Value of theophylline treatment in patients handicapped by chronic obstructive lung disease

Abstract

Background: It is still not certain whether it is worth using theophylline in addition to inhaled bronchodilators and corticosteroids to treat obstructive airways disease. This trial was designed to test whether the addition of prescribed theophylline in doses sufficient for sustained optimal steady state plasma concentrations would produce any detectable additional advantage in spirometric or functional variables in these handicapped patients.

Methods: A randomised, double blind, placebo controlled, crossover study of added theophylline treatment was aimed at steady state plasma concentrations of 10 and 17 mg/l, the dose being calculated individually by Bayesian parameter estimation and maintained for six weeks along with the patient's previously prescribed bronchodilators and steroids. Of 20 patients sequentially recruited, 15 provided data that could be analysed. All had chronic obstructive lung disease with a mean forced expiratory volume in the first second (FEV1) up to about 30% of the predicted value and gave no history of being treated with theophylline. The protocol included spirometry, whole body plethysmography, and treadmill exercise. Measurements also included steady state plasma theophylline concentrations and trapped gas volume. Quality of life was assessed by an established questionnaire method covering breathlessness in everyday activities, fatigue, emotional function, and control over the disease.

Results: Both target plasma concentrations were achieved. Improvements in peak flow (PEF; mean 20%), trapped gas volumes (38%), two stage vital capacity (15%), distances walked (48%), breathlessness in everyday activities (32%), and fatigue (18%) were found at the higher plasma concentration only. FEV1, forced vital capacity (FVC), emotional function, and control did not change.

Conclusion: Theophylline treatment with sustained steady state concentrations about 17 mg/l provides worthwhile objective and subjective further benefits for patients handicapped by chronic obstructive lung disease when it is added to bronchodilators and corticosteroids.