Sullivan, Paul Joseph; (1996) The effect of treatment with low dose oral theophylline on the inflammatory response to allergen in atopic asthma. Doctoral thesis (M.D), UCL (University College London).

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Abstract

Theophylline inhibits a number of immunocompetent cells in vitro at clinically relevant concentrations and reduces the inflammatory response in animal models of asthma. The current study is a of double blind, parallel group design, comparing the effect of theophylline and placebo upon the inflammatory response to allergen in man. Subjects were mild asthmatics who had previously demonstrated an early and late asthmatic response. Allergen inhalation was performed before and after six weeks of treatment with slow release theophylline, 200mg 12 hourly or identical placebo. Blood samples were taken before challenge, during the early and late responses and at 24 hours and bronchoscopy with biopsy and bronchoalveolar lavage (BAL) was performed at 24 hours. Primary outcome parameters were biopsy eosinophil and T lymphocyte counts. A confidence level of 95% was regarded as representing statistical significance. This corresponded to a p value of 0.025 after correction for multiple comparisons. T cell subsets were also enumerated in blood and BAL, cell counts and inflammatory mediator concentrations were measured in BAL and mast cells and activated T cells and eosinophils were counted in biopsy specimens. There was a reduction in the number of eosinophils but not T lymphocytes in biopsies of the airway after theophylline, and a significant treatment effect was shown. Changes were also seen in some secondary parameters. There was a reduction in the number of activated eosinophils in tissue. In the blood there was an increase in the number of activated T helper lymphocytes (CD4+, HLA DR+) following theophylline both before and after allergen. BAL revealed a reduction in the number of lymphocytes after theophylline, and a reduction in CD3+, ICAM+ and CD4+, VLA+ activated T cells. It is concluded that low dose slow release oral theophylline attenuates the airway eosinophilic response to allergen. The results also suggest that theophylline increases circulating activated lymphocytes and reduces the number of lymphocytes in the airway lumen after allergen exposure.

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