Urinary LTE4 excretion in antigen‐provoked asthmatic patients treated with the inhaled LTD4 antagonist, L‐648,051

J. B. Rasmussen, L. ‐O Eriksson, P. Tagari, D. J. Margolskee, Y. Girard, K. ‐E Andersson

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9 Scopus citations


Leukotriene (LT) E4 represents the major LT metabolite in man, and its urinary excretion can be used as an indirect marker of systemic LTC4 and/or LTD4 synthesis and release. In the present study LTE4 excretion was monitored for 24 h in 12 atopic patients with mild asthma undergoing antigen bronchoprovocation as part of a double‐blind, placebo‐controlled, two‐period cross‐over study of the aerosol‐delivered LTD4 antagonist, L‐648,051. Urinary LTE4 excretion was also studied separately in six of the patients after inhaling only diluent. Urine was sampled before, and serially after antigen challenge, at intervals corresponding to the immediate (0–3 h postchallenge) and late (3–6, 6–12, 12–24 h postchallenge) asthmatic reactions. LTE4 was determined by reversed‐phase HPLC and radioimmunoassay. Forced expiratory volume in 1 s (FEV), was recorded serially through 8 h after inhalation of antigen and diluent. Compared to base‐line measurements, antigen bronchoprovocation induced significant increases in mean LTE4 excretion rates 0–3 h postchallenge (i.e. during the immediate asthmatic response) after treatment with both placebo (P<0.01) and L‐648,051 (P<0.05). These mean LTE4 excretion rates in the immediate phase were also significantly higher than the mean rates in the late phase (3–6 h and beyond); the excretion rates of LTE4 at these later time intervals were similar to base‐line values. After inhalation of diluent, the LTE4 excretion rates in the intervals 0–3, 3–6, 6–12 and 12–24 h were unchanged from base‐line values. Administration of L‐648,051 caused a modest but significant inhibition of the immediate airway response, whereas the late response was not significantly reduced. The LTE4 excretion rates did not correlate with the maximum percent falls in FEV, after antigen challenge in the immediate or the late phases. These results suggest that peptidoleukotrienes are released by inhaled antigen in atopic asthmatic patients, and suggest a direct involvement of leukotrienes in the immediate airway response.

Original languageEnglish
Pages (from-to)599-603
Number of pages5
JournalAllergy: European Journal of Allergy and Clinical Immunology
Issue number6
StatePublished - Dec 1992
Externally publishedYes


  • asthma
  • bronchial provocation tests
  • leukotrienes.


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