PT - JOURNAL ARTICLE AU - Xin Xu AU - Tarek Abdalla AU - Preston E. Bratcher AU - Patricia L. Jackson AU - Gina Sabbatini AU - J. Michael Wells AU - Xiang-Yang Lou AU - Rebecca Quinn AU - J. Edwin Blalock AU - J. P. Clancy AU - Amit Gaggar TI - Doxycycline improves clinical outcomes during cystic fibrosis exacerbations AID - 10.1183/13993003.01102-2016 DP - 2017 Apr 01 TA - European Respiratory Journal PG - 1601102 VI - 49 IP - 4 4099 - http://erj.ersjournals.com/content/49/4/1601102.short 4100 - http://erj.ersjournals.com/content/49/4/1601102.full SO - Eur Respir J2017 Apr 01; 49 AB - 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