ORIGINAL ARTICLE European Journal of Cardio-Thoracic Surgery 52 (2017) 982–988 doi:10.1093/ejcts/ezx242 Advance Access publication 31 July 2017 Cite this article as: Perikleous P, Sharkey A, Oey I, Bilancia R, Tenconi S, Rathinam S et al. Long-term survival and symptomatic relief in lower lobe lung volume reduction surgery. Eur J Cardiothorac Surg 2017;52:982–8. Long-term survival and symptomatic relief in lower lobe lung volume reduction surgery† Periklis Perikleous, Annabel Sharkey, Inger Oey, Rocco Bilancia, Sara Tenconi, Sridhar Rathinam and David A. Waller* Department of Thoracic Surgery, Glenfield Hospital, University Hospitals of Leicester, Leicester, UK * Corresponding author. Department of Thoracic Surgery, Glenfield Hospital, University Hospitals of Leicester, Groby Road, Leicester LE3 9QP, UK. Tel: +44-116-2563959; e-mail: email@example.com (D.A. Waller). Received 29 November 2016; received in revised form 12 March 2017; accepted 30 March 2017 Abstract OBJECTIVES: Lung volume reduction surgery (LVRS) has been demonstrated to provide symptomatic relief and improve lung function in patients with end-stage emphysema. The National Emphysema Treatment Trial specifically noted functional benefits in patients with predominantly upper lobe emphysema and demonstrated improvement in quality-of-life parameters, in patients with non-upper lobe emphysema and a low-baseline exercise capacity. We aimed to investigate whether physiological and health status benefits correlated with lower lobe LVRS. METHODS: A retrospective analysis was performed from our prospectively collected patient database. A total of 36 patients with severe, non-upper lobe predominant emphysema underwent lower lobe LVRS in our institution, over a 20-year period. The assessments consisted of measurements of body mass index, pulmonary function tests and health-related quality of life using the Short Form 36-item questionnaires. RESULTS: Forced expiratory volume in 1 s was seen to improve 3 months [coefficient of time = 1.55 (0.88, 2.21); P < 0.0001] after the procedure, maintained until the first 6 months [0.48 (0.12, 0.85); P = 0.010], decline over the second half of the first year and gradually return to preoperative levels after 2 years, while residual volume to total lung capacity (%) ratio was seen to follow a similar pattern with significant decrease from baseline after 3 months [coefficient of time = -1.76 (-2.75, -0.76); P = 0.001] and 6 months [-1.05 (-1.51, -0.59); P < 0.0001]. Quality-of-life improvements were mainly noted in physical components. CONCLUSIONS: Contrary to a widely held misconception following the National Emphysema Treatment Trial that lower lobe lung volume reduction does not offer significant benefits to patients with non-upper lobe predominant emphysema, we feel justified in offering lower lobe LVRS in these patients when they meet the same selection criteria as upper lobe LVRS. Keywords: Lung volume reduction surgery • Emphysema • Lower lobe • LVRS • Thoracic surgery • NETT INTRODUCTION The National Emphysema Treatment Trial (NETT) showed that lung volume reduction surgery (LVRS) provides symptomatic relief and improved lung function in patients with end-stage emphysema. More specifically, it demonstrated that LVRS offers an overall increase in the chance of improved exercise capacity but does not confer a survival advantage over medical therapy, except for patients with both predominantly upper lobe emphysema and low-baseline exercise capacity. Patients previously reported to be at high risk and patients with non-upper lobe emphysema and high-baseline exercise capacity were regarded as †Presented at the 24th Annual Meeting of the European Conference on General Thoracic Surgery, Naples, Italy, 29 May–1 June 2016. poor surgical candidates because of increased mortality and negligible functional gain . Because maximal benefits were found in patients with predominantly upper lobe emphysema and low-baseline exercise capacity, whereas the non-upper predominant group sustained increased mortality and trifle results, many pulmonologists, as well as thoracic surgeons, falsely presumed that lower lobe LVRS was not indicated for all patients. The goal of our study was to challenge this misconception. The NETT remains to this time the largest and most complete collection of patient demographics, clinical, physiological and radiographic data ever compiled in severe emphysema. However, great progress has been made in the constantly evolving field of LVRS since the outcomes of the NETT were published in 2003. Subsequent reports highlighted the importance of examining the overall pathogenesis of emphysema and its response to C The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved. V P. Perikleous et al. / European Journal of Cardio-Thoracic Surgery METHODS Data collection A retrospective analysis was performed from a prospectively populated patient database, operative logbooks and patients’ medical records. The assessments consisted of measurements of body mass index, pulmonary function tests (PFTs) and health-related quality of life using the Short Form 36-item questionnaires (SF-36), over 3-, 6-, 12- and 24-month time intervals. Patient population We identified 40 lower lobe LVRS procedures performed on 36 individual patients [22 male (61.11%)] with severe, non-upper lobe predominant emphysema, from a grand total of 382 LVRS procedures performed in our institution over a 20-year period (1996–2016). Four patients had undergone staged bilateral lower lobe procedures, and we only considered their first procedure in our analysis. Alpha1-antitrypsin deficiency (a1-AD) was diagnosed in 14 (38.89%) patients. Only 1 patient (who was confirmed to be a1-antitrypsin deficient) of the 36 patients had not previously smoked. All patients underwent physical examination, basic spirometry, plethysmography, arterial blood gas analysis, chest radiography, computed tomography and quantitative radionuclide perfusion scintigraphy. For 33 patients (91.67%), unilateral LVRS was performed via video-assisted thoracoscopic surgery (VATS), guided by target areas on the quantitative perfusion scan. For 2 (5.56%) patients, median sternotomy and bilateral lower lobe reduction were performed (1996 and 1998). For 1 patient (2.78%), VATS had to be converted to open thoracotomy to allow lung mobilization because of extensive adhesions. All operations were performed by 1 of 3 surgeons (D.A.W., S.R. and T.J.S.) in the same hospital. All preoperative investigations, operative procedures and postoperative follow-up were paid for by the National Health Service. Patient selection criteria Patients in our institution are offered LVRS following discussion at a dedicated multidisciplinary team (MDT) meeting consisting of a team of thoracic surgeons, pulmonologists and radiologists. Patients with emphysema are considered for LVRS if they are symptomatic with breathlessness, despite optimized medical management, including pulmonary rehabilitation. Our inclusion criteria comprises patients with evidence of obstructive disease [forced expiratory volume in 1 s (FEV1) <40% predicted] and hyperinflation [residual volume to total lung capacity ratio >55%]. Also, for patients to be offered surgical management, a carbon monoxide diffusing capacity >20% is required (a carbon monoxide diffusing capacity of <20% is not considered an absolute contraindication, patients can be considered for LVRS if FEV1 > 20% predicted; written informed consent is obtained for high-risk patients), as well as clear target areas on both high-resolution computed tomography and perfusion scintigraphy. Our exclusion criteria consist of pulmonary hypertension (mean pulmonary arterial pressure >40 mmHg) and hypercapnia with partial pressure of carbon dioxide >7 kPa. Patients who are excluded continue to receive medical management or are referred for lung transplant as appropriate. We have summarized our MDT approach in a retrospective analysis of prospectively collected data on 633 patients referred for LVRS between July 1995 and July 2013 . Of those, 382 did not proceed to surgery for a variety of reasons including absence of target areas for resection on a quantitative perfusion scan, patients were deemed to be ‘too good’ (either by the MDT because their pulmonary function did not show severe enough airway obstruction and/or hyperinflation or because the patients felt they were too good to consider surgery at this stage), respiratory failure (hypercapnia and/or pulmonary hypertension), previous thoracic surgery or other associated respiratory conditions (frequent exacerbations, bronchiectasis or lung fibrosis). Sixteen patients whom the MDT did not consider to be suitable for an intervention during the time they were first discussed were rediscussed on follow-up meetings and offered surgery when deemed appropriate. Before surgery, patients are required to quit smoking for a period of at least 6 months and are encouraged to attend a pulmonary rehabilitation programme following which they would be expected to successfully complete a shuttle walk test at 150 m or more. We do not routinely perform shuttle walk tests during our postoperative follow-ups due to limited resources. Patients who are reassessed for staged bilateral procedures undertake a shuttle walk test as part of their preoperative workup. Prior to surgery, but after rehabilitation, patients were asked to complete SF-36 health status questionnaires. The SF-36 is a generic health status questionnaire, in which 36 questions cover 8 health domains: physical functioning, social functioning, role limitations due to physical problems, role limitations due to emotional problems, mental health, energy/vitality, pain and general health status. For each domain, scores are transformed to range from 0 (worst possible health status) to 100 (best possible health status) . Surgical approach At the start of our LVRS programme, operations were performed bilaterally via median sternotomy or VATS. Throughout the years, THORACIC medical therapy, identified specific risk factors that can attribute to increased mortality, and underlined the potential negative consequences of malnutrition and oxygen desaturation . Updated data proved LVRS to be long-term more cost–effective, compared with medical therapy, and emphasized on alternative approaches for LVRS that are less invasive and could be offered as an alternative treatment to patients unfit for surgical intervention . A valuable lesson that was learned from NETT is that LVRS can be a safe and an effective disease-modifying therapy for a large group of carefully selected patients suffering from severe emphysema . Computed tomographic measurements  and perfusion scintigraphy  can provide significant information towards selection of patients that would be expected to benefit the most out of LVRS, with regard to anatomical disease distribution. Even though the benefits for patients with non-upper lobe predominant emphysema are more modest and short lived, compared with the ones with upper lobe predominant disease , there is still a statistically significant improvement in their functional measurements as well as their quality of life, which can further be extended by a staged bilateral approach to LVRS, dictated by patients’ perception of their condition [7, 8]. 983 P. Perikleous et al. / European Journal of Cardio-Thoracic Surgery 984 our surgical techniques have been revised and optimized to improve postoperative respiratory mechanics, minimize complication rates and reduce hospital stay. Currently, all LVRS procedures performed in our centre are executed via a unilateral VATS approach with 2–3 ports and all our patients are offered epidural analgesia prior to anaesthetic induction to aid with mobilization and expectoration of secretions postoperatively. The epidural infusion contains fentanyl 5 mcg ml with bupivacaine 0.1% in 250 ml 0.9% saline. Patients are discharged home on oral analgesia as appropriate. Patients included in this study at earliest stages had stapled resection of functionless areas of lung using buttresses (Peri Strips, Synovis Life Technologies Inc., St Paul, MN, USA; Gore Seamguard, WL Gore and Associates Inc., Flagstaff, AZ, USA; Peristrips Dry, Veritas, Synovis Life Technologies Inc.; or BiodesignV Staple Line Reinforcement, Cook Medical, Bloomington, IN, USA). Most recently, we have adopted another technique to provide better aerostasis to prevent and reduce the occurrence and duration of postoperative air leaks, in which TissuePatchTM (Tissuemed Surgical Technologies, UK), a synthetic, self-adhesive film with a multilayer structure is applied at the staple lines for reinforcement . BioGlueV Surgical Adhesive (CryoLife Inc., Kennesaw, GA, USA) has also been used according to individual surgeon preference. Lung volume is reduced via non-anatomical stapled resection of the emphysematous and poorly perfused areas of the lobes, as previously identified by imaging. The number of firings used to complete the operation and the weight of the resected tissue are documented in the patient’s operative notes. Most patients had approximately 40% resected (50–80 g) from their lower lobes. Lower lobe LVRS can be technically more challenging compared with the upper lobes, as there are no clear anatomical marks to follow while attempting to remodel the lung. In some patients, lung tissue from other areas of the lung had been resected (bullectomy), guided by intraoperative appearances of the lung. At the end of the procedure, 1 or 2 drains are positioned to the chest cavity and remain connected to Rocket under water seal bottles (Rocket Medical, UK) or Thopaz digital drainage system (Medela, Switzerland). Following their operation, patients are extubated in theatres and transferred to a high-dependency unit. Suction -2 kPa on Thopaz digital drainage system or -5 kPa wall suction for Rocket under water seal bottles is applied only if there is significant lung collapse on the postoperative chest films. Significant surgical emphysema is further managed by insertion of a subcutaneous drain . R R Postoperative follow-up Patients with prolonged air leaks can be discharged home with their drains connected to Heimlich valve bags (Portex Ltd, Hythe, UK) and are regularly reviewed in clinics, until the air leak resolves and then the drain is removed. All patients are routinely reviewed in outpatient clinics at 3, 6, 12 months and then yearly after their surgery. At each visit, patients undergo detailed spirometry and plethysmography. They also complete SF-36 health status questionnaires. Statistical analysis Categorical data are represented as number (percentage), while numerical variables are represented as mean (95% confidence interval). Generalized linear models were used to estimate the effect of time on the various variables considering that repeated measures were made. For each model, the baseline value and time were included as covariates, and the coefficient of time with its 95% confidence intervals was reported as effect of time on each of the variables. Several models were generated, e.g. from 0 to 3 months and 0 to 6 months. To correct for multiple comparison, a pragmatic decision was made to set the significance level at 0.01 for each model. Survival data were analysed using the Kaplan–Meier method. Statistical analyses were performed with the use of IBM SPSS Statistics for Windows (version 23.0, IBM Corp. Released 2016; IBM Corp., Armonk, NY, USA). RESULTS Thirty-six patients [22 male (61.11%)] with a mean age of 59 years underwent a total of 40 procedures (4 second stage) between 1996 and 2016. For the patients with staged procedures, only the first intervention was considered for data analysis. Of the 36 patients, a1-AD was confirmed in 14 (38.89%) patients. Baseline mean values are presented in Table 1. Median follow-up was 9.5 years. There were significant changes in FEV1 from baseline to 3 months and from baseline to 6 months. The results suggest that between 0 and 3 months, for every unit increase in time on the average, the FEV1 increased by 1.55% and the corresponding result for 0–6 months was 0.48% for a unit increase in time (Table 2, Fig. 1). There were also significant changes in the residual volume to total lung capacity ratio from baseline to 3 months and from baseline to 6 months. The results suggest that between 0 and 3 months, for every unit increase in time on the average, the residual volume to total lung capacity ratio decreased by 1.76 and the corresponding result for 0–6 months was 1.05 for a unit increase in time (Table 2, Fig. 2). No statistically significant changes were observed in measurements of body mass index or the a1-AD group. Quality-of-life improvements were mainly noted in physical components. There was sustained improvement in physical function and brief improvement in general health perceptions and role limitations Table 1: Baseline characteristics Variables n Mean (95% CI) FEV1 (%) RV/TLC (%) FVC (%) DLCO (%) BMI (kg/m2) Physical functioning Bodily pain Physical role functioning General health perceptions Vitality Social role functioning Emotional role functioning Mental health 34 33 34 34 30 26 26 26 26 26 26 26 26 27.9 (24.8 to 30.9) 68.0 (64.7 to 71.2) 62.7 (55.9 to 69.5) 40.2 (35.6 to 44.8) 22.8 (21.6 to 23.8) 20.1 (13.3 to 26.8) 70.9 (60.9 to 81.0) 15.4 (5.1 to 25.7) 26.5 (20.9 to 32.0) 30.2 (22.6 to 37.8) 42.3 (31.8 to 52.8) 57.7 (38.4 to 76.9) 63.8 (56.4 to 71.3) FEV: forced expiratory volume in 1 s; RV: residual volume; TLC: total lung capacity; FVC: forced vital capacity; DLCO: carbon monoxide diffusing capacity; BMI: body mass index; CI: confidence interval. P. Perikleous et al. / European Journal of Cardio-Thoracic Surgery 985 Table 2: Results overview: change in parameters over time (using time as covariate in model) Variables Period (months) FEV1 Physical component Mental component Short Form-36 quality-of-life questionnaire RV/TLC Physical functioning Bodily pain Physical role functioning General health perceptions Vitality Social role functioning Emotional role functioning Mental health 0–3 0–6 0–12 0–24 1.55 (0.88 to 2.21) 0.0001 -1.76 (-2.75 to -0.76) 0.001 4.98 (2.52 to 7.44) <0.0001 -8.87 (-9.51 to -4.22) <0.0001 6.69 (2.03 to 11.35) 0.005 3.19 (0.86 to 5.53) 0.007 5.73 (3.56 to 7.90) <0.0001 6.05 (1.52 to 10.58) 0.009 0.53 (-6.27 to 7.33) 0.88 0.99 (-1.78 to 3.77) 0.48 0.48 (0.12 to 0.85) 0.010 -1.05 (-1.51 to -0.59) < 0.0001 1.55 (0.10 to 3.01) 0.036 -2.67 (-4.32 to -1.01) 0.002 1.38 (-1.35 to 4.12) 0.32 0.72 (-0.62 to 2.07) 0.29 1.93 (0.53 to 3.33) 0.007 2.15 (-0.44 to 4.73) 0.10 -1.09 (-5.15 to 2.97) 0.60 1.24 (-0.23 to 2.71) 0.097 0.05 (-0.16 to 0.25) 0.66 -0.31 (-0.56 to -0.06) 0.013 0.89 (0.29 to 1.57) 0.010 -0.92 (-4.32 to -1.01) 0.002 0.003 (-1.30 to 1.30) 0.99 0.19 (-0.62 to 1.00) 0.64 0.36 (-0.35 to 1.07) 0.33 0.96 (-0.22 to 2.14) 0.11 -0.15 (-2.08 to 1.78) 0.88 0.49 (-0.20 to 1.18) 0.16 -0.06 (-0.17 to 0.05) 0.30 -0.04 (-0.18 to 0.09) 0.54 Coeff. time (95% CI) P-value Coeff. time (95% CI) P-value Coeff. time (95% CI) P-value Coeff. time (95% CI) P-value Coefficient time (95% CI) P-value Coeff. time (95% CI) P-value Coeff. time (95% CI) P-value Coeff. time (95% CI) P-value Coeff. time (95% CI) P-value Coeff. time (95% CI) P-value THORACIC FEV1: forced expiratory volume in 1 s; RV: residual volume; TLC: total lung capacity; Coeff. time: coefficient of time; CI: confidence interval. Figure 1: FEV1 improved significantly over a period of 6 months and returned to preoperative levels 2 years postoperatively. FEV1: forced expiratory volume in 1 s. Figure 2: RV/TLC decreased significantly over a period of 6 months and returned to preoperative levels 2 years postoperatively. RV: residual volume; TLC: total lung capacity. due to physical health. Pain was, as expected, worse following the operation and that was sustained for 1 year after the operation (Table 2, Fig. 3). No changes have been evidenced in mental health or role limitations due to emotional problems. Social functioning despite a brief improvement remained practically unchanged while vitality remained improved for a period of 6 months, before returning to preoperative levels at the end of the first year (Table 2, Fig. 4). Overall, median survival was calculated at 5 years (60 months), while 2 patients died within the first 90 days following their operation (mortality: 90 days, 5.6%; 1 year, 8.3%; 2 years, 11.4%; 5 years, 52.9%) (Fig. 5). Of these 2 patients, 1 patient who underwent LVRS via a median sternotomy in 1996, was transferred to intensive care immediately after the procedure and remained there until the time of death 5 days later. The other patient had undergone LVRS via a unilateral VATS procedure in 2007 and was discharged home with a drain in situ due to prolonged air leak. While at home, the patient suffered a cardiac arrest and died 20 days after the procedure while an inpatient at the local hospital. Overall mortality in our series of all LVRS patients is estimated to be 4.2% at 30 days, 8.9% at 90 days and 12% at 1 year. On multivariate analysis, we have found that factors associated independently with death are body mass index of <18.5 kg/m2, FEV1 of <0.71 l and carbon monoxide diffusing capacity of <20%. There was no association between site of lung resection and mortality. For our preoperative assessment, we have implemented a perioperative risk score, ‘The Glenfield BFG score’, according to which we inform patients at higher risk for surgery during their consultation in clinics . DISCUSSION Lung hyperinflation impairs chest wall and respiratory muscle mechanics, increases breathlessness, decreases exercise performance and increases mortality, while it may also have important negative consequences to cardiac performance . LVRS better matches the size of the lungs to the size of the thorax containing them, thus restoring forced expiratory volumes and the mechanical advantage of the 986 P. Perikleous et al. / European Journal of Cardio-Thoracic Surgery Figure 3: Physical component: sustained improvement in physical functioning with brief improvement in general health perception and physical role. Worse pain following the operation which was sustained. Figure 4: Mental component: improvement in vitality was sustained for 6 months following the procedure but returned to baseline levels after the end of the first year. Social role function improved only briefly, and no changes were observed in mental health and role emotional components. inspiratory muscles. In patients with heterogeneous emphysema, LVRS may also allow space occupied by air cysts to be reclaimed by more normal lung . In patients with a good target area (functionless lung) and evident hyperinflation with preserved diffusion capacity, we would expect to see a benefit regardless of which part of lung is resected, as the remodelling of the lung alone should improve the mechanics of breathing and lower the burden that the diseased lung puts on the right ventricular function. The purpose of our study was to emphasize that patients with lower lobe predominant emphysema should not be excluded Figure 5: Kaplan–Meier survival estimate. from consideration of LVRS based on the results of the NETT. Even though the success of the trial is undisputed when it comes to identifying groups of patients that would have the most benefit or be at unnecessary risk from a volume reduction operation, for patients with lower lobe predominant disease there is, undeniably, a grey area. These patients should be appropriately referred by their physicians to dedicated MDT meetings where their cases will be individually assessed. The way NETT was designed does not allow safe conclusions to be drawn for the management of lower lobe emphysema. For the purposes of analysis, the distribution of emphysema was radiologically classified as predominantly affecting the upper lobes, predominantly affecting the lower lobes, diffuse or predominantly affecting the superior segments of the lower lobes, and all 3 latter categories were grouped together as predominantly non-upper lobe emphysema. A ratio of perfusion in the upper lung regions to that in the lower regions was quantified based on radionuclide scans; the results, however, were not interpreted in a uniform way but separately at each centre . A post hoc analysis of the trial, which was performed to determine whether lung perfusion could predict response to LVRS in patients who had complete scintigraphy results at baseline, showed that in patients with non-upper lobe predominant emphysema, measurement of upper zone perfusion did not provide any prognostic information . In our department, only 10% of patients who underwent LVRS had non-upper lobe surgery. Comparing patients who have undergone upper lobe to lower lobe LVRS has been outside of the scope of our study. We do not believe that a direct comparison between upper and lower lobe LVRS patients will result to safe conclusions as to who should have surgery and who should not. The NETT and subsequent studies have shown that there are other disorders that contribute to emphysema , among them a1-AD, which has been found to affect primarily the lower lobes . Apart from the NETT, not many studies have addressed lower lobe LVRS. In our study, 39% of patients had a1-AD, and there was no statistically significant difference between them and the nona1-AD-deficient group. It has been suggested that physiological changes observed in patients with a1-AD having undergone lower lobe LVRS could be attributed to increased lung elastic recoil . A study by Tutic et al.  showed that LVRS in patients with advanced emphysema related to a1-AD resulted in a significant improvement in dyspnoea and lung function as long as 3.5 years; however, the magnitude and duration of these effects are inferior and shorter than those in patients with pure smoker’s emphysema. Further study of individuals who had long-term benefits showed a 987 clear heterogeneity of the destruction of the lung with wellpreserved lung beside a largely destroyed lung as well as minimal signs of chronic inflammatory airway disease. Stoller et al.  highlighted trends of lower magnitude and duration of FEV1 rise after surgery in a1-AD versus a1-antitrypsin-replete subjects and higher mortality in deficient individuals, suggesting caution in recommending LVRS in a1-AD. Several other studies noted benefits from LVRS regardless of different morphologic types. Hamacher et al.  showed maintained functional and subjective improvements for at least 24 months after LVRS in patients with heterogeneous or homogeneous emphysema types . With the advancement of alternative approaches for lung volume reduction [22, 23], data show that patients with lower lobe disease could have comparable benefits without the need to undergo surgery , which can be technically challenging, as resection typically requires shaving of the ‘bottom of the pyramid’. In a minority of cases, where most of the lower lobe is nonfunctional, a lower lobectomy may be considered; however, the same result could potentially be achieved by an endobronchial approach. The relative risks and benefits of LVRS and bronchoscopic lung volume reduction are yet to be prospectively compared, but there is no current evidence to consider one modality and not the other. Specific algorithms consider bronchoscopic lung volume reduction to be the treatment of choice for lower lobe predominant emphysema; however, LVRS should not be ruled out in this context . It should also be noted that for endobronchial volume reduction to be successful, patients will need to have intact fissures; LVRS currently remains the intervention of choice for those with collateral ventilation. We believe that LVRS for patients with non-upper lobe disease is justified in a carefully selected population, who fulfil the same remaining criteria as the ones with upper lobe disease. It can result in reduced morbidity with evident physiological benefits. The advancement of minimally invasive procedures as well as the concept of staged bilateral procedures will act accumulatively in offering symptomatic relief and improvement to quality of life of these patients, by ‘resetting the time’ in the natural progression of their disease. Unfortunately, there may not be sufficient patients with lower lobe predominant emphysema who meet the required selection criteria for a prospective randomized comparison, either with medical therapy or with endobronchial methods. Limitations The limitations of this study are its non-randomized, retrospective nature, the heterogeneity of its population and of the surgical procedures performed, the effect of the learning curve, the relatively small number of patients with lower lobe LVRS and the non-appearance of a control group to compare the natural course of best medical treatment. CONCLUSIONS Contrary to widely held misconception following the NETT that lower lobe lung volume reduction does not offer significant benefits to patients with non-upper lobe predominant emphysema, we feel justified in offering LVRS in patients meeting standard selection criteria with non-upper lobe predominant disease. Our results suggest that lower lobe LVRS results in evident physiological and functional improvements. THORACIC P. Perikleous et al. / European Journal of Cardio-Thoracic Surgery 988 P. Perikleous et al. / European Journal of Cardio-Thoracic Surgery Patients should be considered on an individual case-by-case basis for lower lobe LVRS, especially if they have heterogeneous disease with a clear target area and are significantly hyperinflated. The principle is to remove as much non-functioning lung as possible to restore chest wall mechanics.   ACKNOWLEDGEMENTS The initial few cases were performed by Tomasz J. Spyt who has retired from National Health Service practice.   Funding  This research received no specific grant; all preoperative investigations, operative procedures and postoperative follow-up were paid for by the National Health Service.    Conflict of interest: none declared.  REFERENCES  National Emphysema Treatment Trial Research Group. A randomized trial comparing lung-volume–reduction surgery with medical therapy for severe emphysema. N Engl J Med 2003;348:2059–73.  Criner GJ, Cordova F, Sternberg AL, Martinez FJ. The National Emphysema Treatment Trial (NETT) part I: lessons learned about emphysema. Am J Respir Crit Care Med 2011;184:763–70.  Criner GJ, Cordova F, Sternberg AL, Martinez FJ. The National Emphysema Treatment Trial (NETT) part II: lessons learned about lung volume reduction surgery. Am J Respir Crit Care Med 2011;184:881–93.  Ginsburg ME, Thomashow BM, Yip CK, DiMango AM, Maxfield RA, Bartels MN et al. Lung volume reduction surgery using the NETT selection criteria. Ann Thorac Surg 2011;91:1556–61.  Washko GR, Martinez FJ, Hoffman EA. Physiological and computed tomographic predictors of outcome from lung volume reduction surgery. Am J Respir Crit Care Med 2010;181:494–500.  Chandra D, Lipson DA, Hoffman E, Hansen-Flaschen J, Sciurba FC, DeCamp M et al. Perfusion scintigraphy and patient selection for lung volume reduction surgery. Am J Respir Crit Care Med 2010;182:937–46.  Oey IF, Morgan MDL, Spyt TJ, Waller DA. Staged bilateral lung volume reduction surgery—the benefits of a patient-led strategy. Eur J Cardiothorac Surg 2010;37:846–52.  Waller DA, Oey I. Staged lung volume reduction surgery—rationale and experience. Thorac Surg Clin 2009;19:187–92.  Rathinam S, Oey I, Steiner M, Spyt T, Morgan MD, Waller DA. The role of the emphysema multidisciplinary team in a successful lung volume reduction surgery programme. Eur J Cardiothoracic Surg 2014;46:1021–6.  Ware JE Jr, Sherbourne CD. The MOS 36-item short-form health survey (SF36): conceptual framework and item selection. Med Care 1992;30:473–81.  Bilancia R, Oey I. Use of surgical sealant films to reduce hospital stay after video assisted thoracoscopic lung volume reduction. Societa D’ Italiana di Chirurgia Toracica 35 Congresso, 2016;35:196–7.  Boulemden A, Aifesehi P, Pajaniappane A, Lau K, Bajaj A, Nakas A et al. Subcutaneous drain insertion in patients with post-operative extensive     subcutaneous surgical emphysema: a single centre experience. Gen Thorac Cardiovasc Surg 2013;61:707–10. Greening NJ, Vaughn P, Oey I, Steiner MC, Morgan MD, Rathinam S et al. Individualised risk in patients undergoing lung volume reduction surgery (LVRS): The Glenfield BFG Score. Eur Respir J 2017;49:1601766. DOI: 10.1183/13993003.01766-2016. Fessler HE, Scharf SM, Ingenito EP, McKenna RJ Jr, Sharafkhaneh A. Physiologic basis for improved pulmonary function after lung volume reduction. Proc Am Thorac Soc 2008;5:416–20. Fishman A, Martinez F, Naunheim K, Piantadosi S, Wise R, Ries A et al; National Emphysema Treatment Trial Research Group. A randomized trial comparing lung-volume–reduction surgery with medical therapy for severe emphysema. N Engl J Med 2003;348:2059–73. DeMeo DL, Hersh CP, Hoffman EA, Litonjua AA, Lazarus R, Sparrow D et al. Genetic determinants of emphysema distribution in the national emphysema treatment trial. Am J Respir Crit Care Med 2007;176:42–8. Jones MC, Thomas GO. Alpha1 antitrypsin deficiency and pulmonary emphysema. Thorax 1971;26:652. Gelb AF, McKenna RJ, Brenner M, Fischel R, Zamel N. Lung function after bilateral lower lobe lung volume reduction surgery for a1-antitrypsin emphysema. Eur Respir J 1999;14:928–33. Tutic M, Bloch KE, Lardinois D, Brack T, Russi EW, Weder W. Long-term results after lung volume reduction surgery in patients with alpha1antitrypsin deficiency. J Thorac Cardiovasc Surg 2004;128:408–13. Stoller JK, Gildea TR, Ries AL, Meli YM, Karafa MT, National Emphysema TTRG. Lung volume reduction surgery in patients with emphysema and alpha-1 antitrypsin deficiency. Ann Thorac Surg 2007;83:241–51. Hamacher J, Bloch KE, Stammberger U, Schmid RA, Laube I, Russi EW et al. Two years’ outcome of lung volume reduction surgery in different morphologic emphysema types. Ann Thorac Surg 1999;68:1792–8. Choi M, Lee WS, Lee M, Jeon K, Sheen S, Jheon S et al. Effectiveness of bronchoscopic lung volume reduction using unilateral endobronchial valve: a systematic review and meta-analysis. Int J Chron Obstruct Pulmon Dis 2015;10:703–10. Davey C, Zoumot Z, Jordan S, McNulty WH, Carr DH, Hind MD et al. Bronchoscopic lung volume reduction with endobronchial valves for patients with heterogeneous emphysema and intact interlobar fissures (the BeLieVeR-HIFi study): a randomised controlled trial. Lancet 2015; 386:1066–73. Eberhardt R, Herth FJ, Radhakrishnan S, Gompelmann D. Comparing clinical outcomes in upper versus lower lobe endobronchial valve treatment in severe emphysema. Respiration 2015;90:314–20. Eberhardt R, Gompelmann D, Herth FJ, Schuhmann M. Endoscopic bronchial valve treatment: patient selection and special considerations. Int J Chron Obstruct Pulmon Dis 2015;10:2147–57. APPENDIX. CONFERENCE DISCUSSION Dr I. Polyakov (Krasnodar, Russian Federation): It is interesting for me, because the author used this technique to remove the affected zone in the lower lobe. For me it is not clear why I should remove the targeted zone in the upper lobe if it is not affected by disease. Dr Perikleous: I am not sure I understand the question. It had to do with the lower lobes entirely. Dr Polyakov: Yes, just remove the targeted zone in the lower lobe, but nobody can force me to remove the upper lobe if it is not affected by disease. Dr Perikleous: Yes, of course. Dr Polyakov: But in general, do you prefer removing the targeted zone from the upper lobe or the lower lobe in your practice? Dr Perikleous: We are talking about patients with non-upper lobe predominant disease. So the upper lobe is in better condition and that is why we go for the lower lobes.