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Inhaled adenosine 5'-monophosphate (AMP) has an "indirect" bronchoconstrictive effect through mast cell degranulation and mediator release, whereas inhaled histamine has a "direct" effect on smooth muscle. Prolonged treatment with inhaled glucocorticosteroids attenuates airway responsiveness (AR) to AMP and histamine. We investigated the early effects of inhaled fluticasone propionate (FP) therapy on AR in 3 consecutive double-blind, randomized, placebo-controlled crossover studies in steroid-naive subjects with mild asthma. In one study, each of 12 subjects received FP 1000 microg or matched placebo for 7 inhalations at 12 hourly intervals; AR to AMP and FEV(1) were measured 2 hours after the 3rd and 7th inhalations. In a second study, each of 12 subjects received FP 100, 250, or 1000 microg or matched placebo for 3 inhalations at 12 hourly intervals; AR to AMP and FEV(1) were measured 2 hours after the 1st and 3rd inhalations. In a third study, each of 8 subjects received a single inhalation of FP 1000 microg or matched placebo; AR to histamine was measured 2 hours later. In the first study, FP 1000 microg significantly attenuated AR to AMP by 2.7 and 2.5 doubling doses after 3 and 7 inhalations, respectively (Por =.0001). In the second study, FP 100, 250, and 1000 microg significantly attenuated AR to AMP by 1.9, 2.2, and 2.7 doubling doses, respectively, after 1 inhalation and by 2.4, 2.2, and 3.2 doubling doses, respectively, after 3 inhalations (Por =.0001); a small but significant increase in FEV(1) (0.15 L) was observed after 3 inhalations but not after 1 inhalation of FP irrespective of dose (Por =.05). In the third study, a single inhalation of FP 1000 microg had no effect on AR to histamine. We have demonstrated a reduction in AR to AMP but not AR to histamine within 2 hours of a single inhalation of FP. This reflects a rapid, topical anti-inflammatory action of inhaled FP by a mechanism of action that remains unknown.

Rationale T cells have been implicated in the immunopathology of asthma and COPD. The Dutch Hypothesis proposes that COPD and asthma share common mechanisms. We compared airway and peripheral blood T cell profiles in subjects with COPD and severe asthma. Methods Absolute numbers and percentages of broncholalveolar lavage fluid (BALF) and peripheral blood cells expressing the T cell markers CD3, 4, 8, 27 and 45RA were measured in subjects (age 40-75 yrs, FEV 1 /FVC Results The mean percentages and absolute numbers of BALF cells expressing CD3 were significantly lower in COPD current smokers compared with COPD ex-smokers (0.015% vs 0.296%, p=0.09 and 0.0015 × 10 6 cells/ml BALF vs 0.1615 × 10 6 , p=0.003) and asthmatics (0.148%, p=0.02 and 0.1145 × 10 6 , p=0.002). The smokers also had significantly lower percentages of BALF cells expressing CD4 compared with the asthmatics (33.3% vs 61.7%, p=0.01). Proportions of CD8 T cells, and percentages of CD4 and CD8 cells expressing CD27 and CD45RA did not differ between the groups. However, blood and BALF (in both severe asthma and COPD) were characterized by their differential CD27, CD45RA expression. There were no significant differences in peripheral blood. Conclusions Similar numbers of CD4 and CD8 T cells expressing CD27 and CD45RA are found in BALF of subjects with COPD and severe asthma. Current smoking in COPD subjects appears to suppress the lymphocyte presence in BALF, particularly of the CD4 population.