Doxycycline improves clinical outcomes during cystic fibrosis exacerbations

Eur Respir J. 2017 Apr 5;49(4):1601102. doi: 10.1183/13993003.01102-2016. Print 2017 Apr.


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.

Trial registration: NCT01112059.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Alabama
  • Cystic Fibrosis / drug therapy*
  • Double-Blind Method
  • Doxycycline / therapeutic use*
  • Female
  • Forced Expiratory Volume
  • Humans
  • Kaplan-Meier Estimate
  • Linear Models
  • Lung / physiopathology
  • Male
  • Matrix Metalloproteinase 9 / metabolism*
  • Sputum / chemistry
  • Tissue Inhibitor of Metalloproteinase-1 / metabolism*
  • Young Adult


  • TIMP1 protein, human
  • Tissue Inhibitor of Metalloproteinase-1
  • MMP9 protein, human
  • Matrix Metalloproteinase 9
  • Doxycycline

Associated data