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

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Abstract
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.

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