Cystic fibrosis: pathogenesis, pulmonary infection, and treatment.

Abstract

Cystic fibrosis (CF) is the most common serious recessively inherited genetic disease among whites. There are an estimated 30,000 persons with CF in the United States, and an estimated 7 million persons are asymptomatic heterozygous carriers. Clinical recognition (in the absence of a family history of the disease) has long been codified by the triad of chronic sinopulmonary disease, pancreatic insufficiency, and elevated sweat chloride values. With powerful contemporary management based upon treatment of secondary manifestations of the disease such as pulmonary infection and malnutrition, the median length of survival has increased dramatically over the past 2 decades from early childhood to >29 years. As a result, about one-third of patients with CF are adults. The history of CF, which began with its recognition as a discrete fatal disease of infants in the late 1930s, can be divided into several eras, but no divide has been as dramatic and profound as that before and since 1989, when the gene that causes CF was finally cloned and its molecular basis began to be deciphered. In this review, I shall try to briefly place our current understanding of the pathogenesis and treatment of pulmonary infection-which causes most morbidity and ultimately >90% of CF-related deaths-in the context of recent developments in molecular genetics and cell biology. The insights provided from research in the past 5 years have placed CF front and center in the molecular medicine revolution that is transforming health care as we near the millennium.