The effect of leukotriene-modifier drugs on aspirin-induced asthma and rhinitis reactions


Donald D. Stevenson, Scripps Clinic and The Scripps Research Institute, 10666 North Torrey Pines Road, La Jolla, CA 92037, USA. E-mail:


Background Leukotrienes (LTs) appear to be crucial mediators of aspirin (ASA)-induced lower respiratory tract reactions. Therefore, it is logical to assume that leukotriene-modifier drugs (LTMDs) might block these reactions.

Objective The aim of this study was to determine whether concomitant treatment with LTMDs was associated with a reduction of ASA-provoked lower respiratory tract reactions in patients with aspirin-exacerbated respiratory disease (AERD), when compared to AERD patients who were not treated with LTMDs. Secondly, if ASA-induced lower respiratory tract reactions were prevented in LTMD-treated patients, was there then a higher prevalence of upper respiratory reactors or, alternatively, a higher prevalence of blocked reactions (‘non-reactors’) in this group.

Methods Of 271 patients suspected by history of having AERD, 96 were taking cys-LT receptor antagonists (cys-LTRAs) and 12 were taking zileuton at the time of oral ASA challenges. A matched control group of 163 patients was not receiving LTMDs. All subjects underwent standard oral ASA challenges. Reactions were classified as follows: classic [naso-ocular combined with a 20% or > decline in forced expiratory volume of 1 s (FEV1)]; pure lower (20% or > decline in FEV1 without naso-ocular); partial asthma (naso-ocular + 15–20% decline in FEV1); upper only (naso-ocular with < 15% decline in FEV1); negative (no reactions).

Results In patients treated with cys-LTRAs, there were significant reductions in numbers of patients with ASA-induced bronchospastic reactions and a concomitant increase in upper respiratory reactors. There were no significant differences in mean provoking doses of ASA or the percent changes in FEV1 values in both groups. In the 12 patients receiving zileuton, no reactions to ASA (16%) were similar to the cys-LTRA-treated group (11%) and the control group (15%).

Conclusion During oral ASA challenges, LTMD treatment appeared to shift target organ responses from both upper and lower respiratory tracts to upper tract alone. LTMD blocking of the entire respiratory tract did not appear to occur.