- Email: [email protected]
The Fate of Patients on the Waiting List for Lung Transplantation in Korea
The Fate of Patients on the Waiting List for Lung Transplantation in Korea H.C. Paik, S.J. Haam, D.Y. Lee, G.J. Yi, S.W. Song, Y.T. Kim, C.H. Kang, K.M. Kim, S.I. Park, and S.H. Jheon ABSTRACT Lung transplantation for end-stage lung disease results in prolonged actuarial survival and improved pulmonary function. However, the shortage of donor lungs has been a major limiting factor in transplantation. The purpose of this study was to analyze the waiting time and mortality rate for each disease entity. The medical records of all patients listed in The Korean Network for Organ Sharing (KONOS) from May 1996 to May 2011 were analyzed to identify waiting times and causes of death. During the study period, 146 patients (86 males and 60 females) of mean age of 46.6 years (range; 5 to 73 years) showed idiopathic pulmonary fibrosis (IPF; n ⫽ 61), chronic obstructive pulmonary disease (COPD; n ⫽ 19) or bronchiectasis (n ⫽ 15). Sixty-five patients (44.5%) underwent lung or heart-lung transplantation. Sixty-two patients (42.5%) expired during the waiting period, and 19 patients are still on the waiting list. The mortality rate while waiting was highest among patients with primary pulmonary hypertension (62.5%) followed by IPF (57.4%), and acute respiratory distress syndrome (ARDS) (55.6%). The mean time from diagnosis to registration in KONOS was 15.5 months among the expired and 13.2 months in the transplanted group (P ⫽ .455). The mean time on waiting list was 8.2 months in the expired group and 3.7 months in the transplanted group (P ⫽ .012). In the expired group, the mean survival time was significantly shorter among patients with ARDS (2.2 months, P ⫽ .004) compared to IPF (7.9 months), COPD (10.7 months), and primary pulmonary hypertension (PPH) (30.0 months). The high mortality rate (42.5%) during the waiting period in Korea may result from the lack of donors and the delay in registration. UNG transplantation (LTx) is a life-saving treatment for patients with end-stage lung disease. However, donor organ availability is a serious problem because only 15% to 20% of multiorgan donors are considered to be suitable for LTx.1 Approximately 3000 LTx per year have been performed worldwide2 since the first successful procedure in 1983.3 The LTx program in Korea started in July 1996.4 Until May 2011, five institutions have performed
LTx. The purpose of this study was to review the characteristics waiting times, and mortality rates for each disease entity among patients awaiting LTx.
From the Department of Thoracic and Cardiovascular Surgery (H.C.P., S.J.H., D.Y.L., G.J.Y., S.W.S.), Gangnam Severance Hospital, Seoul, Korea; Department of Thoracic and Cardiovascular Surgery (Y.T.K., C.H.K.), Seoul National University Hospital, Seoul National University School of Medicine, Seoul, Korea; Department of Thoracic and Cardiovascular Surgery (K.M.K.), Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea; Department of Thoracic and Cardiovascular Surgery (S.I.P.), Asan Medical Center, University of Ulsan
College of Medicine, Seoul, Korea; and the Department of Thoracic and Cardiovascular Surgery (S.H.J.), Seoul National University Bundang Hospital, Seoul National University College of Medicine, Gyeonggi, Korea. Address reprint requests to Hyo Chae Paik, Department of Thoracic and Cardiovascular Surgery, Gangnam Severance Hospital, 211, Eonju-Ro, Gangnam-Gu, Seoul, Korea. E-mail: [email protected]
L
© 2012 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710 Transplantation Proceedings, 44, 865– 869 (2012)
METHODS We retrospectively reviewed the medical records of all patients awaiting LTx in five institutions and listed in The Korean Network for Organ Sharing (KONOS) from May 1996 to May 2011. The five institutions
0041-1345/–see front matter doi:10.1016/j.transproceed.2011.12.059 865
866 consisted of Gangnam Severance Hospital, Yonsei University, Seoul National University Hospital, Seoul National University Bundang Hospital, Samsung Medical Center, and Asan Medical Center. The data consisting of patient age, sex, disease entity, blood type, duration from the diagnosis to enlisting for LTx, and the duration on the waiting list until death or LTx were analyzed to identify waiting times and mortality rates for each disease entity.
RESULTS
During the study period, 146 patients (86 males, 60 females) were registered for lung transplantation; their mean age was 46.6 ⫾ 14.1 years (range; 5 to 73 years; Fig 1). The most common disease was idiopathic pulmonary fibrosis (IPF; n ⫽ 61s, 41.8%) followed by chronic obstructive pulmonary disease (COPD; n ⫽ 19s), bronchiectasis (n ⫽ 15s), and lymphangioleiomyomatosis (LAM; n ⫽ 12; Table 1). Sixtyfive patients (44.5%) underwent lung transplantation with 2 retransplantations and 5 heart-lung transplantations. Sixtytwo patients (42.5%) expired during the waiting period; 19 patients are still on the waiting list (Fig 2). There were no significant differences in mean age (P ⫽ .575), gender (P ⫽ .227), or blood type (p ⫽ .899) between the transplanted and the mortality group (Table 2). The mortality rate while awaiting a donor lung was highest among patients with primary pulmonary hypertension (62.5%) followed by IPF (57.4%), and acute respiratory distress syndrome (ARDS; 55.6%). The mean time from the diagnosis to registration in KONOS was 15.5 ⫾ 29.3 months in the mortality versus 13.2 ⫾ 27.4 months in the transplanted group (P ⫽ .455). The mean time on the waiting list was 8.2 ⫾ 15.3 months in mortality versus 3.7 ⫾ 5.4 months in the transplanted group (P ⫽ .012). In the mortality group, mean survival time was significantly shorter among patients with ARDS (2.2 ⫾ 3.2 months, P ⫽ .004) versus IPF (7.9 ⫾ 15.5 months), COPD (10.7 ⫾ 14.1 months), or primary pulmonary hypertension (PPH) (30.0 ⫾ 31.9 months). DISCUSSION
LTx is the only definitive therapy for patients with end-stage lung disease that progresses despite maximal medical treatment. Although the demand for donor lungs has increased
Fig 1. Sex and age distribution of the 146 patients registered for lung transplantation.
PAIK, HAAM, LEE ET AL Table 1. Disease Entities on the Waiting List Disease Entities
Idiopathic pulmonary fibrosis Chronic obstructive pulmonary disease Bronchiectasis Lymphangioleiomyomatosis Acute respiratory distress syndrome Primary pulmonary hypertension Eisenmenger syndrome Cancer (BAC 2, angiosarcoma 1) Cystic fibrosis Eosinophillic granulomatosis Systemic sclerosis Congenital heart disease Bonchiolitis obliterans syndrome after LTx Bronchopulmonary dysplasia Graft vs Host Disease after BMT Secondary pulmonary hypertension
No. of Patients
%
Mortality (%)
61 19
41.8 13.0
35 (57.4) 4 (21.1)
15 12 9 8 7 3 2 2 2 2 1
10.3 8.2 6.2 5.5 4.8 2.1 1.4 1.4 1.4 1.4 0.7
4 (26.7) 2 (16.7) 5 (55.6) 5 (62.5) 2 (28.6) 1 (33.3) 2 (100) 1 (50) 0 1 (50) 0
1 1 1
0.7 0.7 0.7
0 0 0
Abbreviations: BAC, bronchioloalveolar cell carcinoma; LTx, lung transplantation; BMT, bone marrow transplantation.
tremendously in recent years, the number of donors has remained constant, resulting in an increased mortality rate among potential recipients during the waiting period. A few options may help to decrease the mortality rate during the waiting period. One is to increase organ donation by educating the general public via the mass media. Another way is to fully use the potential donor lungs by proper management from the time of hospital admission to the diagnosis of brain death. Optimal management of a potential candidate for multiorgan donation by preventing organ damage during the final period of brain death will decrease the waiting time and associated mortality rate. For example, a simple lung recruitment protocol involving a brief period of controlled sustained lung inflation increased the lung utilization rate from 20% to 33%.5 Because this paper describes the accrual of data from the beginning of LTx in Korea, late referral may be due to a
WAITING FOR LUNG TRANSPLANT IN KOREA
867
Fig 2. Fate of patients on waiting list for lung transplantation.
pessimistic attitude of patients and physicians regarding its outcomes; the perioperative mortality rate was high in the initial era of the LTx programs. The mean time from diagnosis to registration in the KONOS was 15.5 ⫾ 29.3 months among the mortality and 13.2 ⫾ 27.4 months among the transplanted group (P ⫽ .455). The mean waiting list time after the registration in KONOS was 8.2 ⫾ 15.3 months in the mortality group versus 3.7 ⫾ 5.4 months in the transplanted group (P ⫽ .012). The overall waiting period from the diagnosis to mortality during the waiting period was nearly 2 years, implying delayed referral for LTx evaluation. This has changed lately; LTx programs have been active over the last 2 years, resulting in far better surgical outcomes. Once the final decision to undergo LTx has been made, medical personnel and the family member should encourTable 2. Variables in Lung Transplantation and Mortality Group
Gender Male Female Mean Age (years) Blood type A B AB O Disease IPF COPD Bronchiectasis LAM ARDS
Transplanted (n ⫽ 65)
Mortality (n ⫽ 62)
34 31 46.4 ⫾ 11.4
39 23 47.7 ⫾ 15.5
21 13 9 22
21 14 6 21
23 9 6 10 3
35 4 4 2 5
P Value
.227
.575 .899
.158
Abbreviations: IPF, idiopathic pulmonary fibrosis; COPD, chronic obstructive pulmonary disease; LAM, lymphangioleiomyomatosi; ARDS, acute respiratory distress syndrome.
age the patient to accept the LTx as a challenge, and to prepare in every way possible to make themselves optimally fit for the operation. During this period, the coordinator needs to keep in close contact with the patient and the family members, fully discussing the patient’s physical and emotional conditions, and avoiding false expectations regarding transplantation. Respiratory infections are one main reason for admissions during the waiting period, therefore, patients on the waiting list need to be managed using a multidisciplinary team approach. Aggressive management strategies to deal with recipients have occurred in recent years, decreasing waiting list mortality.6 Improvements in extracorporeal life support systems have decreased mortality rats during the waiting period.7–10 The Novalung (Novalung GmbH, Hechingen, Germany) has been reported to be effective to maintain oxygenation in patients with respiratory distress because it uses a lowresistance oxygenator and reduces right ventricular afterload resulting from an oxygenated right-to-left shunt from the pulmonary artery to the left atrium.11,12 Other strategies to increase organ availability for LTx are to use marginal donors13–16 as well as the normothermic ex vivo lung perfusion technique that yields similar clinical outcomes compared with LTxs performed from brain-death donors.17–22 In countries performing LTxs from the cardiac death donors, the length of the transplant waiting list has actually decreased.23 Our 42.5% mortality rate during the waiting period was high compared to the 20% reported by other workers,24 which may suggest either late referral or poor management during the waiting period. Early assessment of a potential LTx candidate is important even when the patient does not want to enlist for transplantation. The patient and family need to know the process of LTx and to understand how fast clinical deterioration may proceed. The timing of referral of a potential candidate to a LTx center has a great impact on patient survival during the waiting period. It is
868
also important for the primary physician to recognize a patient when the symptoms and signs of severe chronic respiratory disease lead to functional deterioration. A patient must be evaluated by a transplant specialist earlier to proceed to transplantation when it is emergently necessary. The mortality rate while awaiting a donor lung was greatest among patients diagnosed with primary pulmonary hypertension (62.5%) in our experience compared with 20% to 30% reported by other workers.24,25 Although the development of specific medical therapies in the past 15 years have resulted in improved survival for patients with pulmonary arterial hypertension,26 –28 less than optimal treatment may have caused the high mortality rate. Another important issue is the timing of LTx. The narrow window between the time of listing and the actual LTx gives the recipient a high risk of mortality during the waiting period, a fact which was not appreciated in the early days of LTx. To determine how early the patient for each disease entity should be listed for transplantation requires study from a more experienced have to decide one facility. The lung allocation score in the United States was developed to facilitate LTx among urgent, critically ill patients.29 It has served its purpose by decreasing the waiting time, reducing wait list mortality, and prioritizing patients based on urgency rather than length of time on the list. There has been no appreciable difference in survival, especially for patients with pulmonary fibrosis.30,31 However, in Korea, the system still follows the duration of the waiting period. Priority is given only for patients with ventilator or extracorporeal membrane oxygenator support. Therefore, the system has not decreased the mortality rate specifically for patients with certain diseases. A high mortality rate during the waiting period necessitates some modifications in the practice of patient referral and selection. The goal behind the creation of a new recipient selection system is to reduce the mortality rate during the waiting period, by prioritizing candidates based on urgency rather than the duration on the waiting list. In conclusion, donation by the general public has improved tremendously over the past decade; however, there is still a shortage of donors, especially considering that only 15% of lungs can be used for LTx. Early patient referral before functional deterioration by the primary physician is important to have sufficient time to evaluate and to wait for matched donor lungs. Patients need to be evaluated by transplant specialists early to be ready to proceed with the transplantation when it is emergently necessary.
REFERENCES 1. de Perrot M, Liu M, Waddell TK, et al: Ischemia-reperfusioninduced lung injury. Am J Respir Crit Care Med 167:490, 2003 2. Christie JD, Edwards LB, Kucheryavaya AY, et al: The Registry of the International Society for Heart and Lung Transplantation: twenty-seventh official adult lung and heart-lung transplant report. J Heart Lung Transplant 29:1104, 2010 3. Toronto Lung Transplantation Group: Unilateral lung transplantation for pulmonary fibrosis. N Engl J Med 314:1140, 1986
PAIK, HAAM, LEE ET AL 4. Haam SJ, Lee DY, Paik HC: An overview of lung transplantation in Korea. Transplant Proc 40:2620, 2008 5. Noiseux N, Nguyen BK, Marsolais P, et al: Pulmonary recruitment protocol for organ donors: a new strategy to improve the rate of lung utilization. Transplant Proc 41:3284, 2009 6. de Perrot M, Granton JT, McRae K, et al: Impact of extracorporeal life support on outcome in patients with idiopathic pulmonary arterial hypertension awaiting lung transplantation. J Heart Lung Transplant 30:997, 2011 7. Mangi AA, Mason DP, Yun JJ, et al: Bridge to lung transplantation using short-term ambulatory extracorporeal membrane oxygenation. J Thorac Cardiovasc Surg 140:713, 2010 8. Garcia JP, Iacono A, Kon ZN, et al: Ambulatory extracorporeal membrane oxygenation: a new approach for bridge-to-lung transplantation. J Thorac Cardiovasc Surg 139:e137, 2010 9. Fadel E, Mercier O, Mussot S, et al: Long-term outcome of double-lung and heart-lung transplantation for pulmonary hypertension: a comparative retrospective study of 219 patients. Eur J Cardiothorac Surg 38:277, 2010 10. Fischer S, Hoeper MM, Tomaszek S, et al: Bridge to lung transplantation with the extracorporeal membrane ventilator Novalung in the veno-venous mode: the initial Hannover experience. ASAIO J 53:168, 2007 11. Strueber M, Hoeper MM, Fischer S, et al: Bridge to thoracic organ transplantation in patients with pulmonary arterial hypertension using a pumpless lung assist device. Am J Transplant 9:853, 2009 12. Schmid C, Philipp A, Hilker M, et al: Bridge to lung transplantation through a pulmonary artery to left atrial oxygenator circuit. Ann Thorac Surg 85:1202, 2008 13. Snell GI, Griffiths A, Levvey BJ, et al: Availability of lungs for transplantation: exploring the real potential of the donor pool. J Heart Lung Transplant 27:662, 2008 14. de Perrot M, Snell GI, Babcock WD, et al: Strategies to optimize the use of currently available lung donors. J Heart Lung Transplant 23:1127, 2004 15. Bhorade SM, Vigneswaran W, McCabe MA, et al: Liberalization of donor criteria may expand the donor pool without adverse consequence in lung transplantation. J Heart Lung Transplant 19:1199, 2000 16. Botha P, Trivedi D, Weir CJ, et al: Extended donor criteria in lung transplantation: impact on organ allocation. J Thorac Cardiovasc Surg 131:1154, 2006 17. Oto T: Lung transplantation from donation after cardiac death (non-heart-beating) donors. Gen Thorac Cardiovasc Surg 56:533, 2008 18. Mason DP, Thuita L, Alster JM, et al: Should lung transplantation be performed using donation after cardiac death? The United States experience. J Thorac Cardiovasc Surg 136:1061, 2008 19. Oto T, Levvey B, McEgan R, et al: A practical approach to clinical lung transplantation from a Maastricht Category III donor with cardiac death. J Heart Lung Transplant 26:196, 2007 20. Snell GI, Levvey BJ, Oto T, et al: Early lung transplantation success utilizing controlled donation after cardiac death donors. Am J Transplant 8:1282, 2008 21. Okamoto T, Chen F, Zhang J, et al: Establishment of an ex vivo lung perfusion model using non-heart-beating large pigs. Transplant Proc 42:1598, 2010 22. Cypel M, Yeung JC, Liu M, et al: Normothermic ex vivo lung perfusion in clinical lung transplantation. N Engl J Med 364:1431, 2011 23. Kirschbaum C: Donation after cardiac death for lung transplant: a case study. Prog Transplant 21:156, 2011 24. Chen H, Shiboski SC, Golden JA, et al: Impact of the lung allocation score on lung transplantation for pulmonary arterial hypertension. Am J Respir Crit Care Med 180:468, 2009 25. Dandel M, Lehmkuhl HB, Mulahasanovic S, et al: Survival of patients with idiopathic pulmonary arterial hypertension after listing for transplantation: impact of iloprost and bosentan treatment. J Heart Lung Transplant 26:898, 2007
WAITING FOR LUNG TRANSPLANT IN KOREA 26. Galie N, Hoeper MM, Humbert M, et al: Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Respir J 34:1219, 2009 27. Chin KM, Rubin LJ: Pulmonary arterial hypertension. J Am Coll Cardiol 51:1527, 2008 28. Benza RL, Park MH, Keogh A, et al: Management of pulmonary arterial hypertension with a focus on combination therapies. J Heart Lung Transplant 26:437, 2007
869 29. Egan TM, Kotloff RM: Pro/Con debate: lung allocation should be based on medical urgency and transplant survival and not on waiting time. Chest 128:407, 2005 30. Egan TM, Murray S, Bustami RT, et al: Development of the new lung allocation system in the United States. Am J Transplant 6:1212, 2006 31. Takahashi SM, Garrity ER: The impact of the lung allocation score. Semin Respir Crit Care Med 31:108, 2010
LTx. The purpose of this study was to review the characteristics waiting times, and mortality rates for each disease entity among patients awaiting LTx.
From the Department of Thoracic and Cardiovascular Surgery (H.C.P., S.J.H., D.Y.L., G.J.Y., S.W.S.), Gangnam Severance Hospital, Seoul, Korea; Department of Thoracic and Cardiovascular Surgery (Y.T.K., C.H.K.), Seoul National University Hospital, Seoul National University School of Medicine, Seoul, Korea; Department of Thoracic and Cardiovascular Surgery (K.M.K.), Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea; Department of Thoracic and Cardiovascular Surgery (S.I.P.), Asan Medical Center, University of Ulsan
College of Medicine, Seoul, Korea; and the Department of Thoracic and Cardiovascular Surgery (S.H.J.), Seoul National University Bundang Hospital, Seoul National University College of Medicine, Gyeonggi, Korea. Address reprint requests to Hyo Chae Paik, Department of Thoracic and Cardiovascular Surgery, Gangnam Severance Hospital, 211, Eonju-Ro, Gangnam-Gu, Seoul, Korea. E-mail: [email protected]
L
© 2012 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710 Transplantation Proceedings, 44, 865– 869 (2012)
METHODS We retrospectively reviewed the medical records of all patients awaiting LTx in five institutions and listed in The Korean Network for Organ Sharing (KONOS) from May 1996 to May 2011. The five institutions
0041-1345/–see front matter doi:10.1016/j.transproceed.2011.12.059 865
866 consisted of Gangnam Severance Hospital, Yonsei University, Seoul National University Hospital, Seoul National University Bundang Hospital, Samsung Medical Center, and Asan Medical Center. The data consisting of patient age, sex, disease entity, blood type, duration from the diagnosis to enlisting for LTx, and the duration on the waiting list until death or LTx were analyzed to identify waiting times and mortality rates for each disease entity.
RESULTS
During the study period, 146 patients (86 males, 60 females) were registered for lung transplantation; their mean age was 46.6 ⫾ 14.1 years (range; 5 to 73 years; Fig 1). The most common disease was idiopathic pulmonary fibrosis (IPF; n ⫽ 61s, 41.8%) followed by chronic obstructive pulmonary disease (COPD; n ⫽ 19s), bronchiectasis (n ⫽ 15s), and lymphangioleiomyomatosis (LAM; n ⫽ 12; Table 1). Sixtyfive patients (44.5%) underwent lung transplantation with 2 retransplantations and 5 heart-lung transplantations. Sixtytwo patients (42.5%) expired during the waiting period; 19 patients are still on the waiting list (Fig 2). There were no significant differences in mean age (P ⫽ .575), gender (P ⫽ .227), or blood type (p ⫽ .899) between the transplanted and the mortality group (Table 2). The mortality rate while awaiting a donor lung was highest among patients with primary pulmonary hypertension (62.5%) followed by IPF (57.4%), and acute respiratory distress syndrome (ARDS; 55.6%). The mean time from the diagnosis to registration in KONOS was 15.5 ⫾ 29.3 months in the mortality versus 13.2 ⫾ 27.4 months in the transplanted group (P ⫽ .455). The mean time on the waiting list was 8.2 ⫾ 15.3 months in mortality versus 3.7 ⫾ 5.4 months in the transplanted group (P ⫽ .012). In the mortality group, mean survival time was significantly shorter among patients with ARDS (2.2 ⫾ 3.2 months, P ⫽ .004) versus IPF (7.9 ⫾ 15.5 months), COPD (10.7 ⫾ 14.1 months), or primary pulmonary hypertension (PPH) (30.0 ⫾ 31.9 months). DISCUSSION
LTx is the only definitive therapy for patients with end-stage lung disease that progresses despite maximal medical treatment. Although the demand for donor lungs has increased
Fig 1. Sex and age distribution of the 146 patients registered for lung transplantation.
PAIK, HAAM, LEE ET AL Table 1. Disease Entities on the Waiting List Disease Entities
Idiopathic pulmonary fibrosis Chronic obstructive pulmonary disease Bronchiectasis Lymphangioleiomyomatosis Acute respiratory distress syndrome Primary pulmonary hypertension Eisenmenger syndrome Cancer (BAC 2, angiosarcoma 1) Cystic fibrosis Eosinophillic granulomatosis Systemic sclerosis Congenital heart disease Bonchiolitis obliterans syndrome after LTx Bronchopulmonary dysplasia Graft vs Host Disease after BMT Secondary pulmonary hypertension
No. of Patients
%
Mortality (%)
61 19
41.8 13.0
35 (57.4) 4 (21.1)
15 12 9 8 7 3 2 2 2 2 1
10.3 8.2 6.2 5.5 4.8 2.1 1.4 1.4 1.4 1.4 0.7
4 (26.7) 2 (16.7) 5 (55.6) 5 (62.5) 2 (28.6) 1 (33.3) 2 (100) 1 (50) 0 1 (50) 0
1 1 1
0.7 0.7 0.7
0 0 0
Abbreviations: BAC, bronchioloalveolar cell carcinoma; LTx, lung transplantation; BMT, bone marrow transplantation.
tremendously in recent years, the number of donors has remained constant, resulting in an increased mortality rate among potential recipients during the waiting period. A few options may help to decrease the mortality rate during the waiting period. One is to increase organ donation by educating the general public via the mass media. Another way is to fully use the potential donor lungs by proper management from the time of hospital admission to the diagnosis of brain death. Optimal management of a potential candidate for multiorgan donation by preventing organ damage during the final period of brain death will decrease the waiting time and associated mortality rate. For example, a simple lung recruitment protocol involving a brief period of controlled sustained lung inflation increased the lung utilization rate from 20% to 33%.5 Because this paper describes the accrual of data from the beginning of LTx in Korea, late referral may be due to a
WAITING FOR LUNG TRANSPLANT IN KOREA
867
Fig 2. Fate of patients on waiting list for lung transplantation.
pessimistic attitude of patients and physicians regarding its outcomes; the perioperative mortality rate was high in the initial era of the LTx programs. The mean time from diagnosis to registration in the KONOS was 15.5 ⫾ 29.3 months among the mortality and 13.2 ⫾ 27.4 months among the transplanted group (P ⫽ .455). The mean waiting list time after the registration in KONOS was 8.2 ⫾ 15.3 months in the mortality group versus 3.7 ⫾ 5.4 months in the transplanted group (P ⫽ .012). The overall waiting period from the diagnosis to mortality during the waiting period was nearly 2 years, implying delayed referral for LTx evaluation. This has changed lately; LTx programs have been active over the last 2 years, resulting in far better surgical outcomes. Once the final decision to undergo LTx has been made, medical personnel and the family member should encourTable 2. Variables in Lung Transplantation and Mortality Group
Gender Male Female Mean Age (years) Blood type A B AB O Disease IPF COPD Bronchiectasis LAM ARDS
Transplanted (n ⫽ 65)
Mortality (n ⫽ 62)
34 31 46.4 ⫾ 11.4
39 23 47.7 ⫾ 15.5
21 13 9 22
21 14 6 21
23 9 6 10 3
35 4 4 2 5
P Value
.227
.575 .899
.158
Abbreviations: IPF, idiopathic pulmonary fibrosis; COPD, chronic obstructive pulmonary disease; LAM, lymphangioleiomyomatosi; ARDS, acute respiratory distress syndrome.
age the patient to accept the LTx as a challenge, and to prepare in every way possible to make themselves optimally fit for the operation. During this period, the coordinator needs to keep in close contact with the patient and the family members, fully discussing the patient’s physical and emotional conditions, and avoiding false expectations regarding transplantation. Respiratory infections are one main reason for admissions during the waiting period, therefore, patients on the waiting list need to be managed using a multidisciplinary team approach. Aggressive management strategies to deal with recipients have occurred in recent years, decreasing waiting list mortality.6 Improvements in extracorporeal life support systems have decreased mortality rats during the waiting period.7–10 The Novalung (Novalung GmbH, Hechingen, Germany) has been reported to be effective to maintain oxygenation in patients with respiratory distress because it uses a lowresistance oxygenator and reduces right ventricular afterload resulting from an oxygenated right-to-left shunt from the pulmonary artery to the left atrium.11,12 Other strategies to increase organ availability for LTx are to use marginal donors13–16 as well as the normothermic ex vivo lung perfusion technique that yields similar clinical outcomes compared with LTxs performed from brain-death donors.17–22 In countries performing LTxs from the cardiac death donors, the length of the transplant waiting list has actually decreased.23 Our 42.5% mortality rate during the waiting period was high compared to the 20% reported by other workers,24 which may suggest either late referral or poor management during the waiting period. Early assessment of a potential LTx candidate is important even when the patient does not want to enlist for transplantation. The patient and family need to know the process of LTx and to understand how fast clinical deterioration may proceed. The timing of referral of a potential candidate to a LTx center has a great impact on patient survival during the waiting period. It is
868
also important for the primary physician to recognize a patient when the symptoms and signs of severe chronic respiratory disease lead to functional deterioration. A patient must be evaluated by a transplant specialist earlier to proceed to transplantation when it is emergently necessary. The mortality rate while awaiting a donor lung was greatest among patients diagnosed with primary pulmonary hypertension (62.5%) in our experience compared with 20% to 30% reported by other workers.24,25 Although the development of specific medical therapies in the past 15 years have resulted in improved survival for patients with pulmonary arterial hypertension,26 –28 less than optimal treatment may have caused the high mortality rate. Another important issue is the timing of LTx. The narrow window between the time of listing and the actual LTx gives the recipient a high risk of mortality during the waiting period, a fact which was not appreciated in the early days of LTx. To determine how early the patient for each disease entity should be listed for transplantation requires study from a more experienced have to decide one facility. The lung allocation score in the United States was developed to facilitate LTx among urgent, critically ill patients.29 It has served its purpose by decreasing the waiting time, reducing wait list mortality, and prioritizing patients based on urgency rather than length of time on the list. There has been no appreciable difference in survival, especially for patients with pulmonary fibrosis.30,31 However, in Korea, the system still follows the duration of the waiting period. Priority is given only for patients with ventilator or extracorporeal membrane oxygenator support. Therefore, the system has not decreased the mortality rate specifically for patients with certain diseases. A high mortality rate during the waiting period necessitates some modifications in the practice of patient referral and selection. The goal behind the creation of a new recipient selection system is to reduce the mortality rate during the waiting period, by prioritizing candidates based on urgency rather than the duration on the waiting list. In conclusion, donation by the general public has improved tremendously over the past decade; however, there is still a shortage of donors, especially considering that only 15% of lungs can be used for LTx. Early patient referral before functional deterioration by the primary physician is important to have sufficient time to evaluate and to wait for matched donor lungs. Patients need to be evaluated by transplant specialists early to be ready to proceed with the transplantation when it is emergently necessary.
REFERENCES 1. de Perrot M, Liu M, Waddell TK, et al: Ischemia-reperfusioninduced lung injury. Am J Respir Crit Care Med 167:490, 2003 2. Christie JD, Edwards LB, Kucheryavaya AY, et al: The Registry of the International Society for Heart and Lung Transplantation: twenty-seventh official adult lung and heart-lung transplant report. J Heart Lung Transplant 29:1104, 2010 3. Toronto Lung Transplantation Group: Unilateral lung transplantation for pulmonary fibrosis. N Engl J Med 314:1140, 1986
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