- Email: [email protected]
Single Versus Double Lung Transplantation in Pulmonary Fibrosis: A Debated Topic
Single Versus Double Lung Transplantation in Pulmonary Fibrosis: A Debated Topic M. Rinaldi, F. Sansone, M. Boffini, S. El Qarra, P. Solidoro, N. Cavallo, E. Ruffini, and S. Baldi ABSTRACT Idiopathic pulmonary fibrosis (IPF) represents the second most frequent indication for lung transplantation after chronic obstructive pulmonary disease. Survival rate after transplantation is poorer compared with other lung diseases for reasons that are not completely clear. Medical therapy with anti-inflammatory drugs may improve symptoms and quality of life, but it does not influence the survival rate. Lung transplantation is the best therapy for end-stage IPF. The debate regarding the superiority of double lung transplantation (DLT) compared with single lung transplantation (SLT) is still ongoing. Until some years ago, SLT was almost uniformly utilized for this indication. In the most recent years, a larger application of DLT has been observed worldwide, probably related to higher 1-year and 5-year survivals. The unanswered question is whether it is ethical to use two lungs for the same patient, considering the donor shortage, when a single lung would suffice. Many reports have demonstrated that SLT offers acceptable pulmonary function and satisfactory early and intermediate survival. Probably DLT should be reserved for younger recipients, for those with concomitant or possible chronic infection of the contralateral lung, or cases of marginal donors. Further studies will be needed to formulate recommendations regarding the preferred surgical approach in IPF.
I
DIOPATHIC PULMONARY FIBROSIS (IPF) is the second most frequent lung pathology after chronic obstructive pulmonary disease leading to transplantation; it is the most common interstitial lung disease of unknown origin in adults.1,2 Therapy is still debated. Anti-inflammatory treatments, such as corticosteroids and azathioprine, have been shown to be useful with a weak effect on disease progression.3 Mortality rate in IPF is higher than the other interstitial lung diseases. IPF represents a progressive, generally fatal disease with a median survival between 2 and 3 years.1,3,4 The clinical course of IPF may usually be characterized by long asymptomatic periods followed by a quick decline with rapid onset of respiratory failure and death. Unfavorable outcomes are related to well-known parameters, like pulmonary arterial hypertension, and greater extent of fibrosis on high-resolution computed tomography (HRCT).5,6 In the last few years, many advancements have been made in the diagnosis and prognosis of IPF patients. As reported by Noth and Martinez, three elements are important for the diagnosis of IPF: the clinical history, the HRCT images, and the pathology findings. Agreement between HRCT images and clinical history provides a robust diagnosis without lung biopsy.6 Among
patients with atypical characteristics on HRCT, a biopsy is still required to obtain a diagnosis.6 These new advancements in the diagnosis and scoring of IFP may be the key to avoiding delays in patient referral to the lung transplantation list. Considering the poor survival of IPF patients and the variable results of medical therapy, early evaluation for lung transplantation may be recommended. As a matter of fact, many IPF patients have median survivals similar to the mean waiting times on the transplant list. Despite that lung transplantation in IPF is associated with the worst survival compared with other lung pathology and the causes of these results are still unknown (UNOS reports a 1-year survival of 74% for IPF recipients),7 lung transplantation has shown survival benefit over the best medical therapy for these patients.4 Traditionally, single lung transplant has been the From the Division of Cardiac Surgery (M.R., F.S., M.B., S.E.), Division of Pneumology (P.S., S.B.), and Division of Thoracic Surgery (N.C., E.R.), University of Turin, S. Giovanni Battista Hospital, Turin, Italy. Address reprint requests to Mauro Rinaldi, Department of Cardiac Surgery, University of Turin, S. Giovanni Battista Hospital, C.so Bramante 88, Turin, Italy. E-mail: [email protected]
0041-1345/08/$–see front matter doi:10.1016/j.transproceed.2008.05.052
© 2008 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
2010
Transplantation Proceedings, 40, 2010 –2012 (2008)
SINGLE VS DOUBLE LT IN PULMONARY FIBROSIS
treatment of choice for this disease, but more recently double lung transplantation has been advocated by many centers and more extensively used. Unfortunately, the numbers of lungs to be transplanted is limited and the questions regarding single versus double lung transplantation for IPF remain debated.8,9 DISCUSSION
In the past years, there have been no clear reports supporting the superiority of bilateral versus single lung transplantation. Meyers et al8 affirmed that there was no functional differences as measured by 6-minute walk distance and FEV1 between single versus bilateral lung transplantation; the difference in survival between the two groups did not reach statistical significance. The high mortality rate of lung transplantation in IPF is probably related to poor preoperative condition of transplant candidates and intraoperative or early postoperative complications, but the real causes are still unknown.10 The most frequent intraoperative complications are lung reperfusion syndrome and hemodynamic instability, especially in patient with pulmonary hypertension. The most frequent postoperative complications are reimplantation response and renal failure.11 There are few reports supporting a survival advantage of single versus double lung transplantation. This is probably related to the higher perioperative mortality of the double lung procedure in a particularly ill category of patients and to the longer ischemic time of the second lung.12,13 In a large review of the UNOS data by Meyer et al, patients younger than 60 years had an early and midterm survival benefit from single lung transplantation with respect to double-lung transplantation. They also suggested that patients older than 60 years should have single lung transplantation as the primary surgical option for patients with IPF.14 In contrast, other authors have suggested that bilateral lung transplantation may reduce the damage to pulmonary function in cases of early complications, like the reimplantation response or acute graft failure. This hypothesis may explain the better 1-year survival of double versus single lung transplantation reported in some papers. Consequently, as reported by ISHLT, there has been greater application of double versus single lung transplantation in recent years (45% vs 55%, respectively).15 A recent paper by Mason et al9 affirmed that single lung transplantation is a risk factor for mortality. They reported the survival for double versus single lung transplantation of 81% versus 67% at 1 year and 55% versus 34% at 5 years. The causes of the better long-term survival rate with double lung transplantation are probably related to better functional parameters like improved pulmonary reserve and respiratory mechanics as well as donor and recipient age. However, in a recent paper Nwakanma et al observed comparable short- and midterm survival for bilateral lung transplantation versus single lung transplantation in patients of at least 60 years of age. Even if they cautiously recommended double lung transplantation, they affirmed
2011
that considering the great disparity between the need and availability of donor organs, single lung transplantation is a reasonable option in older patients with noninfected lung pathology.16 De Perrot et al analyzed the effect of the use of older donors on survival after lung transplantation, reporting a greater 30-day mortality in recipients with IPF and pulmonary hypertension. However, the usual practice, to perform double lung transplantation from marginal donors to IPF patients, must be applied cautiously.17 In conclusion, lung transplantation for IPF offers acceptable survival rates compared to in-listing death, although lower than other lung pathology. The debate regarding the superiority of double lung transplantation versus single lung transplantation in terms of early and late survival, continues. A small number of papers have focused attention on this topic, and many of them include only a small number of patients, leading to uncertainty of the results. In our opinion, single lung transplantation is the primary surgical option to be considered for IPF patients. After single lung transplantation, the appearance of bronchiclitis obliterans syndrome-related graft dysfunction might be treated by transplantation, replacing the other native lung without the difficulty of a retransplantation. Double lung transplantation must be reserved for patients younger than 50 years, cases of simultaneously suppurative lung disease, and marginal donor grafts. Further studies will be needed to formulate recommendations regarding the preferred surgical approach in IPF. However, considering the donors shortage and the progressive increase among patients on the lung transplantation waiting list, we believe that single lung transplantation is the best choice for IPF, ensuring an acceptable quality of life and survival rate.
REFERENCES 1. Ryu JH, Colby TV, Hartman TE: Idiopathic pulmonary fibrosis: current concepts. Mayo Clin Proc 73:1085, 1998 2. American Thoracic Society, European Respiratory Society: American Thoracic Society/European Respiratory Society international multidisciplinary consensus classification of the idiopathic interstitial pneumonias. Am J Respir Crit Care Med 165:277, 2002 3. Hospenthal MA: Diagnosis and management of idiopathic pulmonary fibrosis: implications for respiratory care. Respir Care 51:382, 2006 4. Thabut G, Mal H, Castier Y, et al: Survival benefit of lung transplantation for patients with idiopathic pulmonary fibrosis. J Thorac Cardiovasc Surg 126:469, 2003 5. Harari S, Simonneau G, De Juli E, et al: Prognostic value of pulmonary hypertension in patients with chronic interstitial lung disease referred for lung or heart-lung transplantation. J Heart Lung Transplant 16:460, 1997 6. Noth I, Martinez FJ: Recent advances in idiopathic pulmonary fibrosis. Chest 132:637, 2007 7. De Meester J, Smits JMA, Persijn GG, et al: Listing for lung transplantation: life expectancy and transplant effect, stratified by type of end-stage lung disease, the Eurotransplant Experience. J Heart Lung Transplant 20:518, 2001 8. Meyers BF, Lynch JP, Trulock EP, et al: Single versus bilateral lung transplantation for idiopathic pulmonary fibrosis: a ten-year institutional experience. J Thorac Cardiovasc Surg 120:99, 2000
2012 9. Mason DP, Brizzio ME, Alster JM, et al: Lung transplantation for idiopathic pulmonary fibrosis. Ann Thorac Surg 84:1121, 2007 10. Whelan TP, Dunitz JM, Kelly RF, et al: Effect of preoperative pulmonary artery pressure on early survival after lung transplantation for idiopathic pulmonary fibrosis. J Heart Lung Transplant 24:1269, 2005 11. Vicente R, Morales P, Ramos F, et al: Peri-operative complications of lung transplantation in patients with emphysema and fibrosis: experience from 1992–2002. Transplant Proc 38:2560, 2006 12. Meyer DM, Edwards LB, Torres F, et al: Impact of recipient age and procedure type on survival after lung transplantation for pulmonary fibrosis. Ann Thorac Surg 79:950, 2005 13. Whelan TPM, Dunitz JM, Kelly RF, et al: Effect of preoperative pulmonary artery pressure on early survival after lung
RINALDI, SANSONE, BOFFINI ET AL transplantation for idiopathic pulmonary fibrosis. J Heart Lung Transplant 24:1269, 2005 14. Meyer DM, Edwards LB, Torres F, et al: Impact of recipient age and procedure type on survival after lung transplantation for pulmonary fibrosis. Ann Thorac Surg 79:950, 2005 15. Trulock EP, Edwards LB, Taylor DO, et al: Registry of the International Society for Heart and Lung Transplantation: twentysecond official adult lung and heart-lung transplant report—2005. J Heart Lung Transplant 24:956, 2005 16. Nwakanma LU, Simpkins CE, Williams JA, et al: 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. J Thorac Cardiovasc Surg 133:541, 2007 17. De Perrot M, Waddell TK, Shargall Y, et al: Impact of donors aged 60 years or more on outcome after lung transplantation: results of an 11-year single-center experience. J Thorac Cardiovasc Surg 133:525, 2007
I
DIOPATHIC PULMONARY FIBROSIS (IPF) is the second most frequent lung pathology after chronic obstructive pulmonary disease leading to transplantation; it is the most common interstitial lung disease of unknown origin in adults.1,2 Therapy is still debated. Anti-inflammatory treatments, such as corticosteroids and azathioprine, have been shown to be useful with a weak effect on disease progression.3 Mortality rate in IPF is higher than the other interstitial lung diseases. IPF represents a progressive, generally fatal disease with a median survival between 2 and 3 years.1,3,4 The clinical course of IPF may usually be characterized by long asymptomatic periods followed by a quick decline with rapid onset of respiratory failure and death. Unfavorable outcomes are related to well-known parameters, like pulmonary arterial hypertension, and greater extent of fibrosis on high-resolution computed tomography (HRCT).5,6 In the last few years, many advancements have been made in the diagnosis and prognosis of IPF patients. As reported by Noth and Martinez, three elements are important for the diagnosis of IPF: the clinical history, the HRCT images, and the pathology findings. Agreement between HRCT images and clinical history provides a robust diagnosis without lung biopsy.6 Among
patients with atypical characteristics on HRCT, a biopsy is still required to obtain a diagnosis.6 These new advancements in the diagnosis and scoring of IFP may be the key to avoiding delays in patient referral to the lung transplantation list. Considering the poor survival of IPF patients and the variable results of medical therapy, early evaluation for lung transplantation may be recommended. As a matter of fact, many IPF patients have median survivals similar to the mean waiting times on the transplant list. Despite that lung transplantation in IPF is associated with the worst survival compared with other lung pathology and the causes of these results are still unknown (UNOS reports a 1-year survival of 74% for IPF recipients),7 lung transplantation has shown survival benefit over the best medical therapy for these patients.4 Traditionally, single lung transplant has been the From the Division of Cardiac Surgery (M.R., F.S., M.B., S.E.), Division of Pneumology (P.S., S.B.), and Division of Thoracic Surgery (N.C., E.R.), University of Turin, S. Giovanni Battista Hospital, Turin, Italy. Address reprint requests to Mauro Rinaldi, Department of Cardiac Surgery, University of Turin, S. Giovanni Battista Hospital, C.so Bramante 88, Turin, Italy. E-mail: [email protected]
0041-1345/08/$–see front matter doi:10.1016/j.transproceed.2008.05.052
© 2008 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
2010
Transplantation Proceedings, 40, 2010 –2012 (2008)
SINGLE VS DOUBLE LT IN PULMONARY FIBROSIS
treatment of choice for this disease, but more recently double lung transplantation has been advocated by many centers and more extensively used. Unfortunately, the numbers of lungs to be transplanted is limited and the questions regarding single versus double lung transplantation for IPF remain debated.8,9 DISCUSSION
In the past years, there have been no clear reports supporting the superiority of bilateral versus single lung transplantation. Meyers et al8 affirmed that there was no functional differences as measured by 6-minute walk distance and FEV1 between single versus bilateral lung transplantation; the difference in survival between the two groups did not reach statistical significance. The high mortality rate of lung transplantation in IPF is probably related to poor preoperative condition of transplant candidates and intraoperative or early postoperative complications, but the real causes are still unknown.10 The most frequent intraoperative complications are lung reperfusion syndrome and hemodynamic instability, especially in patient with pulmonary hypertension. The most frequent postoperative complications are reimplantation response and renal failure.11 There are few reports supporting a survival advantage of single versus double lung transplantation. This is probably related to the higher perioperative mortality of the double lung procedure in a particularly ill category of patients and to the longer ischemic time of the second lung.12,13 In a large review of the UNOS data by Meyer et al, patients younger than 60 years had an early and midterm survival benefit from single lung transplantation with respect to double-lung transplantation. They also suggested that patients older than 60 years should have single lung transplantation as the primary surgical option for patients with IPF.14 In contrast, other authors have suggested that bilateral lung transplantation may reduce the damage to pulmonary function in cases of early complications, like the reimplantation response or acute graft failure. This hypothesis may explain the better 1-year survival of double versus single lung transplantation reported in some papers. Consequently, as reported by ISHLT, there has been greater application of double versus single lung transplantation in recent years (45% vs 55%, respectively).15 A recent paper by Mason et al9 affirmed that single lung transplantation is a risk factor for mortality. They reported the survival for double versus single lung transplantation of 81% versus 67% at 1 year and 55% versus 34% at 5 years. The causes of the better long-term survival rate with double lung transplantation are probably related to better functional parameters like improved pulmonary reserve and respiratory mechanics as well as donor and recipient age. However, in a recent paper Nwakanma et al observed comparable short- and midterm survival for bilateral lung transplantation versus single lung transplantation in patients of at least 60 years of age. Even if they cautiously recommended double lung transplantation, they affirmed
2011
that considering the great disparity between the need and availability of donor organs, single lung transplantation is a reasonable option in older patients with noninfected lung pathology.16 De Perrot et al analyzed the effect of the use of older donors on survival after lung transplantation, reporting a greater 30-day mortality in recipients with IPF and pulmonary hypertension. However, the usual practice, to perform double lung transplantation from marginal donors to IPF patients, must be applied cautiously.17 In conclusion, lung transplantation for IPF offers acceptable survival rates compared to in-listing death, although lower than other lung pathology. The debate regarding the superiority of double lung transplantation versus single lung transplantation in terms of early and late survival, continues. A small number of papers have focused attention on this topic, and many of them include only a small number of patients, leading to uncertainty of the results. In our opinion, single lung transplantation is the primary surgical option to be considered for IPF patients. After single lung transplantation, the appearance of bronchiclitis obliterans syndrome-related graft dysfunction might be treated by transplantation, replacing the other native lung without the difficulty of a retransplantation. Double lung transplantation must be reserved for patients younger than 50 years, cases of simultaneously suppurative lung disease, and marginal donor grafts. Further studies will be needed to formulate recommendations regarding the preferred surgical approach in IPF. However, considering the donors shortage and the progressive increase among patients on the lung transplantation waiting list, we believe that single lung transplantation is the best choice for IPF, ensuring an acceptable quality of life and survival rate.
REFERENCES 1. Ryu JH, Colby TV, Hartman TE: Idiopathic pulmonary fibrosis: current concepts. Mayo Clin Proc 73:1085, 1998 2. American Thoracic Society, European Respiratory Society: American Thoracic Society/European Respiratory Society international multidisciplinary consensus classification of the idiopathic interstitial pneumonias. Am J Respir Crit Care Med 165:277, 2002 3. Hospenthal MA: Diagnosis and management of idiopathic pulmonary fibrosis: implications for respiratory care. Respir Care 51:382, 2006 4. Thabut G, Mal H, Castier Y, et al: Survival benefit of lung transplantation for patients with idiopathic pulmonary fibrosis. J Thorac Cardiovasc Surg 126:469, 2003 5. Harari S, Simonneau G, De Juli E, et al: Prognostic value of pulmonary hypertension in patients with chronic interstitial lung disease referred for lung or heart-lung transplantation. J Heart Lung Transplant 16:460, 1997 6. Noth I, Martinez FJ: Recent advances in idiopathic pulmonary fibrosis. Chest 132:637, 2007 7. De Meester J, Smits JMA, Persijn GG, et al: Listing for lung transplantation: life expectancy and transplant effect, stratified by type of end-stage lung disease, the Eurotransplant Experience. J Heart Lung Transplant 20:518, 2001 8. Meyers BF, Lynch JP, Trulock EP, et al: Single versus bilateral lung transplantation for idiopathic pulmonary fibrosis: a ten-year institutional experience. J Thorac Cardiovasc Surg 120:99, 2000
2012 9. Mason DP, Brizzio ME, Alster JM, et al: Lung transplantation for idiopathic pulmonary fibrosis. Ann Thorac Surg 84:1121, 2007 10. Whelan TP, Dunitz JM, Kelly RF, et al: Effect of preoperative pulmonary artery pressure on early survival after lung transplantation for idiopathic pulmonary fibrosis. J Heart Lung Transplant 24:1269, 2005 11. Vicente R, Morales P, Ramos F, et al: Peri-operative complications of lung transplantation in patients with emphysema and fibrosis: experience from 1992–2002. Transplant Proc 38:2560, 2006 12. Meyer DM, Edwards LB, Torres F, et al: Impact of recipient age and procedure type on survival after lung transplantation for pulmonary fibrosis. Ann Thorac Surg 79:950, 2005 13. Whelan TPM, Dunitz JM, Kelly RF, et al: Effect of preoperative pulmonary artery pressure on early survival after lung
RINALDI, SANSONE, BOFFINI ET AL transplantation for idiopathic pulmonary fibrosis. J Heart Lung Transplant 24:1269, 2005 14. Meyer DM, Edwards LB, Torres F, et al: Impact of recipient age and procedure type on survival after lung transplantation for pulmonary fibrosis. Ann Thorac Surg 79:950, 2005 15. Trulock EP, Edwards LB, Taylor DO, et al: Registry of the International Society for Heart and Lung Transplantation: twentysecond official adult lung and heart-lung transplant report—2005. J Heart Lung Transplant 24:956, 2005 16. Nwakanma LU, Simpkins CE, Williams JA, et al: 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. J Thorac Cardiovasc Surg 133:541, 2007 17. De Perrot M, Waddell TK, Shargall Y, et al: Impact of donors aged 60 years or more on outcome after lung transplantation: results of an 11-year single-center experience. J Thorac Cardiovasc Surg 133:525, 2007