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

Department of Pediatrics, Montreal Children's Hospital, 2300 Tupper Street, Montreal, Quebec, Canada, H3H-1PA.
Cochrane database of systematic reviews (Online) (Impact Factor: 6.03). 06/2013; 6(6):CD001505. DOI: 10.1002/14651858.CD001505.pub3
Source: PubMed


Inflammation contributes to lung damage. In the long term this is the most common reason for early death in cystic fibrosis. In high doses, non-steroidal anti-inflammatory drugs, particularly ibuprofen, may work against inflammation, but in low doses there is some evidence that they may cause inflammation. The use of high doses has also raised concerns about the potential for unwanted effects, which has limited the use of these drugs in cystic fibrosis. We looked for trials comparing oral non-steroidal anti-inflammatory drugs to placebo, at any dose for at least two months in people with cystic fibrosis.This updated review includes twice as many participants as the original review. We found evidence showing that high-dose non-steroidal anti-inflammatory drugs, most notably ibuprofen, can slow the progression of lung damage in people with cystic fibrosis, especially in younger people. There are limited long-term safety data; however, there are enough data to recommend that non-steroidal anti-inflammatory drugs be temporarily stopped when patients are receiving intravenous aminoglycosides or other agents toxic to the kidneys.

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    • "It is established that ICS use can have adverse effects on growth. A systematic review of the efficacy of non-steroidal anti-inflammatory drugs in CF concluded that treatment with high-dose ibuprofen was associated with a significantly lower annual rate of decline in lung function (especially in children), however, the adoption of ibuprofen into therapy has not been universally accepted [11, 12]. Redressing the imbalance in fatty acid metabolism described in CF, by supplementation of Docosahexaenoic Acid may be helpful, and efforts are ongoing to evaluate the potential therapeutic benefit [13]. "
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    ABSTRACT: In the decade since the gene for cystic fibrosis (CF) was discovered, research into potential therapeutic interventions has progressed on a number of different fronts. The vast majority of morbidity and mortality in CF results from inflammation and infection of the airways. Direct delivery of antibacterials to the airway secretions via a nebuliser is an attractive therapeutic option, and a novel formulation of tobramycin designed for such a purpose has been demonstrated to improve spirometry and decrease the need for intravenous antibacterials. In addition, early clinical trials are studying the effects of small peptides with antibiotic properties (defensins) delivered directly to the airways. Inflammation, whether secondary to infection or an independent feature of CF, leads to progressive bronchiectasis. Anti-inflammatories such as prednisone and possibly ibuprofen have been shown to decrease the rate of respiratory decline in patients with CF but have tolerability profiles that limit clinical usefulness. Macrolides also have anti-inflammatory properties and clinical trials are now ongoing to assess the efficacy of these agents in CF. Multiple agents, including uridine triphosphate (UTP), genistein, phenylbutyrate and CPX (cyclopentyl dipropylxanthine), have been demonstrated in cell culture to at least partially correct the primary defect of ion transport related to mutations in the cystic fibrosis transmembrane conductance regulator (CFTR). No agent of this class has yet demonstrated clinical effectiveness, but several are in preclinical and early clinical trials. Finally, gene therapy that allows for the incorporation and expression of wild-type CFTR in respiratory epithelial cells would be definitive therapy for CF. However, multiple barriers to delivery and expression need to be overcome. With research proceeding on these multiple fronts, new therapies for pulmonary complications promise to continue to increase the life expectancy of individuals with CF.
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