Claire Davey

Bronchoscopic lung volume reduction with endobronchial valves for patients with heterogeneous emphysema and intact interlobar fissures (the BeLieVeR-HIFi study): a randomised controlled trial

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. FINDINGS 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. INTERPRETATION 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. FUNDING 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.

Bronchoscopic lung volume reduction with endobronchial valves for patients with heterogeneous emphysema and intact interlobar fissures (The BeLieVeR-HIFi trial): study design and rationale

Although lung volume reduction surgery improves survival in selected patients with emphysema, there has been ongoing interest in developing and evaluating bronchoscopic approaches to try to reduce lung volumes with less morbidity and mortality. The placement of endobronchial valves is one such technique, and although some patients have had a significant improvement, responses have been inconsistent because collateral ventilation prevents lobar atelectasis. We describe the protocol of a trial (ISRCTN04761234) aimed to show that a responder phenotype, patients with heterogeneous emphysema and intact interlobar fissures on CT scanning, can be identified prospectively, leading to a consistent benefit in clinical practice.

The Impact of Homogeneous Versus Heterogeneous Emphysema on Dynamic Hyperinflation in Patients With Severe COPD Assessed for Lung Volume Reduction

Abstract Dynamic hyperinflation (DH) is a pathophysiologic hallmark of Chronic Obstructive Pulmonary Disease (COPD). The aim of this study was to investigate the impact of emphysema distribution on DH during a maximal cardiopulmonary exercise test (CPET) in patients with severe COPD. This was a retrospective analysis of prospectively collected data among severe COPD patients who underwent thoracic high-resolution computed tomography, full lung function measurements and maximal CPET with inspiratory manouvers as assessment for a lung volume reduction procedure. ΔIC was calculated by subtracting the end-exercise inspiratory capacity (eIC) from resting IC (rIC) and expressed as a percentage of rIC (ΔIC %). Emphysema quantification was conducted at 3 predefined levels using the syngo PULMO-CT (Siemens AG); a difference >25% between best and worse slice was defined as heterogeneous emphysema. Fifty patients with heterogeneous (62.7% male; 60.9 ± 7.5 years old; FEV1% = 32.4 ± 11.4) and 14 with homogeneous emphysema (61.5% male; 62.5 ± 5.9 years old; FEV1% = 28.1 ± 10.3) fulfilled the enrolment criteria. The groups were matched for all baseline variables. ΔIC% was significantly higher in homogeneous emphysema (39.8% ± 9.8% vs.31.2% ± 13%, p = 0.031), while no other CPET parameter differed between the groups. Upper lobe predominance of emphysema correlated positively with peak oxygen pulse, peak oxygen uptake and peak respiratory rate, and negatively with ΔIC%. Homogeneous emphysema is associated with more DH during maximum exercise in COPD patients.

Endobronchial valves for patients with heterogeneous emphysema and without interlobar collateral ventilation: open label treatment following the BeLieVeR-HIFi study

Outcomes in early trials of bronchoscopic lung volume reduction using endobronchial valves for the treatment of patients with advanced emphysema were inconsistent. However improvements in patient selection with focus on excluding those with interlobar collateral ventilation and homogeneous emphysema resulted in significant benefits in the BeLieVeR-HIFi study compared with sham treated controls. In this manuscript we present data from the control patients in the BeLieVeR-HIFi study who went on to have open label endobronchial valve treatment after completion of the clinical trial (n=12), combined with data from those in the treatment arm who did not have collateral ventilation (n=19). Three months after treatment FEV1 increased by 27.3 (36.4)%, residual volume reduced by 0.49 (0.76) L, the 6 min walk distance increased by 32.6 (68.7) m and the St George Respiratory Questionnaire for COPD score improved by 8.2 (20.2) points. These data extend the evidence for endobronchial valve placement in appropriately selected patients with COPD. Trial registration number: ISRCTN04761234; Results.

Significance of Patent Foramen Ovale in Patients with GOLD Stage II Chronic Obstructive Pulmonary Disease (COPD)

Background: Patent foramen ovale (PFO) is a common finding in adults. A PFO is associated with right to left shunting but its importance in the aetiology of hypoxia in early COPD remains uncertain, although it has not proved possible to demonstrate a role for PFOs in the aetiology of hypoxia in patients with Global Initiative for chronic Obstructive Lung Disease (GOLD) stage III/IV disease. We compared the characteristics of GOLD stage II patients with or without a PFO and assessed its impact on exercise performance. Methods: In 22 GOLD stage II COPD patients we measured exercise performance, arterial oxygen tension and lung function and used contrast transcranial Doppler ultrasonography (TCD) to assess the presence of a PFO. Patients (n=20) underwent TCD measurements during incremental cycle ergometry with respiratory pressures measured using an esophageal balloon catheter (n=13). Results:Twelve individuals (54%) had a PFO. Patients with a PFO were more hypoxic; mean(SD) partial pressure of oxygen in arterial blood (PaO2)10.2(1.1) kilopascals (kPa) vs. 11.7(0.9)kPa (p<0.01), but the presence of a PFO was not associated with reduced exercise performance either on cycle ergometry or a 6 Minute Walk Test (6MWT). A strong relationship was noted between the esophageal pressure swing (PSwingEs) and the degree of shunting observed during exercise (r=0.7; p<0.001). Conclusions:The presence of a PFO in GOLD stage II COPD patients does not appear to influence exercise performance despite increased right-to-left shunting.

British Thoracic Society quality standards for home oxygen use in adults

Introduction The purpose of the quality standards document is to provide healthcare professionals, commissioners, service providers and patients with a guide to standards of care that should be met for home oxygen provision in the UK, together with measurable markers of good practice. Quality statements are based on the British Thoracic Society (BTS) Guideline for Home Oxygen Use in Adults. Methods Development of BTS Quality Standards follows the BTS process of quality standard production based on the National Institute for Health and Care Excellence process manual for the development of quality standards. Results 10 quality statements have been developed, each describing a key marker of high-quality, cost-effective care for home oxygen use, and each statement is supported by quality measures that aim to improve the structure, process and outcomes of healthcare. Discussion BTS Quality Standards for home oxygen use in adults form a key part of the range of supporting materials that the society produces to assist in the dissemination and implementation of a guideline’s recommendations.

Endobronchial valves for emphysema: an individual patient-level reanalysis of randomised controlled trials

Introduction Endobronchial valve placement has potential as a treatment for patients with chronic obstructive pulmonary disease (COPD). However, a robust evidence base will be needed to convince commissioners of healthcare that it is a high-value treatment. We sought to develop the evidence base by performing an individual patient-level analysis of randomised controlled trials in people with heterogeneous emphysema and an absence of collateral ventilation. Methods A literature search (PROSPERO register CRD42016048127) identified two trials meeting these criteria, the BelieVeR-HIFi and STELVIO studies. Anonymised individual patient data were obtained from investigators and analysed. The primary outcome measure was a comparison of change in forced expiratory volume in 1 s (FEV1) from baseline between the treatment and control groups. Secondary end points were change from baseline in 6 min walk distance (6MWD), Medical Research Council dyspnoea score and St George’s Respiratory Questionnaire (SGRQ). Results 114 individuals were treated with 3-month to 6-month follow-up data available for 101 individuals. FEV1 improved by 23.1 (±28.3)% in patients treated with valves with a mean (95% CI) difference in response between groups of 17.8 (26.5, 9.2)% (p<0.0001). Relative to controls valve placement was associated with a fall in residual volume of 0.64 (0.43, 0.86) L (p<0.0001), a 9.5 (3.5, 15.6) unit fall in SGRQ (p=0.0022) and a 64.2 (94.0, 34.5) m increase in 6MWD. There were three deaths in the treatment arm and the pneumothorax rate was 15%. Conclusions These data strengthen the evidence that endobronchial valve treatment can produce clinically meaningful improvements in appropriately selected COPD patients.