Effect of theophylline withdrawal on airway inflammation in asthma

K. Minoguchi, Y. Kohno, N. Oda, K. Wada, M. Miyamoto, T. Yokoe, T. Hashimoto, T. Akabane, H. Kobayashi, S. Mita, N. Kihara, M. Adachi

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28 Citations (Scopus)


Theophylline has been used as a bronchodilator in acute and chronic asthma management, although there is accumulating evidence that it may have anti-inflammatory effects. We have investigated the effect of theophylline withdrawal for 6 weeks in asthmatic subjects whose peak expiratory flow (PEF) readings were more than 80% of the predicted value and its variability was less than 20% (Green Zone) by treatment with both a moderate dose of inhaled corticosteroids (BDP), 400-800 μg/day) and low dose theophylline (400 mg/day) for more than 3 months. In 38 asthmatic subjects, changes in clinical symptoms, respiratory function and airway inflammation detected with hypertonic saline induced sputum, and airway reactivity to histamine were investigated. One half of the patients were randomly withdrawn from theophylline, while the other half continued to take the same dose of theophylline for a period of 6 weeks. Mean steady state plasma theophylline concentrations when receiving treatment with theophylline were 8.08 μg/mL in the theophylline withdrawal group and 7.64 μg/mL in the control theophylline group, respectively. Although a significant increase in asthma symptoms emerged in the theophylline group, there were no significant changes in the theophylline administration group. In the theophylline withdrawal group, there were small but significant falls in PEF in the morning, FEV1 and ̇50 at the end of the study period. Analysis of induced sputum showed that there was also a significant increase in the percentage of total and activated (EG2*) eosinophils only in those patients who withdrew from theophylline. These results indicate that chronic treatment with low dose theophyiline exerts an anti-inflammatory effect and that the additional use of theophylline with inhaled corticosteroids provides an effective treatment for moderate asthma. Taken together, we conclude that theophylline has long- term beneficial effects on the chronic asthma management.

Original languageEnglish
Pages (from-to)57-63
Number of pages7
JournalClinical and Experimental Allergy, Supplement
Issue number3
Publication statusPublished - 1998 Aug
Externally publishedYes


  • Airway inflammation
  • Eosinophil
  • Theophylline

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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