Doxycycline improves clinical outcomes during cystic fibrosis exacerbations

[摘要] 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 1xe2x80x85s (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.

[学科分类] 呼吸医学