The Effect of Alpha-1 Proteinase Inhibitor on Biomarkers of Elastin Degradation in Alpha-1 Antitrypsin Deficiency: An Analysis of the RAPID/RAPID Extension Trials
| Autor: | Robert A. Sandhaus, Shuren Ma, Jerome O. Cantor, Gerard M. Turino, Jonathan M. Edelman, Michael Fries, Yong Y. Lin, Kenneth R. Chapman, N. Gerard McElvaney |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Pulmonary and Respiratory Medicine medicine.medical_specialty Pathology Alpha (ethology) Placebo Gastroenterology 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Internal medicine medicine Isodesmosine Original Research COPD Alpha 1-antitrypsin deficiency biology business.industry medicine.disease Confidence interval Desmosine 030104 developmental biology 030228 respiratory system chemistry biology.protein business Elastin |
| Zdroj: | Chronic obstructive pulmonary diseases (Miami, Fla.). 4(1) |
| ISSN: | 2372-952X |
| Popis: | The RAPID (NCT00261833; N=180) and RAPID Extension (NCT00670007; N=140) trials demonstrated significantly reduced lung density decline in patients with alpha-1 antitrypsin deficiency (AATD) receiving alpha-1 proteinase inhibitor (A1PI) versus placebo. Desmosine and isodesmosine (DES/IDES) are unique crosslinkers of mature elastin fibers and are utilized as measures of elastin degradation. The aim of this post-hoc study was to determine the effect of A1PI therapy on DES/IDES levels in patients from RAPID/RAPID Extension. Plasma levels of DES/IDES were measured using high-performance liquid chromatography and tandem mass spectrometry. Correlation between changes in DES/IDES levels and computed tomography (CT) lung density decline was assessed. Analysis showed that DES/IDES levels were significantly reduced versus baseline in patients receiving A1PI at all time points, from month 3 through month 48. A significant increase from baseline in DES/IDES was observed with placebo at month 24 (n=54; 0.016; p=0.018). DES/IDES change from baseline was significantly different with A1PI versus placebo at months 3 (-0.021; 95% confidence interval [CI] -0.037, 0.004; p=0.026), 12 (-0.040; 95% CI -0.055, 0.025; p |
| Databáze: | OpenAIRE |
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