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.