Oral non-steroidal anti-inflammatory drug therapy for lung disease in cystic fibrosis

Background Progressive lung damage causes most deaths in cystic fibrosis (CF). Non-steroidal anti-inflammatory drugs (NSAIDs) may prevent progressive pulmonary deterioration and morbidity in CF. Objectives To assess the effectiveness of treatment with NSAIDs in CF. Search methods We searched the Cochrane CF and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, hand searches of relevant journals and abstract books of conference proceedings. We contacted manufacturers of NSAIDs. Latest search of the Group's Trials Register: 15 May 2013. Selection criteria Randomized controlled trials comparing oral NSAIDs, at any dose for at least two months, to placebo in people with CF. Data collection and analysis Two authors independently assessed trials for the review. Main results The searches identified eight trials; five are included (334 participants aged five to 39 years; maximum follow up of four years). Three trials compared ibuprofen to placebo (two from the same centre with some of the same participants); one trial assessed piroxicam versus placebo, a fifth trial compared cycloxygenase-2 inhibitor nimesulide and clarithromycin. The three ibuprofen trials were deemed to have good or adequate methodological quality, but used various outcomes and summary measures. Reviewers considered measures of lung function, nutritional status, radiological assessment of pulmonary involvement, intravenous antibiotic usage, hospital admissions, survival and adverse effects. Combined data from the two largest ibuprofen trials showed a significantly lower annual rate of decline for lung function, % predicted forced expiratory volume in one second (FEV1) mean difference (MD) 1.32 (95% confidence interval (CI) 0.21 to 2.42); forced vital capacity (FVC) MD 1.27 (95% CI 0.26 to 2.28); forced expiratory flow (25-75%) MD 1.80 (95% CI 0.15 to 3.45). The post-hoc analysis of data from two trials split by age showed a statistically significant slower rate of annual decline of % predicted FEV1 and FVC in the ibuprofen group in younger children, MD 1.41% (95% CI 0.03 to 2.80) and MD 1.32% (95% CI 0.04 to 2.60) respectively. In one trial, long-term use of high-dose ibuprofen was associated with reduced intravenous antibiotic usage, improved nutritional and radiological pulmonary status. No major adverse effects were reported, but the power of the trials to identify clinically important differences in the incidence of adverse effects was low. Authors' conclusions High-dose ibuprofen can slow the progression of lung disease in people with CF, especially in children, which suggests that strategies to modulate lung inflammation can be beneficial for people with CF.