Rationale and design of the National Emphysema Treatment Trial (NETT): A prospective randomized trial of lung volume reduction surgery

Emphysema Treatment Trial (NETT). This trial is a collaborative effort of 17 clinical centers, a study coordinating/statistical center, the National Heart, Lung, and Blood Institute (NHLBI), and the Health Care Financing Administration (HCFA).The study protocol and procedures were finalized in 1997-1998.Screening began in October 1997 and randomization began in January 1998. OverviewTerminology.Emphysema is a condition of the lung characterized by abnormal permanent enlargement of air spaces distal to the terminal bronchiole, accompanied by destruction of their walls in the absence of obvious fibrosis. 1 The cardinal physiologic defect in emphysema is a decrease in elastic recoil.This decrease in elastic recoil results in the principal physiologic abnormalities of emphysema: decreased maximum expiratory air flow, hyperinflation, and air trapping.The destruction of the alveolar-capillary membrane surface leads to a reduction in diffusing capacity.Emphysema is usually the result of cigarette smoking, although it can occur occasionally without this exposure, notably in α 1 -antitrypsin deficiency.It is a chronic progressive disorder that ultimately leads to disability and early death.Emphysema is esti-mated to be present in 2 million adults in the United States and, along with other forms of chronic obstructive pulmonary disease (COPD), accounts for more than 90,000 deaths annually. 2Present state of treatment for emphysema.Guidelines for the diagnosis and management of emphysema have been recently promulgated. 1,3The goals of therapy in emphysema, as in other forms of COPD, are to halt the progressive decline in lung function, prevent and shorten exacerbations of the disease, improve exercise capacity and quality of life, and prolong survival.The only treatment that has been shown to alter the rate of progression of COPD is cessation of smoking. 4Influenza immunization and pneumococcal vaccination are recommended for prevention of intercurrent life-threatening infections. 5,6As a rule, exacerbations of disease are treated with antibiotics, steroids, and bronchodilators.Although these interventions are believed to shorten the duration of individual episodes and minimize symptoms, there is little evidence that they either alter the natural history of the disease or reduce mortality. 7,8Bronchodilators improve lung function, exercise capacity, and quality of life in patients with COPD but are of limited benefit to patients without reversible airway disease. 9][12][13] Long-term domiciliary oxygen therapy in hypoxemic patients is the only treatment for COPD that has been documented to decrease mortality rates. 14,15Adjunctive forms of therapy, such as mucolytics to control respiratory secretions or narcotics to reduce the sensation of dyspnea, have been used in selected patients with COPD. 16In patients with α 1 -protease inhibitor deficiency, protective serum levels of the enzyme may be restored by regular infusions of exogenous α 1 -protease inhibitor, 17 but it is unclear whether restoring serum levels protects against progression of the disease or prolongs survival. 11In patients with far-advanced COPD, single or double lung transplantation has been used as a From the National Emphysema Treatment Trial Research Group.