O9.2 Lung volume reduction surgery and bronchoscopic interventions

van Geffen et al performed a meta-analysis of data from randomised controlled trials across all modalities of lung volume reduction (surgical and endobronchial) (van Geffen 2019).  The mean differences compared with the control were an increase in FEV1 of 15∙87% (95% CI 12∙27 to 19∙47), improvement in 6-minute walk test (6MWT) of 43∙28m (31∙36 to 55∙21), and reduction in the St George’s Respiratory Questionnaire (SGRQ) of 9∙39 points (–10∙92 to –7∙86) [evidence level I].  The authors noted a high risk of bias due to lack of blinding.  The odds ratio for a severe adverse event, which included mortality, was 6∙21 (95% CI 4∙02 to 9∙58) following intervention.

Surgical Lung Volume Reduction

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 vs. 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) [evidence level I].  96% of the patients contributing to the long term mortality data was from patients enrolled in the NETT study. The authors made note of high post-operative complications, especially persistent air leak and pneumonia. A retrospective analysis of 2,815 LVRS cases performed in America demonstrated an in-hospital mortality rate of 5.5% (Attaway 2019).  Pulmonary hypertension was associated with an increased risk in mortality (adjusted OR 4.4; 95% CI 1.7 to 1.5).

Endobronchial lung volume reduction

A variety of nonsurgical techniques have been investigated. These include endobronchial one-way valves, self-activating coils, targeted destruction of emphysematous tissue, bypass tract airway stenting and transpleural ventilation. Of these techniques, only valves are in regular clinical use in Australia.

van Geffen performed a meta-analysis of endobronchial lung volume reduction surgery (van Geffen 2019).  6 trials were included in the analysis of endobronchial valves (620 participants) and 3 trials were included in the analysis of endobronchial coils (458 participants).  The authors reported improvements in lung function, 6-minute walk distance and symptom scores with both modalities.  The odds ratio for an adverse event for trials examining endobronchial valves was (9∙58, 95% CI 5∙56 to 16∙50).  The most frequent adverse events with endobronchial valve treatment were pneumothorax (1∙4 -to 25%) and COPD exacerbations (4 to 20%).  A large multi-centre randomised controlled trial reported a 27% pneumothorax rate and a 3% 45-day mortality rate (Criner 2018).  The odds ratio (OR) for an adverse event for trials examining coils was 8∙73, 95% CI 2∙69 to 28∙32; figure 3A). The most common adverse events were pneumonia (5 to 20%),  COPD exacerbations (7 to 28%) and pneumothorax (5 to 10%).  There was no difference in early mortality between valves/ coils and control in this meta-analysis. However, a 2021 randomised controlled study of coils in patients with severe COPD (FEV1 15-45% predicted) was terminated early with only 120 of the > 200 planned participants recruited. There were 6 month follow up results available for 57 coil and 34 control participants, demonstrating clinically significant improvements in SGRQ of -10.6 (95%CI -15.9 to -5.4) and improvement in FEV1 +10.3% predicted (95% CI 4.7-16.0) in the coil arm. There were no deaths in the control arm, whilst there were 5 deaths in the coil arm. Also, the incidence of serious adverse events was higher in the coil arm (n=30 of the coil participants, n=3 of the control participants) (Klooster 2021). Overall, these results indicate mixed results for coils.

There was concern regarding the lack of sham bronchoscopy and/or unclear status of blinding in some studies that may cause a risk of bias (van Agteren 2017).

Endobronchial valves may be appropriate in highly selected patients with severe COPD and hyperinflation, if collateral ventilation can be excluded (intact fissure on imaging and Chartis negative during bronchoscopy). Based on the data above the role of coils is unclear.

LVRS therapy should only be considered in high volume specialised centres (Herth 2017).  All patients being considered for lung volume reduction surgery and bronchoscopic interventions should be referred for pulmonary rehabilitation and discussed by an expert panel that includes a radiologist, respiratory physician, interventional pulmonologist and thoracic surgeon (Herth 2017).