The effect of inhaled heparin on bronchial reactivity to sodium metabisulphite and methacholine in patients with asthma.
Inhaled heparin inhibits the early response to allergen and exercise-induced asthma, probably by inhibiting mast cell mediator release. Recent animal studies suggest that heparin might also inhibit cholinergic neurotransmission in asthma by restoring inhibitory M2 receptor function. We have tested the hypothesis that heparin inhibits neurally-mediated bronchoconstriction in asthma by examining the effect of inhaled heparin on bronchial reactivity to sodium metabisulphite. We also examined the effect of inhaled heparin on methacholine-induced bronchoconstriction to exclude a direct effect on airway smooth muscle. Eleven patients with mild asthma inhaled nebulized heparin (1,000 U.kg-1) or placebo (normal saline) in a randomized, double-blind fashion, 10 min before a challenge with sodium metabisulphite. Nine patients were also challenged with methacholine after the same dose of heparin or placebo. Inhaled heparin did not significantly change forced expiratory volume in one second (FEV1), nor did it alter the provocative dose of sodium metabisulphite or methacholine required to cause a 20% fall in FEV1 (PD20). Geometric mean sodium metabisulphite PD20 was 2.54 and 2.15 mumol after placebo and heparin, respectively (mean difference -0.24 doubling doses; 95% confidence interval (95% CI) -0.64-0.17). Geometric mean methacholine PD20 was 1.00 and 1.51 mumol after placebo and heparin, respectively (mean difference 0.6 doubling doses; 95% CI -0.25-1.5). Thus, heparin inhaled at doses sufficient to inhibit allergen and exercise-induced bronchoconstriction has no effect on the response to sodium metabisulphite and methacholine challenge in asthma. This argues against an inhibitory effect on neural pathways or airway smooth muscle.
Pavord
I
I
Respiratory Medicine Unit. City Hospital, Nottingham, UK.
Mudassar
T
T
Bennett
J
J
Wilding
P
P
Knox
A
A
D000280:Administration, Inhalation; D000328:Adult; D001249:Asthma / Q000150:complications / Q000503:physiopathology*; D016535:Bronchial Hyperreactivity / Q000209:etiology / Q000503:physiopathology*; D001985:Bronchial Provocation Tests; D016084:Bronchoconstriction / Q000187:drug effects; D016085:Bronchoconstrictor Agents; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D005541:Forced Expiratory Volume; D006493:Heparin / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D008297:Male; D016210:Methacholine Chloride; D009130:Muscle, Smooth / Q000502:physiology; D009330:Nebulizers and Vaporizers; D013447:Sulfites
D016085:Bronchoconstrictor Agents; D005343:Fibrinolytic Agents; D013447:Sulfites; D016210:Methacholine Chloride; C005200:sodium metabisulfite; D006493:Heparin