Therapeutic effects of co-inhaled roflumilast or formoterol and fluticasone on asthma-induced ultrastructural changes in murine airways

Purpose: To investigate the therapeutic effects of "inhaled" roflumilast and formoterol separately or combined with fluticasone on the ultrastructural airway changes in ovalbumin-induced asthmatic mice.Methods: The asthmatic mice were divided randomly into seven groups (n = 8): positive control, vehicle, and five treated groups. The following treatments were given by inhalation (15 min once/day) for seven days: roflumilast (500 μg/kg), formoterol (50 μg/kg), fluticasone (1000 μg/kg), roflumilast + fluticasone (500 + 1000 μg/kg), and formoterol + fluticasone (50 + 1000 μg/kg). Ultrathin lung sections (50 - 70 nm thick) were examined by transmission electron microscopy.Results: The asthmatic mice showed marked degenerative changes in bronchiolar epithelial cells. The alveolar septal walls were thickened with cellular changes and capillary congestion. The basement membranes showed marked thickening and the airway lumens contained abundant mucinous secretions. These ovalbumin-induced ultrastructural airway changes were markedly-reversed in the roflumilast + fluticasone group, moderately-reversed in the roflumilast, fluticasone, and formoterol + fluticasone groups, but were not affected in the formoterol group.Conclusion: Co-inhalation of roflumilast + fluticasone significantly improved the ultrastructural airway changes than co-inhalation of formoterol + fluticasone in ovalbumin-asthmatic mice due to its antiinflammatory and antifibrotic effects.Keywords: Asthma, Fluticasone Propionate, Formoterol, Roflumilast, Ovalbumin, Remodeling, Bronchiolar epitheliu