high-dose ibuprofen in cystic fibrosis高剂量布洛芬在囊性纤维化.pdfVIP

Pharmaceuticals 2010, 3, 2213-2224; doi:10.3390/ph3072213 OPEN ACCESS pharmaceuticals ISSN 1424-8247 /journal/pharmaceuticals Review High-Dose Ibuprofen in Cystic Fibrosis Larry C. Lands 1, 2,* and Nurlan Dauletbaev 2 1 Division of Respiratory Medicine, Montreal Children’s Hospital, D-380, 2300 Tupper Street, Montreal, Quebec, H3H 1P3, Canada 2 Research Institute of McGill University Health Centre, Montreal Children’s Hospital, C-1223, 2300 Tupper Street, Montreal, Quebec, H3H 1P3, Canada; E-Mail: nurlan.dauletbaev@muhc.mcgill.ca (N.D.) * Author to whom correspondence should be addressed; E-Mail: larry.lands@muhc.mcgill.ca; Tel.: +1-514-412-4444; Fax: +1-514-412-4364. Received: 23 June 2010; in revised form: 6 July 2010 / Accepted: 8 July 2010 / Published: 13 July 2010 Abstract: Cystic Fibrosis (CF) is the most common lethal genetic disorder in North America and Europe. Most patients succumb to progressive lung disease characterized by an exaggerated neutrophilic inflammation. In animal models of chronic infection, high- dose ibuprofen was demonstrated to reduce inflammation without hindering bacterial clearance. This led to two clinical trials, which demonstrated a benefit in slowing the progression of lung disease in CF. However, concerns about potential adverse effects have limited the use of high-dose ibuprofen in CF patients. There are a variety of potential mechanisms to account for the observed clinical benefit. A better understanding of