The case of hepatitis reported by Dr. Grieco and Ms. Burstein-Stein concerns a patient who was receiving zafirlukast, a cysteinyl leukotriene receptor antagonist. The clinical history and course indicate only that the patient's hepatitis appeared after the patient had been receiving zafirlukast for 4 months and resolved after zafirlukast therapy was discontinued. This temporal association falls far short of the evidence needed to conclude that the patient's hepatitis was drug-induced. Furthermore, because montelukast is chemically distinct from zafirlukast, it is incorrect to generalize from this single case to all antileukotriene drugs unless a mechanism-related cause has been identified. Clearly, this case report does not support such a cause.

We carefully monitored the effects of montelukast on liver function during development of the drug in more than 2600 adolescent and adult patients, 320 pediatric patients between the ages of 6 and 14 years, and 314 patients between the ages of 2 and 5 years, as well as in postmarketing surveillance (1). We found no evidence of hepatotoxic effects associated with the use of montelukast.

We respectfully disagree with Dr. Brestel's comments on the ethical issues and scientific importance of our research question. The study was conducted at 17 centers, each of which received approval from their institutional review board before conducting the study. Exercise-induced bronchoconstriction is a common condition, with a prevalence exceeding 5% in the adult population, and even higher in children (2). Salmeterol is widely used for the prevention of exercise-induced asthma and is approved by the U.S. Food and Drug Administration for this use (3). Montelukast is a new therapy that has also demonstrated inhibition of exercise-induced asthma (4). Rigorously conducted randomized clinical trials represent the basis of the evidence on which treatment decisions are made. Our study, which directly compared these two therapies, provided important new information about the differences between them.