A 2-year randomised placebo-controlled trial of doxycycline for lymphangioleiomyomatosis

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 progressi...

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Main Authors: Chang, William Y.C., Cane, Jennifer L., Kumaran, Maruti, Lewis, Sarah, Tattersfield, Anne E., Johnson, Simon R.
Format: Article
Published: European Respiratory Society 2014
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Online Access:https://eprints.nottingham.ac.uk/31531/
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author Chang, William Y.C.
Cane, Jennifer L.
Kumaran, Maruti
Lewis, Sarah
Tattersfield, Anne E.
Johnson, Simon R.
author_facet Chang, William Y.C.
Cane, Jennifer L.
Kumaran, Maruti
Lewis, Sarah
Tattersfield, Anne E.
Johnson, Simon R.
author_sort Chang, William Y.C.
building Nottingham Research Data Repository
collection Online Access
description 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.
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spelling nottingham-315312020-05-04T16:43:39Z https://eprints.nottingham.ac.uk/31531/ A 2-year randomised placebo-controlled trial of doxycycline for lymphangioleiomyomatosis Chang, William Y.C. Cane, Jennifer L. Kumaran, Maruti Lewis, Sarah Tattersfield, Anne E. Johnson, Simon R. 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. European Respiratory Society 2014-04-01 Article PeerReviewed Chang, William Y.C., Cane, Jennifer L., Kumaran, Maruti, Lewis, Sarah, Tattersfield, Anne E. and Johnson, Simon R. (2014) A 2-year randomised placebo-controlled trial of doxycycline for lymphangioleiomyomatosis. European Respiratory Journal, 43 (4). pp. 1114-1123. ISSN 1399-3003 Rare Lung Diseases Lung Proteases Tuberous sclerosis http://erj.ersjournals.com/content/43/4/1114 doi:10.1183/09031936.00167413 doi:10.1183/09031936.00167413
spellingShingle Rare Lung Diseases
Lung Proteases
Tuberous sclerosis
Chang, William Y.C.
Cane, Jennifer L.
Kumaran, Maruti
Lewis, Sarah
Tattersfield, Anne E.
Johnson, Simon R.
A 2-year randomised placebo-controlled trial of doxycycline for lymphangioleiomyomatosis
title A 2-year randomised placebo-controlled trial of doxycycline for lymphangioleiomyomatosis
title_full A 2-year randomised placebo-controlled trial of doxycycline for lymphangioleiomyomatosis
title_fullStr A 2-year randomised placebo-controlled trial of doxycycline for lymphangioleiomyomatosis
title_full_unstemmed A 2-year randomised placebo-controlled trial of doxycycline for lymphangioleiomyomatosis
title_short A 2-year randomised placebo-controlled trial of doxycycline for lymphangioleiomyomatosis
title_sort 2-year randomised placebo-controlled trial of doxycycline for lymphangioleiomyomatosis
topic Rare Lung Diseases
Lung Proteases
Tuberous sclerosis
url https://eprints.nottingham.ac.uk/31531/
https://eprints.nottingham.ac.uk/31531/
https://eprints.nottingham.ac.uk/31531/