Theophylline for Irreversible Chronic Airflow LimitationA Randomized Study Comparing n of 1 Trials to Standard Practice
The role of theophylline for patients with irreversible chronic airflow limitation (CAL) remains unclear despite decades of experience., Theophylline has several potentially useful effects in these patients. However, randomized placebo-controlled trials have not consistently shown that theophylline improves their quality of life or exercise capacity. Small samples, the use of incompletely characterized quality-of-life indexes, and the failure to assess exercise capacity may partly explain the discordance.
Thus, theophylline improved validated quality-of-life measures in three trials, improved dyspnea according to a visual analog scale in the largest trial, and improved exercise capacity in three trials. These positive results suggest that theophylline is effective in at least some patients with CAL and support recommendations to consider its use for those patients who remain symptomatic despite the use of inhaled bronchodilators. In this case, the usual clinical approach is a before-after therapeutic trial, in which theophylline is prescribed openly and its effectiveness is judged by the patient’s subsequent responses using subjective (eg, dyspnea) and objective (eg, pulmonary function tests and/or exercise capacity) parameters.
Open therapeutic trials in single patients carry inherent biases in detail buy tavist online. These include the placebo effect, the tendency for physicians and patients to want and to expect the therapy to work, and regression to the mean. These biases probably favor false conclusions that a treatment is effective and can, therefore, be expected to lead to the unnecessary use of a therapy in some patients. As well, many chronic diseases including irreversible CAL show fluctuations in severity that cannot be explained clearly by extraneous events. This variability in “natural history” may result in false conclusions that a treatment is not effective in some patients if it is started simultaneously with a period of decline. The n of 1 trial (randomized, double-blind, multiple crossover comparisons of active and placebo treatments in a single patient) is a potential way to limit such biases.