TY - T1的强力霉素临床outco改善mes during cystic fibrosis exacerbations JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.01102-2016 VL - 49 IS - 4 SP - 1601102 AU - Xu, Xin AU - Abdalla, Tarek AU - Bratcher, Preston E. AU - Jackson, Patricia L. AU - Sabbatini, Gina AU - Wells, J. Michael AU - Lou, Xiang-Yang AU - Quinn, Rebecca AU - Blalock, J. Edwin AU - Clancy, J. P. AU - Gaggar, Amit Y1 - 2017/04/01 UR - //www.qdcxjkg.com/content/49/4/1601102.abstract N2 - Matrix metalloprotease-9 (MMP-9) plays a role in progression of cystic fibrosis, and doxycycline can reduce MMP-9 in vitro. Here, we explore the effect of doxycycline during cystic fibrosis exacerbation treatment on MMP-9 related readouts and clinical end-points.This randomised, double-blind, placebo-controlled study enrolled hospitalised patients with cystic fibrosis undergoing exacerbation. In total, 20 participants were given doxycycline and 19 participants were given placebo over an 8-day period during hospitalisation. Biospecimens were collected at the beginning and the end of the study period. Primary end-points were total MMP-9 levels in the sputum and safety/tolerability. Secondary end-points included change in lung function, time to next exacerbation, and markers of MMP-9-related protease activity (active MMP-9 and TIMP-1). Nonparametric testing was used for within-group and between-group analyses.Doxycycline was well tolerated, with no treatment discontinuations or serious adverse events. Doxycycline reduced total sputum MMP-9 levels by 63.2% (p<0.05), and was also associated with a 56.5% reduction in active MMP-9 levels (p<0.05), a 1.6-fold increase in sputum TIMP-1 (p<0.05), improvement in forced expiratory volume in 1 s (p<0.05), and an increase in time to next exacerbation (p<0.01).Adjunctive use of doxycycline improved dysregulated MMP-9 levels in sputum, along with biomarkers consistent with a reduced proteolytic pulmonary environment. Improvement in clinical outcome measures suggests an important therapeutic benefit of doxycycline for individuals with cystic fibrosis.Doxycycline improved protease/antiprotease imbalance and clinical end-points during CF acute pulmonary exacerbation http://ow.ly/lF9p308Ov6i ER -