Inhaled heparin prevents exercise-induced asthma without influencing histamine-induced bronchoconstriction. This non-anticoagulant action of heparin is more likely to be related to a modulation of mediator release than to a direct effect on smooth muscle.

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.

As an inflammatory airway disease, asthma is expected to be associated with an increase in airway blood flow. We therefore compared airway mucosal blood flow (Qaw) among normal subjects (n = 11) and patients with stable asthma receiving (n = 13) or not receiving (n = 10) long-term inhaled glucocorticosteroid (GS) therapy. Qaw was calculated from the uptake of dimethyl ether in the anatomic dead space minus the most proximal 50 ml (DS), and expressed as blood flow per ml DS. Mean (+/- SE) Qaw was 38.5 +/- 5. 3 microl . min-1 . ml-1 in normals, 68.2 +/- 7.9 microl . min-1 . ml-1 in GS-naive asthmatics (p < 0.01), and 55.4 +/- 5.3 microl . min-1 . ml-1 in GS-treated asthmatics (p < 0.05). Ten minutes after administration of 180 microg albuterol by metered dose inhaler, mean Qaw increased by 83 +/- 26% in normal subjects (p < 0.01), but did not change significantly in GS-naive (+5 +/- 8%) or GS-treated (+32 +/- 15%) asthmatics. These results demonstrate that Qaw is increased in stable asthmatics and resistant to further increase by a standard inhaled dose of a beta-adrenergic agonist.

The vasoconstrictive efficacies of glucocorticosteroids (GS) are usually compared by the McKenzie skin-blanching test and taken as an index of relative potency. The rationale for the present study was to transpose the McKenzie test to the airway and to compare the airway vascular effects of three inhaled GS: beclomethasone dipropionate (BDP), fluticasone propionate (FP) and budesonide (BUD), in healthy subjects and patients with mild stable asthma.A soluble, inert gas-uptake method was used to measure airway blood flow (Qaw). Baseline mean¡SD Qaw normalised for anatomical dead space was 53.1¡1.4 mL?minin healthy subjects (n=10) and 67.8¡3 mL?min -1 ?mL -1 in asthmatics (n=10). All GS caused a transient decrease in Qaw. The magnitude of the vasoconstriction was greater in asthmatics. The relative vasoconstrictive effect of BDP, FP and BUD was 1, 1.9, and 2.7, respectively, in asthmatics and 1, 3.3 and 3.0, respectively, in healthy subjects, as assessed by the dose required to decrease Qaw by 20% from the baseline, 30-min postdrug inhalation.Therefore, measuring airway blood flow may be a useful, site-specific parameter to assess the tissue bioavailability and vasoconstrictive efficacy of inhaled glucocorticosteroids. Eur Respir J 2003; 21: 989-993.