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). LVRS is still an experimental, palliative, surgical procedure. 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]. Longer term follow up from NETT has now been published (Criner 2011). In a subgroup of patients who underwent right heart catheterisation, there was no evidence for an increase in pulmonary artery pressures. Nonetheless, surgical lung volume reduction is now rarely performed either in the US or Australia.

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). 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 specifically recruited patients with intact interlobar fissures on CT chest. Klooster went further by excluding patients with collateral ventilation detected at bronchoscopy by the Chartis system. 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 and Klooster. Data on adverse events was significant. The Sciurba and Wood trials reported high hospital admissions for COPD exacerbations, Klooster reported an 18% 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. In summary, endobronchial valves may provide a benefit to highly selected patients but should only be considered in specialised centres (Shah 2014). All patients being considered for lung volume reduction should be discussed by an expert panel that includes a radiologist, respiratory physician, interventional pulmonologist and thoracic surgeon (Herth 2016). 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).

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].