Mode of Action of Bronchodilating Drugs on Histamine-Induced Bronchoconstriction in Asthmatic Children

Abstract

Summary23,25,35) that in adult asthmatic patients, atropine-like substances predominantly dilate larger upstream airways and that /3r-symThe bronchodilator~ response of three Pz-agonists (fenoterol, pathomimetics predominantly dilate smaller upstream airways. salbutamol, and terbutaline), administered by a metered aerosolThe relative contribution made by large and small airways to inhaler, was assessed in 19 asthmatic children after histamine-flow limitation is of major interest to several research groups. hi^ induced bronchoconstriction. At 1-min intervals, the changes in determination is important from the therapeutical point of view, total pulmonary flow resistance (RI) and dynamic lung compliance ,in,, it is preferable to use a bronchodilating substance that (C dyn) were measured. ~f t e r rank-ordering according to the base specifically affects the area of broncho-obstruction in the particline value of C dyn (62 to 200% predicted), the patients were ular patient. divided into two groups according to lung compliance: (1) patientsThere have been numerous studies on the effect of Ps-agonists with greater compliance (C dyn, 129 to 200% predicted) and (2) in &Idren. Little is known about their specific action on the small patients with lesser compliance (C dyn, 69 to 116% predicted). The and/or large especially the site of their action, since most effect of the three bronchodilators on the mean decrease of R1 and of the published studies conducted lung function tests in the form on the increase of C dyn was studied and analyzed for each drug of breathing manoeuvres-( F~~, = forced expiratory separately. In all patients, salbutamol was the most efficient volume set, FVC = forced vital capacity, PF = peak flow, FEF bronchodilator of small airways (P < 0.02). The most striking = forced expiratory flow at different percent of the vital capacity).feature of this fin-mimetic was observed in patients whose lungs These tests fail to detect changes in small airway caliber. Moreover were initially overinflated (functional residual capacity over 120% they are effort and cooperat~on-~epen~ent, ~redicted) but not obstructed before the histamine challenge (P The present study was, therefore, designed to ascertain whether < 0.005). In these subjects C dyn and R1 are normalized after the immediate bronchodilatory response of three Pr-sympathoinhalation of salbutamol. mimetic aerosols (fenoterol, salbutamol, and terbutaline) is similar After fenoterol and terbutaline inhalation, obstruction of the in asthmatic children after histamine respiratory challenge and large airways was not fully alleviated. In addition, these two drugs whether the preferential sites of action of these three drugs can be seemed not to affect the ventilatory asynchronism (C dyn altera-detected within the bronchial tree, tions) in patients whose lungs had been overinflated before drug inhalation (C dyn again around 150% predicted).

Effects of salbutamol and Ro-20-1724 on airway and parenchymal mechanics in rats

“…Clinical studies indicate that, after the induction of constriction, salbutamol (a selective ␤ 2 -adrenoceptor agonist) causes increases in forced expiratory lung volumes (13) and decreases in high-frequency respiratory resistance (16,17,23,29); i.e., it increases the airway caliber. Most of the previous studies, however, also report a significant increase in respiratory compliance (which describes the elasticity of the respiratory tissues) after intravenous (iv) (16) or aerosolized salbutamol (17,23,29). Recently, Kaczka et al (14) separated the airway and tissue responses after inhalation of another ␤-agonist, albuterol, in asthmatic patients.…”