期刊
EUROPEAN RESPIRATORY JOURNAL
卷 49, 期 4, 页码 -出版社
EUROPEAN RESPIRATORY SOC JOURNALS LTD
DOI: 10.1183/13993003.01102-2016
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资金
- Division Of Mathematical Sciences
- Direct For Mathematical & Physical Scien [1701433] Funding Source: National Science Foundation
- NHLBI NIH HHS [K08 HL123940] Funding Source: Medline
- BLRD VA [I01 BX001756] Funding Source: Medline
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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