Aerosol probes of emphysema progression in dogs treated with all trans retinoic acid: An exploratory study

• Published in: Journal of aerosol medicine Vol. 20; no. 2; pp. 83 - 96
• Main Author: ROSENTHAL, Frank S
• Format: Journal Article
• Language: English
• Published: Larchmont, NY Liebert 01.06.2007; Mary Ann Liebert, Inc
• Subjects: Aerosols; Animals; Antineoplastic Agents - administration & dosage; Biological and medical sciences; Disease Progression; Dogs; Forced Expiratory Volume; General pharmacology; Inspiratory Capacity; Male; Medical sciences; Papain - adverse effects; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Pulmonary Emphysema - chemically induced; Pulmonary Emphysema - diagnosis; Pulmonary Emphysema - drug therapy; Rats; Respiratory Function Tests; Respiratory System Agents - administration & dosage; Total Lung Capacity; Treatment Outcome; Tretinoin - administration & dosage; Vital Capacity; Antineoplastic agent; Fissipedia; Lung disease; Carnivora; Pharmaceutical technology; Respiratory disease; Retinoid; Probe; Vertebrata; Mammalia; Animal; Aerosols; Bronchus disease; Evolution; Obstructive pulmonary disease; Dog; Emphysema; Tretinoin
• ISSN: 0894-2684; 1941-2711; 1557-9026; 1941-2703
• DOI: 10.1089/jam.2007.0581

This study used aerosol probes and lung function tests to investigate whether all trans retinoic acid (RA) can reverse experimental emphysema in dogs. Three dogs were evaluated with lung mechanics tests, including inspiratory capacity (IC), total lung capacity (TLC), and the ratio of forced expired volume in 0.5 sec to forced vital capacity (FEV0.5/FVC), an aerosol-derived measure of pulmonary airspace size (effective airspace diameter, EAD), and an aerosol-derived measure of nonuniform ventilation (aerosol dispersion, AD). Emphysema was induced by exposure to aerosolized papain. At 11 or 12 weeks post-papain exposure, dogs received oral RA (2 mg/kg/day) for 8 weeks, and were followed for an additional 4 weeks after stopping RA treatment. In all dogs, lung injury increased in the first 11-12 weeks following papain exposure, as evidenced by increasing trends of inspiratory capacity IC, TLC, EAD, and AD, and a decreasing trend of FEV0.5/FVC. These parameters of lung injury partially and transiently reversed their trends between 2 and 6 weeks following the initiation of RA treatment. A sham RA-treated group was not studied. However, similar reversals of lung injury were not seen in a previous study of dogs treated with papain but not RA, suggesting that RA altered emphysema progression in the current study. The limited reversal of lung injury in this study contrasts with more pronounced treatment effects seen in previous studies with rats. This paper discusses possible reasons for differences in these studies, as well as suggestions for improved experimental investigations of emphysema therapies.