Feasibility of retinoids for the treatment of emphysema study
| Autor: | Jonathan G. Goldin, Robert E. Walter, George T. O'Connor, Robert A. Wise, Steven M. Scharf, Robert F. Foronjy, Frank C. Sciurba, Neil W. Schluger, John E. Connett, Joe W. Ramsdell, Christine H. Wendt, Josephia R. Muindi, Jenny T. Mao, Andrew L. Ries, Thomas A. Louis, Melissa Skeans, Jeanine D'Armiento, Paul J. Friedman, Michael D. Roth |
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| Rok vydání: | 2006 |
| Předmět: |
Pulmonary and Respiratory Medicine
Male medicine.medical_specialty Time Factors Tretinoin Critical Care and Intensive Care Medicine Placebo Gastroenterology Pulmonary function testing Keratolytic Agents Double-Blind Method Internal medicine Diffusing capacity Medicine Humans Lung volumes Isotretinoin Aged Emphysema COPD Lung Cross-Over Studies Dose-Response Relationship Drug business.industry Respiratory disease Middle Aged medicine.disease Surgery Respiratory Function Tests medicine.anatomical_structure Treatment Outcome Quality of Life Feasibility Studies Female Cardiology and Cardiovascular Medicine business Tomography X-Ray Computed medicine.drug |
| Zdroj: | Chest. 130(5) |
| ISSN: | 0012-3692 |
| Popis: | Retinoids promote alveolar septation in the developing lung and stimulate alveolar repair in some animal models of emphysema.One hundred forty-eight subjects with moderate-to-severe COPD and a primary component of emphysema, defined by diffusing capacity of the lung for carbon monoxide (Dlco) [37.1 +/- 12.0% of predicted] and CT density mask (38.5 +/- 12.8% of voxels- 910 Hounsfield units) [mean +/- SD] were enrolled into a randomized, double-blind, feasibility study at five university hospitals. Participants received all-trans retinoic acid (ATRA) at either a low dose (LD) [1 mg/kg/d] or high dose (HD) [2 mg/kg/d], 13-cis retinoic acid (13-cRA) [1 mg/kg/d], or placebo for 6 months followed by a 3-month crossover period.No treatment was associated with an overall improvement in pulmonary function, CT density mask score, or health-related quality of life (QOL) at the end of 6 months. However, time-dependent changes in Dlco (initial decrease with delayed recovery) and St. George Respiratory Questionnaire (delayed improvement) were observed in the HD-ATRA cohort and correlated with plasma drug levels. In addition, 5 of 25 participants in the HD-ATRA group had delayed improvements in their CT scores that also related to ATRA levels. Retinoid-related side effects were common but generally mild.No definitive clinical benefits related to the administration of retinoids were observed in this feasibility study. However, time- and dose-dependent changes in Dlco, CT density mask score, and health-related QOL were observed in subjects treated with ATRA, suggesting the possibility of exposure-related biological activity that warrants further investigation. |
| Databáze: | OpenAIRE |
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