ASTHMA

Relation between bronchial responsiveness to inhaled leukotriene D₄ and markers of leukotriene biosynthesis

P Gyllfors¹, M Kumlin², S-E Dahlén², F Gaber², P-O Ehrs^2,3, B Dahlén⁴

¹ Division of Respiratory Medicine, Department of Medicine at Karolinska University Hospital Solna, Centre for Allergy Research at Karolinska Institutet, Stockholm, Sweden
² Division of Physiology, The National Institute of Environmental Medicine, Centre for Allergy Research at Karolinska Institutet, Stockholm, Sweden
³ Family Medicine Stockholm, Department of Clinical Science, Centre for Allergy Research at Karolinska Institutet, Stockholm, Sweden
⁴ Division 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; Barbro.dahlen{at}medhs.ki.se

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.

Abbreviations: 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

Keywords: asthma; bronchial responsiveness; leukotrienes

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