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J Thorac Cardiovasc Surg 2007;133:541-547
© 2007 The American Association for Thoracic Surgery

Cardiothoracic Transplantation

Impact of bilateral versus single lung transplantation on survival in recipients 60 years of age and older: Analysis of United Network for Organ Sharing database

^a Division of Cardiac Surgery, The Johns Hopkins Medical Institutions, Baltimore, Md
^b Department of Surgery, The Johns Hopkins Medical Institutions, Baltimore, Md.

Read at the Eighty-sixth Annual Meeting of The American Association for Thoracic Surgery, Philadelphia, Pa, April 29–May 3, 2006.

Received for publication April 28, 2006; revisions received August 25, 2006; accepted for publication September 29, 2006.

^_* Address for reprints: Ashish S. Shah, MD, Division of Cardiac Surgery, The Johns Hopkins Hospital, 600 North Wolfe St, Blalock 618, Baltimore, MD 21287. (Email: ashah29{at}csurg.jhmi.jhu.ed).

	Abstract

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OBJECTIVE: Lung transplantation has been increasingly applied to patients over the age of 60 years. Importantly, the procedure of choice, single versus bilateral lung transplantation, remains unclear. Therefore, the purpose of this study was to examine short- and midterm outcomes in this age group with particular attention to procedure type.

METHODS: All first lung transplant recipients, 60 years of age or older, reported to the United Network for Organ Sharing from 1998 to 2004 were divided into two groups: bilateral and single lung transplantation. A retrospective review of pertinent baseline characteristics, clinical parameters, and outcomes was performed. Kaplan–Meier methodology was used to estimate and Cox proportional hazards regression modeling was used to compare posttransplant survival between these groups. Additionally, propensity scores analysis was performed.

RESULTS: During the study period, 1656 lung transplant recipients were 60 years of age or older (mean 62.7 ± 2.4 years, median 62 years). Of these, 364 (28%) had bilateral and 1292 (78%) had single lung transplantation. Survival was not statistically different between the two groups. In the multivariate analysis, bilateral versus single lung transplantation was not a predictor of mortality. Idiopathic pulmonary fibrosis and a donor tobacco history of more than 20 pack-years were significantly associated with mortality (P = .003, CI 1.12–1.76; and P = .006, CI 1.09–1.63; respectively).

CONCLUSIONS: The survival of lung transplant recipients 60 years of age or older who underwent bilateral versus single lung transplantation is comparable. These data suggest that type of procedure is not a predictor of mortality in this age group. Idiopathic pulmonary fibrosis and donor cigarette use of more than 20 pack-years were independently associated with mortality.

	Introduction

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Drs. Simpkins, Conte, Shah, Borja, and Nwakanma (left to right)

Results of clinical lung transplantation (LTx) over the past two decades have progressively improved. Nonetheless, LTx is limited by the availability of donor organs, and a careful selection of LTx recipients is critically important. The International Society for Heart and Lung Transplantation (ISHLT) guidelines for selection of appropriate candidates for LTx have suggested an age limit of 60 years for bilateral (BLT) and 65 years for single (SLT) lung transplantation.¹ The age limitation was based on previous reports showing that older patients have significantly higher mortality than younger patients.² However, the age distinction for BLT versus SLT has not been clearly supported by the literature. The few reports that address this issue have been limited to disease-specific database analyses^3,4 and a single-center report with a small number of patients.⁵

As the number of older patients listed for LTx increases, the procedure of choice (BLT vs SLT) for these patients requires further scrutiny. We therefore analyzed the impact of procedure type on short- and midterm survival in recipients 60 years of age or older for all disease types, using data reported to the United Network for Organ Sharing (UNOS) registry in the recent era, between 1998 and 2004.

	Materials and Methods

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Patient Population
Data reported to the UNOS registry for LTx performed between January 1, 1998 and December 31, 2004 were analyzed. The follow-up period was up to September 2005, which is when the files were created. This time period was chosen to represent a modern cohort of patients in light of advancements made in LTx. Among the 6785 first-time LTx recipients, we identified 1656 patients 60 years of age or older, and these were stratified by type of transplant procedure: BLT (n = 364) and SLT (n = 1292). The patient characteristics are shown in Table 1.

	Results

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Patient Characteristics
Of the 1656 first LTx recipients, 364 patients received BLT and 1292 had SLT. Their ages ranged from 60 to 87 years old (mean 62.7 ± 2.4 years, median 62 years). The age distribution is shown in Figure 1. Eighty-eight percent of the patients were between 60 and 65 years old. Interestingly, there were 196 patients (12%) above the age of 65 years. Furthermore, from 1998 to 2004, there was an increase from 19% to 27% in the number of first LTx recipients 60 years of age and older. Likewise, the number of BLTs performed among these patients increased from 14% in 1998 to 34% in 2004 (Figure 2). Table 1 compares the details of patient preoperative clinical characteristics between the two groups. Patients who received BLT versus SLT were statistically younger (62.3 ± 2.1 years vs 62.8 ± 2.5 years; P = .002. There were fewer female patients in the BLT group (37% vs 43%; P = .04), lower body mass index (24.1 ± 3.9 vs 25.2 ± 6.2; P = .001), higher percent predicted FVC (55.5% ± 17.9% vs 53.1% ± 16.3%; P = .025), and mean pulmonary artery pressure (26.2 ± 8.1 mm Hg vs 24.7 ± 8.5 mm Hg; P = .01). Graft ischemia time, recorded as the time from recovery to implantation of the second lung in BLT, was longer in the BLT group (5.3 ± 1.6 hours vs 3.8 ± 1.3 hours; P < .001). Furthermore, the BLT group had shorter mean follow-up time than the SLT group (21 ± 19 months vs 26 ± 21 months; P = .001).

View larger version (18K): [in this window] [in a new window]   Figure 1. Age distribution.

View larger version (18K): [in this window] [in a new window]   Figure 2. Distribution of type of procedure. BLT, Bilateral lung transplantation; SLT, single lung transplantation.

View larger version (20K): [in this window] [in a new window]   Figure 3. Kaplan–Meier estimates of survival for all patients, stratified by type of procedure. BLT, Bilateral lung transplantation; SLT, single lung transplantation.

View larger version (16K): [in this window] [in a new window]   Figure 4. Kaplan–Meier estimates of survival for patients with chronic obstructive pulmonary disease, stratified by type of procedure. BLT, Bilateral lung transplantation; SLT, single lung transplantation.

View larger version (17K): [in this window] [in a new window]   Figure 5. Kaplan–Meier estimates of survival for patients with idiopathic pulmonary fibrosis, stratified by type of procedure. BLT, Bilateral lung transplantation; SLT, single lung transplantation.

Furthermore, propensity scores analysis by the regression adjustment technique was performed, whereby both the propensity scores and type of procedure, as well as other potential risk factors, were included as predictors of outcome. BLT versus SLT still did not emerge as predictors of mortality, whereas donor cigarette use for more than 20 pack-years and IPF remained independent predictors.

	Discussion

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This study of a large cohort of elderly patients (60 years of age and older) who received LTx from 1998 to 2004 did not show significant differences in short- and midterm survival between BLT and SLT. In addition, IPF and heavy donor tobacco use were independently associated with mortality. Moreover, operative mortality was less than 10%, which is better than previous reports.

Steady improvements in the management of LTx patients have led to better outcomes. This has emboldened programs to offer LTx to older patients. The ISHLT/UNOS registry has shown a steady increase in the proportion of LTx recipients 60 years of age and older.⁶ This raises the important and persistently controversial question of which procedure type (BLT vs SLT) is optimal in patients over the age of 60. Meyer and associates³ analyzed the ISHLT/UNOS registry for all recipients who received LTx for COPD between 1991 and 1997. They concluded that SLT offered acceptable early survival, but long-term survival data favored BLT except in patients over the age of 60. Likewise, a single-center study of 126 LTx recipients from 1991 to 1996 demonstrated survival advantages of BLT over SLT in patients with COPD, but increased morbidity in BLT patients over the age of 55 years. The authors therefore discouraged the use of BLT in patients above this age.⁷ A more recent analysis of 1994-2000 UNOS data for patients with IPF found no difference in survival between SLT and BLT in the subanalysis of patients 60 to 69 years of age.⁴

Nonetheless, we hypothesized that modern improvements in LTx have led to better outcomes in elderly patients. Our analysis of first LTx recipients 60 years of age or older reported to UNOS from 1998 to 2004 showed that procedure type was not a predictor of mortality by unadjusted or adjusted analysis. In contrast to older studies, survival was markedly better in this study. According to the report by Meyer and colleagues,³ patients older than 60 years with COPD who received LTx between 1991 and 1997 had 30-day and 1-year survivals of 93.5% and 72.9%, respectively, for SLT versus 77.8% and 66%, respectively, for BLT. In our study, 30-day survival was about 95% for both the BLT and SLT groups and 1-year survival was 77.2% for SLT and 78% for BLT for the entire cohort. Furthermore, when only patients with COPD are analyzed, the 30-day and 1-year survivals are 95.8% and 81.5% respectively, for SLT and 95% and 81.2%, respectively, for BLT. This suggests that concerns over increased perioperative mortality for BLT owing to a more complex operation are unfounded in the recent cohort. The favorable survival trend observed by 5 years with BLT did not achieve statistical significance in our study. However, since we chose a recent time period, the number of patients who could be analyzed at 5 years was small. The 5-year survival of 45% for BLT and 39% for SLT for this cohort of elderly patients is lower than the 49% overall 5-year survival for LTx reported by the 2005 ISHLT registry.⁶

The multivariate analysis identified IPF and donor cigarette use of more than 20 pack-years as independent predictors of mortality. Donor tobacco use has been previously reported in the ISHLT data set as a risk factor for long-term mortality, but it is interesting that IPF remains a risk in the elderly cohort. Although this study does not allow further exploration of this phenomenon, it suggests that one should exercise caution when using a donor with more than 20 pack-years of cigarette use in elderly patients with IPF.

The decision to perform BLT or SLT in elderly patients is somewhat entrenched in institutions. Although, guidelines exist with age cutoffs (BLT in patients > 60 and SLT in patients > 65), several centers perform BLT in all patients preferentially. Overall, proponents of SLT in LTx have argued that SLT is an easier procedure to perform, has less morbidity and mortality associated with it than BLT, and results in less ischemic time; therefore, an SLT has better early graft function, has improved early survival, and will allow more patients to receive LTx. Proponents of BLT have argued that BLTs result in fewer ventilation/perfusion mismatches, are easier to care for in the perioperative period, will provide better overall lung function, are protective against the physiologic manifestations of obliterative bronchiolitis, and offer a better long-term survival.⁸ Furthermore, although BLT does entail longer donor ischemic times for the second lung implanted, this has not translated into measurable adverse sequelae.^9,10

Both procedures have been accepted by practitioners and likely will be acceptable for the foreseeable future, and the percentage of BLTs performed in elderly patients has been increasing. Our current report refutes the concerns about higher perioperative mortality for BLT in this patient population, and although a statistical survival advantage was not demonstrated, other single-center reports suggest that BLT is overall associated with better long-term survival and freedom from bronchiolitis obliterans.¹¹ Our findings also agree with a recently published report of 107 consecutive LTx recipients 61 years of age and older that demonstrated comparable short- and midterm outcomes achieved with BLT and SLT.¹² In their study, Palmer and associates¹² also reported 1-, 2-, and 5-year survival estimates of 82%, 75%, and 68%, respectively, for BLT and 78%, 70%, and 44%, respectively, for SLT. The survival advantage of BLT also did not achieve statistical significance. Even if use of BLT for the elderly population has a positive impact on patient survival, concerns remain about whether this strategy may decrease the availability of donor organs.

Our institution prefers the use of BLT for all patients because we believe that there are short- and long-term advantages. However, owing to the limited number of organs available, we recognize that SLT is a reasonable option for older patients with COPD and IPF as compared with the alternative, which is death. In general, it appears that BLT has already been empirically accepted by many in the transplant community inasmuch as the percentage of patients over 60 receiving BLT continuously increased between 1998 and 2004. Ultimately, more studies and the analysis of long-term results from this database will be necessary to determine an advantage of one procedure type over another.

The current study has the inherent limitations of the review of a multi-institutional voluntary registry. Analysis of survival data may be compromised by lack of uniformity of reporting and nonstandardized organ preservation and surgical techniques, as well as postoperative and immunosuppressive management. Only first LTx recipients were included to help achieve a more uniform cohort of patients. The 1998 to 2004 era was also selected to reflect the advancements that have recently evolved in LTx. There may have been selection bias in favor of BLT because our data did show that the BLT patients were statistically younger. The clinical significance of 6 months’ difference is, however, questionable. This difference is most likely a reflection of the tendency to perform transplantation in patients who are relatively younger and to use BLT. However, age is one of the clinical cofounders that was controlled for in the Cox proportional hazards model. There were fewer female recipients, lower body mass index, and higher percent predicted FVC in the BLT group, although these patients also had higher mean pulmonary artery pressure. On the other hand, the differences in these parameters between the two groups do not appear to have significant clinical implications. When these parameters are controlled for in a multivariate model as well as propensity scores analysis, the same results were obtained. Evaluation of other secondary end points such as bronchiolitis obliterans may also provide important insights into the advantage of one procedure over another.

	Conclusions

Top Abstract Introduction Materials and Methods Results Discussion Conclusions References

 
Our analysis of the UNOS database from a recent era showed comparable short- and midterm survival for BLT versus SLT in patients 60 years of age or older. These data suggest that recipients older than 60 years should not be excluded from the use of BLT based on concerns of higher early mortality. Long-term outcomes will better define any survival advantage of BLT over SLT, and future studies will help to determine the best use of BLT versus SLT in the older population.

	Footnotes

 
The content is the responsibility of the authors alone and does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government.

This work was supported in part by Health Resources and Services Administration contract 231-00-0115.

¹ Dr Nwakanma is a Hugh R. Sharp Cardiac Surgery Research Fellow.

² Dr Williams is an Irene Piccinini Investigator in Cardiac Surgery.

	References

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