The effect of inhaled budesonide on the maximal degree of airway narrowing to leukotriene D4 and methacholine in normal subjects in vivo.
In normal humans in vivo, maximal airway narrowing to LTD4 is more severe than to methacholine. Moreover, LTD4 heightens the maximal response to methacholine for several days. To investigate whether or not this is due to inflammatory changes in the airway wall, we studied the effects of the corticosteroid budesonide on the dose-response curves to inhaled LTD4 and to methacholine. In a two-period, double-blind, placebo-controlled design, budesonide (400 micrograms twice a day) or placebo was inhaled by eight normal subjects on six consecutive days, with a 3-wk washout. Complete dose-response curves to LTD4 (0.36 to 43 nmol) were performed on Day 5, and to methacholine (1.28 to 655 mumol) on Days 4 and 6 of each period using a validated method. The response was measured by FEV1 and standardized partial expiratory flow-volume curves (V40p), and was expressed as the percent fall from baseline. A maximal response plateau was considered if more than two doses fell within a 5% response range. All subjects reached plateaus to methacholine and to LTD4. Budesonide reduced the maximal response to LTD4 (mean difference with placebo, 7.9% fall for FEV1, and 8.4% fall for V40p; p less than 0.05). During placebo the maximal response to methacholine 24 h after LTD4 was higher than 24 h before (mean change, 2.7% fall in FEV1 and 5.5% fall in V40p; p less than 0.05), but not during budesonide (mean change, -2.5% fall in FEV1 and -0.1% fall in V40p; p greater than 0.2), the changes being significantly different between the two periods (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Bel
E H
EH
Department of Pulmonology, University Medical Centre, Leiden, The Netherlands.
van der Veen
H
H
Dijkman
J H
JH
Sterk
P J
PJ
D000280:Administration, Inhalation; D000328:Adult; D000336:Aerosols; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D019819:Budesonide; D003251:Constriction, Pathologic / Q000139:chemically induced / Q000517:prevention & control; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008168:Lung / Q000187:drug effects*; D008297:Male; D016210:Methacholine Chloride; D008688:Methacholine Compounds / Q000494:pharmacology*; D008875:Middle Aged; D011282:Pregnenediones / Q000008:administration & dosage*; D012107:Research Design; D013189:SRS-A / Q000494:pharmacology*; D013997:Time Factors
D000336:Aerosols; D000893:Anti-Inflammatory Agents; D008688:Methacholine Compounds; D011282:Pregnenediones; D013189:SRS-A; D016210:Methacholine Chloride; D019819:Budesonide