Doxycycline improves clinical outcomes during cystic fibrosis exacerbations.

Academic Article

Abstract

  • 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.
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    Keywords

  • Adolescent, Adult, Alabama, Cystic Fibrosis, Double-Blind Method, Doxycycline, Female, Forced Expiratory Volume, Humans, Kaplan-Meier Estimate, Linear Models, Lung, Male, Matrix Metalloproteinase 9, Sputum, Tissue Inhibitor of Metalloproteinase-1, Young Adult
  • Digital Object Identifier (doi)

    Author List

  • Xu X; Abdalla T; Bratcher PE; Jackson PL; Sabbatini G; Wells JM; Lou X-Y; Quinn R; Blalock JE; Clancy JP
  • Volume

  • 49
  • Issue

  • 4