Lung transplantation: An overview
- Ramsey R Hachem, MD
Ramsey R Hachem, MD
- Professor of Medicine
- Washington University School of Medicine
Over the past 25 years, lung transplantation has become a viable treatment option for patients with a variety of end-stage lung diseases. The first human lung transplant procedure was performed in 1963, and the recipient survived 18 days, ultimately succumbing to renal failure and malnutrition . Despite the outcome, this demonstrated that lung transplantation was technically feasible and that rejection could be averted with the available immunosuppressive agents, at least for a short time.
Over the ensuing 15 years, few lung transplant procedures were performed, and the majority of recipients died perioperatively because of bronchial anastomotic complications. However, in 1981, the first successful heart-lung transplantation was performed for idiopathic pulmonary arterial hypertension . This was followed in 1983 by the first successful single lung transplantation for idiopathic pulmonary fibrosis  and in 1986 by the first double lung transplantation for emphysema . These successes were attributed to improved surgical techniques and the advent of cyclosporine. Over the following several years, the number of lung transplant procedures performed rapidly increased, and the operation became an accepted treatment for end-stage lung disease.
An overview of lung transplantation, including a discussion of outcomes, is presented here. Lung transplantation indications, recipient selection, choice of procedure, post-operative management and complications are presented separately. (See "Lung transplantation: General guidelines for recipient selection" and "Lung transplantation: Disease-based choice of procedure" and "Lung transplantation: Procedure and postoperative management" and "Noninfectious complications following lung transplantation" and "Evaluation and treatment of acute lung transplant rejection".)
Between 1988 and 1993, the number of lung transplants performed worldwide increased dramatically from 89 to 1160 annually (figure 1) . Between 1993 and 2000, the number of transplants reported to the International Society for Heart and Lung Transplantation (ISHLT) Registry increased modestly as activity appeared to plateau around 2000 procedures annually . However, there has been a steady growth in the number of procedures performed annually since 2000, and over 3700 transplants were reported in 2012 . While part of this increase may be attributable to greater participation in the ISHLT Registry, the rapid rise in activity since 2005 suggests that the lung allocation system implemented in the US in 2005 has increased the number of transplants performed.
Donor lung shortage has been the major limiting factor to the number of transplants performed. Lung organ procurement rates from deceased donors have consistently been substantially lower than kidney, liver, and heart procurement rates. Lungs are harvested from only 15 percent of all cadaveric donors, whereas kidneys and livers are harvested from 88 percent and hearts from 30 percent of deceased donors . These disparities are likely due to the lung's vulnerability to potential complications that often arise before and after donor brain death such as thoracic trauma, aspiration, ventilator associated lung injury, pneumonia, and neurogenic pulmonary edema. Nonetheless, as many as 40 percent of rejected donor lungs may have been suitable for transplantation . In addition, studies suggest that ex vivo lung perfusion and reconditioning may ameliorate lung injury in some cases and allow transplantation from donors previously deemed unsuitable [8,9]. Standard and extended criteria for donor lung selection and their impact on short and long-term outcomes are presented separately. (See "Lung transplantation: Donor lung preservation".)
- HARDY JD, WEBB WR, DALTON ML Jr, WALKER GR Jr. LUNG HOMOTRANSPLANTATION IN MAN. JAMA 1963; 186:1065.
- Reitz BA, Wallwork JL, Hunt SA, et al. Heart-lung transplantation: successful therapy for patients with pulmonary vascular disease. N Engl J Med 1982; 306:557.
- Toronto Lung Transplant Group. Unilateral lung transplantation for pulmonary fibrosis. N Engl J Med 1986; 314:1140.
- Cooper JD, Patterson GA, Grossman R, Maurer J. Double-lung transplant for advanced chronic obstructive lung disease. Am Rev Respir Dis 1989; 139:303.
- Yusen RD, Edwards LB, Kucheryavaya AY, et al. The Registry of the International Society for Heart and Lung Transplantation: Thirty-second Official Adult Lung and Heart-Lung Transplantation Report--2015; Focus Theme: Early Graft Failure. J Heart Lung Transplant 2015; 34:1264.
- Division of Transplantation, Bureau of Health Resources Development. 2005 Annual Report of the US Scientific Registry for Transplant Recipients and the Organ Procurement and Transplantation Network — Transplant Data:1995-2004. Health Resources and Services Administration; US Department of Health and Human Services, Rockville, MD 2005.
- Ware LB, Wang Y, Fang X, et al. Assessment of lungs rejected for transplantation and implications for donor selection. Lancet 2002; 360:619.
- Ingemansson R, Eyjolfsson A, Mared L, et al. Clinical transplantation of initially rejected donor lungs after reconditioning ex vivo. Ann Thorac Surg 2009; 87:255.
- Cypel M, Rubacha M, Yeung J, et al. Normothermic ex vivo perfusion prevents lung injury compared to extended cold preservation for transplantation. Am J Transplant 2009; 9:2262.
- Gries CJ, Mulligan MS, Edelman JD, et al. Lung allocation score for lung transplantation: impact on disease severity and survival. Chest 2007; 132:1954.
- McCurry KR, Shearon TH, Edwards LB, et al. Lung transplantation in the United States, 1998-2007. Am J Transplant 2009; 9:942.
- Davis SQ, Garrity ER Jr. Organ allocation in lung transplant. Chest 2007; 132:1646.
- Iribarne A, Russo MJ, Davies RR, et al. Despite decreased wait-list times for lung transplantation, lung allocation scores continue to increase. Chest 2009; 135:923.
- Egan TM, Edwards LB. Effect of the lung allocation score on lung transplantation in the United States. J Heart Lung Transplant 2016; 35:433.
- Yusen RD, Shearon TH, Qian Y, et al. Lung transplantation in the United States, 1999-2008. Am J Transplant 2010; 10:1047.
- Russo MJ, Iribarne A, Hong KN, et al. High lung allocation score is associated with increased morbidity and mortality following transplantation. Chest 2010; 137:651.
- Liu V, Zamora MR, Dhillon GS, Weill D. Increasing lung allocation scores predict worsened survival among lung transplant recipients. Am J Transplant 2010; 10:915.
- Tsuang WM, Vock DM, Finlen Copeland CA, et al. An acute change in lung allocation score and survival after lung transplantation: a cohort study. Ann Intern Med 2013; 158:650.
- Maxwell BG, Levitt JE, Goldstein BA, et al. Impact of the lung allocation score on survival beyond 1 year. Am J Transplant 2014; 14:2288.
- 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 2005; 79:950.
- Titman A, Rogers CA, Bonser RS, et al. Disease-specific survival benefit of lung transplantation in adults: a national cohort study. Am J Transplant 2009; 9:1640.
- Trulock EP, Edwards LB, Taylor DO, et al. Registry of the International Society for Heart and Lung Transplantation: twenty-second official adult lung and heart-lung transplant report--2005. J Heart Lung Transplant 2005; 24:956.
- Christie JD, Sager JS, Kimmel SE, et al. Impact of primary graft failure on outcomes following lung transplantation. Chest 2005; 127:161.
- Thabut G, Vinatier I, Stern JB, et al. Primary graft failure following lung transplantation: predictive factors of mortality. Chest 2002; 121:1876.
- Christie JD, Carby M, Bag R, et al. 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.
- Prekker ME, Nath DS, Walker AR, et al. Validation of the proposed International Society for Heart and Lung Transplantation grading system for primary graft dysfunction after lung transplantation. J Heart Lung Transplant 2006; 25:371.
- Daud SA, Yusen RD, Meyers BF, et al. Impact of immediate primary lung allograft dysfunction on bronchiolitis obliterans syndrome. Am J Respir Crit Care Med 2007; 175:507.
- Huang HJ, Yusen RD, Meyers BF, et al. Late primary graft dysfunction after lung transplantation and bronchiolitis obliterans syndrome. Am J Transplant 2008; 8:2454.
- Sundaresan S, Trulock EP, Mohanakumar T, et al. Prevalence and outcome of bronchiolitis obliterans syndrome after lung transplantation. Washington University Lung Transplant Group. Ann Thorac Surg 1995; 60:1341.
- Boehler A, Estenne M. Post-transplant bronchiolitis obliterans. Eur Respir J 2003; 22:1007.
- Valentine VG, Robbins RC, Berry GJ, et al. Actuarial survival of heart-lung and bilateral sequential lung transplant recipients with obliterative bronchiolitis. J Heart Lung Transplant 1996; 15:371.
- Lehto JT, Koskinen PK, Anttila VJ, et al. Bronchoscopy in the diagnosis and surveillance of respiratory infections in lung and heart-lung transplant recipients. Transpl Int 2005; 18:562.
- Solé A, Morant P, Salavert M, et al. Aspergillus infections in lung transplant recipients: risk factors and outcome. Clin Microbiol Infect 2005; 11:359.
- Malouf MA, Glanville AR. The spectrum of mycobacterial infection after lung transplantation. Am J Respir Crit Care Med 1999; 160:1611.
- Glanville AR, Scott AI, Morton JM, et al. Intravenous ribavirin is a safe and cost-effective treatment for respiratory syncytial virus infection after lung transplantation. J Heart Lung Transplant 2005; 24:2114.
- 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--2010. J Heart Lung Transplant 2010; 29:1104.
- Amital A, Shitrit D, Raviv Y, et al. Development of malignancy following lung transplantation. Transplantation 2006; 81:547.
- Ramsey SD, Patrick DL, Lewis S, et al. Improvement in quality of life after lung transplantation: a preliminary study. The University of Washington Medical Center Lung Transplant Study Group. J Heart Lung Transplant 1995; 14:870.
- Gross CR, Savik K, Bolman RM 3rd, Hertz MI. Long-term health status and quality of life outcomes of lung transplant recipients. Chest 1995; 108:1587.
- Kugler C, Fischer S, Gottlieb J, et al. Health-related quality of life in two hundred-eighty lung transplant recipients. J Heart Lung Transplant 2005; 24:2262.
- Vasiliadis HM, Collet JP, Poirier C. Health-related quality-of-life determinants in lung transplantation. J Heart Lung Transplant 2006; 25:226.
- van Den BERG JW, Geertsma A, van Der BIJ W, et al. Bronchiolitis obliterans syndrome after lung transplantation and health-related quality of life. Am J Respir Crit Care Med 2000; 161:1937.
- Ramsey SD, Patrick DL, Albert RK, et al. The cost-effectiveness of lung transplantation. A pilot study. University of Washington Medical Center Lung Transplant Study Group. Chest 1995; 108:1594.
- Anyanwu AC, McGuire A, Rogers CA, Murday AJ. An economic evaluation of lung transplantation. J Thorac Cardiovasc Surg 2002; 123:411.
- Arnaoutakis GJ, Allen JG, Merlo CA, et al. Impact of the lung allocation score on resource utilization after lung transplantation in the United States. J Heart Lung Transplant 2011; 30:14.
- Vasiliadis HM, Collet JP, Penrod JR, et al. A cost-effectiveness and cost-utility study of lung transplantation. J Heart Lung Transplant 2005; 24:1275.
- Gartner SH, Sevick MA, Keenan RJ, Chen GJ. Cost-utility of lung transplantation: a pilot study. J Heart Lung Transplant 1997; 16:1129.
- Hauboldt RH, Hanson SG, Bernstein GR: 2008 U.S. organ and tissue transplant cost estimates and discussion. http://publications.milliman.com/research/health-rr/pdfs/2008-us-organ-tisse-RR4-1-08.pdf (Accessed on February 01, 2011).