title: Salbutamol but not ipratropium abolishes leukotriene D4-induced gas exchange abnormalities in asthma.
abstract: OBJECTIVE
  Leukotriene D(4) (LTD(4)) is a central mediator in asthma inducing bronchoconstriction and profound disturbances in pulmonary gas exchange in asthmatic subjects. The aim of the study was to compare, for the first time, the influence of the bronchodilators salbutamol (400 μg) and ipratropium (80 μg) on lung function changes induced by inhaled LTD(4).
  
  
  METHODS
  Treatments were evaluated in a randomized, three-period, double-blind, placebo-controlled, cross-over study where spirometric and pulmonary gas exchange indices were followed in 12 subjects with mild asthma before and after LTD(4) challenge.
  
  
  RESULTS
  Compared with placebo, salbutamol provided significant protection against the fall in FEV(1) (forced expiratory volume in 1 s) after LTD(4) challenge. Salbutamol also abolished the LTD(4)-induced gas exchange disturbances [decreased arterial oxygen tension (PaO(2)) and increased alveolar-arterial oxygen tension difference (AaPO(2))]. Ipratropium provided significant but less marked attenuation of the changes in FEV(1) and arterial oxygenation induced by LTD(4).
  
  
  CONCLUSIONS
  Despite the equal bronchodilatory effects of salbutamol and ipratropium before the challenge with LTD(4), salbutamol was superior to ipratropium in preventing spirometric and gas exchange abnormalities. This result indicates a broader action of salbutamol on several of the disturbances that contribute to airway obstruction including, for example, exudation of plasma in the airway mucosa. The clinical implication of this new finding is that in this model of acute asthmatic airway obstruction, salbutamol was more effective than ipratropium.
authors.affiliation: Lung and Allergy Clinic, Department of Medicine at Karolinska University Hospital Huddinge and The Centre for Allergy Research, Karolinska Institutet, 141 86, Stockholm, Sweden. barbro.dahlen@ki.se
authors.forename: Barbro
authors.initials: B
authors.lastname: Dahlén
authors.forename: Federico P
authors.initials: FP
authors.lastname: Gómez
authors.forename: Alejandro
authors.initials: A
authors.lastname: Casas
authors.forename: Peter H
authors.initials: PH
authors.lastname: Howarth
authors.forename: Sven-Erik
authors.initials: SE
authors.lastname: Dahlén
authors.forename: Robert
authors.initials: R
authors.lastname: Rodriguez-Roisin
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D000402:Airway Obstruction / Q000188:drug therapy / Q000378:metabolism; D000420:Albuterol / Q000627:therapeutic use*; D001158:Arteries / Q000187:drug effects / Q000503:physiopathology; D001249:Asthma / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D016084:Bronchoconstriction / Q000187:drug effects / Q000502:physiology; D001993:Bronchodilator Agents / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects / Q000502:physiology; D006801:Humans; D009241:Ipratropium / Q000627:therapeutic use*; D017998:Leukotriene D4 / Q000008:administration & dosage* / Q000037:antagonists & inhibitors; D008297:Male; D010100:Oxygen / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000503:physiopathology; D011659:Pulmonary Gas Exchange / Q000187:drug effects* / Q000502:physiology; D013147:Spirometry / Q000379:methods; D055815:Young Adult
chemical_list: D001993:Bronchodilator Agents; D017998:Leukotriene D4; D009241:Ipratropium; D000420:Albuterol; D010100:Oxygen