Maximal airway narrowing to inhaled leukotriene D4 in normal subjects. Comparison and interaction with methacholine.
We investigated whether or not leukotriene D4 can influence the maximal degree of airway narrowing in normal humans by comparing the maximal responses to inhaled methacholine and LTD4, and evaluating the interaction between both agonists. In 8 normal subjects, methacholine challenges were performed 24 h before and 24 and 72 h after a LTD4 challenge. Doubling doses of methacholine (1.3 to 655 mumol) or LTD4 (0.007 to 192 nmol) were inhaled by using a recently validated method. The highest dose of LTD4 was followed by the maximal dose of methacholine. The response was measured by FEV1 and volume history standardized partial expiratory flow-volume curves (V40p), and was expressed as percent fall from baseline. All subjects reached a maximal response plateau to both agonists. The maximal response plateau to LTD4 was systematically higher than to methacholine on the preceding day (mean difference, 13.4 and 12.7% fall for FEV1 and V40p, respectively) (p less than 0.01). Addition of methacholine on top of the LTD4 plateau caused a further increase in the response (mean, 6.6 and 4.8% fall, respectively) (p less than 0.005). The maximal responses to methacholine at 24 and 72 h after the LTD4 challenge were higher than at 24 h before (mean difference at 24 h, 4.0 and 8.5% fall for FEV1 and V40p, respectively, and at 72 h 5.7 and 9.3% fall) (p less than 0.05). However, the provocative dose of methacholine causing a 10% fall in FEV1 (PD10) or a 40% fall in V40p (PD40) was not altered by the previous LTD4 challenge test.(ABSTRACT TRUNCATED AT 250 WORDS)
Bel
E H
EH
Department of Pulmonology, University Medical Centre, Leiden, The Netherlands.
van der Veen
H
H
Kramps
J A
JA
Dijkman
J H
JH
Sterk
P J
PJ
D000280:Administration, Inhalation; D000328:Adult; D000336:Aerosols; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008168:Lung / Q000187:drug effects*; D008176:Lung Volume Measurements; D008297:Male; D016210:Methacholine Chloride; D008688:Methacholine Compounds / Q000494:pharmacology*; D008875:Middle Aged; D013189:SRS-A / Q000494:pharmacology*; D013997:Time Factors
D000336:Aerosols; D008688:Methacholine Compounds; D013189:SRS-A; D016210:Methacholine Chloride