I read with interest the recent article by Meijer and colleagues on the effects of inhaled fluticasone and prednisolone on clinical and inflammatory parameters in patients with asthma.1 Rather than focusing on the differences between oral and inhaled corticosteroid, I believe that a more important finding is the effect of a fourfold increase in the dose of fluticasone on the therapeutic ratio. For airway parameters there were no significant differences in the effects on bronchial hyperresponsiveness to methacholine and adenosine monophosphate or on sputum eosinophils between fluticasone in doses of 500 μg and 2000 μg per day. However, for systemic bioactivity markers there were significant differences between the two doses of fluticasone on serum cortisol levels and blood eosinophils. Taken together these findings suggest that, at least for effects on airway hyperresponsiveness and inflammation, the therapeutic ratio for fluticasone declines sharply above a watershed dose of 500 μg per day. This result is perhaps not surprising, given the high glucocorticoid topical potency for in vitro anti-inflammatory activity with fluticasone.2

It is also important to point out that the study by Meijeret al was performed using fluticasone delivered via a Diskhaler dry powder inhaler device, which delivers a twofold lower respirable fine particle dose than a fluticasone propionate pressurised metered dose inhaler.3 This is due to the larger particle size from the fluticasone dry powder inhaler. Hence, increasing the nominal dose of fluticasone dry powder may result in a proportionately greater …