Simon Jordan

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.

Emphysema: time to say farewell to therapeutic nihilism

It is an interesting time for the management of emphysema. In this condition, destruction of lung parenchyma associated with reduced elastic recoil and dynamic airways closure produce gas trapping and increased operating lung volumes, leading to breathlessness and exercise limitation. It has historically been defined as an irreversible process, which has led to a degree of therapeutic nihilism. One manifestation of this has been the curious neglect of lung volume reduction surgery (LVRS). Clinical guidelines,1 reflecting trial evidence,2 recommend consideration of LVRS in selected patients with upper lobe predominant emphysema and poor exercise capacity, the phenotype where surgery has been shown to produce a survival benefit. Modern surgical techniques, unilateral treatment and improved postoperative care and patient selection mean that LVRS is also associated with lower morbidity and mortality than data published at the turn of the century had suggested,3 ,4 with one recent case series reporting zero 90-day mortality following unilateral surgery.5 Nevertheless, little effort seems to be going into identifying this patient population and LVRS remains vastly underused with just 90 procedures taking place in the UK in 2010–2011. A partial explanation for this may be found in a recent survey of British Thoracic Society members that revealed that a significant proportion overestimated the morbidity and mortality associated with LVRS.6 Only 30% had access to a dedicated chronic obstructive pulmonary disease (COPD) multidisciplinary meeting to review patients, and there was no consensus as to the correct strategy to adopt to identify appropriate patients. Over the last decade, bronchoscopic approaches for lung volume reduction in emphysema have proliferated. These include one-way endobronchial valves to induce lobar collapse,7–10 airway bypass approaches to create low-resistance extra-anatomical pathways that allow trapped …

Unilateral extrapulmonary airway bypass in advanced emphysema.

BACKGROUND Gas trapping in emphysema results in resting and dynamic hyperinflation. We tested the hypothesis that a direct connection between the lung parenchyma and the atmosphere could increase expiratory flow and thereby potentially improve dyspnea through the relief of gas trapping. METHODS Ex vivo we studied 7 emphysematous lungs and 3 fibrotic lungs (as controls) and measured expiratory flow before and after airway bypass insertion during a forced maneuver in an artificial thorax. Pilot studies were conducted in vivo in 6 patients with advanced emphysema using a size 9 endotracheal tube as a bypass surgically placed through the chest wall into the upper lobe. RESULTS In the ex vivo emphysematous lungs the volume expelled during a forced expiratory maneuver increased from 169 to 235 mL (p < 0.05). In the in vivo group 4 patients retained the bypass tube for 3 months or more; total lung capacity was reduced, and the forced expiratory volume in 1 second increased by 23% (mean percent predicted at baseline versus 3 months, 24.4% versus 29.5%). CONCLUSIONS An extrapulmonary airway bypass increases expiratory flow in emphysema. This may be a useful approach in hyperinflated patients with homogeneous emphysema.

A prospective, randomized trial comparing BioGlue and Vivostat for the control of alveolar air leak

OBJECTIVE BioGlue (CryoLife, Europa Ltd, Surrey, UK) is effective in reducing alveolar air leak after pulmonary resection. However, concerns exist regarding the use of bovine-derived products. Vivostat (Vivostat A/S, Alleroed, Denmark) is an autologous fibrin sealant that confers certain advantages. It shows superior elastic properties, a faster absorption time, and the absence of risk of transmission of blood-borne diseases. METHODS We conducted a randomized, single blind controlled study to compare BioGlue and Vivostat in the control of postoperative air leak. Primary endpoints were duration of air leak, time to intercostal drain removal, and length of hospital stay. Secondary endpoints related to postoperative complications. RESULTS Between December 2005 and December 2007, 103 patients were randomized. The analysis included 102 patients; 67% were male. Median age was 56 +/- 19 years. Indications for surgery were primary lung cancer in 41 patients (40%), secondary malignancy in 48 patients (47%), carcinoid in 6 patients (6%), and 7 patients underwent surgery for benign disease (7%). Bilobectomy was performed in 2 patients (2%), lobectomy in 41 patients (40%), lobectomy with lesser resection in 3 patients (3%), segmentectomy in 16 patients (16%), precision excision in 34 patients (33%), and 6 patients underwent other resections (6%). Median duration of air leak was 3 (0-32) days versus 2 (0-33) days for patients who received BioGlue and Vivostat, respectively (P = .677). Time to intercostal drain removal was 5 (1-32) days in the BioGlue group compared with 5 (1-34) days for the Vivostat group (P = .473). Median hospital stay was 8 (3-22) days versus 7 (2-29) days for the BioGlue and Vivostat groups, respectively (P = .382). There was no significant difference in the incidence of complications between the 2 groups (20 patients receiving BioGlue versus 19 patients receiving Vivostat, P = .839). CONCLUSIONS There were no significant differences in the 3 clinical outcome measures of duration of air leak, time to intercostal drain removal, and length of hospital stay in those patients receiving BioGlue or Vivostat. Given the inherent advantages of our institutional preference is to use Vivostat in the control of postoperative air leaks after pulmonary resection.

Predicting the need for intensive care following lung resection.

On the basis of the evidence available, the authors would suggest a decision making algorithm to determine the need for ICU admission postoperatively similar to that shown in Fig. 1. First, patients should quit smoking at least 1 month and preferably 2 months before surgery. Those over the age of 70 years should receive elective ICU admission. Second, those at increased risk of general anesthesia, as judged by ASA and performance status scores and cardiovascular risk assessment, should be prebooked into the ICU in the postoperative period. A ppo FEV1 of less than 44% should warrant additional monitoring rather than mandate ICU admission. Pre-existing fibrotic lung disease mandates ICU admission. Third, perioperatively, protective (low tidal volume) ventilatory strategies should be applied during one lung ventilation. Patients undergoing one lung ventilation, and especially those undergoing extensive lymphatic dissection, should be monitored closely for signs of ALI in the first 5 days postoperatively. This, together with any indication of postoperative complications such as POP, BPF or empyema, should mandate immediate transfer to the ICU.

Lung Volume Reduction in Emphysema Improves Chest Wall Asynchrony

BACKGROUND: Lung volume reduction (LVR) techniques improve lung function in selected patients with emphysema, but the impact of LVR procedures on the asynchronous movement of different chest wall compartments, which is a feature of emphysema, is not known. METHODS: We used optoelectronic plethysmography to assess the effect of surgical and bronchoscopic LVR on chest wall asynchrony. Twenty-six patients were assessed before and 3 months after LVR (surgical [n = 9] or bronchoscopic [n = 7]) or a sham/unsuccessful bronchoscopic treatment (control subjects, n = 10). Chest wall volumes were divided into six compartments (left and right of each of pulmonary ribcage [Vrc,p], abdominal ribcage [Vrc,a], and abdomen [Vab]) and phase shift angles (θ) calculated for the asynchrony between Vrc,p and Vrc,a (θRC), and between Vrc,a and Vab (θDIA). RESULTS: Participants had an FEV1 of 34.6 ± 18% predicted and a residual volume of 217.8 ± 46.0% predicted with significant chest wall asynchrony during quiet breathing at baseline (θRC, 31.3° ± 38.4°; and θDIA, −38.7° ± 36.3°). Between-group difference in the change in θRC and θDIA during quiet breathing following treatment was 44.3° (95% CI, −78 to −10.6; P = .003) and 34.5° (95% CI, 1.4 to 67.5; P = .007) toward 0° (representing perfect synchrony), respectively, favoring the LVR group. Changes in θRC and θDIA were statistically significant on the treated but not the untreated sides. CONCLUSIONS: Successful LVR significantly reduces chest wall asynchrony in patients with emphysema.

Attitudes and access to lung volume reduction surgery for COPD: a survey by the British Thoracic Society.

Objective Lung volume reduction surgery for emphysema leads to improved survival in appropriately selected individuals, and it is therefore recommended in national and international guidelines for this group of patients. Despite this, fewer than 100 patients undergo the procedure each year in the UK. Our objective was to establish whether this reflects concerns about morbidity and mortality or difficulties in the referral pathway. Design and setting We conducted a survey of members of the British Thoracic Society by email to investigate this in the second half of 2013. The survey included questions about access to investigations, the indications for lung volume reduction surgery (LVRS), whether a multidisciplinary meeting discussed eligibility of patients for LVRS and what the morbidity and mortality associated with the procedure was. Results There were 65 responses, 82% from respiratory physicians. Roughly half of the respondents were either unsure about the risks of death or prolonged (>30 days) hospital stay involved or significantly over-estimated them. In total, 70% did not have a specific multidisciplinary team to discuss the management of patients with advanced chronic obstructive pulmonary disease (COPD). There was no consensus as to which patients with COPD should undergo a CT scan to evaluate them for possible surgery. Conclusions Patients with COPD require a systematic and multidisciplinary approach to assessment for LVRS and these survey data suggest that work is needed to deliver this evidence-based therapy in a consistent and comprehensive way across the UK.

Type A and AB thymomas: histological features associated with increased stage.

The current WHO classification of thymic epithelial neoplasms describes type A and type AB thymomas as behaving ‘like benign neoplasms’. However, recent published data suggest that rare cases may show more aggressive behaviour. The aim of this study was to assess the frequency of atypical cases, and to determine whether atypia is associated with more advanced disease.

Evidence of mycobacterial disease in COPD patients with lung volume reduction surgery; the importance of histological assessment of specimens: a cohort study

BackgroundPatients with COPD are at risk of non-tuberculous mycobacterial infection (NTM). This study examined the histology of lung tissue from COPD patients following lung volume reduction with particular focus on evidence of mycobacterial infection.MethodsRetrospective histological study of 142 consecutive lung volume reduction surgical specimens (126 separate patients) at Royal Brompton Hospital between 2000 – 2013, with prospectively collected preoperative data on exacerbation rate, lung function and body mass index.Results92% of patients had at least one other histological diagnosis in addition to emphysema. 10% of specimens had histological evidence of mycobacterial infection, one with co-existent aspergilloma. Mycobacteria were only identified in those patients with granulomas that were necrotising. These patients had higher exacerbation rates, lower TLCO and FEV1.ConclusionA proportion of severe COPD patients will have evidence of mycobacterial infection despite lack of clinical and radiological suspicion. This may have implications for long-term management of these patients.