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October 18, 2007 — Oral high-dose ibuprofen can slow the progression of lung disease in people with cystic fibrosis (CF), especially children, according to a review in the October 17 Online First issue of the Cochrane Database of Systematic Reviews. This suggests that strategies to modulate lung inflammation can benefit people with CF.
"Progressive lung damage causes the majority of deaths in cystic fibrosis (CF)," write Larry C. Lands, MD, PhD, and Sanja Stanojevic, CPEB, ICH. "Non-steroidal anti-inflammatory drugs [NSAIDs] may prevent progressive pulmonary deterioration and morbidity in CF."
The investigators searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register through October 2006, including references identified from comprehensive electronic database searches, hand searches of relevant journals, and searches of abstract books of conference proceedings. They also contacted pharmaceutical companies manufacturing NSAIDs for pertinent trial results.
The authors independently evaluated trials for review. Selection criteria for inclusion in the review were published and unpublished randomized or quasi-randomized controlled trials in patients with CF, comparing any dose of oral NSAIDs vs placebo for at least 2 months.
Of 6 trials identified in the searches, 4 were eligible for inclusion in the review. These included 287 participants aged 5 to 39 years, with a maximum follow-up of 4 years. Two of the trials reporting effectiveness of ibuprofen in people with mild lung disease were performed at the same center and enrolled some of the same participants. A third trial evaluated piroxicam in participants with more severe impairment of respiratory function, and the Trans-Canada trial compared ibuprofen vs placebo for 2 years.
Although 3 of the included trials were of good or adequate methodologic quality, variation in reported outcomes and summary measures prevented calculation of pooled treatment estimates. Parameters considered were objective measures of lung function, nutritional status, radiologic evaluation of pulmonary involvement, intravenous (IV) antibiotic usage, hospital admissions, survival, frequency of all adverse effects, and treatment compliance.
Adding data from the Canadian trial showed evidence of a moderate absolute annual decline in percent predicted forced expiratory volume in 1 second and forced vital capacity in the placebo group vs the ibuprofen group. Another trial showed that long-term use of high-dose ibuprofen was associated with decreased usage of IV antibiotics as well as improved nutritional and radiologic pulmonary status.
No major adverse effects were reported, but the power of the trials was low to identify clinically important differences in the incidence of adverse effects.
"High-dose ibuprofen can slow the progression of lung disease in people with CF, especially in children, and this suggests that strategies to modulate lung inflammation can be beneficial for people with CF," the authors write. "There may also be a beneficial effect on the number of days spent in hospital and ibuprofen appears to be relatively well-tolerated. However, the long-term effects of prolonged use of high doses of NSAIDs have yet to be determined."
The review authors recommend gastrointestinal tract protection, regular pharmacokinetic trials, and safety profiles. Future research should address the mechanism of action to facilitate development of agents with enhanced safety profiles, as well the age of the patient at which NSAIDs are most effective. Secondary outcome measures and cost-effectiveness should also be studied.
Despite the paucity of long-term safety data, the available evidence suggests that NSAIDs should be temporarily discontinued during administration of IV aminoglycosides or other nephrotoxic agents.
"All trials should be designed to be of adequate power to reliably identify important adverse events such as, for example, major gastrointestinal haemorrhage," the review authors conclude. "The results of this review suggest that the beneficial effects of anti-inflammatory treatment with NSAIDs may be greatest among young children with mild disease, in whom fixed structural damage to the lungs has not yet occurred."
Tenovus, Scotland, United Kingdom, and the Institute of Child Health, Ninewells Hospital and Medical School, Dundee, United Kingdom, supported this review. Dr. Lands has reported being the lead investigator in the Trans-Canadian trial.
Cochrane Database Syst Rev. Published online October 17, 2007.
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