Cystic fibrosis

Investigators in CF can study at the molecular level a disease in which a single-gene defect gives rise to a variety of pathophysiologic disorders in many organ systems, most notably the lung. Despite the enormous recent progress in CF research, unanswered questions remain, some of which are highly relevant to the de sign of new therapies, especially those directed at the basic defect. Of particular importance is discovering how the defect in CFTR gives rise to infection and inflammation in the CF lung. Widespread acceptance of aggressive treatment programs at Centers around the country has increased median survival for patients with CF nationwide to 29 yr. However, the symptomatic therapies that have brought the patients this far, even if they can be refined, will probably not take us much farther. The CFF Data Registry reports that survival of patients with CF has not increased in 5 yr (9). New strategies of treatment will be necessary to improve survival further. One such new strategy may be wider application of anti-inflammatory therapy, which was reported only last year to slow the rate of pulmonary decline in young, relatively healthy patients with CF (318). There has not been time to see the impact of anti-inflammatory therapy on survival, and it will probably take several years. However, even this is a rear guard action, addressing a consequence of CF and not a cause. There is hope that the understanding of the underlying pathophysiology of CF will allow us to attack the disease at its root, possibly by manipulation of epithelial ion transport, or by activation of mutant protein, or by provision of the normal gene for CFTR to the appropriate cells. These therapies are in various stages of development, and they have raised important basic questions that must now be answered before further progress can occur. CF is a striking example of the bench to bedside continuum of research.