Ten questions are posed to the indications for oral use of theophylline, some of them controversial. The role of theophylline has become more selective, but its indications are firmly rooted in the following useful properties: (a) additive action to other bronchodilators, both at peak and trough; (b) sustained action, tailored according to need; (c) systemic availability to sites of action; and (d) economy and convenience. Besides bronchodilation, it has some anti-inflammatory action, as yet undefined, and favorable action on respiratory muscle force production and respiratory drive, the latter useful in neonatal apnea. Mechanisms of action involve its nonspecific inhibition of cyclic-AMP phosphodiesterase isozymes (an area now under intense study), and antagonism of adenosine at the receptor level.
Disadvantages are its variable metabolism and narrow therapeutic index, necessitating careful administration and monitoring of serum levels. Definite indications are: (a) severe chronic obstructive pulmonary disease (COPD); (b) severe asthma to minimize use of oral corticosteroids; and (c) nocturnal asthma. A strong case can be made for its use in: (a) impending respiratory failure caused by asthma or COPD; (b) mechanical ventilation, primarily for obstructed airways; and (c) sleep apnea or hypopnea in which continuous positive airway pressure or surgery either is rejected or not indicated. Optimal serum levels are near the midtherapeutic range (i.e., 12–15 μg/ml). More general use is dictated by cost, convenience, or preference, and lower levels may suffice. Theophylline's use may be further modified as new agents are introduced, especially the long-acting β2-agonists. However, it will remain a definite part of our armamentarium.