European Journal of Clinical Pharmacology

, Volume 68, Issue 10, pp 1375–1383 | Cite as

Salbutamol but not ipratropium abolishes leukotriene D4-induced gas exchange abnormalities in asthma

  • Barbro DahlénEmail author
  • Federico P Gómez
  • Alejandro Casas
  • Peter H Howarth
  • Sven-Erik Dahlén
  • Robert Rodriguez-Roisin



Leukotriene D4 (LTD4) 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 LTD4.


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 LTD4 challenge.


Compared with placebo, salbutamol provided significant protection against the fall in FEV1 (forced expiratory volume in 1 s) after LTD4 challenge. Salbutamol also abolished the LTD4-induced gas exchange disturbances [decreased arterial oxygen tension (PaO2) and increased alveolar–arterial oxygen tension difference (AaPO2)]. Ipratropium provided significant but less marked attenuation of the changes in FEV1 and arterial oxygenation induced by LTD4.


Despite the equal bronchodilatory effects of salbutamol and ipratropium before the challenge with LTD4, 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.


Bronchoconstriction Bronchoprovocation Beta2 adrenergic bronchodilator Anti-muscarinic bronchodilator Pulmonary gas exchange. 



We thank Josep L. Valera RN and Laurie Lau for technical assistance. The study was supported by The Swedish Heart Lung Foundation, the Swedish MRC, the Stockholm County Council Research Funds (ALF) and Vinnova (CiDAT), the Fondo de Investigación Sanitaria (FIS 00/617). the Generalitat de Catalunya (2009SGR 00911) and the Sociedad Española de Neumología y Cirugıa Torácica (SEPAR).

Conflict of interest statement

This is an investigator-initiated and -conducted study. There is no conflict of interest to declare.


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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Barbro Dahlén
    • 1
    Email author
  • Federico P Gómez
    • 2
    • 3
  • Alejandro Casas
    • 2
    • 3
  • Peter H Howarth
    • 4
  • Sven-Erik Dahlén
    • 5
  • Robert Rodriguez-Roisin
    • 2
    • 3
  1. 1.Lung and Allergy Clinic, Department of Medicine at Karolinska University Hospital Huddinge and The Centre for Allergy ResearchKarolinska InstitutetStockholmSweden
  2. 2.Servei de Pneumologia (Thorax Institute), Hospital Clínic, Institut d’Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS)Universitat de BarcelonaBarcelonaSpain
  3. 3.Ciber Enfermedades Respiratorias (CIBERES)BarcelonaSpain
  4. 4.Southampton General HospitalUniversity of SouthamptonSouthamptonUK
  5. 5.Unit for Experimental Asthma & Allergy Research, The National Institute of Environmental Medicine and The Centre for Allergy ResearchKarolinska InstitutetStockholmSweden

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