Montelukast 10 mg improves nasal function and nasal response to aspirin in ASA-sensitive asthmatics: a controlled study vs placebo.

Abstract

Aspirin-induced asthma (AIA) is a clinical syndrome characterized by acute airway reaction to aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDS). The most recent etiological hypothesises is that an overexpression of the enzyme LTC(4) synthase occurs in AIA, with the consequent production of sulfidopeptide leukotrienes (LTs). Aim of the present study was to assess the effect of Montelukast, a selective cys-LT receptor antagonist, on nasal function, nasal reactivity to ASA and blood markers of eosinophilic inflammation in mild-to-moderate AIA. Thirty-six nonsmoker subjects with AIA (17 males, 22-52 years) performed a nasal provocation test (NPT) with lysine-aspirin (L-ASA) in baseline and after a 4-week Montelukast 10 mg or placebo treatment. Nasal function was assessed by the acoustic rhinomanometry, and they also performed a lung function test (forced expiratory volume in 1 s), and a blood sample for the eosinophil count and the eosinophil cationic protein (ECP) plasma measurements. After both treatments, all subjects repeated the NPT, the lung function, and the ECP and the eosinophil blood count. t-Test was used to compare mean values +/- SD between groups, and P < 0.05 was assumed as the level for statistical significance. Airway patency was never affected by the NPT with L-ASA. In baseline, NPT with L-ASA precipitated a nasal reaction in all subjects, with a substantial increase in nasal resistance (calculated resistance [REQ]; from 0.89 +/- 0.18 to 2.2 +/- 0.17 cmH(2)O/l/min in group M, P < 0.001; and from 0.91 +/- 0.48 to 2.3 +/- 0.21 cmH(2)O/l/min in group P, P < 0.001); and a significant reduction in total nasal volume in at least one nostril (volume [VOL]; from 11.1 +/- 3.2 to 8.1 +/- 4.1 cm(3) in the group M, P < 0.001, and from 12.3 +/- 4.1 to 7.9 +/- 4.5 cm(3) in the group P, P < 0.001). The nasal reaction to L-ASA remained unchanged following placebo, but it was completely minimized following a 4-week treatment with Montelukast. Also nasal function, the nasal symptom score, and the markers of eosinophilic inflammation proved significantly affected and improved by the active drug only. Montelukast 10 mg daily for 4 weeks, but not placebo, improves nasal function and nasal response to Aspirin substantially in ASA-sensitive asthmatics.