title: Doxycycline use in patients with lymphangioleiomyomatosis: safety and efficacy in metalloproteinase blockade.
abstract: OBJECTIVE
  Lymphangioleiomyomatosis (LAM) is characterized by lung cysts, whose development is associated with matrix metalloproteinase (MMP) hyperactivity, principally that of MMP-2 and MMP-9. Our objective was to compare LAM patients and controls in terms of the levels of these MMPs, as well as to determine the safety and efficacy of treatment with doxycycline, a potent MMP inhibitor.
  
  
  METHODS
  Prospective clinical study involving female LAM patients who received doxycycline (100 mg/day) for six months. Urine and blood samples were collected for the quantification of MMP-2 and MMP-9 before and after the treatment period. Samples from 10 healthy women were also collected.
  
  
  RESULTS
  Of the 41 LAM patients who started the treatment, 34 completed the protocol. Serum and urinary MMP-9 levels were significantly lower in the controls than in the LAM patients (p < 0.0001). Comparing pre- and post-treatment values, we found that the median level of MMP-9 in serum decreased from 919 ng/mL to 871 ng/mL (p = 0.05), whereas that of MMP-9 in urine decreased from 11,558 pg/mL to 7,315 pg/mL (p = 0.10). After treatment, the median level of MMP-2 in serum was significantly lower (p = 0.04) and urinary MMP-2 levels were undetectable. Nausea, diarrhea, and epigastric pain were the most prevalent adverse affects and were often self-limiting. There was only one case in which the patient discontinued the treatment because of side effects.
  
  
  CONCLUSIONS
  We have demonstrated, for the first time, a decrease in serum and urine levels of MMPs in LAM patients treated with doxycycline, which proved to be a safe medication, with mild and well-tolerated side effects.
authors: University of São Paulo School of Medicine Hospital das Clínicas, São Paulo, Brazil. spp3847@yahoo.com.br
authors: Suzana Pinheiro
authors: SP
authors: Pimenta
authors: Bruno Guedes
authors: BG
authors: Baldi
authors: Milena Marques Pagliarelli
authors: MM
authors: Acencio
authors: Ronaldo Adib
authors: RA
authors: Kairalla
authors: Carlos Roberto Ribeiro
authors: CR
authors: Carvalho
mesh_terms: D000328:Adult; D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use*; D016022:Case-Control Studies; D004318:Doxycycline / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D018192:Lymphangioleiomyomatosis / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000097:blood / Q000652:urine; D011446:Prospective Studies; D011480:Protease Inhibitors / Q000627:therapeutic use
chemical_list: D020533:Angiogenesis Inhibitors; D000900:Anti-Bacterial Agents; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D020782:Matrix Metalloproteinases; D004318:Doxycycline