High-dose aspirin in severe uncontrolled asthma associated with chronic rhinosinusitis with nasal polyps (CRwNP) : the ASTHMIRINE trial

Introduction Aspirin desensitization in patients with aspirin-induced asthma (AIA) is effective on CRwNP symptoms, but its effect on asthma symptoms is unknown. AIA and severe asthma (SA) share lipoxin A4 and PGE2 deficiency and increased PGD2 levels, that can be modified by aspirin Aims To evaluate the effect of high-dose aspirin in uncontrolled SA patients (ACQ >1.5) associated with CRwNP regardless of aspirin tolerance Methods Multicenter randomized controlled trial double arm evaluating Aspirin Protect (1200mg/day) or placebo for 6 months. Prior to randomization, patients with suspected/proven AIA performed aspirin provocation-desensitization over 3 days Results 24 patients were included. Among the 18 who performed the provocation-desensitization test, 3 didn't tolerated the maximal dose of 1g, without severe reaction, 18 patients (placebo n=11, aspirin n=7) were randomized (62.5% male, median age 48.5[IQR 42.5:54], FEV1 80%[64,8 : 92,1]). At 6 months, ACQ-6 score decreased from 2.7[1.8:3.8] to 1.7[0.5:2.1] in the aspirin group and from 2 [1.8:3.6] to 1[0.3:1.2] in the placebo group. One patient (16,7%) in the aspirin group and 3 (30%) in the control group had an exacerbation during the trial. AQLQ score increased from 4.2[3.5:5.2] to 5.2 [3.8:6.7] for the aspirin group and from 5.2[3.8:6.1] to [4.8:6.8] for placebo. FEV1 was unchanged. The effect on nasal symptoms was maximal at 3 months. No adverse event was reported during the treatment Conclusion In this population of SA patients with CRwNP, provocation-desensitization and long-term high-dose aspirin treatment were well tolerated. Clinical effect needs to be evaluated in a larger population