title: Doxycycline use in patients with lymphangioleiomyomatosis: biomarkers and pulmonary function response.
abstract: OBJECTIVE
  To assess blockade of matrix metalloproteinase (MMP)-2 and MMP-9, as well as the variation in FEV1, in patients with lymphangioleiomyomatosis (LAM) treated with doxycycline (a known MMP inhibitor) for 12 months.
  
  
  METHODS
  An open-label, single-arm, interventional clinical trial in which LAM patients received doxycycline (100 mg/day) for 12 months. Patients underwent full pulmonary function testing, a six-minute walk test, and quality of life assessment, as well as blood and urine sampling for quantification of MMP-2, MMP-9, and VEGF-D levels-at baseline, as well as at 6 and 12 months after the initiation of doxycycline.
  
  
  RESULTS
  Thirty-one LAM patients received doxycycline for 12 months. Although there was effective blockade of urinary MMP-9 and serum MMP-2 after treatment, there were no significant differences between pre- and post-doxycycline serum levels of MMP-9 and VEGF-D. On the basis of their response to doxycycline (as determined by the variation in FEV1), the patients were divided into two groups: the doxycycline-responder (doxy-R) group (n = 13); and the doxycycline-nonresponder (doxy-NR) group (n = 18). The patients with mild spirometric abnormalities responded better to doxycycline. The most common side effects were mild epigastric pain, nausea, and diarrhea.
  
  
  CONCLUSIONS
  In patients with LAM, doxycycline treatment results in effective MMP blockade, as well as in improved lung function and quality of life in those with less severe disease. However, these benefits do not seem to be related to the MMP blockade, raising the hypothesis that there is a different mechanism of action. (Brazilian Registry of Clinical Trials - ReBEC; identification number RBR-6g8yz9 [http://www.ensaiosclinicos.gov.br]).
authors.affiliation: A. C. Camargo Hospital, São Paulo, Brazil.
authors.forename: Suzana Pinheiro
authors.initials: SP
authors.lastname: Pimenta
authors.forename: Bruno Guedes
authors.initials: BG
authors.lastname: Baldi
authors.forename: Ronaldo Adib
authors.initials: RA
authors.lastname: Kairalla
authors.forename: Carlos Roberto Ribeiro
authors.initials: CR
authors.lastname: Carvalho
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood / Q000652:urine; D004318:Doxycycline / Q000009:adverse effects / Q000627:therapeutic use*; D005080:Exercise Test; D005260:Female; D006801:Humans; D018192:Lymphangioleiomyomatosis / Q000188:drug therapy* / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011788:Quality of Life; D012372:ROC Curve; D018709:Statistics, Nonparametric; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014797:Vital Capacity / Q000187:drug effects*; D016138:Walking
chemical_list: D015415:Biomarkers; D061965:Matrix Metalloproteinase Inhibitors; D042461:Vascular Endothelial Growth Factor A; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D004318:Doxycycline