National Emphysema Treatment Trial (NETT)

BACKGROUND:

LVRS is intended primarily for those patients whose chronic obstructive pulmonary disease (COPD) is predominantly emphysema. Emphysema is characterized anatomically "by abnormal, persistent enlargement of the airspaces distal to the terminal bronchioles, accompanied by the destruction of the airspace walls and without obvious fibrosis". The loss of the lung architecture leads to compressible peripheral airways that close at higher than normal lung volumes (early airway closure). The increased compliance and the air trapping from early closure leads to hyperinflation of the lung, over distention of the chest wall, a flattened, disadvantaged diaphragm, and ventilation-perfusion mismatch. In the 1950s and 1960s, Dr. Otto Brantigan theorized that surgical excision of multiple wedges of lung would reduce lung volumes, thereby restoring the outward elastic pull on the small airways and reduce airway obstruction. Dr. Brantigan reported that the surgical excision of lung tissue resulted in significant clinical improvement in some cases, but mortality was high. With little objective data and high mortality, the procedure did not gain widespread acceptance.

The experience that diaphragmatic and chest wall function could be restored in emphysema with lung transplantation renewed interest in Dr. Brantigan's work. Improvements in surgical technique have opened the possibility of performing surgical excisions of lung tissue. Recent reports on LVRS have shown improvements in FEV1, FVC, TLC, RV and dyspnea and quality of life assessments.

These reports generated enormous excitement among patients and their doctors. Many centers around the country started performing LVRS with the result that hundreds of patients had the procedure, despite the preliminary nature of the results, the lack of rigorous patient selection criteria and the lack of information on long term outcome. Basic questions remain such as which patient should have the surgery, what protocol should be followed, what physiological tests should be obtained, and what is the long term efficacy of the technique on morbidity, mortality, and quality of life. The mechanisms of benefit and the full cardiopulmonary consequences are unknown.

The concept for the trial originated in the NHLBI Workshop on Evaluation and Research in Lung Volume Reduction Surgery. The initiative was reviewed and approved at the May 1996 National Heart, Lung, and Blood Advisory Council meeting. The Requests for Proposals were released in June, 1996.