Feasibility of Retinoids for the Treatment of Emphysema Study

• Published in: Chest Vol. 130; no. 5; pp. 1334 - 1345
• Main Authors: Roth, Michael D., Connett, John E., D’Armiento, Jeanine M., Foronjy, Robert F., Friedman, Paul J., Goldin, Jonathan G., Louis, Thomas A., Mao, Jenny T., Muindi, Josephia R., O’Connor, George T., Ramsdell, Joe W., Ries, Andrew L., Scharf, Steven M., Schluger, Neil W., Sciurba, Frank C., Skeans, Melissa A., Walter, Robert E., Wendt, Christine H., Wise, Robert A.
• Format: Journal Article
• Language: English
• Published: Northbrook, IL Elsevier Inc 01.11.2006; American College of Chest Physicians
• Subjects: Acids; Aged; Biological and medical sciences; Bronchoscopy; Carbon monoxide; Cardiology. Vascular system; Chronic obstructive pulmonary disease, asthma; clinical trial; Cross-Over Studies; CT scan; Dose-Response Relationship, Drug; Double-Blind Method; Drug dosages; Emphysema; Emphysema - diagnostic imaging; Emphysema - drug therapy; Feasibility Studies; Female; health-related quality of life; Humans; Isotretinoin - adverse effects; Isotretinoin - blood; Isotretinoin - therapeutic use; Keratolytic Agents - adverse effects; Keratolytic Agents - blood; Keratolytic Agents - therapeutic use; Male; Medical imaging; Medical sciences; Middle Aged; Pneumology; pulmonary function test; Quality of Life; Questionnaires; radiograph; Respiratory Function Tests; retinoic acid; Time Factors; Tomography, X-Ray Computed; Treatment Outcome; Tretinoin - adverse effects; Tretinoin - blood; Tretinoin - therapeutic use; clinical trial; radiograph; RV; 13-cRA; FORTE; health-related quality of life; TLC; VA; HU; emphysema; QOL; retinoic acid; Dlco; SGRQ; LD; pulmonary function test; ATRA; HD; CT scan; Drug; Lung disease; Radiodiagnosis; Respiratory disease; Retinoid; Exploration; Cardiovascular disease; Health-Related Quality of Life; Radiography; Lung function; Treatment; clinical trial; CT scan; emphysema; health-related quality of life; pulmonary function test; radiograph; retinoic acid; Bronchus disease; Medical imagery; Clinical trial; Feasibility; Computerized axial tomography; Obstructive pulmonary disease; Emphysema; Retinoic acid
• ISSN: 0012-3692; 1931-3543
• DOI: 10.1378/chest.130.5.1334

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.