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J Thorac Cardiovasc Surg 2008;135:166-171
© 2008 The American Association for Thoracic Surgery

Cardiothoracic Transplantation

The impact of the lung allocation score on short-term transplantation outcomes: A multicenter study

^a Department of Surgery, University of Virginia Health System, Charlottesville, Va
^b Department of Surgery, Washington University School of Medicine, St Louis, Mo
^c Department of Cardiothoracic Surgery, University of Southern California, Los Angeles, Calif
^d Department of Surgery, University of Wisconsin, Madison, Wis
^e Department of Surgery, Mayo Clinic, Rochester, Minn
^f Department of Public Health Sciences, University of Virginia Health System, Charlottesville, Va

Read at the Eighty-seventh Annual Meeting of The American Association for Thoracic Surgery, Washington, DC, May 5–9, 2007.

Received for publication May 3, 2007; revisions received August 13, 2007; accepted for publication August 15, 2007.

^_* Address for reprints: Benjamin D. Kozower, MD, University of Virginia Health System, General Thoracic Surgery, PO Box 800679, Charlottesville, VA 22908-0679. (Email: bdk8g{at}virginia.edu).

	Abstract

Top Abstract Introduction Patients and Methods Results Conclusions Limitations of the Study References

 
Objective: The lung allocation score restructured the distribution of scarce donor lungs for transplantation. The algorithm ranks waiting list patients according to medical urgency and expected benefit after transplantation. The purpose of this study was to evaluate the impact of the lung allocation score on short-term outcomes after lung transplantation.

Methods: A multicenter retrospective cohort study was performed with data from 5 academic medical centers. Results of patients undergoing transplantation on the basis of the lung allocation score (May 4, 2005 to May 3, 2006) were compared with those of patients receiving transplants the preceding year before the lung allocation score was implemented (May 4, 2004, to May 3, 2005).

Results: The study reports on 341 patients (170 before the lung allocation score and 171 after). Waiting time decreased from 680.9 ± 528.3 days to 445.6 ± 516.9 days (P < .001). Recipient diagnoses changed with an increase in idiopathic pulmonary fibrosis and a decrease in emphysema and cystic fibrosis (P = .002). Postoperatively, primary graft dysfunction increased from 14.1% (24/170) to 22.9% (39/171) (P = .04) and intensive care unit length of stay increased from 5.7 ± 6.7 days to 7.8 ± 9.6 days (P = .04). Hospital mortality and 1-year survival were the same between groups (5.3% vs 5.3% and 90% vs 89%, respectively; P > .6)

Conclusions: This multicenter retrospective review of short-term outcomes supports the fact that the lung allocation score is achieving its objectives. The lung allocation score reduced waiting time and altered the distribution of lung diseases for which transplantation was done on the basis of medical necessity. After transplantation, recipients have significantly higher rates of primary graft dysfunction and intensive care unit lengths of stay. However, hospital mortality and 1-year survival have not been adversely affected.

	Introduction

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Dr Kozower

The lung allocation score (LAS) was implemented in May 2005 by the Organ Procurement and Transplantation Network (OPTN).¹ The LAS dramatically changed lung allocation from a system based purely on waiting time to an algorithm based on survival probability on the waiting list and after transplantation. The impetus for change was the scarcity of suitable donor lungs and the increasing number of deaths for patients on the waiting list.^2-4

The OPTN began allocating lungs in 1990 on the basis of blood type and the amount of time candidates had spent on the waiting list.⁵ In 1995, a minor change was made to this system when 90 days of waiting time were added for patients with idiopathic pulmonary fibrosis to offset the increased risk of mortality on the waiting list. In 1998, the Department of Health and Human Services published the Final Rule.⁶ This required the OPTN to emphasize the broader sharing of organs, reduce the use of waiting time as an allocation criterion, and create an allocation system based on objective medical criteria and measures of medical urgency.

The LAS was developed by multivariate modeling and was approved by the OPTN in 2004. The three main objectives were as follows: (1) reduce the number of deaths on the lung transplant waiting list, (2) increase transplant benefit for lung recipients, and (3) ensure the efficient and equitable allocation of lungs to active transplant candidates.⁷ The LAS assigns a score to all candidates over the age of 12 years ranging from 0 to 100. It is a weighted combination of predicted risk of death during the following year on the waiting list and the predicted likelihood of survival during the first year after transplantation.

The purpose of this study was to evaluate the impact of the LAS system on the waiting list and short-term outcomes after lung transplantation. Many lung transplant surgeons have the impression that the LAS has increased the complexity of the cases and their complication rates. Our hypothesis was that the LAS would decrease waiting time for recipients but would also increase morbidity and mortality after transplantation.

	Patients and Methods

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Transplant Recipients
A multicenter retrospective cohort study was performed with data from five academic medical centers: University of Virginia, Washington University, University of Southern California, University of Wisconsin, and the Mayo Clinic. The two cohorts were patients undergoing transplantation the year preceding the introduction of the LAS (May 4, 2004, to May 3, 2005) (pre-LAS group) and patients undergoing transplantation the year after the LAS was implemented (May 4, 2005, to May 3, 2006) (LAS group). In an effort to compare the severity of illness between the groups, the LAS was calculated for the pre-LAS group using the appropriate variables available close to the time of transplant. Primary graft dysfunction was defined according to the International Society of Heart and Lung Transplantation definition: arterial oxygen tension/inspired oxygen fraction less than 300 and a chest radiograph with a characteristic diffuse bilateral infiltrate.⁸ The human studies committees at each institution granted approval for this research.

Waiting List Estimates
Data from the waiting lists at the five institutions were gathered for the same two groups. To calculate the percentage of patients dying on the waiting list, we estimated the size of the waiting list for both groups. Because the waiting lists are dynamic, this is not a straightforward process. We identified the actual number of patients on the waiting lists at 4 interval time points for both cohorts (May 15, August 15, November 15, and February 15). These numbers were averaged (total number divided by 4) to estimate the size (denominator) of the waiting list. The numerator was the actual number of patients who died on the waiting lists.

Statistical Analysis
Categorical variables were compared by the ² test. Continuous variables were compared with the Student t test or Kruskal–Wallis test where appropriate. Estimates of the cumulative death rate at 1 year were calculated by the Kaplan–Meier method, and the survival differences between the pre-LAS and LAS groups were assessed by the log–rank test. Short-term results were controlled for diagnosis by the Mantel–Haenszel test. All data analysis was performed with SAS 9.1.3 software (SAS Institute, Inc, Cary, NC).

	Results

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Patient Characteristics
There were 170 patients in the pre-LAS group and 171 in the LAS group. The numbers of patients per group from each institution were as follows: Washington University 59 and 52, University of Southern California 37 and 38, University of Virginia 31 and 35, University of Wisconsin 34 and 33, and Mayo Clinic 9 and 13. The baseline characteristics are listed in Table 1. The pre-LAS group had fewer retransplants and a lower calculated LAS (P < .05). The recipient diagnoses changed significantly with the initiation of the LAS (Table 2). There were an increase in the number of patients with idiopathic pulmonary fibrosis and a decrease in patients with chronic obstructive pulmonary disease and cystic fibrosis (P = .002).

Surgical Morbidity
Surgical morbidity is illustrated in Table 3. Primary graft dysfunction was higher in the LAS group (P < .04). The total number of days mechanically ventilated and lengths of stay in the intensive care unit (ICU) were also higher in the LAS group (3.3 ± 5.1 days vs 6.8 ± 14.4 days; P = .004; and 5.7 ± 6.7 days vs 7.8 ± 9.3 days; P = .02, respectively). However, the total number of hospital days was similar between the two groups (22.8 ± 34.0 days vs 22.2 ± 22.5 days; P = .86).

When the groups were adjusted for diagnosis, primary graft dysfunction and days mechanically ventilated were no longer associated with group (P > .2). When the rates of primary graft dysfunction for patients with pulmonary fibrosis were examined, there was no significant difference between the groups (32% [8/25] vs 22% [9/41]; P = .4). However, ICU length of stay continued to be associated with group (P = .04).

Mortality
Perioperative mortality was defined as a death within 30 days of transplantation or during the same hospitalization. Perioperative mortality was not different between the two groups (5.3% [9/170] vs 5.3% [9/171]; P = .99). The Kaplan–Meier 1-year survival was also similar between the two groups (86.4% vs 89.9%; P = .6).

	Conclusions

Top Abstract Introduction Patients and Methods Results Conclusions Limitations of the Study References

 
The LAS significantly changed the allocation process for donor lungs in the United States. It was initiated because the previous system, based on waiting time, failed to accommodate patients with a rapidly deteriorating course who could not tolerate the prolonged waiting times and who were more likely to die on the waiting list.^2,9,10 The LAS algorithm attempts to balance waiting list urgency with posttransplant survival. Because these vary among patients with different lung diseases, diagnosis is included as a variable in the LAS calculation. This report demonstrates a marked shift in the lung diseases being treated by transplantation with an increase in idiopathic pulmonary fibrosis and a decrease in cystic fibrosis and emphysema. These changes are consistent with the goals of the LAS inasmuch as patients with idiopathic pulmonary fibrosis had a higher mortality on the waiting list under the previous allocation system.^4,10 However, this contradicts an earlier report by Lingaraju and colleagues,¹¹ which simulated the effects of the LAS on the lung diseases being treated by transplantation. Their simulation showed that patients with pulmonary fibrosis had improved rankings and patients with emphysema had worse rankings but the number of transplants for each disease category did not change significantly.

Importantly, our results demonstrate that the LAS reduced the waiting time for transplantation by 35% (P < .001). It will be very interesting to see whether this is sustainable as data from the LAS system mature. One could hypothesize that if the number of donor lungs remains fixed, sicker patients will populate the waiting list and waiting times may begin to increase over time. Our data would not reflect this inasmuch as there was a significant increase in the number of patients with pulmonary fibrosis receiving transplants during the first year of the LAS system.

Our estimation of the percent of patients dying on the waiting list showed that the LAS group may have fewer deaths (15.3% [74/485] pre-LAS group vs 11.3% [51/450] LAS group; P = .08). The true number is dynamic and very difficult to identify precisely. If one looks only at the number of deaths on the waiting list, it is not easy to compare groups because the denominator, the total number of patients on the waiting list, is unknown. However, the absolute number of patients dying on the waiting list did decrease from 74 to 51, a 30% decrease.

In addition, there are patients listed now who would never have been listed before because they had little chance of surviving on the waiting list in the old system. These "sick" patients might die on the waiting list in the new LAS system, but they would never have been listed in the old system. In this way, the LAS system might inflate death rates. On the other hand, the old system denominator was inflated with relatively healthier patients with emphysema who had little chance of undergoing transplantation in the current LAS system. It is quite likely that these patients are not even listed now because they would have a low LAS and placing them on the list to accrue time is no longer advantageous. Thus, the change in systems not only changes who dies on the waiting list, but it also changes who is listed in the first place, thus making a difference in mortality very difficult to interpret.

The pre-LAS and LAS groups were comparable with respect to age, gender, procedure performed, and ischemic time (Table 1). However, the score of the LAS group had more retransplants and a higher LAS than had the calculated score for the pre-LAS group. This is an expected difference because the donor lungs in the LAS group were allocated to patients with higher LASs. The International Society of Heart and Lung Transplantation, along with other reported series, have identified retransplantation as a significant risk factor for primary graft dysfunction.^12,13 In addition, diagnoses of pulmonary fibrosis and pulmonary hypertension are established risk factors for the development of primary graft dysfunction. Our data demonstrate that as the number of transplants for pulmonary fibrosis increased, so did the rates of primary graft dysfunction. However, when we controlled for diagnoses, the rates of primary graft dysfunction were no longer different between the groups. Therefore, much of the increased morbidity seen in the LAS group is due to the shift in lung diseases being treated by transplantation.

The increase in primary graft dysfunction with the LAS group explains the doubling of the length of mechanical ventilation and the increase in ICU length of stay. Interestingly, although primary graft dysfunction is the most important predictor of postoperative mortality and was present in almost 25% of the LAS group, there was no difference in mortality between the cohorts in the study.¹⁴ In fact, the mortality for both groups was only 5.3% (P = .99). It is also important to note that there was no significant relationship between elevated pulmonary artery pressure and primary graft dysfunction in this study.

	Limitations of the Study

Top Abstract Introduction Patients and Methods Results Conclusions Limitations of the Study References

 
Limitations of this study are that it is a retrospective review with a short follow-up. The real impact of the LAS will not be realized for several years. It is important to understand that the LAS system is dynamic. It was designed to update the models every 6 months to include the most recent data with at least 3 years of follow-up.⁵

In conclusion, this multicenter retrospective study of short-term outcomes supports that the LAS is achieving its objectives. The LAS has reduced waiting time and altered the lung diseases being treated by transplantation. Although transplant recipients have higher rates of primary graft dysfunction and longer stays in the ICU, the overall hospital stay and mortality are not affected. However, we do not know whether the LAS will reduce mortality on the waiting list and what the long-term effects of these changes will be. We do know that if the LAS system increases the rates of primary graft dysfunction and the length of ICU stay, it will increase the medical and financial resources required to care for these patients. Finally, despite increased morbidity, the 1-year survival approached 90% in the LAS group. This is an excellent early result for a sick group of patients, but longer follow-up is needed to draw definitive conclusions about the success of the LAS system and to modify the algorithm with more comprehensive data.

	References

Top Abstract Introduction Patients and Methods Results Conclusions Limitations of the Study References

 

1. Levine GN, McCullough KP, Rodgers AM, Dickinson DM, Ashby VB, Schaubel DE. Analytical methods and database design: implications for transplant researchers, 2005. Am J Transplant 2006;6:1228-1242.[Medline]
   
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3. De Meester J, Smits JM, Persijn GG, Haverich A. Listing for lung transplantation: life expectancy and transplant effect, stratified by type of end-stage lung disease, the Eurotransplant experience. J Heart Lung Transplant 2001;20:518-524.[Medline]
   
4. Travaline JM, Cordova FC, Furukawa S, Criner GJ. Discrepancy between severity of lung impairment and seniority on the lung transplantation list. Transplant Proc 2004;36:3156-3160.[Medline]
   
5. Egan TM, Murray S, Bustami RT, Shearon TH, McCullough KP, Edwards LB, et al. Development of the new lung allocation system in the United States. Am J Transplant 2006;6:1212-1227.[Medline]
   
6. Department of Health and Human Services Organ procurement and transplantation network, HHS: final rule; 42 CFR-part 121. Fed Regist 1999:56650-56661.
   
7. D’Alonzo GE, Barst RJ, Ayres SM, Bergofsky EH, Brundage BH, Detre KM, et al. Survival in patients with primary pulmonary hypertension. results from a national prospective registry. Ann Intern Med 1991;115:343-349.[Abstract/Free Full Text]
   
8. Christie JD, Carby M, Bag R, Corris P, Hertz M, Weill D, ISHLT Working Group on Primary Lung Graft Dysfunction Report of the ISHLT Working Group on Primary Lung Graft Dysfunction part II: Definition. A consensus statement of the International Society for Heart and Lung Transplantation. J Heart Lung Transplant 2005;24:1454-1459.[Medline]
   
9. De Meester J, Smits JM, Persijn GG, Haverich A. Lung transplant waiting list: differential outcome of type of end-stage lung disease, one year after registration. J Heart Lung Transplant 1999;18:563-571.[Medline]
   
10. Pierson RN, Milstone AP, Loyd JE, Lewis BH, Pinson CW, Ely EW. Lung allocation in the United States, 1995-1997: an analysis of equity and utility. J Heart Lung Transplant 2000;19:846-851.[Medline]
    
11. Lingaraju R, Blumenthal NP, Kotloff RM, Christie J, Ahya VN, Sager JS, et al. Effects of lung allocation score on waiting list rankings and transplant procedures. J Heart Lung Transplant 2006;25:1167-1170.[Medline]
    
12. Kozower BD, Sweet SC, de la Morena M, Schuler P, Guthrie TJ, Patterson GA, et al. Living donor lobar grafts improve pediatric lung retransplantation survival. J Thorac Cardiovasc Surg 2006;131:1142-1147.[Abstract/Free Full Text]
    
13. Barr ML, Kawut SM, Whelan TP, Girgis R, Böttcher H, Sonett J, et al. Report of the ISHLT Working Group on Primary Lung Graft Dysfunction part IV: recipient-related risk factors and markers. J Heart Lung Transplant 2005;24:1468-1482.[Medline]
    
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This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Benjamin D. Kozower Bryan F. Meyers Michael A. Smith Nilto C. De Oliveira Stephen D. Cassivi Tracey J. Guthrie Thomas M. Daniel David R. Jones Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kozower, B. D. Articles by Jones, D. R. Search for Related Content PubMed Articles by Kozower, B. D. Articles by Jones, D. R. Related Collections Related Article