data variables. Model assumptions were tested, and regression diagnostics were performed. The Cox models calculated hazard ratios, corresponding 95% confidence intervals, and p-values. Tables and forest plots show hazard ratios and 95% confidence intervals for categoric variables in the final models. A more detailed explanation of the analytical methodology is available online1The International Society for Heart and Lung Transplantation. ISHLT Registries. Available at: www.ishlt.org/registries/Google Scholar and in previous annual reports.2Yusen, Edwards LB Kucheryavaya A.Y. et al.for the International Society of Heart and Lung Transplantation. Registry of the International Society for Heart and Lung Transplantation: 31st adult lung and heart-lung transplant report–2014; focus theme: retransplantation.J Heart Lung Transplant. 2014; 33: 1009-1024Abstract Full Text Full Text PDF PubMed Scopus (383) Google Scholar The report refers to specific online eSlides when particular data are discussed but not shown due to space limitations. The eSlide numbers in the respective sections of this report refer to the online lung adult and heart-lung adult slides.1The International Society for Heart and Lung Transplantation. ISHLT Registries. Available at: www.ishlt.org/registries/Google Scholar We recommend cautious interpretation of unadjusted analyses and predictive/comparative risk models in the context of limitations typical of registry data. For this report, the Registry Steering Committee selected the focus theme of early graft failure (EGF). The granularity of data collected in the Registry influenced the definition of EGF. We defined EGF as a composite end point of death or retransplant associated with graft failure within the first 30 days after transplant. Death or retransplant events associated with causes we believed were not due to intrinsic graft failure were excluded from the EGF definition. However, if the center reported the cause for a transplant recipient’s death or retransplant as unknown, we counted the recipient as having EGF because we assumed graft failure would be a more likely event than an easily identifiable cause that was not reported. If the center did not report a cause for a transplant recipient’s death or retransplant (i.e., field left blank), we did not count the recipient as having EGF. Because our EGF definition required an association between these outcome events and graft failure, rather than using all-cause death or all-cause retransplant for defining EGF, a large number of transplant recipients died or experienced retransplant events that did not meet the EGF criteria. The composite end point excluded graft failure that did not lead to death or retransplant within 30 days, although such events were rarely reported. The definition of EGF in this report certainly differs from the definition of primary graft dysfunction in thoracic transplantation. EGF reflects the most severe sub-group of early graft injury resulting in graft loss. For estimating the cumulative incidence of EGF at 30 days and the percentage of transplant recipients that developed EGF within 30 days, we used a competing risks extension of the Kaplan-Meier method. Competing events within 30 days after transplant consisted of (1) death or retransplant that did not meet the EGF criteria, and (2) “graft failure” not associated with death or retransplant within 30 days. We used consistent EGF definitions for the pediatric and adult age groups within each organ (i.e., heart and lung). However, causes of death or retransplant that were included in the definition of EGF differed between heart3Dipchand A. Rossano J.W. Edwards L.B. et al.The Registry of the International Society for Heart and Lung Transplantation: Eighteenth Official Pediatric Heart Transplantation Report -- 2015; Focus Theme: Early Graft Failure.J Heart Lung Transplant. 2015; 34: 1233-1243Abstract Full Text Full Text PDF PubMed Scopus (104) Google Scholar, 4Lund L.H. Edwards L.B. Kucheryavaya A.Y. et al.The Registry of the International Society for Heart and Lung Transplantation: Thirty-second Official Adult Heart Transplantation Report -- 2015; Focus Theme: Early Graft Failure.J Heart Lung Transplant. 2015; 34: 1244-1254Abstract Full Text Full Text PDF PubMed Scopus (357) Google Scholar and lung transplant.5Goldfarb S.B. Benden C. Edwards L.B. et al.The Registry of the International Society for Heart and Lung Transplantation: Eighteenth Official Pediatric Lung and Heart-Lung Transplantation Report -- 2015; Focus Theme: Early Graft Failure.J Heart Lung Transplant. 2015; 34: 1255-1263Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar The Registry now contains data from 51,440 adult lung transplants performed through June 2014. Of these, 49,422 (96.1%) had primary lung transplantation and 2,018 (3.9%) had lung retransplantation. Data were submitted from 136 participating transplant centers for 3,893 adult lung transplantation procedures performed in 2013. Since the inception of the Registry, 2013 had the highest reported annual activity (Figure 1). The number of adult primary lung transplants reported in 2013 was approximately 30-times greater than the number of pediatric primary lung transplants.5Goldfarb S.B. Benden C. Edwards L.B. et al.The Registry of the International Society for Heart and Lung Transplantation: Eighteenth Official Pediatric Lung and Heart-Lung Transplantation Report -- 2015; Focus Theme: Early Graft Failure.J Heart Lung Transplant. 2015; 34: 1255-1263Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar A total of 155 centers reported at least 1 adult lung transplant performed between January 2009 and June 2014 (Figure 2). During this period, almost 66% of the transplant procedures were performed at 44 centers (28% of centers) that had an average activity of 30 or more transplants per year. Fourteen centers (9% of centers) had an average activity of 50 or more transplants per year and performed 33% of procedures reported during this period, and 43 centers (28% of centers) averaged fewer than 10 transplants per year and conducted just under 4% of the procedures. Of the 51,400 adult lung transplants that were reported through June 2014, 1,973 (3.8%) had a first retransplantation, and 45 (0.1%) had a second retransplantation. Overall, the annual proportion of reported adult lung retransplants has hovered around 4% to 5% since 2005 (Figure 3), despite the marked increase in the total number of transplants (Figure 1). Just over 10% of lung retransplants occurred within the first month after a prior lung or heart-lung transplant. Most the lung retransplants occurred between 1 and 10 years, although about 5% occurred at least 10 years after the primary transplant (eSlide 6). For adult lung transplants that occurred between January 1995 and June 2014 (Table 1),6Travis W.D. Costabel U. Hansell D.M. et al.ATS/ERS Committee on Idiopathic Interstitial Pneumonias. An official American Thoracic Society/European Respiratory Society statement: update of the international multidisciplinary classification of the idiopathic interstitial pneumonias.Am J Respir Crit Care Med. 2013; 188: 733-748Crossref PubMed Scopus (2524) Google Scholar, 7Simonneau G. Gatzoulis M.A. Adatia I. et al.Updated clinical classification of pulmonary hypertension.J Am Coll Cardiol. 2013; 62: D34-D41Crossref PubMed Scopus (2041) Google Scholar the most common primary indications consisted of COPD (32%), followed by ILD (24%), CF (16%), and A1ATD (5%). For the 49,685 lung transplants that occurred in 1990 through 2013, recipients who had COPD, ILD, or CF contributed the most to the growth in the number of transplants (Figure 4). However, for the more recent period of 1999 through 2013, the percentage of recipients with COPD gradually decreased from 40% to below 30%, whereas the percentage of transplants for ILD increased from 16% to 31% (eSlide 12).Table 1Primary IndicationsaDiagnostic groupings are based on reporting classification categories; recipients may have secondary diagnoses that overlap with other categories (e.g., sarcoidosis with interstitial lung disease and PAH); diagnostic misclassification may occur. for Adult Lung Transplants (Transplants January 1995—June 2014)SLTBLTTotal(n = 16,226)(n = 29,457)(N = 45,683)DiagnosisNo. (%)No. (%)No. (%)COPD7,618 (46.9)9,523 (32.3)17,141 (35.7) Without A1ATD6,826 (42.1)7,856 (26.7)14,682 (32.1) With A1ATD792 (4.9)1,667 (5.7)2,459 (5.4)Diffuse parenchymal lung diseasebCategories may include other types of idiopathic and non-idiopathic interstitial pneumonia.66,319 (38.9)6,567 (22.3)12,886 (28.2) Interstitial lung diseasebCategories may include other types of idiopathic and non-idiopathic interstitial pneumonia.65,561 (34.3)5,442 (18.5)11,003 (24.1) Pulmonary fibrosis, otherbCategories may include other types of idiopathic and non-idiopathic interstitial pneumonia.6758 (4.7)1,125 (3.8)1,883 (4.1)Bronchiectasis293 (1.8)8,358 (28.4)8,651 (18.9) CFcPresumably associated with bronchiectasis.228 (1.4)7,191 (24.4)7,419 (16.2) Not associated with CF65 (0.4)1,167 (4.0)1,232 (2.7)PAH184 (1.1)1,583 (5.4)1,767 (3.9) Idiopathic PAHdLikely includes other types of World Health Organization Group 1 PAH.791 (0.6)1,250 (4.2)1,341 (2.9) Congenital heart disease93 (0.6)333 (1.1)426 (0.9)RetransplantationeRetransplant includes those with a known previous lung or heart-lung transplant.2548 (3.4)686 (2.3)1,234 (2.7) OB/BOS338 (2.1)440 (1.5)778 (1.7) Not due to OB/BOS210 (1.3)246 (0.8)456 (1.0)Less common diagnoses Sarcoidosis301 (1.9)857 (2.9)1,158 (2.5) Connective tissue disease200 (1.2)481 (1.6)681 (1.5) OB (not retransplant)110 (0.7)381 (1.3)491 (1.1) Lymphangioleiomyomatosis142 (0.9)330 (1.1)472 (1.0) Cancer7 (0.0)30 (0.1)37 (0.1) Other504 (3.1)661 (2.2)1,165 (2.6)A1ATD, α1-anti-trypsin deficiency; BLT, bilateral lung transplant; BOS, bronchiolitis obliterans syndrome; CF, cystic fibrosis; COPD, chronic obstructive lung disease; OB, obliterative bronchiolitis; PAH, pulmonary arterial hypertension; SLT, single lung transplant.a Diagnostic groupings are based on reporting classification categories; recipients may have secondary diagnoses that overlap with other categories (e.g., sarcoidosis with interstitial lung disease and PAH); diagnostic misclassification may occur.b Categories may include other types of idiopathic and non-idiopathic interstitial pneumonia.6Travis W.D. Costabel U. Hansell D.M. et al.ATS/ERS Committee on Idiopathic Interstitial Pneumonias. An official American Thoracic Society/European Respiratory Society statement: update of the international multidisciplinary classification of the idiopathic interstitial pneumonias.Am J Respir Crit Care Med. 2013; 188: 733-748Crossref PubMed Scopus (2524) Google Scholarc Presumably associated with bronchiectasis.d Likely includes other types of World Health Organization Group 1 PAH.7Simonneau G. Gatzoulis M.A. Adatia I. et al.Updated clinical classification of pulmonary hypertension.J Am Coll Cardiol. 2013; 62: D34-D41Crossref PubMed Scopus (2041) Google Scholare Retransplant includes those with a known previous lung or heart-lung transplant.2Yusen, Edwards LB Kucheryavaya A.Y. et al.for the International Society of Heart and Lung Transplantation. Registry of the International Society for Heart and Lung Transplantation: 31st adult lung and heart-lung transplant report–2014; focus theme: retransplantation.J Heart Lung Transplant. 2014; 33: 1009-1024Abstract Full Text Full Text PDF PubMed Scopus (383) Google Scholar Open table in a new tab A1ATD, α1-anti-trypsin deficiency; BLT, bilateral lung transplant; BOS, bronchiolitis obliterans syndrome; CF, cystic fibrosis; COPD, chronic obstructive lung disease; OB, obliterative bronchiolitis; PAH, pulmonary arterial hypertension; SLT, single lung transplant. For the most recent decade of reporting, the geographic location of transplant centers showed differences as far as indications for lung transplantation. North American centers, compared with European and centers in other countries, had a smaller proportion of recipients who received transplants for CF and a larger proportion who received transplants for ILD (eSlide 14). The most common known retransplant indication for adult lung transplants in January 1995 through June 2014 was BOS (Table 1). Although the large majority of recipients who had CF or idiopathic pulmonary arterial hypertension (IPAH) underwent bilateral transplantation over the years, a marked change from unilateral to bilateral transplantation occurred for recipients who had COPD, A1ATD, or ILD (eSlide 10). The increased number of procedures occurred in association with the consistent growth in the number of bilateral lung transplants since the mid-1990s, whereas the number of single lung transplants performed annually during this time remained relatively stable (Figure 1). In recent years, most recipients who had the most common indications for lung transplantation underwent bilateral procedures. The 45,542 adults who underwent primary lung transplantation between January 1990 and June 2013 had a median survival of 5.7 years (Figure 5), with unadjusted survival rates of 89% at 3 months, 80% at 1 year, 65% at 3 years, 54% at 5 years, and 31% at 10 years. The recipients who survived to 1 year after primary transplant had a conditional median survival of 7.9 years. Primary lung transplant recipient groups stratified by transplant type (single/unilateral vs double/bilateral) had markedly different unadjusted survival rates (Figure 6). Transplant recipients who underwent bilateral lung transplant had better survival than those who underwent single-lung transplant (median of 7.1 years vs 4.5 years, respectively; p < 0.001), and the difference remained prominent for 1-year conditional survival (median of 9.7 years vs 6.4 years, respectively). Survival of adult recipients varied by era (e.g., 1990–1998, 1999–2008, and 2009–June 2013; Figure 7, eSlide 23). The more recent eras showed better survival for primary transplants than the oldest era, and the survival curves separated in the early period after transplant: 3-month survival improved between the earliest and the most recent of three eras, from 83% to 91%, and 1-year survival improved from 73% to 84%. Median survival for the older 2 eras improved over time from just over 4 years to just over 6 years (median not reached for the latest era). Unadjusted survival of adult primary lung transplant recipients was better for women than men (eSlide 25). The 2013 Registry report provided more detailed survival analyses related to age.8Yusen R.D. Christie J.D. Edwards L.B. et al.for the International Society of Heart and Lung Transplantation. Registry of the International Society for Heart and Lung Transplantation: 30th adult lung and heart-lung transplant report–2013; focus theme: age.J Heart Lung Transplant. 2013; 32: 965-978Abstract Full Text Full Text PDF PubMed Scopus (416) Google Scholar Survival also varied by indication for primary transplantation (Figure 8, eSlide 27). By 3 months after transplant, lung recipients who received transplants for COPD or CF had the lowest unadjusted mortality (9%), whereas those who received transplants for IPAH had the highest mortality (23%). However, for primary transplant patients during the same era who survived to 1 year, conditional median survival was higher for CF (11.1 years), IPAH (10.0 years), sarcoidosis (9.1 years), and A1ATD (8.7 years) than for those with COPD (7.0 years) or ILD (6.9 years). For the 3 most common indications for transplant, recipients had worse survival after retransplant than after primary transplant (Figure 8). The 1,799 adults who underwent a first lung retransplantation in the era of January 1990 through June 2013 had a very high early mortality and a subsequent median survival of 2.5 years (Figure 5), with unadjusted survival rates of 78% at 3 months, 65% at 1 year, 47% at 3 years, 37% at 5 years, and 19% at 10 years. Recipients who survived to 1 year after the first retransplant had a conditional median survival of 6.0 years. Those undergoing first retransplantation had a much lower survival than those undergoing primary lung transplantation. Lung transplant recipient groups stratified by pre-transplantation cytomegalovirus (CMV) serologic status in donors and recipients had different survival rates (eSlide 48). Transplant recipients who received lungs from CMV-negative donors had better survival than those who received lungs from CMV-positive donors. The major reported causes of death (January 1990 through June 2014) within the first 30 days after transplantation were graft failure and non-CMV infections (Table 2). Other significant contributors to early post-transplant death included cardiovascular and technical (i.e., related to the transplant procedure) causes. During the remainder of the first post-transplant year, non-CMV infection became the most prominent cause of death. After the first post-transplant year, bronchiolitis, graft failure, and non-CMV infection caused most deaths. Especially after the first post-transplant year, malignancy became an important contributor to mortality.Table 2Known Causes of Death for Adult Lung Transplant Recipients (Deaths: January 1990–June 2014)0–30 days31 days–1 year>1–3 years>3–5 years>5–10 years>10 years(n = 3,224)(n = 5,578)(n = 5,256)(n = 3,015)(n = 3,655)(n = 1,294)Cause of deathaSome misclassification may occur among the cause of death terms of bronchiolitis, acute rejection, and graft failure. Owing to variation in reporting, graft failure may represent acute rejection, primary graft dysfunction, or other causes of death early post-transplant, or bronchiolitis obliterans syndrome, obliterative bronchiolitis, or other causes of death late post-transplant.No. (%)bData in parentheses indicate percentage of deaths out of all deaths with known cause in the respective time period.No. (%)bData in parentheses indicate percentage of deaths out of all deaths with known cause in the respective time period.No. (%)bData in parentheses indicate percentage of deaths out of all deaths with known cause in the respective time period.No. (%)bData in parentheses indicate percentage of deaths out of all deaths with known cause in the respective time period.No. (%)bData in parentheses indicate percentage of deaths out of all deaths with known cause in the respective time period.No. (%)bData in parentheses indicate percentage of deaths out of all deaths with known cause in the respective time period.Bronchiolitis9 (0.3)256 (4.6)1,378 (26.2)892 (29.6)914 (25.0)274 (21.2)Acute rejection115 (3.6)102 (1.8)83 (1.6)18 (0.6)20 (0.5)2 (0.2)Malignancy Lymphoma1 (0.0)120 (2.2)96 (1.8)46 (1.5)64 (1.8)38 (2.9) Other6 (0.2)159 (2.9)418 (8.0)339 (11.2)514 (14.1)174 (13.4)Infection CMV3 (0.1)122 (2.2)50 (1.0)7 (0.2)4 (0.1)1 (0.1) Non-CMV623 (19.3)1,964 (35.2)1,122 (21.3)548 (18.2)655 (17.9)211 (16.3)Graft failure783 (24.3)928 (16.6)985 (18.7)532 (17.6)615 (16.8)206 (15.9)Cardiovascular370 (11.5)295 (5.3)232 (4.4)152 (5.0)201 (5.5)95 (7.3)Technical363 (11.3)201 (3.6)48 (0.9)14 (0.5)29 (0.8)10 (0.8)Other951 (29.5)1,431 (25.7)844 (16.1)467 (15.5)639 (17.5)283 (21.9)CMV, cytomegalovirus.a Some misclassification may occur among the cause of death terms of bronchiolitis, acute rejection, and graft failure. Owing to variation in reporting, graft failure may represent acute rejection, primary graft dysfunction, or other causes of death early post-transplant, or bronchiolitis obliterans syndrome, obliterative bronchiolitis, or other causes of death late post-transplant.b Data in parentheses indicate percentage of deaths out of all deaths with known cause in the respective time period. Open table in a new tab CMV, cytomegalovirus. Lung retransplant recipients (eSlide 91) had similar trends of major reported causes of death (1990–June 2014) as those seen with primary lung transplant recipients. However, lung retransplant recipients had a slightly higher proportion of deaths due to the combination of bronchiolitis and graft failure than seen in primary lung transplant recipients. For 17,755 adult lung transplants performed between January 2001 and June 2013, the pre-transplant and peri-transplant categoric risk factors significantly associated with death during first post-transplant year in multivariable analyses included recipient male gender, type of underlying lung disease, pre-transplant chronic steroid use, retransplantation, earlier era of transplant, increased severity of recipient illness at the time of transplantation (i.e., intensive care unit, ventilator, dialysis), donor history of diabetes or hypertension, CMV mismatch (donor CMV+ and recipient CMV–), and non-identical donor and recipient blood groups (Figure 9). Continuous risk factors significantly associated with death included lower transplant center volume, shorter donor height, older recipient age at transplant, higher pre-transplant bilirubin, higher amount supplemental oxygen required at rest, lower cardiac output, lower percentage predicted value of the forced vital capacity, higher creatinine, and longer lung allograft ischemia time (eSlides 96–106). The continuous factors with the highest hazard ratios were the transplant center volume and the recipient age. Lower volume was associated with a higher mortality rate (Figure 10). The increased risk of 1-year post-transplant death with older recipient age began at approximately 55 years and rose exponentially thereafter (Figure 10). For the 10,584 lung transplant recipients with substantially complete data performed between January 2001 and June 2009, pre-transplant and peri-transplant risk factors for 5-year post-transplant mortality (Figure 11) showed some overlap with risk factors for 1-year post-transplant mortality (Figure 9). Categoric risk factors that showed an independent association with risk of death during the first 5 post-transplant years included recipient type of underlying lung disease, previous pregnancy, history of pulmonary embolism, retransplantation, earlier era of transplant, increased severity of recipient illness at the time of transplantation (i.e., intensive care unit, ventilator), donor history of diabetes, and CMV mismatch. Statistically significant continuous risk factors included lower transplant center volume, more negative donor-recipient height difference (i.e., donor shorter than recipient), and recipient factors of older age at transplant, higher amount of supplemental oxygen required at rest, lower cardiac output, higher bilirubin, and higher creatinine (eSlides 124–132). Risk factors for 5-year mortality, conditional on survival to 1-year (n = 8,539; Figure 12) showed some differences in the effect of the indication for lung transplant compared with the 1-year (Figure 9) and 5-year (Figure 11) non-conditional models. This conditional analysis showed that the diagnosis of retransplantation was no longer associated with risk of death. In contrast to the non-conditional analyses, the conditional analysis also included post-transplant variables. Recipients with BOS (the highest hazard ratio) or rejection in the first post-transplant year had a higher risk of death at 5 years. Statistically significant continuous risk factors included lower transplant center volume, donor with smaller donor body mass index compared with the recipient, extremes of recipient age at transplant, and higher recipient pre-transplant amount of supplemental oxygen required at rest, lower pulmonary vascular resistance, and lower cardiac output (eSlides 133–140). Similar to the non-conditional 1-year and 5-year mortality risk models, the conditional 5- year mortality risk model found a negative effect on longer-term survival for advanced recipient age and lower transplant center volume. The latter finding suggests that programmatic differences associated with transplant volume exist beyond those related to the transplant procedure. For adult lung transplants performed between January 1998 and June 2004, the 10-year post-transplant mortality model (eSlide 141–149) included some of the same risk factors that the 1-year (Figure 9, Figure 10), 5-year (Figure 11), and 5-year conditional (Figure 12) post-transplant mortality models included. The on-line slide set describes induction and maintenance immunosuppression for transplant recipients (eSlides 49–56 and 59–63). Follow-up assessments between July 2004 and June 2014 showed that 29% of 12,890 adult primary lung transplant surviving recipients who had known rejection status had at least 1 episode of treated rejection between discharge and the 1-year follow-up (eSlides 44 and 46). BOS, conditioned on surviving to 2 weeks after transplant (to avoid biases introduced by early death), remained a common long-term complication. For follow-up assessments performed between April 1994 and June 2014, the Kaplan-Meier time-to-event analysis estimated that BOS developed in 50% (n = 18,757) of primary adult lung transplant recipients within 5 years of transplantation and in 76% by 10 years post-transplant (Figure 13). Freedom from BOS for the combined group of primary transplants and retransplants did not appear to vary much according to the indication for transplant (eSlides 80) or use of induction immunosuppression (eSlides 81). Adult lung recipients who survived and for whom data were reported for every annual follow-up through 5 years post-transplant had a BOS rate of 41.1% at 5 years (Table 3).Table 3Cumulative Morbidity Rates in Adult Lung TransplantaCombined group of primary transplants and retransplants. Survivors (Follow-ups: April 1994—June 2014)Within 1 YearbPercentage of patients with known responses that experienced various morbidities as reported on forms at or before the 1-year and the 5-year