Respiratory disease in cystic fibrosis: from pathophysiology to therapy

Respiratory disease is the major cause of morbidity and mortality in cystic fibrosis. Cystic fibrosis was long treated in the pediatric setting, but i mproved survival has led to the implication of adult pneumology in therapeu tic management. Since the gene causing cystic fibrosis has been clone, our knowledge of the pathophysiology of the disease has literally exploded, par ticularly concerning the deleterious consequences of defective expression a nd distribution of CFTR (cystic fibrosis transmembrane conductance regulato r) protein in chronic lung inflammation and infection. This knowledge has l ed to an optimization of existing therapeutic strategies and to the formula tion of hypotheses for the development of new pharmaceutical reagents, allo wing an assessment of disease outcome not only in terms of survival but als o in terms of quality of life. Early in vivo clinical trials have been enco uraging although the efficacy of gene transfer and expression remain modest and the optimal vector remains to be deter-mined. Different potential phar macological approaches are being studied in order to correct for defective CFTR function at different levels of gene mutation, and to modulate the dis order in transepithelial ionic transfer. One could expect in the near futur e to see combinations of complementary genotype-specific drugs used for the treatment of cystic fibrosis after patient genotyping to categorize the ty pe of mutation.