Response to Endobronchial Valves in Moderate Obstructive Airways Disease and Exercise Limitation - The REMODEL Trial

Chronic Obstructive Pulmonary disease (COPD) is a common condition that affects millions of adults worldwide with a prevalence and burden projected to increase in the coming decades. This projected increase is explained by the ongoing exposure to cigarette smoke and other COPD risk factors, particularly in the developing world, along with population demographic changes and increasing life expectancy. The Global Burden of Disease Study predicted that by 2020 COPD will be ranked 5th behind ischaemic heart disease, depression, road traffic accidents and cerebrovascular disease as a cause of disability-adjusted life years lost1. The UK population prevalence of clinically significant COPD was estimated to be 1.7% for men and 1.4% for women.

Emphysema can be a debilitating illness and can result in death. The damaged alveoli lose their elasticity, and loss of structural elements leads to collapse of the terminal bronchioles on expiration. This leads to gas trapping and hyperinflation. In severe cases, alveolar walls can become destroyed creating bullae and collateral ventilation. Overinflated areas of lung may compress adjacent lung tissue reducing perfusion and ventilation to healthier tissue. Because the principal defect in emphysema is hyperinflation owing to destruction of the elastic tissue of the lung, usual medical therapies targeted at alleviating dyspnoea provide only limited benefit compared to patients with other forms of COPD. Therefore, non-pharmacological methods of palliating dyspnoea in this patient group have been developed, specifically lung volume reduction procedures.

Lung volume reduction improves function by the return of more normal respiratory muscle shape and function, and also by improving the elastic recoil of the lung which in turn increases the outward pull on the bronchioles. This reduces terminal bronchiole collapse and improves expiratory airflow thereby reducing gas trapping. The decrease in the functional residual capacity improves diaphragmatic and intercostal muscle function and reduces the work of breathing. In carefully selected patients, lung volume reduction surgery (LVRS) has been clearly shown to be effective at improving outcomes. It is, however, associated with significant morbidity, a 5% mortality rate and a modest cost-benefit return. Unfortunately, only a small minority of patients with emphysema are fit enough to undergo such major surgeries, and therefore a variety of alternative less invasive techniques are being developed to achieve lung volume reduction. These techniques include insertion of unidirectional endobronchial valves (EBVs), lung volume reduction coils (RePneu©) to internally compress hyperinflated emphysematous areas of lung, and the injection of sclerosant material to induce scarring and fibrosis of the most damaged portions of lung.

Endobronchial valves work by allowing air to be expelled from the treated areas of lung during expiration whilst preventing inspiratory airflow, with subsequent collapse of the distal lung. This results in volume loss and allows reinflation of healthier lung tissue with improved ventilation-perfusion matching. The Zephyr Valve (PulmonX, Redwood City, CA, USA) allows exhaled air and secretions to be expelled through or around the valve but prevent ventilation to the distal lung. It is implanted using a flexible bronchoscope under conscious sedation as a day case procedure.

The Valves for Emphysema palliatioN Trial (VENT) is the largest randomised controlled trial of valves published to date. Endobronchial valves were placed in the most diseased lobe to achieve unilateral occlusion. This trial together with its European counterpart, EuroVENT, demonstrated that significant improvements in lung function, exercise capacity, and quality of life could be achieved.