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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.

Authors

William Y.C. Chang

Jennifer L. Cane

Maruti Kumaran

Anne E. Tattersfield

SIMON JOHNSON simon.johnson@nottingham.ac.uk
Professor of Respiratory Medicine



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.

Journal Article Type Article
Publication Date Apr 1, 2014
Journal European Respiratory Journal
Print ISSN 0903-1936
Electronic ISSN 1399-3003
Publisher European Respiratory Society
Peer Reviewed Peer Reviewed
Volume 43
Issue 4
APA6 Citation Chang, W. Y., Cane, J. L., Kumaran, M., Lewis, S., Tattersfield, A. E., & Johnson, S. R. (2014). A 2-year randomised placebo-controlled trial of doxycycline for lymphangioleiomyomatosis. European Respiratory Journal, 43(4), doi:10.1183/09031936.00167413
DOI https://doi.org/10.1183/09031936.00167413
Keywords Rare Lung Diseases, Lung Proteases, Tuberous sclerosis
Publisher URL http://erj.ersjournals.com/content/43/4/1114
Copyright Statement Copyright information regarding this work can be found at the following address: http://eprints.nottingh.../end_user_agreement.pdf
Additional Information This is an author-submitted, peer-reviewed version of a manuscript that has been accepted for publication in the European Respiratory Journal, prior to copy-editing, formatting and typesetting. This version of the manuscript may not be duplicated or reproduced without prior permission from the copyright owner, the European Respiratory Society. The publisher is not responsible or liable for any errors or omissions in this version of the manuscript or in any version derived from it by any other parties. The final, copy-edited, published article, which is the version of record, is available without a subscription 18 months after the date of issue publication.

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Chang et al 2014 Eur Resp journal.pdf (165 Kb)
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Copyright Statement
Copyright information regarding this work can be found at the following address: http://eprints.nottingham.ac.uk/end_user_agreement.pdf





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