3375 Review Article Lung volume reduction followed by lung transplantation— considerations on selection criteria and outcome Alexis Slama1, Christian Taube2, Markus Kamler3, Clemens Aigner1 1Department of Thoracic Surgery, 2Department of Pneumology, West German Center for Lung Transplantation, University Medicine Essen - Ruhrlandklinik, Essen, Germany; 3Department of Thoracic Transplantation, West German Center for Lung Transplantation, University Medicine Essen - University Clinic, Essen, Germany Contributions: (I) Conception and design: A Slama, C Aigner; (II) Administrative support: None; (III) Provision of study materials or patients: None; (IV) Collection and assembly of data: A Slama, C Aigner; (V) Data analysis and interpretation: A Slama, C Aigner; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors. Correspondence to: Clemens Aigner, MD. Professor of Thoracic Surgery, University Medicine Essen - Ruhrlandklinik, Tueschener Weg 40, 45239 Essen, Germany. Email: [email protected]. Abstract: Lung transplantation (LuTX) and lung volume reduction (LVR), either surgical (LVRS: lung volume reduction surgery) or endoscopic (ELVR: endoscopic lung volume reduction), are established therapies in the treatment of end-stage chronic obstructive pulmonary disease (COPD) patients. Careful patient selection is crucial for each intervention. If these techniques are sequentially applied there is a paucity of available data and individual center experiences vary depending on details in selection criteria and operative technique. This review aims to summarize the published data with a focus on LuTX after LVRS. This review covers patient selection for LuTX and LVR, technical considerations, limitations and outcomes. Published literature was identified by systematic search on Medline and appropriate papers were reviewed. Seven case reports/series, 7 comparative observational studies and one multicenter database analysis incorporating a total of 284 patients with LuTX and LVR were evaluated. Prior LVR can significantly affect intraoperative and postoperative risks after subsequent LuTX. Careful patient selection and timing and the choice of appropriate techniques such as minimal invasive LVRS and using ECMO as extracorporeal support during LuTX if required can minimize those risks, ultimately leading to very good postoperative outcomes in terms of lung function and survival. LVRS has the potential to delay listing and to bridge patients to LuTX by improving their physical condition while on the waiting list. After single lung transplantation (SLuTX) contralateral LVRS can counteract the deleterious effects of native lung hyperinflation (NLH). LVR and LuTX are adjunct therapies in the treatment of end-stage COPD. The combination of both can safely be considered in selected patients. Keywords: Lung transplantation (LuTX); lung volume reduction surgery (LVRS); endoscopic lung volume reduction (ELVR); chronic obstructive pulmonary disease (COPD); primary graft dysfunction (PGD); emphysema Submitted Jun 25, 2018. Accepted for publication Jun 29, 2018. doi: 10.21037/jtd.2018.06.164 View this article at: http://dx.doi.org/10.21037/jtd.2018.06.164 Introduction for affected patients. Surgical treatment options in end- stage COPD patients are lung volume reduction surgery As chronic obstructive pulmonary disease (COPD) remains (LVRS) and lung transplantation (LuTX). Bronchoscopic one of the leading causes of morbidity and mortality in the LVR techniques have evolved in parallel, however no developed world, tremendous effort has been undertaken prospective randomized data comparing surgical and to improve medical therapy and surgical treatment options bronchoscopic LVR techniques are available yet. LVR is © Journal of Thoracic Disease. All rights reserved. jtd.amegroups.com J Thorac Dis 2018;10(Suppl 27):S3366-S3375 Journal of Thoracic Disease, Vol 10, Suppl 27 October 2018 S3367 considered independent of LuTX however might also serve malignancy, incompliance or an untreatable infectious as a means to delay the listing for LuTX and bridge patients disease (5,7). Relative contraindications include: age >65 to the transplant procedure. The choice which procedure is years, obesity, cachexia, osteoporosis, hepatitis/HIV suitable in individual situations has been highly debated in infection, acute respiratory failure (under mechanical literature and different algorithms have been suggested for ventilation or ECMO) and cardiac comorbidities. individual decision-making (1). It is unanimously accepted that LVRS does not preclude subsequent LuTX. The Patient selection for LVRS first report on LVRS as an option to bridge patients to LuTX dates back to 1995 (2). In addition, LVRS has been To this date, the strongest evidence regarding LVRS reported on the contralateral side after previous single lung derives from the NETT-trial (national emphysema transplantation (SLuTX) to reduce hyperinflation of the treatment trial) published in 2003 and updated in 2006 after remaining native lung (3). In this review will discuss optimal a four-year follow-up (8,9). In this series of 1,218 patients patient selection, special consideration and published (randomized 1:1 into a LVRS group and a best SOC group) outcomes of patients undergoing both LVR and LuTX. four subgroups were identified based on their differential risk and benefit after LVRS. Their inclusion criteria in terms of patient candidacy for LVRS are still valid and with COPD patient selection for LuTX the knowledge about the patient outcome an algorithm was Generally, patients with emphysema are referred to LuTX suggested to decide between LVRS and LuTX (1). Briefly, after exhaustion of all other treatment options. It is of LVRS should be considered for patients with an upper-lobe utmost importance to select candidates whose quality of life predominant emphysema, an FEV1 between 45% and 20% and disease related survival will improve after LuTX (1,4), of the predicted value and a DLCO not less than 20% as since particularly in COPD patients the overall survival those patients will have a significant advantage in exercise benefit of LuTX is not as clear as in other indications. capacity and dyspnea related quality of life (10). Findings According to the guidelines published by the International of the NETT trial have been reproduced in a study of Society of Heart and Lung Transplantation (ISHLT) in the STS database (11) and in the Canadian Lung Volume 2014, patients suffering from emphysema should be referred Reduction Surgery (CLVRS) trial (12). The first, compared early to a lung transplant for assessment of transplant post-operative results of 538 patients to the data published suitability (5). Criteria for referral are: ongoing progression in the NETT trial (n=608). Although a significantly higher of disease despite maximum therapy, hypercapnia (paCO2 30-day mortality was observed in comparison with the >50 mmHg), hypoxemia (paO2 <60 mmHg) or a significantly NETT non-high-risk subset (5.6% vs. 2.2%; P=0.005), the reduced lung function (FEV1 <25% of predicted). analysis with the total NETT cohort didn’t showed those Alternatively, a BODE index of or above five has been differences. This demonstrates the importance of precise suggested as a suitable threshold for referral (6). Further, and strict patient selection. The latter study assed the long- those guidelines suggest a listing for LuTX when certain term survival of patients randomized within the multicentric functional criteria are fulfilled. The proposed criteria are: Canadian Lung Volume Reduction Surgery (CLVRS) trial. heavily reduced lung function (FEV1 <20% of predicted), Although not significant, an improved median survival frequent exacerbations (≥3/Y), hypercapnic respiratory was observed for the LVRS group compared to the best- failure, a BODE Index ≥7 or an associated pulmonary medical-care group (63 vs. 47 months; P=0.2) leading the hypertension (only one criterion needed). However, the authors to conclude that LVRS offers better outcomes for optimal timing for listing is also depending on the local patients who survive the initial increased mortality within organ availability and the allocation algorithm in use. the early post-operative period. There are only few absolute contraindications for LuTX, Even repeat LVRS (Re-LVRS) has been described to be however there is a long list of relative contraindications successful in highly selected patients (13). In this series of which have to be considered on an individual basis. 22 patients, lung function was improved and breathlessness Those vary in detail depending on the center approach. reduced after Re-LVRS with outcomes comparable by any Absolute contraindications are: multi organ failure (with means (Hospitalization, drainage time; surgical revisions, the exception of temporary kidney failure in selected perioperative mortality) to those after the patients first LVRS. patients and planned multi-organ transplantation), recent Recently, all evidence about the effectiveness of LVRS © Journal of Thoracic Disease. All rights reserved. jtd.amegroups.com J Thorac Dis 2018;10(Suppl 27):S3366-S3375 S3368 Slama et al. LVRS and LuTX Table 1 Reported literature on LVRS prior to LuTX LuTX LVRS/ Significant different Comparable parameters Author Year Center (n) LuTX (n) parameters at/after LuTX at/after LuTX Zenati 1995 Pittsburg – 1 Zenati 1996 Pittsburg – 7 Bavaria 1998 Philadelphia – 3 Meyers 2001 St. Louis – 15 Wisser 2000 Vienna 15 15 Mortality Bleeding complications