European Respiratory Society
Lung Transplantation (out of print)

This book has been superseded by a newer edition.

Since the first attempt at human lung transplantation (LTx) by Hardy in the early 1960s, LTx has become an established treatment for a wide variety of end-stage cardiopulmonary diseases. Initially limited to patients with primary pulmonary hypertension or Eisenmenger’s complex, this procedure was extended to patients with a variety of end-stage pulmonary disorders, such as end-stage fibrotic lung disease and end-stage obstructive lung disease, as well as suppurative lung disorders, such as bronchiectasis or cystic fibrosis. A successful LTx is the culmination of a complex and costly series of surgical, medical and social interventions aimed at both prolonging life and enhancing quality of life for the patient with end-stage disease. The rapid advances in patient care would not be possible without the dramatic advances in the understanding of the immune response and the new development of immunological management following transplantation. This issue of the European Respiratory Monograph offers the reader excellent state-of-the-art information regarding experiences with LTx four decades after the first procedure. Increased physician awareness of LTx by discussion of the possibilities of organ donation, especially in the critical care setting, may also help to offer new perspectives for those patients suffering from otherwise fatal lung pathologies.

  • European Respiratory Society Monographs
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  3. Page 1
    Correspondence: A.R. Glanville, The Lung Transplant Unit, Xavier 4, St Vincent's Hospital, Victoria Street, Darlinghurst, Sydney NSW 2010, Australia.

    Lung transplantation (LTx) is now generally accepted as a useful modality of care for patients with severe life-threatening respiratory diseases that are refractory to other medical therapies. While LTx has been performed for most causes of respiratory failure, in practice, the majority of transplant procedures are performed for emphysema (either primarily smoking-related or due to α1-antitrypsin deficiency), cystic fibrosis (CF), idiopathic pulmonary fibrosis (IPF), primary pulmonary hypertension, sarcoidosis, bronchiectasis and congenital heart disease. Selection criteria for placement on the active waiting list for LTx vary between centres, but necessarily balance the chance of an enduring enhanced quality of life after LTx with the known risks associated with transplant for the individual recipient. Timing of referral, therefore, must incorporate local knowledge of the waiting times to transplant with the local success rates for particular disease indications. Unfortunately, mortality on the waiting list remains high for patients with IPF and CF, suggesting that referrals tend to occur late in the evolution of the disease process. While reluctance to refer early may reflect concerns regarding the likelihood of achieving benefits that may accrue with LTx, there are now accumulating data that attest both to survival benefits in these diseases and to improvements in quality-of-life issues across a broad range of health domains. In addition, early referral allows an orderly process of assessment for transplant suitability with adequate time to address important medical and psychological issues, thereby maximising the chance of providing a worthwhile experience.

  4. Page 16
    Correspondence: J.J. Egan, Advanced Lung Disease and Irish National Lung Transplant Programme, The Mater Misericordiae Hospital and St Vincent's University Hospital, University College Dublin, Eccles Street, Dublin 7, Ireland.

    Pulmonary rehabilitation is an important component of the management of patients with advanced lung disease. Small increments in exercise capacity are important to patients and potentially complement post-transplant rehabilitation and the preservation of bone density. Noninvasive positive pressure ventilatory support (NIPPV) is an accepted strategy for bridging cystic fibrosis (CF) patients to transplantation. However, for patients with chronic obstuctive pulmonary disease (COPD), the indications for NIPPV are more contentious. Recent data suggests that no survival advantage is acquired from NIPPV in COPD. However, indirect benefits may be achieved by enhancing pulmonary rehabilitation and reducing the need for invasive ventilation. Many patients with advanced COPD find NIPPV difficult to tolerate. Malnourishment is associated with both increased mortality, awaiting transplantation and impaired survival following transplantation. Therefore, every effort should be made to optimise the patients body mass index. This frequently involves the placement of gastrostomy feeding devices in patients with CF.

    Oxygen therapy is the cornerstone for the management of secondary pulmonary hypertension and this should be pursued aggressively. There are a number of potential important developments in this area including nebulised iloprost, the administration of nitric oxide and/or new oral therapies including sildenafil and bozantin.

    Occult infection is an important aspect of the management of patients with advanced lung disease. Infection frequently remains undiagnosed because of the difficulty performing invasive techniques to identify or exclude infection. The application of palliative strategies is a key component of the management of patients with advanced lung disease. Discussions should be undertaken with the patient and their family, regarding mechanical ventilation (MV) strategies or the absence of such treatment. Broadly speaking, MV is contraindicated in patients awaiting lung transplantation, except in specific reversible situations.

  5. Page 31
    Correspondence: J-L. Vachiéry, Dept of Cardiology, Erasme University Hospital-ULB, 808 route de Lennik, 1070 Brussels, Belgium.

    Pulmonary arterial hypertension (PAH) is a life-threatening and rapidly evolving disease for which there is no cure. Although lung transplantation (LTx) or heart LTx has been considered as the first option for end-stage PAH, effective medical therapies are now available, even for advanced cases. Over the last years, several multicentric, randomised, controlled trials have shown that prostaglandin I2 derivates (treprostinil, iloprost and epoprostenol) and the dual endothelin-receptor antagonist bosentan improve exercise tolerance and symptoms of severe PAH. The choice of each therapeutic option should be based on indicators of prognosis, appropriate risk/benefit ratio and be acceptable for each individual. However, efficacy may weaken in the long term and a survival benefit has not been uniformly reported yet. Medical treatment is therefore recommended as the first step for treating PAH but LTx will eventually remain the best option for a significant number of patients with end-stage PAH.

  6. Page 40
    Correspondence: W. Weder, Division of Thoracic Surgery, University Hospital Zurich, Raemistrasse 100, CH-8091 Zurich, Switzerland.

    Lung volume reduction surgery (LVRS) has become a palliative therapeutic option for selected patients with advanced pulmonary emphysema who suffer from shortness of breath at minimal activity. The beneficial effects have been documented by numerous case series and by several randomised, controlled trials. In well-selected patients, the perioperative mortality does not exceed >5% in experienced centres, and the expected improvement in forced expiratory volume in one second ranges 30–60% at 3–6 months. Thereafter, the lung function steadily declines, but the effect lasts for up to 4–6 yrs. This therapeutic option was used alternatively in patients who were suitable candidates for lung transplantation, and several groups demonstrated that transplantation could be postponed by 2–4 yrs after bilateral LVRS. The procedure itself does not jeopardise the chances for subsequent successful transplantation.

  7. Page 47
    Correspondence: E. Mayer, Dept for Cardiothoracic and Vascular Surgery, Johannes Gutenberg University Hospital, Langenbeckstrasse 1, 55101, Mainz, Germany.

    Chronic thromboembolic pulmonary artery obstruction due to unresolved and recurrent pulmonary embolism causes a persistent elevation of pulmonary vascular resistance (PVR) and progressive right ventricular dysfunction, and failure in ∼0.1–0.5% of patients who survive a clinically recognised acute pulmonary embolism. The prognosis for patients with thromboembolic pulmonary hypertension is poor and the survival rate is dependent on the degree of pulmonary hypertension.

    As symptoms are nonspecific, the diagnosis can be difficult and is often missed. Furthermore, there is a general lack of awareness of this condition and the possibility of effective surgical therapy. Pulmonary angiography still remains the gold standard for the diagnosis of thromboembolic pulmonary hypertension and the assessment of operability. The decision for thromboendarterectomy is based on the severity of symptoms, pulmonary haemodynamics and the accessibility of the obstructive lesions in the pulmonary artery branches.

    Although pulmonary thromboendarterectomy is a potentially curative option, only 2,000–2,500 operations have been performed in a few centres worldwide. The operation is technically demanding and resembles a true endarterectomy of the pulmonary artery branches using extracorporeal circulation and periods of hypothermic circulatory arrest. Based on the experience of a multidisciplinary team, the operative risk could be reduced to an acceptable level.

    The long-term outcome is excellent with a persistent improvement of New York Heart Association functional class, PVR and right heart function suggesting a longer life expectancy for these patients. The outcome compares very favourably to that of lung transplantation, and therefore transplantation is inappropriate for most of the patients with chronic thromboembolic pulmonary hypertension.

  8. Page 62
    Correspondence: B. Miranda, Organización Nacional de Trasplantes, Sinesio Delgado, 8, 28029 Madrid, Spain.

    Organ transplantation not only provides the possibility of saving lives, but it also has the best cost/benefit ratio in terms of economics and the quality of life. Despite all the advantages conferred by organ transplantation, many people cannot benefit from such an opportunity.

    Different alternatives have been proposed to even this gap. The continuous overview on the donation and retrieval process will provide both the opportunity for improvement and the guarantee that all potential is transformed into actual. The possibility of widening the criteria for accepting organs or to move to other alternatives, such as living or nonheart-beating donation, is also another possibility. A comprehensive and effective organ allocation system needs to be put in place. Although there are no universally accepted rules, there are official recommendations from the Council of Europe, indicating the need for public and transparent allocation rules that should ensure, as far as possible, that no group of patients is waiting longer than another.

  9. Page 78
    Correspondence: P.A. Corris, Dept of Respiratory Medicine, Newcastle University and Regional Cardiothoracic Centre, Freeman Hospital, Newcastle upon Tyne, UK.

    Optimising and increasing the donor pool of lungs remains an important challenge for transplantation. The wider application of well-characterised methods of donor management represents an important first step to maximise the successful use of offered organs. This management includes the role of therapeutic bronchoscopy to clear secretions and reduce atelectasis and the use of vasopressin to maintain haemodynamic suitability. Pulmonary care is aimed at protecting the lung from excessive ventilatory pressures and maintaining low inspired partial pressures of oxygen.

  10. Page 86
    Correspondence: D. van Raemdonck, Dept of Thoracic Surgery, University Hospital Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium.

    Primary graft dysfunction remains a potentially devastating problem in 10–20% after lung transplantation with a significant impact on early and late clinical outcomes. Risk factors that have been identified are donor-, preservation- or recipient-related.

    Ischaemia/reperfusion injury is the term commonly used to summarise the insult that leads to graft dysfunction. A better understanding of the pathophysiological mechanisms that take place during ischaemia and subsequent reperfusion has resulted in new refinements in lung preservation techniques and solutions over the last decade. Reperfusion models for ex vivo assessment and conditioning of the pulmonary graft have recently been developed that may allow the safe expansion of the pulmonary donor pool using lungs from nonheart-beating donors (NHBDs) as well as from extended (marginal) heart-beating donors.

    The purpose of this chapter is to describe, what is believed to be, the optimal method of lung procurement and preservation based on current scientific knowledge. In addition the latest developments in preservation and ex vivo assessment of lungs from NHBDs are presented.

  11. Page 98
    Correspondence: H. Reichenspurner, Universitatsklinikum, Hamburg Eppendorf, Dept of Cardiovascular Surgery, Martinistrasse 52, D-202 46 Hamburg, Germany.

    The operative techniques of state-of-the-art single-, bilateral- and heart-lung transplantations (LTx) will be described in this chapter. Indications for single LTx are principally parenchymal or pulmonary vascular diseases, while septic diseases and severe pulmonal hypertension require bilateral-lung procedures. Combined heart LTx are indicated in cases of end-stage lung diseases with irreversible heart failure and in patients suffering from complex Eisenmenger's syndrome.

    Cardiopulmonary bypass (CPB) is rarely used in LTx but mandatory in all heart LTx and in patients with moderate or severe pulmonary hypertension. For single LTx the patient is placed in a lateral position and an anterolateral thoracotomy in the fourth to fifth intercostal space is performed. Vessel loops and bands are placed around pulmonary veins, the pulmonary artery and the mainstem bronchus. Test clamping of the pulmonary artery reveals if cannulation for CPB must be performed. After clamping and resection of the pulmonary veins, the pulmonary artery and the bronchus, the lung is removed from the chest. The donor lung is then taken into the chest cavity and permanently cooled with iced pads and saline. At first, the anastomosis of the atrial cuffs is achieved followed by the bronchial and pulmonary artery anastomoses. An intraoperative steroid bolus is given, the anastomosis de-aired and the lung flushed to remove preservation solution before orthograde reperfusion of the organ is started.

    Bilateral LTx is performed as subsequent single LTx, replacing one side after the other through a transverse thoracosternotomy or even through minithoracotomies. Heart LTxs are commonly performed through a median sternotomy. The bicaval technique is the method of choice in most centres offering the possibility of a supraphrenic transplantation of the lungs. After organ removal, implantation starts with the tracheal anastomosis, followed by the bicaval anastomoses and the connection of donor and recipient aorta. The patient is then carefully weaned from bypass.

  12. Page 105
    Correspondence: C. Knoop, Dept of Chest Medicine, Erasme Hospital, 808 Route de Lennik, 1070 Brussels, Belgium.

    Immunosuppressive strategies after lung transplantation (LTx) concern induction therapy, maintenance immunosuppression and the treatment of acute and chronic rejection.

    In 2002, equal numbers of LTx were performed with or without induction therapy with antilymphocyte antibodies, monoclonal anti-CD3 antibody or anti-interleukin-2-receptor monoclonal antibodies. It remains to be established if induction therapy after LTx is beneficial or deleterious for long-term graft and patient survival.

    The vast majority of lung transplant recipients receive a triple-drug maintenance regimen including a calcineurin inhibitor, a cell-cycle inhibitor and steroids. Equal proportions receive cyclosporin A (CsA) and tacrolimus (Tac). There is also a trend to prescribe mycophenolate mofetil (MMF) instead of azathioprine (Aza). Steroid withdrawal is uncommon even 5 yrs after transplantation. The superiority of Tac over CsA as a maintenance agent has not been established to date. An international, prospective, randomised, controlled trial comparing CsA with Tac in combination with MMF and steroids is currently under way. In contrast to trials in renal and heart transplant recipients, the administration of MMF instead of Aza in combination with CsA and steroids did not result in improved graft or patient survival in a recent international, prospective, randomised, controlled trial. It is possible that the MMF dose was not optimal in this trial.

    High-dose intravenous steroid pulses are the first-line treatment of uncomplicated acute rejection. The shift from CsA to Tac has emerged as the first treatment step of refractory acute rejection followed by high-dose steroids or antilymphocyte agents, total lymphoid irradiation or photopheresis.

    The treatment of chronic rejection remains deceptive and includes varied strategies such as modification of the maintenance regimen, augmentation of the net immunosuppression, addition of inhaled immunosuppressants and/or other immunomodulatory treatments, such as total lymphoid irradiation and photopheresis.

  13. Page 130
    Correspondence: G. Snell, Lung Transplant Service, Alfred Hospital, Monash University, Melbourne 3004, Australia.

    Lung transplantation is potentially a very demanding procedure and attention to detail is required before, during and after the procedure if optimum clinical outcomes are to be achieved. Regular surveillance of waiting-list patients in order to assess the progression of illness and potential perioperative complications is important. Postoperatively the first 24 h are critical, mandating invasive monitoring and the timely correction of evolving clinical problems. It is usual to prefer relative circulatory underfilling to minimise the propensity for significant alveolar leak associated with early reperfusion injury. Pre-emptive antibiotic, antifungal and antiviral therapies aimed at known and likely organisms are appropriate. Baseline immunosuppression is usually protocol determined but must be flexible to allow modification in the setting of renal, gastrointestinal, neurological and infectious complications. Skilled critical care and anaesthetic management assists with weaning invasive ventilation and optimising analgesia. Ensuing discharge from the intensive care unit, rehabilitation and patient education are further relevant steps. Clinical, radiological and bronchoscopic follow-up is required to diagnose and monitor the common clinical problems of infection and rejection. It is apparent that many important long-term issues, graft and renal function in particular, are dependent on specific aspects of management in these first weeks.

  14. Page 143
    Correspondence: S. Stewart, Dept of Pathology, Papworth Hospital, Papworth Everard, Cambridge, CB3 8RE, UK.

    Lung transplantation pathology is a challenging topic for the specialised pulmonary pathologist. The pathological journey begins with the accurate diagnosis of the condition requiring transplantation and its confirmation in the explanted organ, together with the identification of other unsuspected or supplementary pathological processes. Following transplantation, histological diagnosis is required of early, mid and late complications, which include ischaemic and reperfusion injury, acute rejection and infection followed by chronic rejection. There is an established grading system for the diagnosis of acute and chronic lung rejection based on perivascular and airway infiltrates acutely, and fibrosis of the airway with and without infiltrates chronically. Infrequently, transbronchial biopsies are insufficient for diagnosis and thoracoscopic or open-lung biopsies are required, the commonest unsuspected diagnoses in these being obliterative bronchiolitis and post-transplant lymphoproliferative disease.

    Opportunistic infections are particularly common in lung transplant recipients although are much reduced in incidence by improvements in management including prophylaxis and targeted antimicrobial therapy. Most commonly, the pathologist sees nonspecific features in biopsy material that need careful interpretation in a multidisciplinary setting, and where the exclusion of significant pathology is as critical as the less common specific entities. Full autopsies are critical in the evaluation of lung transplant deaths at all intervals following implantation.

    Unsuspected findings are common as in general autopsy practice and their evaluation is critical to the success of lung transplant programmes. A full understanding of lung transplant pathology is also essential to the interpretation of experimental and molecular studies that will no doubt impact clinically in the near future.

  15. Page 158
    Correspondence: M. Estenne, Chest Service, Erasme University Hospital, 808, Route de Lennik, B-1070, Brussels, Belgium.

    After successful reduction of early complications, chronic allgraft dysfunction histologically characterised by small airway obliteration has become the major obstacle to long-term survival. Bronchiolitis obliterans and its clinical correlate bronchiolitis obliterans syndrome affect up to 50–60% of patients who survive 5 yrs after surgery. Accumulated experience from human and animal studies suggests that alloimmune and nonalloimmune injury to the airway epithelium is the initial event followed by ineffective epithelial regeneration and massive inflammation producing aberrant repair with scar tissue obliterating the airway lumen. Risk factors include severe and persistant acute rejection episodes, viral infections, gastro-oesophageal reflux and medication noncompliance. Since most therapies, to date, work by an anti-inflammatory and not an antifibrotic effect, early detection of this complication may be important. Potential early markers in induced sputum, bronchoalveolar lavage and exhaled breath condensate are discussed. The clinical presentation, clinical management and therapeutic strategies, as well as suggestions for future research, are reviewed.

  16. Page 179
    Correspondence: J.B. Orens, Johns Hopkins Hospital, 1830 East Monument Street, 5th floor, Baltimore, MD 21205, USA.

    The success of lung transplantation (LTx) has improved over time as evidenced by better long-term survival and functional outcomes. Despite the success of this procedure, there are numerous problems and complications that may develop over the life of a lung transplant recipient. With proper monitoring and treatment, the frequency and severity of these problems can be decreased. Still, significant improvement for the overall outcomes of LTx will only occur when better methods exist to prevent or effectively treat chronic rejection.

  17. Page 193
    Correspondence: W. van der Bij, Dept of Pulmonology, University Hospital Groningen, P.O. Box 30001, 9700 RM Groningen, The Netherlands.

    Although the results of lung transplantation have shown a gradual improvement over the past 15 yrs, infectious complications remain an important limitation to patient survival at all stages after transplantation. Lessons from the early years have provided tools to deal with these infectious episodes. During the last decade sophisticated diagnostic techniques and modern antimicrobial agents were developed and implemented in the clinical arena. This progress is landmarked by the following: 1) a drastic reduction of mortality of bacterial infections by well-selected combinations of prophylactic perioperative antibiotics; 2) evolution of cytomegalovirus infection from a potentially lethal disease to a manageable infectious episode, by the development of pp65 antigenaemia and polymerase chain reaction and the introduction of ganciclovir and foscarnet; 3) progress in the therapy (rituximab) of post-transplant lymphoproliferative disorder, and recognition of Epstein-Barr virus as a potential harmful infection in a broader context; 4) the introduction of newer formulations of amphotericin B and a choice of azoles in the battle against fungal disease; 5) the recognition of respiratory viruses as possible co-pathogens in the pathogenesis of bronchiolitis obliterans syndrome, and the development of selective neuraminidase inhibitors as antiviral agents.

    In the near future a number of hurdles still have to be overcome; for example, diagnostic tools to define the immunosuppressed state of the individual transplant recipient, in order to reduce the a priori risk of infection, need to be developed, and the increasing resistance against antibacterial, antiviral and antifungal agents needs to be repelled.

  18. Page 208
    Correspondence: J. Boe, Dept of Respiratory Medicine, Rikshospitalet, 0027 Oslo, Norway.

    Noninfectious complications after lung transplantation (LTx) can be divided according to time post-transplantation into initial postoperative, intermediate and late complications.

    Initial postoperative complications of the bronchial anastomosis are early necrosis, dehiscence or disruption followed by stenosis due to ceased bronchial artery circulation. Bronchial dehiscence and disruption could be managed by bronchoplastic surgery but may need acute retransplantation. Bronchial stenosis is mostly managed by repeated-use dilating balloon catheters, neodymium:yttrium aluminium garnet laser treatment or introduction of bronchial stents and only occasionally bronchoplastic surgery is needed. Phrenic nerve dysfunction as well as vagus nerve injury or other initial operative-related complications are also included in this category.

    Intermediate and late complications, such as reactivated Epstein-Barr virus may cause a post-transplant lymphoproliferative disease (PTLD) of a mostly B-cell phenotype. PTLD treatment includes reduced immunosuppression and antiviral therapy alone or in combination with a variety of treatments. Late complications are also often immunosuppressant drug-induced cancers, nephrotoxicity, systemic hypertension, hyperlipedaemia and osteoporosis.

    Single LTx represents a specific situation as only one of the diseased organs is transplanted. The native lung may influence both the clinical outcome and the occurrence of complications (e.g. hyperinflation, distension of bullae, pneumothorax), and be the source of early and late problems related to the progression of the underlying disease. Differences in compliance between the graft and the native lung can result in ventilation/perfusion mismatches. Noninfectious complications following single LTx are successfully treated in most cases, even when a surgical approach is required.

  19. Page 220
    Correspondence: L.L. Schulman, Columbia University, College of Physicians & Surgeons, 161 Fort Washington Avenue, New York, NY 10032, USA.

    By disrupting pre-existing bronchial, neural, lymphatic and vascular attachments, lung transplantation (LTx) has dramatic effects on pulmonary physiology. These effects extend from the macroscopic level (for example, lung volumes, pulmonary arterial pressures, exercise tolerance) to the microscopic level (for example, alveolar type-II and endothelial cell function). Advances in understanding pulmonary physiological function in the transplanted lung have facilitated clarification of disease states in LTx, as well as providing insight into lung function in nontransplant disease states.

  20. Page 243
    Correspondence: G.B. Mallory Jr, Texas Children's Hospital, 6621 Fannin, CC 1040.00, Houston, TX 77030, USA.

    Lung transplantation (LTx) was pioneered in adults with end-stage lung disease. Over the past decade, this life-saving procedure has been applied to a small but significant number of infants, children and adolescents in a relatively small number of centres around the world. The published results of paediatric LTx demonstrate that post-transplant survival approaches that seen in adults. With the exception of cystic fibrosis, the single leading indication for LTx in individuals <18 yrs of age, the disease entities leading to transplant candidacy are decidedly different in the paediatric age group.

    The majority of patients with pulmonary vascular disease have associated congenital heart disease. The remainder of diagnoses represents a small number of a heterogeneous group of disorders. The surgical approach usually includes cardiopulmonary bypass and single LTx and is much less common than in the adult population. Immunosuppression and antimicrobial prophylaxis are similar to those used in adult LTx. Post-transplant complications of greater prevalence and importance in paediatric lung transplant recipients include a much higher incidence of severe primary viral infections, post-transplant lymphoproliferative disease, and disorders of growth and development. Furthermore, the fact that the transplantation of a child often involves translocation and marked disruption of an entire family leads to potentially deep psychosocial costs to the patient and their family, requiring devoted comprehensive, multidisciplinary team care.

    It seems reasonable to expect that further refinements in the details of care together with improvements in antimicrobial diagnosis and therapy and in both immunosuppression and immunomodulation will lead to better survival, both qualitatively and quantitatively, in the years to come.

  21. Page 257
    Correspondence: M.L. Barr, Dept of Cardiothoracic Surgery, University of Southern California Keck School of Medicine, 1510 San Pablo St, Suite 415, Los Angeles, CA, 90033, USA.

    Living-donor lung transplantation (LTx) was developed as a procedure for adult and paediatric patients considered too ill to await cadaveric transplantation. In lobar LTx, a right and left lower lobe from two healthy donors are implanted in the recipient in place of the complete right and left lungs. Appropriate donor selection is critical to minimise donor morbidity while providing lobes with sufficient pulmonary reserve for the recipient.

    The postoperative management of the lobar recipient can be quite challenging as this creates a physiological condition where the entire cardiac output flows through only two lobes. Efforts to maximise lobar function and minimise pulmonary artery pressure, risk of reperfusion injury, and pulmonary oedema are undertaken through the use of mechanical ventilation, intravenous nitroglycerin, inhaled nitric oxide, maintaining a hypovolaemic state, and careful chest-tube management. Immunosuppression, antibiotic use and prophylaxis, and subsequent follow-up are as with standard cadaveric transplantation.

    Living lobar transplants (n=128) have been performed at the authors' institution since 1992. Actuarial 1-, 3- and 5-yr survival are similar to International Society for Heart and Lung Transplant registry data. Infection has been the major cause of mortality consistent with the high percentage of cystic fibrosis patients in the cohort. Most episodes of rejection have been mild in grade. The incidence of bronchial stenosis and bronchiolitis obliterans syndrome appear to be reduced in lobar transplant recipients. There has been no donor mortality, and morbidity has been relatively low. Long-term postoperative pulmonary function studies demonstrated that the relatively smaller-sized lobes provide similar pulmonary function and exercise capacity to bilateral cadaveric lung transplants. Living lobar LTx should be considered a viable option in patients with end-stage lung disease deemed unable to await a cadaveric organ and in those patients in which further deterioration would make cadaveric transplantation inappropriate.

  22. Page 269
    Correspondence: E.M. TenVergert, Office for Medical Technology Assessment, Groningen University Hospital, PO BOX 30001, 9700 RB Groningen, The Netherlands.

    During the last decades, most Western countries began to experience rising expenditures for healthcare. Since then, health policy-makers try to control these healthcare expenditures. Economic evaluations provide important information on the costs and consequences of different healthcare interventions. For this reason, economic evaluations are a particularly useful tool for decision-makers. The following four types of economic evaluation can be distinguished: the cost-minimisation analysis, the cost-effectiveness analysis, the cost-utility analysis, and finally, the cost-benefit analysis. Results of cost-effectiveness analyses of lung transplantation (LTx) programmes showed that LTx is an effective but expensive treatment. The effectiveness is reflected by the considerable number of life-yrs provided to the recipient.

    However, survival is not the only yardstick by which to measure treatment effectiveness. Quality-of-life data are increasingly important for evaluating the consequences of an intervention such as LTx. Results of most studies showed that patients surviving LTx can expect a considerable improvement in most domains of quality of life.

  23. Page 285
    Correspondence: R.D. Davis Jr, Dept of Surgery, Division of Cardiothoracic Surgery, Duke University Medical Center 3864, Durham, NC 27710, USA.

    While lung transplantation (LTx) has evolved into an effective therapy for the treatment of end-stage lung disease, there are significant limitations to its applicability because of an insufficient number of suitable donor organs. Pulmonary xenotransplantation using swine lungs in humans could provide a solution to this problem. However, pulmonary xenografts are rapidly rejected by mechanisms that are dependent on the expression of antigens by the donor, which are recognised by xenoreactive antibodies in the recipient activating complement and by mechanisms distinct from those causing hyperacute rejection of other organs, including the greater susceptibility of the lung to complement anaphylatoxins, the presence of pulmonary intravascular macrophages, and activation and dysregulation of the coagulation system. By understanding these barriers, prolonged xenograft survival has been achieved.

    Additionally, LTx is limited by the inadequacy of current immunosuppression, which allows ongoing injury to the transplanted organ through immunological attack, and toxicity of immunosuppression causing organ dysfunction, malignancy and infection. Tolerance to donor-specific antigens holds the promise for prolonging graft function and limiting these toxicities. Using methods that have been successful at achieving tolerance in the laboratory (including administration of depleting or blocking agents and those that involve the injection of immunomodulatory cellular populations), tolerance strategies are being applied in humans with success.