Theophylline does not inhibit allergen-induced increase in airway responsiveness to methacholine

D. W. Cockcroft, K. Y. Murdock, B. P. Gore, P. M. O'Byrne, P. Manning

Research output: Contribution to journalArticlepeer-review

Abstract

Allergen-induced increase in airway hyperresponsiveness can be used as a model of airway inflammation for assessing antiasthma pharmacologic agents. Steroids and cromolyn, but not βn-agonists, inhibit this increase; theophylline, recently suggested as having anti-inflammatory effects, has not been evaluated in this model. Six atopic subjects with asthma and with late asthmatic responses (N = 5) and postallergen reduction in a provocative concentration of methacholine causing a 20% fall in FEV1 (PC20) (N = 6) were studied. Sustained-release theophylline (Theo-Dur; Astra Pharmaceuticals Canada, Ltd., Mississauga, Canada), 300 mg, and placebo were administered single-blind twice daily for eight doses up to 1 hour before allergen inhalation; cromolyn sodium, 10 mg, was administered in a single dose 10 minutes before allergen inhalation on another day as a "positive control." Mean theophylline levels were in the low therapeutic range, 57 ± 17 and 58 ± 13 μmol/L 1 and 8 hours after the last tablet. The FEV1 was 7% and 9% greater after the seventh and eighth doses of theophylline versus placebo (p < 0.05). Theophylline also produced a significant (p < 0.05) twofold increase in methacholine PC20. There was a 40% (p = 0.06) reduction in early asthmatic fall in FEV1 and a 25% (not significant) reduction in late FEV1 fall when theophylline was compared to placebo. Theophylline did not influence the geometric mean allergen-induced fall in methacholine PC20 Δ log PC20; this was true individually in five of the six subjects. By contrast, cromolyn sodium inhibited all aspects of the allergen response completely. When FEV1 had returned to baseline, the cromolyn sodium Δ log PC20 (-0.02 ± 0.06) was significantly less than the theophylline Δ log PC20 (0.42 ± 0.27) (p = 0.016). These data fail to provide evidence for an anti-inflammtory effect of theophylline in this in vivo human model. Theophylline appears to have primarily a bronchodilator effect.

Original languageEnglish
Pages (from-to)913-920
Number of pages8
JournalThe Journal of allergy and clinical immunology
Volume83
Issue number5
DOIs
Publication statusPublished - 1 Jan 1989

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