Leukotriene E(4)-induced persistent eosinophilia and airway obstruction are reversed by zafirlukast in patients with asthma.
BACKGROUND
We have shown that inhalation of leukotriene (LT) E 4 contributes to specific recruitment of eosinophils to the airway mucosa in patients with asthma at the time of maximal decrease in airway-specific conductance.


OBJECTIVE
We examined the ability of the cysteinyl LT 1 receptor antagonist, zafirlukast, to improve or prevent LT-mediated eosinophilia and airway obstruction in asthma.


METHODS
Bronchial biopsies were taken and pulmonary function was measured before and 4 to 6 hours after the dose of inhaled LTE 4 causing a > or =15% fall in FEV 1 at baseline both at week 0 and after 6-week randomly assigned treatment with a high dose of zafirlukast, 80 mg twice daily.


RESULTS
Leukotriene E 4 inhalation at week 0 doubled the number of eosinophils in the airway mucosa in 21 of 25 patients with mild asthma, increased the numbers of neutrophils and lymphocytes, and decreased FEV 1 (-17%). Zafirlukast reduced both airway eosinophilia and obstruction in FEV 1 , whereas with a double-blind placebo treatment, the effect of LTE 4 on both parameters persisted for 6 weeks. On repeat LTE 4 inhalation challenge after 6 weeks, zafirlukast treatment prevented further airway eosinophilia and decrease in FEV 1 seen in the placebo group.


CONCLUSIONS
Persistent LTE 4 -induced airway eosinophilia may form the basis of an amplification mechanism for further eosinophil recruitment. Zafirlukast prevents LTE 4 -induced eosinophilic airway inflammation in mild asthma.
Laitinen
Annika
A
Institute of Biomedicine, Department of Anatomy, University of Helsinki, Helsinki, Finland.
Lindqvist
Ari
A
Halme
Maija
M
Altraja
Alan
A
Laitinen
Lauri A
LA
D000280:Administration, Inhalation; D000328:Adult; D000402:Airway Obstruction / Q000139:chemically induced / Q000188:drug therapy*; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D001985:Bronchial Provocation Tests; D004311:Double-Blind Method; D004802:Eosinophilia / Q000139:chemically induced / Q000188:drug therapy*; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D007211:Indoles; D020024:Leukotriene Antagonists / Q000627:therapeutic use*; D017999:Leukotriene E4 / Q000008:administration & dosage*; D008168:Lung / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D048448:Phenylcarbamates; D013449:Sulfonamides; D014105:Tosyl Compounds / Q000627:therapeutic use*
D018927:Anti-Asthmatic Agents; D007211:Indoles; D020024:Leukotriene Antagonists; D048448:Phenylcarbamates; D013449:Sulfonamides; D014105:Tosyl Compounds; D017999:Leukotriene E4; C062735:zafirlukast