Use of modulators of airways inflammation in patients with CF

One of the hallmarks of cystic fibrosis (CF) lung disease is the presence of intense, neutrophil-dominated airway inflammation, and many researchers have focused on developing therapies to reduce inflammation in CF lung disease. Systemic corticosteroids can delay progression of lung disease, but at the cost of unacceptable side effects. Inhaled corticosteroids are widely used, but their efficacy has yet to be demonstrated in a controlled fashion. Ibuprofen has also been shown to delay disease progression, but its use has been limited by the need to obtain individual pharmacokinetics and concern about side effects. Other treatments with potential anti-inflammatory effects include pentoxifylline, leukotriene antagonists, docosahexaenoic acid, and azithromycin. Few, if any, large clinical studies of these therapies have been published, but several are presently underway. Because neutrophil elastase appears to be a key mediator of tissue damage in CF lung disease, anti-elastase compounds have also been studied, including alpha-1-protease inhibitor, secretory leukocyte protease inhibitor, and small molecule inhibitors. There have been no large-scale controlled trials of these therapies in CF. More recently, investigators have focused on cytokine modulation, using either interleukin-10 or interferon gamma. Some complementary and alternative medicine therapies may also have anti-inflammatory effects, although their clinical value has yet to be demonstrated in a rigorously-controlled fashion. In summary, numerous anti-inflammatory therapies have been applied to CF lung disease, but more large, well-controlled studies will need to be performed to determine their true clinical usefulness.