Differential anti-inflammatory effects of large and small particle size inhaled corticosteroids in asthma

Background: Extra-fine particle formulations of hydrofluoroalkane-134a beclometasone dipropionate (HFA-BDP) exhibit clinical effects comparable with conventional particle formulations of chlorofluorocarbon beclometasone dipropionate (CFC-BDP) at half the dose. There is little data comparing their effects on inflammation. We have evaluated the effects of HFA-BDP and CFC-BDP on pulmonary and systemic markers of asthmatic inflammation.

Methods: A double-blind randomized crossover trial was undertaken comparing the anti-inflammatory effects of HFA-BDP (100 and 400 μg/day) and CFC-BDP (200 and 800 μg/day). Treatment with montelukast was evaluated as add-on to the higher dose of BDP.

Results: Compared with baseline after withdrawal of usual asthma therapy, 100 μg of HFA-BDP significantly attenuated serum eosinophilic cationic protein levels (0.61-fold change, 95% CI 0.49–0.77; a 39% reduction, P < 0.001), but 200 μg of CFC-BDP did not (0.87-fold change, 95% CI 0.63–1.23; P = 1). A dose of 800 μg of CFC-BDP and 400 μg of HFA-BDP led to reductions in exhaled nitric oxide (0.57-fold change, 95% CI 0.44–0.73; a 43% reduction, P < 0.001 and 0.65-fold change, 95% CI 0.47–0.91; a 35% reduction, P = 0.008, respectively); and peripheral eosinophils (−74 cells/μl, 95% CI −146 to −2; P = 0.020 and −77 cells/μl, 95% CI −140 to −14; P = 0.012, respectively). Montelukast further reduced exhaled nitric oxide (0.81-fold change, 95% CI 0.66–0.98; P = 0.028) with 400 μg HFA-BDP and eosinophils (−44 cells/μl, 95% CI −80 to −8; P = 0.012) with 800 μg CFC-BDP, but not vice versa.

Conclusion: Chlorofluorocarbon beclometasone dipropionate and HFA-BDP have differential effects on pulmonary and systemic inflammation, which dictate the additive effects of montelukast.