New and emerging therapies for pulmonary complications of cystic fibrosis

In the decade since the gene for cystic fibrosis (CF) was discovered, resea rch into potential therapeutic interventions has progressed on a number of different fronts. The vast majority of morbidity and mortality in CF result s from inflammation and infection of the airways. Direct delivery of antiba cterials to the airway secretions via a nebuliser is an attractive therapeu tic option, and a novel formulation of tobramycin designed for such a purpo se has been demonstrated to improve spirometry and decrease the need for in travenous antibacterials. In addition, early clinical trials are studying t he effects of small peptides with antibiotic properties (defensins) deliver ed directly to the airways. Inflammation, whether secondary to infection or an independent feature of C F, leads to progressive bronchiectasis. Anti-inflammatories such as prednis one and possibly ibuprofen have been shown to decrease the rate of respirat ory decline in patients with CF but have tolerability profiles that limit c linical usefulness. Macrolides also have anti-inflammatory properties and c linical trials are now ongoing to assess the efficacy of these agents in CF . Multiple agents, including uridine triphosphate (UTP), genistein, phenyl-bu tyrate and CPX (cyclopentyl dipropylxanthine), have been demonstrated in ce ll culture to at least partially correct the primary defect of ion transpor t related to mutations in the cystic fibrosis transmembrane. conductance re gulator (CFTR). No agent of this class has yet demonstrated clinical effect iveness, but several are in preclinical and early clinical trials. Finally, gene therapy that allows for the incorporation and expression of w ild-type CFTR in respiratory epithelial cells would be definitive therapy f or CF. However, multiple barriers to delivery and expression need to be ove rcome. With research proceeding on these multiple fronts, new therapies for pulmonary complications promise to continue to increase the life expectanc y of individuals with CF.