Anti-Inflammatory AgentsA Clinical Perspective

摘要

Neutrophil-dominated airway inflammation begins early in cystic fibrosis (CF) and is integral to progressive lung damage. It is, therefore, logical to attempt to modify this inflammatory response, ideally as early as possible, and before sustained severe inflammation is established. Oral corticosteroids have been shown to slow the progression of lung disease, but have unacceptable side effects for long-term use. Inhaled corticosteroids, although widely prescribed, have not been shown to be an effective anti-inflammatory agent in CF, and they may not be as safe as previously assumed. High-dose oral ibupro-fen has proven efficacy, but its potential adverse effects have limited its uptake in clinical practice. Antileukotrienes have had limited study in CF, but as yet no significant benefit has been demonstrated. There were encouraging early phase trials of aerosolized antiproteases but they have not been developed further, and the focus is now on novel synthetic anti-elastase agents. Nebulized recombinantDNase, despite concerns of a possible pro-inflammatory effect, in fact appears to stabilize airway inflammation in mild lung disease. Macro-lide antibiotics have been shown to have a small but significant beneficial effect on pulmonary function, and although the mechanism is unclear, it is likely that it relates to an anti-inflammatory effect. Other anti-inflammatory therapies that have been tried in difficult asthma, e.g. cyclosporine, metho-trexate and intravenous immunoglobulin, have had very limited study, and their effect in CF is unproven. Finally, there are a number of novel agents, which target individual inflammatory mediators and pathways, which are being studied in thelaboratory setting. Although it is quite likely their actions are too specific to cope with the generalized inflammatory response in CF, there is hope that an agent will be found that significantly limits inflammation, but that also has an acceptable side-effect profile and a suitable route of delivery.