Endobronchial valves in a highly parsed emphysema population
Authors: Joseph B Shrager
Journal: The Lancet (2015)

Lung volume reduction surgery is a thoracic surgical procedure whereby the hyperexpanded lungs of patients with severe emphysema are reduced in size by surgical excision of, ideally, the areas that are most severely destroyed.1Brantigan O Mueller E Surgical treatment of pulmonary emphysema.Am Surg. 1957; 23: 789-804PubMed Google Scholar, 2Cooper J Trulock E Triantafillou A et al.Bilateral pneumectomy (volume reduction) for chronic obstructive pulmonary disease.J Thorac Cardiovasc Surg. 1995; 109: 106-116Summary Full Text Full Text PDF PubMed Scopus (894) Google Scholar This operation, usually done bilaterally and almost always by video-assisted thoracoscopy, substantially improves pulmonary function, dyspnoea, and quality of life in appropriately selected patients. Several clinical series show about a 50% mean improvement in forced expiratory volume in 1 s (FEV1),3Cooper JD Patterson GA Sundaresan RS et al.Results of 150 consecutive bilateral lung volume reduction procedures in patients with severe emphysema.J Thorac Cardiovasc Surg. 1996; 112: 1319-1329Summary Full Text Full Text PDF PubMed Scopus (472) Google Scholar and increased survival has been shown in one subgroup of patients.4Fishman A Martinez F Naunheim K et al.A randomized trial comparing lung-volume-reduction surgery with medical therapy for severe emphysema.N Engl J Med. 2003; 348: 2059-2073Crossref PubMed Scopus (1685) Google Scholar Lung volume reduction surgery is among the most carefully studied operations in medicine, having been subjected to many randomised controlled trials, all of which established its effectiveness.4Fishman A Martinez F Naunheim K et al.A randomized trial comparing lung-volume-reduction surgery with medical therapy for severe emphysema.N Engl J Med. 2003; 348: 2059-2073Crossref PubMed Scopus (1685) Google Scholar, 5Miller J Malthaner R Goldsmith C A randomized clinical trial of lung volume reduction surgery versus best medical care for patients with advanced emphysema: a two-year study from Canada.Ann Thorac Surg. 2006; 81: 314-320Summary Full Text Full Text PDF PubMed Scopus (54) Google Scholar, 6Hillerdal G Lofdahl C Strom K et al.Comparison of lung volume reduction surgery and physical training on health status and physiologic outcomes: a randomized controlled clinical trial.Chest. 2005; 128: 3489-3499Crossref PubMed Scopus (37) Google Scholar, 7Goldstein R Todd T Guyatt G et al.Influence of lung volume reduction surgery (LVRS) on health related quality of life in patients with chronic obstructive pulmonary disease.Thorax. 2003; 58: 405-410Crossref PubMed Scopus (68) Google Scholar, 8Geddes D Davies M Koyama H et al.Effect of lung-volume-reduction surgery in patients with severe emphysema.N Engl J Med. 2000; 343: 329-345Crossref Scopus (353) Google Scholar However, as with all operations, lung volume reduction surgery engenders some risk. To receive the benefits, even appropriate candidates for lung volume reduction surgery must accept a 3–4% risk of perioperative death,4Fishman A Martinez F Naunheim K et al.A randomized trial comparing lung-volume-reduction surgery with medical therapy for severe emphysema.N Engl J Med. 2003; 348: 2059-2073Crossref PubMed Scopus (1685) Google Scholar a 1–2 week hospitalisation, and a several week period of recovery. Thus, there has been an effort to try to reduce the risk of lung volume reduction surgery and achieve the same physiological benefits by less invasive approaches. The best studied non-surgical approach to lung volume reduction is bronchoscopic placement of one-way endobronchial valves (bronchoscopic lung volume reduction) designed to shut down air inflow to a segment or lobe, thereby allowing that region to collapse. Randomised studies with these valves, however, have shown very disappointing mean group improvements in various measures of lung function. These studies showed statistically, but not clinically, significant changes when all patients were analysed.9Ninane V Geltner C Bezzi M et al.Multicentre European study for the treatment of advanced emphysema with bronchial valves.Eur Respir J. 2012; 39: 1319-1325Crossref PubMed Scopus (115) Google Scholar, 10Wood DE Nader DA Springmeyer SC et al.The IBV Valve trial: a multicenter, randomized, double-blind trial of endobronchial therapy for severe emphysema.J Bronchol Interv Pulmonol. 2014; 21: 288-297Crossref PubMed Scopus (45) Google Scholar, 11Sciurba F Ernst A Herth F et al.A randomized study of endobronchial valves for advanced emphysema.N Engl J Med. 2010; 363: 1233-1244Crossref PubMed Scopus (649) Google Scholar Post-hoc analyses have suggested, not surprisingly, that those with markedly heterogeneous disease and complete interlobar fissures (which do not allow collateral ventilation across them) improve more with valves than do other patients.11Sciurba F Ernst A Herth F et al.A randomized study of endobronchial valves for advanced emphysema.N Engl J Med. 2010; 363: 1233-1244Crossref PubMed Scopus (649) Google Scholar In The Lancet, Claire Davey and colleagues12Davey C Zoumot Z Jordan S 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; (published online June 24.)http://dx.doi.org/10.1016/S0140-6736(15)60001-0Google Scholar compare bronchoscopic lung volume reduction with sham bronchoscopy in a randomised trial comprising 50 patients with heterogeneous emphysema and intact interlobar fissures. The authors show convincingly that prospective selection of patients with heterogeneous disease and minimal collateral ventilation yields substantially greater improvements than treatment of those without these characteristics. Although the results are not quite as impressive as in the post-hoc analysis of Sciurba and colleagues' study,11Sciurba F Ernst A Herth F et al.A randomized study of endobronchial valves for advanced emphysema.N Engl J Med. 2010; 363: 1233-1244Crossref PubMed Scopus (649) Google Scholar the present trial does show a median 8·77% (IQR 2·27–35·85) improvement in FEV1 after unilateral valve placement, as well as significant improvements in exercise capacity (the higher mean improvement in FEV1 of 24·8% is skewed by a few high-responding outliers). Extrapolation, however unscientific, to expect a nearly doubled effect if bronchoscopic lung volume reduction is done bilaterally might achieve results that are perhaps half of what can be achieved by surgery (18% improvement in FEV1 with valves vs 30–50% with surgery). There are some real strengths to Davey and colleagues' study.12Davey C Zoumot Z Jordan S 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; (published online June 24.)http://dx.doi.org/10.1016/S0140-6736(15)60001-0Google Scholar The design is impressive in its inclusion of sham bronchoscopy in the control group. Very few studies of invasive procedures in medicine have included an actual operated sham group. This truly double-masked design meets the most stringent definition of a high quality clinical trial. It is also notable that the study was funded by the UK Medical Research Council rather than the commercial producer of the valve, eliminating the potential for commercial bias, which has been present in many previous studies of endobronchial valves, nearly entirely. Some very important findings, however, deserve to be more clearly highlighted. First, Davey and colleagues' study12Davey C Zoumot Z Jordan S 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; (published online June 24.)http://dx.doi.org/10.1016/S0140-6736(15)60001-0Google Scholar does not bear out the expectation that bronchoscopic lung volume reduction is substantially less morbid that surgical lung volume reduction. In fact, two (8%) of the patients in the bronchoscopic lung volume reduction group died after the procedure (vs none in the control group). This death rate is higher than the perioperative death rate in nearly all modern surgical series of bilateral surgical lung volume reduction surgery. Although not statistically different between groups, there was also an apparent increase in respiratory and infectious complications in the valve patients: two patients needed valve removal, four expectorated a valve, two had pneumonia (vs zero controls), and two suffered pneumothorax (vs one control). It might be that the better lobar isolation achieved in these patients with intact fissures led to more trouble as well as more benefit. These problems could explain why, despite the improvements in FEV1, the St George's Respiratory Questionnaire scores were no better in treated patients than in controls. Worse, would the rates of each of these problems be doubled if the bronchoscopic lung volume reduction procedure was done bilaterally, as would probably be needed for improvements after the procedure to reach the same ballpark as surgical results? Doubling an 8% mortality reaches a higher death rate than has been seen in any published series of surgical lung volume reduction other than the publication that defined the high-risk subgroup within the NETT trial13National Emphysema Treatment Trial Research GroupPatients at high risk of death after lung-volume-reduction surgery.N Engl J Med. 2001; 345: 1075-1083Crossref PubMed Scopus (599) Google Scholar—a group which now never undergoes the operation. Lung volume reduction surgery is supported by very strong evidence establishing dramatic benefits in properly selected patients. The study by Davey and colleagues12Davey C Zoumot Z Jordan S 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; (published online June 24.)http://dx.doi.org/10.1016/S0140-6736(15)60001-0Google Scholar does suggest that bronchoscopic lung volume reduction might ultimately provide an alternative, albeit one which affords a lesser degree of palliation than surgical lung volume reduction, in the few patients with intact interlobar fissures. However, we must be careful not to let this finding make us forget the great value of surgical lung volume reduction in patients both with and without intact fissures. It seems clear that surgery achieves improvements that are substantially higher than bronchoscopic lung volume reduction will ever be able to achieve—even in the most ideal candidates for bronchoscopic lung volume reduction—and surgery might not even be more morbid. I declare no competing interests. Bronchoscopic lung volume reduction with endobronchial valves for patients with heterogeneous emphysema and intact interlobar fissures (the BeLieVeR-HIFi study): a randomised controlled trialUnilateral lobar occlusion with endobronchial valves in patients with heterogeneous emphysema and intact interlobar fissures produces significant improvements in lung function. There is a risk of significant complications and further trials are needed that compare valve placement with lung volume reduction surgery. Full-Text PDF Open Access