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.