Relation between bronchial responsiveness to inhaled leukotriene D4 and markers of leukotriene biosynthesis
- 1Division of Respiratory Medicine, Department of Medicine at Karolinska University Hospital Solna, Centre for Allergy Research at Karolinska Institutet, Stockholm, Sweden
- 2Division of Physiology, The National Institute of Environmental Medicine, Centre for Allergy Research at Karolinska Institutet, Stockholm, Sweden
- 3Family Medicine Stockholm, Department of Clinical Science, Centre for Allergy Research at Karolinska Institutet, Stockholm, Sweden
- 4Division of Respiratory Medicine, Department of Medicine at Karolinska University Hospital Huddinge, Centre for Allergy Research at Karolinska Institutet, Stockholm, Sweden
- Correspondence to:
Dr B Dahlén
Division of Respiratory Medicine, Department of Medicine, Karolinska University Hospital Huddinge, SE-141 46 Stockholm, Sweden;
- Received 4 February 2005
- Accepted 13 July 2005
- Published Online First 29 July 2005
Background: While clinical trials with antileukotrienes have shown overall beneficial effects in asthma, the factors that determine leukotriene dependent asthma are still unclear. A study was undertaken to determine whether or not leukotriene responsiveness in the airways correlates with endogenous leukotriene biosynthesis.
Methods: Bronchial responsiveness to leukotriene (LT) D4 was assessed as PD20FEV1 in 20 subjects with mild asthma and 10 healthy controls, and compared with bronchial responsiveness to methacholine and two global measures of leukotriene production—urinary LTE4 and ex vivo production of LTB4 in whole blood.
Results: In patients with asthma the bronchoconstrictor activity of LTD4 was about 1300 times greater than methacholine (geometric mean PD20 0.69 nmol v 887 nmol). Those who were most responsive to LTD4 were relatively less responsive to methacholine (p<0.01). There was, however, no correlation between bronchial responsiveness to LTD4 and urinary LTE4 or blood ex vivo LTB4 levels in asthmatic subjects or healthy controls. Subjects with asthma treated with inhaled corticosteroids produced higher levels of LTB4 (p<0.05).
Conclusions: General measures of leukotriene production cannot predict bronchial responsiveness to LTD4. The unique bronchoconstrictive potency of LTD4 on human airways may relate to the locally regulated expression of the cysteinyl LT1 receptor.
- CysLT, cysteinyl leukotriene
- FEV1, forced expiratory volume in 1 second
- Feno, fractional exhaled nitric oxide
- ICS, inhaled corticosteroids
- MCh, methacholine
- PD10, PD15, PD20, provocative dose causing a 10%, 15% and 20% decrease in FEV1
Supported by Karolinska Institutet, Centre for Allergy Research and the Stockholm County Council (ALF), and the following Swedish foundations: Heart Lung Foundation, Association Against Asthma and Allergy, Consul Bergh’s Foundation, Medical Research Council (projects 14X-9071 and 74X-15067), and the Foundation for Health Care Sciences and Allergy Research (Vårdal). This study received no support from the pharmaceutical industry.
Competing interests: none declared
Published Online First 29 July 2005