O9.2 Lung volume reduction surgery and other techniques

Lung volume reduction surgery (LVRS) involves resection of the most severely affected areas of emphysematous, non-bullous lung (Cooper 1995). This can improve lung elastic recoil and diaphragmatic function (Geddes 2000). The National Emphysema Treatment Trial was a large randomised multicentre study which investigated the effectiveness and cost-benefit of this procedure (NETT 1999). A total of 1,218 patients with severe emphysema underwent pulmonary rehabilitation and were then randomised to LVRS or continued medical therapy. Pulmonary rehabilitation plays an important role in preparing patients for interventions such as lung volume reduction (Ries 2005). There was no overall survival advantage of surgery, but after 24 months there was significant improvement in exercise capacity in the surgical group. Patients allocated to LVRS took significantly longer (median 2 v 1 year) than those who continued medical therapy to reach a composite endpoint of death or meaningful deterioration in disease related quality of life (Benzo 2009). Among patients with predominantly upper lobe emphysema and impaired exercise capacity, mortality was significantly lower in the surgical than the medical group. However, high risk patients with diffuse emphysema and well preserved exercise capacity are poor candidates for surgery because of increased mortality and negligible functional gain (Fishman 2003) [evidence level II]. A 2016 Cochrane review on lung volume reduction surgery was very heavily influenced by data from the NETT study (van Agteren 2016) [evidence level I]. The authors concluded that short-term mortality was higher for LVRS (odds ratio (OR) 6.16, 95% CI 3.22 to 11.7 than for control, but long-term mortality favoured LVRS (OR 0.76, 95% CI 0.61 to 0.95) level 1. 96% of the patients contributing to the long term mortality data is from patients enrolled in the NETT study. The authors made note of high post-operative complications, especially persistent air leak and pneumonia.

A variety of nonsurgical techniques are currently under investigation. These include endobronchial one-way valves, self-activating coils, targeted destruction of emphysematous tissue, bypass tract airway stenting and transpleural ventilation.

Several randomised controlled trials examining endobronchial valves have been reported (Sciurba 2010, Herth 2012, Davey 2015, Klooster 2015, Wood 2014, Valipour 2016). All trials recruited highly selected COPD patients with severe obstruction and gas trapping and excluded patients with significant hypercapnia (PaCO2 > 50mmHg) and poor mobility (6MWD < 140m). The Wood trial was unique in that stents were placed bilaterally and collateral ventilation was not excluded. Patients in the trials by Sciurba, Herth and Davey underwent pulmonary rehabilitation prior to randomisation. Only the Davey and Wood trials used a sham placebo bronchoscopy. Davey and Klooster and Valipour specifically recruited patients with intact interlobar fissures on CT chest. Klooster and Valipour went further by excluding patients with collateral ventilation detected at bronchoscopy by the Chartis system. Valipour specifically recruited patients with homogenous rather than upper lobe predominant emphysema. All but the Wood trial reported improvements in FEV1. Data on improvement in exercise outcomes was variable with positive results in the trials by Herth, Davey, Klooster and Valipour. Data on adverse events was significant. The Sciurba and Wood trials reported high hospital admissions for COPD exacerbations, Klooster reported an 18% pneumothorax rate, Valipour reported a 26% pneumothorax rate and Davey reported small numbers of severe complications.

The Klooster trial was most thorough in excluding patients with collateral ventilation using both the intact lobar fissure on CT chest and the Chartis system during bronchoscopy. This may explain why this trial had the most impressive results. The trials where the control arm used sham placebo bronchoscopy reported no difference between the study arms with respect to improvement in quality of life. Valves cannot yet be recommended as routine therapy. Davey recognises the high complication rates and appropriately calls for future trials to compare valve placement with surgical lung volume reduction.

A small (n=45) non blinded randomised controlled trial comparing lung volume reduction coils to standard care showed significant improvement in quality of life, lung function and six minute walk distance at 90 days (Shah 2013). Of the 23 patients receiving the intervention, two sustained a pneumothorax. 22 patients from the control arm went on to receive endobronchial coils, with significant improvement in quality of life, six minute walk distance (and to a lesser degree lung function) at day 180 and 360 (Zoumot 2015). Deslee has reported on the largest randomised control trial (non-blinded) to date (Deslee 2014). 100 highly selected patients were randomised to usual care or bilateral coil placement. All patients had under gone pulmonary rehabilitation. The pre-specified primary end point of percentage of patients achieving a 54m improvement in 6 minute walk distance at 6 months was met (36% vs. 18% P=0.03). However at 12 month follow up there was no significant difference in mean improvement in 6 minute walk distance. There were sustained improvements in spirometry and quality of life at 12 months. Pneumonia rates were far higher in the coil group (18% vs 4% P=0.03) but pneumothorax rates were similar between the two groups. Cost effectiveness analysis found the treatment to be prohibitively expensive (12 month incremental cost effectiveness ratio was approximately $1,000,000 per QALY).

van Agteren performed a meta-analysis of endobronchial lung volume reduction surgery (van Agteren 2017) [evidence level I].  Results from 14 trials comprising almost 2,000 participants were analysed.  The authors concluded that evidence for short-term (up to one year) improvements in disease status were most evident for studies testing endobronchial valves (five studies) and coils (three studies), including improvements in lung function and quality of life.  The authors note a significant increase in adverse events. The odds ratio for an adverse event reported for trials examining endobronchial valves was 5.85 (95% CI 2.16-15.84) and the overall odds ratio for an adverse event amongst all endobronchial lung volume reduction techniques was 3.00 (95% CI 2.04-4.43). Pneumothorax rates of over 20% were reported in several endobronchial valve trials.  It is important to note the authors’ concerns regarding the lack of sham bronchoscopy and/or unclear status of blinding in some studies that may cause a risk of bias.

Herth et al (Herth 2016b) performed an open label, multi centre, randomised control trial of staged, single lobe segmental steam thermal ablation on 70 patients with severe COPD and hyperinflation. All patients had undergone pulmonary rehabilitation and had a six minute walk distance over 140m. Patients with incomplete fissures and collateral ventilation were not excluded. At six months, there was a significant improvement in lung function and quality of life but not six minute walk distance. 24% of patients undergoing steam thermal ablation experienced a COPD exacerbation compared with 4% of controls. This procedure is not available in Australasia and its precise role is not yet clear, but as further long term data emerge this may be an option for patients with severe COPD and hyperinflation with collateral ventilation.

A non-blinded randomised control trial comparing endobronchial lung volume reduction using Emphysematous Lung Sealant (ELS) was terminated early due to loss of funding prior to the 12 month pre-specified endpoints (Come 2015). Limited data at 6 months showed significant improvements in spirometry, 6MWD, QoL and dyspnoea. However the complication rate was unacceptably high with increased hospitalisations (44% vs. 17%) and serious adverse events with two deaths in the intervention arm and no deaths in the control arm [evidence level II].

In appropriate, highly selected patients with severe COPD and hyperinflation endobronchial valves may be appropriate if collateral ventilation can be excluded and endobronchial coils may be an option if collateral ventilation is present.  Currently coils are not available in Australia.  These therapies should only be considered in specialised centres (Shah 2014).  All patients being considered for lung volume reduction should be referred for pulmonary rehabilitation and discussed by an expert panel that includes a radiologist, respiratory physician, interventional pulmonologist and thoracic surgeon (Herth 2016a).