Eur Respir Rev 2012; 21: 126, 271–305 DOI: 10.1183/09059180.00006312 CopyrightßERS 2012 EUROPEAN RESPIRATORY UPDATE Update on lung transplantation: programmes, patients and prospects Tom Kotsimbos*,#, Trevor J. Williams*,# and Gary P. Anderson" The will is infinite and the execution confined…the desire is (BLTx) from 1985 [3], this decade saw the true genesis of boundless and the act a slave to limit clinical lung transplant programmes. Shakespere W. Troilus and Cressida. Act III, Scene ii. HLTx became the early option for lung replacement with Stanford University (Stanford, CA, USA) leading the way Discovery consists of seeing what everyone has seen and thinking under the leadership of Bruce Reitz. A second key US centre in what nobody has thought Pittsburgh was also active. Europe, under the leadership of Anonymous Magdi Yacoub at Harefield Hospital (London, UK) and John Wallwork at Papworth Hospital (Cambridge, UK), developed t has been over 30 yrs since the modern era of lung very active HLTx programmes utilising donors from through- transplantation commenced and what was then the ‘‘new out the UK and the continent. Isolated lung transplantation I frontier and exceptional’’ has now become ‘‘routine and (SLT and BLTx) grew initially out of the Toronto programme expected’’. Strong vision, bold action and creative thinking and with the move of Cooper and Patterson to St Louis (Barnes have led to outstanding progress in the management of end- Hospital, Washington University, St Louis, MO, USA) by the stage lung and pulmonary vascular disease. The purpose of end of the 1980’s these were the dominant programmes. All this article is to highlight what has been achieved, critically these programmes in their infancy had a small nucleus of assess where we are in terms of a ‘‘cure’’ for severe lung surgeons, physicians and co-ordinators who made transplan- disease, and (re)stimulate the creative thinking, action and tation happen, often without well-defined resources. vision that are still very much required to solve the ongoing The most recent report of the International Society for Heart impediments to achieving a durable lung allograft and long- and Lung Transplantation (ISHLT) registry gives a clear view term recipient survival following the life-giving procedure that of the changes in lung transplant activity over 20 yrs [4]. From lung transplantation is, and can be. the mid-1980s, HLTx numbers reported to the ISHLT registry PROGRAMMES: MULTIDISCIPLINARY TEAMS increased rapidly to a peak in 1990 of 276 HLTx in that year. Where did we come from: where are we now? This dropped steadily such that by the late 2000s, 85–100 HLTx are reported to the registry annually. SLT numbers rose History and programme evolution: from cottage industry to rapidly from 1987, reaching a plateau by 1995. Since this time, just expected SLT numbers have been relatively static (700–850) as outlined Lung transplantation has evolved over the last 60 yrs from a in the ISHLT registry reports. BLTx procedures have increased series of remarkable animal experiments to an established every year since 1985. This is now the most commonly treatment of severe end-stage lung and pulmonary vascular performed lung transplant procedure. In 2009, approximately disease fully funded in many jurisdictions. In its infancy it was 2,300 BLTx were reported to the ISHLT registry; the greatest swept along by the determination and drive of surgical number to date. The number of centres now transplanting and pioneers. Amongst them the names Demikhov, Hardy, reporting to the ISHLT registry is 158 for isolated lung Schumway, Cooley, Reitz, Cooper and Patterson have exem- transplants. For HLTx, 114 centres report activity to the plified the surgeons’ drive to bring lung transplantation to ISHLT registry; however 95 centres report two or less HLTx clinical fruition. With long-term survivors of heart–lung per year [4]. transplantation (HLTx) from 1981 [1], single lung transplanta- tion (SLT) from 1983 [2] and bilateral lung transplantation It is fair to say that survival following lung transplantation started at a low base. More than 40 attempts were undertaken over a period of almost 18 yrs before the first long-term *Heart and Lung Transplant Service, Alfred Hospital, Monash University. #Dept of Allergy, survivor was achieved. In 1988–1994, the ISHLT registry Immunology and Respiratory Medicine, Alfred Hospital, Monash University, and "Dept of reported 1-, 2- and 5-yrs survival of 72%, 65% and 49%, Pharmacology, University of Melbourne, Melbourne, Australia. respectively. In the most recent reported era, 2000–2009, this CORRESPONDENCE: T. Kotsimbos, Dept of Medicine, Central and Eastern Clinical School, Monash had improved to 80%, 72% and 54%, respectively [4]. The University, Alfred Hospital, Melbourne, Australia. E-mail: [email protected] substantial improvement in survival is almost completely attributable to improved early survival post-lung transplant. Received: Oct 23 2012. Accepted after revision: Oct 29 2012 Despite a concerted effort in multidisciplinary team-led care of c PROVENANCE: Submitted article, peer reviewed. transplant survivors little impact has been evident on survival EUROPEAN RESPIRATORY REVIEW VOLUME 21 NUMBER 126 271 UPDATE ON LUNG TRANSPLANTATION T. KOTSIMBOS ET AL. beyond the first year [5]. The ISHLT registry reports survival initially performed to expedite revascularisation and anasto- contingent on surviving the first year. What is evident is that motic healing. This proved to be unnecessary in SLT and BLTx. patients who had cystic fibrosis (CF) and pulmonary vascular As noted previously, BLTx was initially performed as an en disease have better survival after the first year compared to bloc procedure with a tracheal anastomosis but, unfortunately, those with chronic obstructive pulmonary disease (COPD) or the death rate due to anastomotic breakdown was unaccep- pulmonary fibrosis. Presumably this reflects the latter being tably high [12]. The procedure was subsequently modified to older patients with more comorbidities. Overall, however, the the bilateral sequential lung transplant procedure with fash- ISHLT registry does not show any significant improvement in ioning of the two telescoped bronchial anastomoses [13]. survival in patients having survived the first year post-lung Airway complications have been commonly seen in up to 20% transplant in more recent eras [4]. of anastomoses, although technical innovations seem to be reducing this incidence [14–16]. Surgical/anaesthetic/intensive care unit management Surgical innovations Post-operative care Incisions The marked improvements in outcome from lung transplanta- There have been relatively minor changes in the surgical tion that have been seen in the last 30 yrs have predominantly approach to lung replacement procedures since the original been driven by improvements in early (3-month) survival. description of these procedures. HLTx is now a very Better recipient selection and surgical improvements have uncommon procedure but midline sternotomy is still utilised. contributed to this, but much of this improved survival SLT is generally performed via a standard lateral thoracotomy; appears attributable to the evolution of improved intensive however, it is sometimes performed via a midline sternotomy care management [17, 18]. facilitating surgical repair or revascularisation of the heart Fluid/inotropes when this is simultaneously performed. A clear understanding of the pathophysiology of the newly Double lung replacement was initially performed via a midline transplanted lung is crucial in developing post-operative fluid sternotomy utilizing a tracheal anastomosis. A high rate of and inotrope strategies. An injured lung is prone to alveolar tracheal anastomotic breakdown led to a redesign of the capillary leak and this situation is confounded by lack of procedure to the ‘‘bilateral sequential’’ BLTx. In this proce- lymphatic drainage of the newly transplanted lung allograft (due dure, a bilateral thoracotomy with transaction of the lower to cutting of lymphatics without re-anastomosis), low oncotic sternum (the so called ‘‘clam shell incision’’) is most often pressure (due to low serum albumin) and sometimes an elevated utilised. The clam shell incision can be particularly problematic pulmonary capillary wedge pressure and a high cardiac output in terms of post-operative pain control (generally mandating state (e.g. in the setting of left ventricle diastolic dysfunction). prolonged epidural anaesthesia) and its impact on respiratory Thus, a rise in hydrostatic pressure readily produces pulmonary muscle function. Variants that have evolved include bilateral oedema, which, when present, can be very slow to resolve. thoracotomy with sternal sparing, as well as a reversion to the Careful management of fluid and inotropes, as well as routine use of a midline sternotomy (especially where revascularisa- monitoring of the circulation utilising a central venous catheter, tion of the bronchial anastomosis with an internal mammary an arterial line and a Swan–Ganz catheter, is therefore needed to artery pedicle is performed) [6]. help minimise early allograft dysfunction syndromes [19, 20]. Echocardiography has also proven valuable in guiding appro- BLTx versus SLT versus HLTx priate setting of fluid input and ionotrope support and to assess As noted previously, HLTx remained the predominant post-transplant complications [21]. technique for lung replacement into the early 1990s. From that time the number