Protective effects of fluticasone on allergen-induced airway responses and sputum inflammatory markers.

BACKGROUND: A direct comparison of the protective effects of single and regular doses of inhaled glucocorticoid on allergen-induced asthmatic responses and inflammation has not been made. OBJECTIVE: To compare the effects of pretreatment with fluticasone 250 microg 30 min before allergen inhalation and two weeks of 250 microg twice daily (last dose 24 h before challenge) with single and regular (twice daily) placebo doses on early and late asthmatic responses, induced sputum cell counts and measures of eosinophil activation at 7 h and 24 h, and methacholine airway responsiveness at 24 h. PATIENTS AND METHODS: Ten mild asthmatic patients were studied in a randomized, double-blind, placebo controlled crossover study. RESULTS: Regular fluticasone increased the baseline mean provocative concentration of methacholine to cause a 20% fall (PC20) in forced expiratory volume in 1 s (FEV1) from 2.6 to 6.4 mg/mL (P<0.05) and lowered the eosinophil count from 3.1% to 0.4% (P<0.05) compared with regular placebo. Neither single nor regular fluticasone had any effect on the early asthmatic response. Single fluticasone attenuated the late asthmatic response, the mean +/- SEM maximum percentage fall in FEV1 (10.8+/-3.6 compared with single placebo 18. 8+/-3.5, P=0.03), the allergen-induced increase of airway responsiveness (P<0.05), and the eosinophilia (P<0.005) and activated eosinophils at 7 h (P<0.01) but not at 24 h. Regular fluticasone also attenuated the late asthmatic response (11.1+/-2.5) compared with regular placebo (19.6+/-4.5), but this was not statistically significant and did not protect against the induced increase in airway responsiveness or the sputum eosinophilia. CONCLUSION: Two weeks of regular inhaled fluticasone discontinued 24 h before allergen challenge does not offer any additional protection against the early or late asthmatic responses, increased airway responsiveness or sputum eosinophilia compared with a single dose of 250 microg immediately before allergen challenge, despite increasing baseline PC20 and decreasing sputum eosinophilia prechallenge. The significance of the protective effect of a single dose of inhaled steroid before an allergen inhalation and the duration of the protective effect need further investigation.

Effect of frusemide on the induction and potentiation of cough induced by prostaglandin F2 alpha.

We examined whether inhaled frusemide could reduce the potentiation of capsaicin-induced cough by prostaglandin (PG) F2 alpha. Eight non-smoking normal subjects, after a baseline capsaicin challenge were given inhaled frusemide or saline followed by capsaicin challenge, then PGF2 alpha and finally capsaicin challenge again. PGF2 alpha-induced coughs were reduced after frusemide to 3.6 +/- 1.0 compared with 5.7 +/- 1.2 after saline (P less than 0.05). PGF2 alpha increased capsaicin-induced coughs by 11.1 +/- 3.7 and 7.9 +/- 3.4 after placebo and frusemide, respectively (P less than 0.05). Frusemide had no effect on capsaicin-induced cough alone. Changes in local ionic concentrations by frusemide, particularly chloride ions within the vicinity of epithelial cough receptors, may determine the cough response to low chloride solutions and to PGF2 alpha, but not to capsaicin which acts directly on the cough receptors, and alter the sensitivity of the receptors to capsaicin.

Effects of storage, iron and time of day on indices of lipid peroxidation in plasma from healthy volunteers.

The concentrations of thiobarbituric acid reactive substances and conjugated dienes in human plasma are often used as indices of lipid peroxidation. However, concentrations of thiobarbituric acid reactive substances in plasma are markedly affected by the iron content of reagents used in the analysis and by storage of samples at -70 degrees C. The assay also has a large interbatch coefficient of variation (14%). Plasma concentrations of conjugated dienes are not affected by storage and the coefficient of variation is only 4%. However, there is a marked diurnal variation in levels of conjugated dienes which is similar to the changes in concentrations of plasma triglycerides. Precise standardisation of analytical procedures is required before these assays can be reliably used in clinical medicine.

Inhaled furosemide inhibits cough induced by low chloride content solutions but not by capsaicin.

Inhaled furosemide prevents bronchoconstriction induced by nebulized distilled water, exercise, and antigen challenge. We examined the effect of furosemide on cough induced by low chloride content solutions and by capsaicin in double-blind, placebo-controlled studies. A group of eight nonsmoking normal subjects was given furosemide (3.75 mg/ml inhaled for 8 min) and placebo (saline) immediately before consecutive 1-min inhalations of four isosmolar solutions with decreasing chloride content every 5 min from an ultrasonic nebulizer. Decreasing concentrations of chloride induced dose-related coughing, which was inhibited by furosemide. Thus, chloride-free solution induced 13.1 +/- 1.6 coughs after placebo and 8.4 +/- 1.9 coughs after furosemide (p less than 0.005). In a separate study, six of the same normal subjects were given inhaled furosemide or placebo before inhaling one breath of capsaicin solution given in three consecutive increasing concentrations. Capsaicin induced dose-related coughing, which was not inhibited by furosemide. Thus, after placebo the highest concentration of capsaicin induced 20.8 +/- 1.8 coughs and after furosemide, 21.5 +/- 2.7 coughs. We conclude that furosemide may act by inhibiting the cough reflex indirectly, perhaps by changing local chloride ions within the vicinity of epithelial cough receptors.