Endoscopic lung volume reduction in patients with chronic obstructive pulmonary disease: mechanisms, pathophysiology and outcomes

Background. Chronic obstructive pulmonary disease is a progressive and disabling condition which is common and is associated with significant morbidity and mortality, despite medical treatment and pulmonary rehabilitation. Endoscopic lung volume reduction (ELVR) therapy is a relatively new treatment option for a select group of sufferers of severe emphysema in Australia. 

The aim of this thesis is to address many of the unanswered questions in the role, mechanisms of action and effects of ELVR in COPD, and to apply the lessons learnt from international studies to the Australian setting, using local resources and expertise. 

Methods. Patients with severe heterogeneous emphysema were prospectively recruited and underwent ELVR procedures using endobronchial valves or intrabronchial valves. Clinical data were collected at baseline, one month, three months and twelve months to investigate the effects of ELVR on lung function, exercise capacity, quality of life, ventilation and perfusion, cardiac parameters and small airway physiology. 

Results. Sixty one patients were recruited and underwent ELVR. Targeted lobe atelectasis was an important predictor of lung function improvement, rendering a significant increase in FEV1 (+9.6%, p<0.01) and a reduction in RV (-6.4%, p<0.05) at three months; these changes were sustained for 12 months. Improvements in six-minute walk distances (+77.4 metres, p<0.01) and quality of life scores (-11 units, p<0.01) were more notable than changes in FEV1 (+6.1%, p=NS) at 12 months. There were reversible complications including pneumothoraces (n=3), valve revision (n=22) and valve removal (n=8). There were 2 peri-procedural deaths. 

In our planar VQ studies of both upper and lower lobe treated patients, we found that regional ventilation and perfusion were redistributed to the contralateral upper zones. Associated improvements in gas transfer factor were observed in subjects with upper lobe treatment. Subsequent data obtained using VQ-SPECT/CT were also consistent with the above findings of VQ redistribution to the contralateral upper lobe; these results were also correlated with improvements in FEV1 (r=0.61, p<0.01). By contrast, there were no such improvements in pulmonary hypertension at 12 months in our cohort. 

Reduced gas trapping with ELVR was correlated with an improvement in FEV1 (r=-0.83, p=0.01) and a reduction in resistance of the respiratory system (r=0.71, p=0.03); whilst improved reactance was correlated with an improvement in six-minute walk distance (r=0.83, p=0.04). 

Conclusions. Our studies confirmed the efficacy and safety profile of ELVR in the Australian setting. In addition, the studies provided insight into the mechanisms, physiological basis and clinical outcomes of ELVR in COPD.