Transient Effect of Inhaled Fluticasone on Airway Mucosal Blood Flow in Subjects with and without Asthma

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Abstract
Topically applied glucocorticosteroids (GS) have been shown to cause local vasoconstriction in normal skin and this phenomenon is commonly used to assess the potency of topical GS (McKenzie skin blanching test). The purpose of the present study was to determine if an inhaled GS, fluticasone propionate (FP), similarly leads to vasoconstriction in the airway mucosa and if subjects with and without asthma have differential vascular responsiveness to GS. In 10 nonsmokers with stable asthma and 10 nonasthmatic nonsmokers, airway mucosal blood flow (Qaw) expressed per milliliter of anatomical dead space and the forced expiratory volume in 1 s (FEV (1)) were determined before and serially after inhalation of FP (88 to 1,760 microg) or placebo. Baseline mean (+/- SE) Qaw was 55.1 +/- 1.0 and 44.2 +/- 1.1 microl x min(-1) x ml(-1) in subjects with and without asthma, respectively (p < 0.001). The corresponding mean FEV(1) values were 2.34 +/- 0.13 and 3.22 +/- 0.12 L (p < 0.001). FP at 880 microg but not placebo produced a transient decrease in mean Qaw with a nadir at 30 min and return toward baseline at 90 min post-inhalation; the maximum mean decrease was 37% in subjects with asthma and 21% in unaffected subjects (p < 0.01); 880 microg of FP was the lowest effective dose. FEV(1) did not change after FP administration in either group. These results demonstrate a transient vasoconstrictive action of inhaled FP in the airway mucosa, with a greater vascular responsiveness in subjects with asthma than in unaffected subjects. The measurement of Qaw may provide a more relevant means of assessing the potency of inhaled GS than the McKenzie skin blanching test. In addition, our observation suggests that inhaled GS have potentially beneficial effects in asthma that is not related to their antiinflammatory action.