Theophylline administration in children with asthma: optimal pulmonary function and possible tolerance to chronic administration.

This study was performed to assess the need of obtaining serum theophylline (T) levels between 10--20 micrograms/ml to achieve maximum reversibility of airway obstruction in chronic childhood asthma. Twenty-seven children with daily asthma (ages 9--16 years mean 11.7) were studied to determine the serum T levels required to obtain optimal pulmonary function tests as measured by FEV1 and FEF25--75. Two parallel groups were created. Group 1 (13 subjects) received rapid release (RR) anhydrous T. Group 2 (14 subjects) received sustained release (SR) anhydrous T. The groups were identical in age, weight, height and PFT: p = values greater than or equal to .21 (t test for equivalent means). During initial titration maximal PFT's were obtained in Group 1 subjects with mean T level of 7.1 micrograms/ml and in Group 2 subjects with mean T level of 8.5 micrograms/ml. The PFT responses and theophylline dose responses of each group were not significantly different from each other. After two months of continuous high dose (10--20 micrograms/ml) therapy each subject was again titrated for dose response of PFT with serum T levels. PFT's were not significantly different from the acute studies. After continuous high dose theophylline therapy serum T levels needed (mean 11.5 micrograms/ml) to obtain the maximal PFT response were significantly higher than during the initial titration (mean 7.1 to 8.5 micrograms/ml). Maximal PFT's in many asthmatic children do not require serum T greater than or equal to 10 micrograms/ml in an acute dosage. The continuous use of high dose theophylline may lead to tolerance, thus requiring a higher theophylline dose and subsequent serum level to obtain maximal PFT.