Chronic obstructive pulmonary disease is a major health problem and a leading cause for hospital admission in the United States. A severe form of chronic obstructive pulmonary disease that is accompanied by weight loss is commonly referred to as pulmonary cachexia. Studies in the 1960s demonstrated associations in chronic obstructive pulmonary disease patients between weight loss, low FEV1, and early mortality. This observation was strengthened by a retrospective analysis of the Intermittent Positive Pressure Breathing Trial data that suggested malnutrition was an independent predictor of outcome in men with chronic obstructive pulmonary disease. The underlying basis relating malnutrition to adverse outcome in chronic obstructive pulmonary disease was unknown, although there was a large body of information indicating that pulmonary cachexia was associated with respiratory muscle atrophy, myofibrillar substrate depletion, and impaired skeletal and respiratory muscle function. The primary question was whether the nutrition-related functional deficits observed in underweight patients could be reversed.