Histamine-induced bronchospasm. Its reproducibility and usage in clinical evaluation of the sub-threshold bronchodilating dose of a new beta-agonist, KWD 2131.
The reproducibility of the histamine challenge in seven asymptomatic patients with extrinsic asthma, provoked four times each with 1-2 weeks interval, was investigated. The method was thereafter used in order to find the sub-threshold bronchodilating dose of a new beta-agonist KWD 2131 with a preferably anti-allergic property. Selection of patients and methodology of the histamine challenge procedure were carefully standardized. Histamine was administered during quiet breathing  at 3-min intervals in a step-wise cumulative manner up to a point where greater than 20% decrease in FEV 1.0 was reached. The pooled intra-individual standard deviation was 4.6% in FEV 1.0, 5.0% in PEFR, and 4.7% in FVC. Pretreatment with KWD 2131, before histamine challenge, showed that the subthreshold dose for bronchodilatation was 0.5 mg in nine patients and 0.25 mg in three patients compared with 1 mg in patients with intrinsic asthma. It  was important to perform individualized dose-titration of the sub-threshold bronchodilating dose of KWD 2131 before initiation of a subsequent allergen provocation study.
D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000627:therapeutic use*; D000328:Adult; D001249:Asthma / Q000188:drug therapy*; D001985:Bronchial Provocation Tests; D001986:Bronchial Spasm / Q000139:chemically induced*; D001993:Bronchodilator Agents / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D004305:Dose-Response Relationship, Drug; D005260:Female; D005541:Forced Expiratory Volume; D006632:Histamine; D006801:Humans; D008297:Male; D008875:Middle Aged; D013726:Terbutaline / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use
D000318:Adrenergic beta-Agonists; D001993:Bronchodilator Agents; C025075:KWD 2131; D006632:Histamine; D013726:Terbutaline