The possible role of LTD4 in asthma in humans investigated in vivo.
The bronchoconstrictor effect of LTD4 was tested in a double blind design in 9 healthy volunteers who inhaled 10 and 40 nmol synthetic LTD4, 10 and 100 mumol histamine, and placebo on 5 different days. As the nebulized testsolutions were administered via a settling bag, an even deposition on the airways could be expected, and consequently a relative predominans of the changes measuring the airflow in the small airways. Accordingly the PEF values were reduced by less than 5% for both active substances. The function of the small airways was measured by (1) the volume of trapped gas in percentage of the total lung capacity, and (2) maximal expiratory flow rate at 30% of vital capacity above residual volume, determined from partial flow-volume curves. A dose-dependent bronchial obstruction was revealed. LTD4 was 3 to 4 decades more potent than histamine on a log molar scale. Pronounced dyspnoea and systemic side effects were experienced after inhalation of histamine whereas LTD4 did not cause any symptoms. Adrenergic beta 2-agonist (Fenoterol) was in all cases capable of reversing the LTD4 induced bronchospasm. 6 patients with verified exogenous asthma were tested in a similar double blind set-up for their reactivity to LTD4. The asthmatics were hyperreactive to LTD4.
D000293:Adolescent; D000328:Adult; D001249:Asthma / Q000503:physiopathology*; D002986:Clinical Trials as Topic; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012016:Reference Values; D012129:Respiratory Function Tests; D013189:SRS-A
D013189:SRS-A