title: A 2-year randomised placebo-controlled trial of doxycycline for lymphangioleiomyomatosis.
abstract: Lymphangioleiomyomatosis (LAM) is characterised by lung cysts and airflow obstruction. Matrix metalloproteinases have been implicated in lung destruction in LAM. We performed a randomised, double-blind trial, comparing the matrix metalloproteinases inhibitor doxycycline with placebo on the progression of LAM. 23 females with LAM were randomised to doxycycline 100 mg daily for 3 months followed by 200 mg daily for 21 months, or matched placebo. Lung function, exercise capacity, quality of life and matrix metalloproteinases levels were measured. 21 patients completed 6 months of treatment, 17 completed 1 year of treatment and 15 completed 2 years of treatment. Eight withdrew from the trial due, four due to a pneumothorax and four because of other reasons. The mean±sd decline in FEV1, the primary endpoint, did not differ between the groups being -90±154 mL·year(-1) in the placebo group and -123±246 mL·year(-1) in the doxycycline group (difference -32.5, 95% CI -213-148; p=0.35). Doxycycline had no effect upon vital capacity, gas transfer, shuttle walk distance or quality of life. Urine matrix metalloproteinases-9 measurements were lower with doxycycline treatment (p=0.03). Although with limited numbers we cannot completely exclude an effect of doxycycline, the lack of effect on any outcome makes it unlikely that doxycycline has a useful effect in LAM.
authors: University of Nottingham, Nottingham.
authors: William Y C
authors: WY
authors: Chang
authors: Jennifer L
authors: JL
authors: Cane
authors: Maruti
authors: M
authors: Kumaran
authors: Sarah
authors: S
authors: Lewis
authors: Anne E
authors: AE
authors: Tattersfield
authors: Simon R
authors: SR
authors: Johnson
mesh_terms: D000328:Adult; D004311:Double-Blind Method; D004318:Doxycycline / Q000627:therapeutic use*; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D017079:Exercise Tolerance; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D018192:Lymphangioleiomyomatosis / Q000188:drug therapy*; D061965:Matrix Metalloproteinase Inhibitors / Q000627:therapeutic use; D020782:Matrix Metalloproteinases / Q000097:blood / Q000652:urine; D008875:Middle Aged; D010100:Oxygen / Q000737:chemistry; D011788:Quality of Life; D013147:Spirometry; D011795:Surveys and Questionnaires
chemical_list: D004791:Enzyme Inhibitors; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases; D004318:Doxycycline; D010100:Oxygen