The efficacy of the oral leukotriene-receptor antagonist zafirlukast was assessed as maintenance therapy for patients with mild-to-moderate asthma. A total of 762 patients aged 12 to 76 years were enrolled in a 13-week, multicenter, double-masked, placebo-controlled, parallel-group trial and randomly assigned to receive either zafirlukast (20 mg twice daily) or placebo. Patients were maintained on as-needed beta-agonist therapy throughout the study and had to have a cumulative daytime asthma symptoms score > or = 8 (on a daily scale of 0 to 3) over 7 consecutive days before randomization. Efficacy was assessed by changes in symptoms, beta-agonist use, and pulmonary function. Safety was assessed by adverse experiences, laboratory test results, physical examination, and electrocardiography. Zafirlukast significantly decreased daytime asthma symptoms scores (-26.5%), nighttime awakenings (-19.8%), mornings with asthma (-29.0%), and beta-agonist use (-22.3%) and significantly increased morning peak expiratory flow rate (6.9%) and forced expiratory volume in 1 second (6.3%) compared with placebo. Changes in symptoms, beta-agonist use, and pulmonary function occurred within 2 days of zafirlukast treatment and continued throughout the trial. Zafirlukast was well tolerated. Pharyngitis and headache were the most common adverse events, occurring with similar frequency in both the zafirlukast and placebo groups. No clinically significant changes were observed in laboratory test results, findings on physical examination, or electrocardiographic findings. We conclude that zafirlukast produces early and sustained effects in the treatment of mild-to-moderate asthma.

Adolescent↗

PubMedDate not supplied

Effect of a synthetic leukocyte elastase inhibitor on thrombin-induced pulmonary edema in the rat.

The effect of a synthetic leukocyte elastase inhibitor on thrombin-induced pulmonary edema was studied in rats. The chloromethylketone human neutrophil elastase inhibitor, ICI 200,355, blunted rat leukocyte elastase activity in rat lung tissue. Administration of thrombin produced a significant increase (p < .01) in lung weight. The wet weight to dry weight ratio (WW/DW) and relative water contents were also significantly elevated (p < .01). Pretreatment with ICI 200,355 (200 micrograms/kg h-1) resulted in significant reductions (p < .05) in lung weight and a tendency to decrease WW/DW and water content compared with animals given thrombin alone. It is possible that the elastase inhibitor effectively reduced the rate of thrombin-induced pulmonary edema by attenuation of increased vascular permeability.

Amino Acid Sequence↗

PubMedDate not supplied

Crisis intervention in the problems of a pre-school diabetic child.

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Child, Preschool↗