Airway hyperreactivity: assessment with helical thin-section CT.

PURPOSE: To determine the accuracy of helical computed tomography (CT) for assessing reversible changes in bronchial size and air trapping due to airway hyperreactivity. MATERIALS AND METHODS: Spirometry and helical CT were performed in 15 patients with mild asthma and six healthy control subjects before and after bronchial provocation with methacholine chloride and after reversal of provocation with albuterol. CT was performed at suspended functional residual capacity and at residual volume in two lung regions (above and below the carina). Bronchial area and lung attenuation measurements were compared. RESULTS: At baseline, lung attenuation frequency distribution curves were similar between the control and asthma groups. After methacholine, control subjects showed a decrease of less than 10% in the forced expiratory volume at 1 second (FEV1) and no significant differences in lung attenuation curves. Patients with asthma showed a 20%-36% decrease in FEV1, with significant decreases in the median and lowest 10th percentile regions of the attenuation curves and in the cross-sectional area of small (< 5-mm2) airways (P < .001 for all comparisons). After albuterol, control subjects showed no change in spirometric measurements, lung attenuation, or bronchial size, whereas all such parameters returned to baseline levels in patients with asthma. CONCLUSION: Functional helical CT can accurately demonstrate reversible airflow obstruction resulting from airway hyperreactivity.

Effects of oral cetirizine, a selective H1 antagonist, on allergen- and exercise-induced bronchoconstriction in subjects with asthma.

The protective efficacy of oral cetirizine, a selective and potent H1-receptor antagonist, against the immediate bronchoconstrictive response to allergen inhalation and exercise challenge was evaluated in 16 subjects with stable, predominantly mild asthma. The subjects underwent double-blind, crossover pretreatments in randomized order in two separate protocols with (1) three daily oral doses of 20 mg of cetirizine and placebo, followed by allergen inhalation, and (2) single oral doses of cetirizine (5, 10, and 20 mg), albuterol (4 mg), and placebo, followed by exercise with cold-air inhalation. Cetirizine failed to decrease bronchial sensitivity to inhaled allergen in eight of 10 subjects. Neither cetirizine nor albuterol uniformly inhibited exercise-induced bronchoconstriction. Serum concentrations of cetirizine were consistent with systemic H1-blocking activity. Modest bronchodilation occurred after administration of cetirizine and albuterol before exercise but not after the third dose of cetirizine in the allergen protocol. One subject developed moderate drowsiness during multiple dosing with cetirizine. Thus, cetirizine, in the doses studied, is not uniformly effective in preventing allergen- or exercise-induced bronchoconstriction. Histamine is one of many mediators participating in immediate asthmatic responses, and selective H1 antagonists do not completely block these airway events. However, cetirizine may still clinically benefit some patients with asthma, such as patients with allergic rhinitis or urticaria.

Effects of inhaled thiazinamium chloride on histamine-induced and exercise-induced bronchoconstriction.

The protective efficacy of aerosolized thiazinamium chloride (TC) against histamine-induced and exercise-induced bronchoconstriction was evaluated in 15 subjects with stable, mild asthma. Following reproducible bronchoprovocation with these stimuli, each subject underwent randomized, double-blind, crossover pretreatment with single doses of nebulized TC (300, 600, and 900 micrograms), placebo, and an active control drug (metaproterenol or cromolyn), followed by histamine or exercise challenge (two separate protocols). The results indicated that all doses of TC significantly blocked histamine-induced bronchoconstriction as compared with placebo. Overall, aerosolized TC was ineffective in blocking exercise-induced bronchoconstriction, although 900 micrograms TC tended to be more effective than placebo. Thiazinamium (900 micrograms) produced a modest bronchodilator effect. No clinically significant adverse effects related to TC occurred. We conclude that aerosolized TC is effective in attenuating histamine-induced but not exercise-induced bronchoconstriction in the doses studied. Further studies are warranted to evaluate the role of TC in asthma therapy.

Effect of cetirizine, a new histamine H1 antagonist, on airway dynamics and responsiveness to inhaled histamine in mild asthma.

Cetirizine, a major human metabolite of hydroxyzine, preserves the histamine H1-antagonist activity of the parent compound but poorly penetrates the blood-brain barrier, thus minimizing sedative and anticholinergic effects. In 10 young (mean age 27.7 years) subjects with mild asthma (FEV1 greater than 70% predicted), we evaluated the bronchodilator and protective efficacy of 5, 10, and 20 mg of cetirizine against bronchospasm induced by histamine inhalation (0.03 to 20 mg/ml) in comparison with placebo and hydroxyzine, 25 mg, using a random, double-blind crossover design. The provocative concentration of histamine causing a 20% decline in FEV1 for all 10 subjects from the postdiluent control value was more than fourfold greater after each active drug than after placebo. Cetirizine, 5 to 20 mg, provided significantly greater protection against histamine-induced bronchospasm than hydroxyzine (p less than 0.001); moreover, a dose-dependent protective effect was noted with cetirizine. Significant bronchodilation was also found: at 60 minutes, FEV1 increased significantly after all active antihistamines compared to placebo and after 20 mg of cetirizine compared to hydroxyzine (p less than 0.05). FEV1 increased significantly at 120 minutes after hydroxyzine and after cetirizine in both the 20 and 10 mg doses compared to placebo (p less than 0.05). We conclude that in subjects with mild asthma, orally administered cetirizine provides significant dose-dependent protection against histamine-induced bronchoconstriction, which in the doses studied is superior to that produced by the parent compound, hydroxyzine. In addition, cetirizine in 5 to 20 mg doses causes acute bronchodilation. These results suggest a possible role of cetirizine in asthma therapy.

Rebound hyperresponsiveness to muscarinic stimulation after chronic therapy with an inhaled muscarinic antagonist.

In 9 young subjects with mild asthma, we investigated the possibility that chronic daily administration of an inhaled muscarinic antagonist (ipratropium bromide) might increase the response of muscarinic receptors in airway smooth muscle to agonist stimulation caused by receptor upregulation. Subjects inhaled 60 micrograms of ipratropium 4 times daily for 3 wk. Methacholine bronchoprovocation (with or without acute pretreatment with ipratropium) was performed before (control period) and during 3 wk of daily ipratropium therapy (medication period). At the end of the medication period, subjects returned at 12, 24, 48, and 72 h after the last dose of ipratropium (withdrawal period) to determine the provocative concentration of methacholine producing a 20% decrease in FEV1 (PC20). During the medication period, there was no significant diminution of the acute bronchodilator response to ipratropium or of the protective effect of ipratropium against methacholine-induced bronchospasm when compared with the control period. During the withdrawal period, mean in PC20 was significantly less (increased airway responsiveness) at 24 h than during the control period (p less than 0.01) and returned to the control period value within 48 to 72 h. We conclude that daily administration of ipratropium to mildly asthmatic subjects for 3 wk does not produce tolerance to either the bronchodilator effect of ipratropium or to its inhibition of methacholine-induced bronchospasm but does induce transient supersensitivity of airway cholinergic receptors to muscarinic stimulation.