Abstract | BACKGROUND: METHODS: In the MILES trial, patients with lymphangioleiomyomatosis who had forced expiratory volume in 1 second (FEV1) of 70% or less of predicted were randomly assigned (1:1) to 12 months masked treatment with sirolimus or placebo. Serum VEGF-D concentrations were measured at baseline, 6 months, and 12 months. We used a linear regression model to assess associations of baseline VEGF-D concentrations with markers of disease severity, and a linear mixed effects model to assess the associations of VEGF-D concentrations with between-group differences in clinical, physiological, and patient-reported outcomes. FINDINGS: We included 42 patients from the placebo group and 45 from the sirolimus group in our analysis. Baseline VEGF-D concentrations in individual patients varied from 0·34 ng/mL to 16·7 ng/mL. Baseline VEGF-D concentrations were higher in patients who needed supplemental oxygen than in those who did not need supplemental oxygen (1·7 ng/mL [IQR 0·99–3·36] vs 0·84 ng/mL [0·52–1·39]; p<0·0001) and in those who had a bronchodilator response than in those who did not (2·01 ng/mL [0·99–2·86] vs 1·00 ng/mL [0·61–2·15]; 0·0273). Median serum VEGF-D concentrations were similar at baseline in the sirolimus and placebo groups, and fell from baseline at 6 and 12 months in the sirolimus group but remained roughly stable in the placebo group. Each one-unit increase in baseline log( VEGF-D) was associated with a between-group difference in baseline-to-12-month FEV1 change of 134 mL (p=0·0007). In the sirolimus group, improvement in baseline-to-12-month FEV1 occurred in 15 of 23 (65%) VEGF-D responders (ie, those in whom baseline-to-12-month VEGF-D concentrations decreased by more than they did in any patients in the placebo group) and four of 15 (27%) VEGF-D non-responders (p=0·0448). INTERPRETATION: FUNDING: National Institutes of Health, US Department of Defense.
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Authors | Lisa Young, Hye-Seung Lee, Yoshikazu Inoue, Joel Moss, Lianne G Singer, Charlie Strange, Koh Nakata, Alan F Barker, Jeffrey T Chapman, Mark L Brantly, James M Stocks, Kevin K Brown, Joseph P Lynch 3rd, Hilary J Goldberg, Gregory P Downey, Jeffrey J Swigris, Angelo M Taveira-DaSilva, Jeffrey P Krischer, Bruce C Trapnell, Francis X McCormack, MILES Trial Group |
Journal | The Lancet. Respiratory medicine
(Lancet Respir Med)
Vol. 1
Issue 6
Pg. 445-52
(Aug 2013)
ISSN: 2213-2600 [Print] England |
PMID | 24159565
(Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
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Chemical References |
- Antibiotics, Antineoplastic
- Biomarkers
- VEGFD protein, human
- Vascular Endothelial Growth Factor D
- Sirolimus
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Topics |
- Adult
- Aged
- Antibiotics, Antineoplastic
(therapeutic use)
- Biomarkers
(metabolism)
- Double-Blind Method
- Female
- Forced Expiratory Volume
(drug effects)
- Humans
- Lung Neoplasms
(blood, drug therapy)
- Lymphangioleiomyomatosis
(blood, drug therapy)
- Middle Aged
- Prospective Studies
- Sirolimus
(therapeutic use)
- Vascular Endothelial Growth Factor D
(metabolism)
- Vital Capacity
(drug effects)
- Young Adult
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