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.
"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 . "
[Show abstract][Hide abstract] ABSTRACT: In Cystic Fibrosis (CF), mutations of the CFTR gene result in defective Cl(-) secretion and Na(+) hyperabsorption by epithelia which leads to airway lumen dehydration and mucus plugging and favours chronic bacterial colonization, persistent inflammation and progressive lung destruction. Beyond this general description, the pathogenesis of CF lung disease remains obscure due to an incomplete understanding of normal innate airway defense. This mini-review aims to highlight the role of the pro-resolution lipid mediator, Lipoxin A4, which is inadequately produced in CF, on several aspects of innate immunity that are altered in CF airway disease.
Computational and Structural Biotechnology Journal 03/2013; 6(7):e201303018. DOI:10.5936/csbj.201303018
[Show abstract][Hide abstract] ABSTRACT: Since the discovery of the cystic fibrosis transmembrane conductance regulator (CFTR) gene nearly 12 years ago, cystic fibrosis (CF) has become one of the most intensively investigated monogenetic disorders considered approachable by gene therapy. This has resulted in over 20 clinical trials currently under way, concluded or awaiting approval. Despite the initial promise of gene therapy for CF, and the demonstration of successful gene transfer to the nose and airways of individuals, it has not so far been as effective as initially projected. Here we discuss the rationale behind CF gene therapy and dissect the vast array of literature representing the work that ultimately brought about the current phase I/II clinical trials. In the context of human trials, we review the limitations of current vector systems for CF gene therapy. We come to the conclusion that at present none of the application methods and vector systems are able to achieve the level and persistence of CFTR gene expression in the affected epithelia of CF patients that is required for therapeutic success. We also outline the challenges that must be overcome and describe some of the novel approaches to be taken in order to attain the curative therapy that was originally envisaged for this disease.
[Show abstract][Hide abstract] 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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