Histamine‐Induced Bronchospasm

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 β-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 >20% decrease in FEV1.0 was reached. The pooled intra-individual standard deviation was 4.6% in FEV1.0, 5.0% in PEFR, and 4.7% in FVC. Pretreatment with KWD 2131, before histamine challenge, showed that the sub-threshold 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.