title: Bronchoscopic lung volume reduction with endobronchial valves for patients with heterogeneous emphysema and intact interlobar fissures (the BeLieVeR-HIFi study): a randomised controlled trial.
abstract: BACKGROUND
  Lung volume reduction surgery improves survival in selected patients with emphysema, and has generated interest in bronchoscopic approaches that might achieve the same effect with less morbidity and mortality. Previous trials with endobronchial valves have yielded modest group benefits because when collateral ventilation is present it prevents lobar atelectasis.
  
  
  METHODS
  We did a single-centre, double-blind sham-controlled trial in patients with both heterogeneous emphysema and a target lobe with intact interlobar fissures on CT of the thorax. We enrolled stable outpatients with chronic obstructive pulmonary disease who had a forced expiratory volume in 1 s (FEV1) of less than 50% predicted, significant hyperinflation (total lung capacity >100% and residual volume >150%), a restricted exercise capacity (6 min walking distance <450 m), and substantial breathlessness (MRC dyspnoea score ≥3). Participants were randomised (1:1) by computer-generated sequence to receive either valves placed to achieve unilateral lobar occlusion (bronchoscopic lung volume reduction) or a bronchoscopy with sham valve placement (control). Patients and researchers were masked to treatment allocation. The study was powered to detect a 15% improvement in the primary endpoint, the FEV1 3 months after the procedure. Analysis was on an intention-to-treat basis. The trial is registered at controlled-trials.com, ISRCTN04761234.
  
  
  RESULTS
  50 patients (62% male, FEV1 [% predicted] mean 31·7% [SD 10·2]) were enrolled to receive valves (n=25) or sham valve placement (control, n=25) between March 1, 2012, and Sept 30, 2013. In the bronchoscopic lung volume reduction group, FEV1 increased by a median 8·77% (IQR 2·27-35·85) versus 2·88% (0-8·51) in the control group (Mann-Whitney p=0·0326). There were two deaths in the bronchoscopic lung volume reduction group and one control patient was unable to attend for follow-up assessment because of a prolonged pneumothorax.
  
  
  CONCLUSIONS
  Unilateral 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.
  
  
  BACKGROUND
  Efficacy and Mechanism Evaluation Programme, funded by the Medical Research Council (MRC) and managed by the National Institute for Health Research (NIHR) on behalf of the MRC-NIHR partnership.
authors.affiliation: NIHR Respiratory Disease, Biomedical Research Unit at the Royal Brompton and Harefield NHS Foundation Trust, and Imperial College London, London, UK.
authors.forename: Claire
authors.initials: C
authors.lastname: Davey
authors.affiliation: NIHR Respiratory Disease, Biomedical Research Unit at the Royal Brompton and Harefield NHS Foundation Trust, and Imperial College London, London, UK.
authors.forename: Zaid
authors.initials: Z
authors.lastname: Zoumot
authors.affiliation: NIHR Respiratory Disease, Biomedical Research Unit at the Royal Brompton and Harefield NHS Foundation Trust, and Imperial College London, London, UK.
authors.forename: Simon
authors.initials: S
authors.lastname: Jordan
authors.affiliation: NIHR Respiratory Disease, Biomedical Research Unit at the Royal Brompton and Harefield NHS Foundation Trust, and Imperial College London, London, UK.
authors.forename: William H
authors.initials: WH
authors.lastname: McNulty
authors.affiliation: NIHR Respiratory Disease, Biomedical Research Unit at the Royal Brompton and Harefield NHS Foundation Trust, and Imperial College London, London, UK.
authors.forename: Dennis H
authors.initials: DH
authors.lastname: Carr
authors.affiliation: NIHR Respiratory Disease, Biomedical Research Unit at the Royal Brompton and Harefield NHS Foundation Trust, and Imperial College London, London, UK.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Hind
authors.affiliation: NIHR Respiratory Disease, Biomedical Research Unit at the Royal Brompton and Harefield NHS Foundation Trust, and Imperial College London, London, UK.
authors.forename: David M
authors.initials: DM
authors.lastname: Hansell
authors.affiliation: NIHR Respiratory Disease, Biomedical Research Unit at the Royal Brompton and Harefield NHS Foundation Trust, and Imperial College London, London, UK.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Rubens
authors.affiliation: NIHR Respiratory Disease, Biomedical Research Unit at the Royal Brompton and Harefield NHS Foundation Trust, and Imperial College London, London, UK.
authors.forename: Winston
authors.initials: W
authors.lastname: Banya
authors.affiliation: NIHR Respiratory Disease, Biomedical Research Unit at the Royal Brompton and Harefield NHS Foundation Trust, and Imperial College London, London, UK.
authors.forename: Michael I
authors.initials: MI
authors.lastname: Polkey
authors.affiliation: NIHR Respiratory Disease, Biomedical Research Unit at the Royal Brompton and Harefield NHS Foundation Trust, and Imperial College London, London, UK.
authors.forename: Pallav L
authors.initials: PL
authors.lastname: Shah
authors.affiliation: NIHR Respiratory Disease, Biomedical Research Unit at the Royal Brompton and Harefield NHS Foundation Trust, and Imperial College London, London, UK. Electronic address: n.hopkinson@ic.ac.uk.
authors.forename: Nicholas S
authors.initials: NS
authors.lastname: Hopkinson
mesh_terms: D000368:Aged; D001999:Bronchoscopy / Q000379:methods*; D004311:Double-Blind Method; D017079:Exercise Tolerance / Q000502:physiology; D005260:Female; D005541:Forced Expiratory Volume / Q000502:physiology; D006801:Humans; D008176:Lung Volume Measurements / Q000379:methods; D008297:Male; D008875:Middle Aged; D019736:Prostheses and Implants; D019919:Prosthesis Implantation / Q000379:methods; D011656:Pulmonary Emphysema / Q000000981:diagnostic imaging / Q000503:physiopathology / Q000601:surgery*; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome