RT Journal Article SR Electronic T1 Late Breaking Abstract - Phenotyping Mepolizumab EXacerbations in severe eosinophilic asthma (MEX) JF European Respiratory Journal JO Eur Respir J FD European Respiratory Society SP 2250 DO 10.1183/13993003.congress-2020.2250 VO 56 IS suppl 64 A1 Pamela Jane McDowell A1 Sarah Diver A1 Jieqiong Freda Yang A1 Catherine Borg A1 John Busby A1 Vanessa Brown A1 Rahul Shrimanker A1 Ciara Cox A1 Christopher Brightling A1 Rekha Chaudhuri A1 Ian Pavord A1 Liam Heaney YR 2020 UL http://erj.ersjournals.com/content/56/suppl_64/2250.abstract AB Background: Clinical trials with anti-IL5 therapies show a 50% reduction in severe asthma exacerbations; exacerbations on mepolizumab appear different from placebo questioning their inflammatory phenotype and physiological characteristics.Methods: Observational study in mepolizumab treated patients (n=145) at 4 UK Severe Asthma Specialist clinics. Patients attended study centre for exacerbation assessment pre-treatment.Results: 172 exacerbations with 96 assessed pre-treatment; peak flow & symptoms diaries showed no difference in assessed & missed exacerbations. At initial exacerbation/participant, 45/69 (65%) produced sputum of whom 47% were sputum eosinophil (SE) high ≥2% & 53% were SE low <2%. SE≥2% were FeNO high (57[30,111] vs 24[16,45] ppb, p<0.001), had low FEV1% predicted (56(15) vs 72(21), p=0.008), obstructive spirometry (FEV1/FVC% 58(14) vs 68(9), p=0.004), higher blood eosinophils (70[50,90] vs 30[10,50]cells/µL, p<0.001) and median SE 10%[5,21] vs 0.4%[0.2, 0.8], p<0.001. In contrast, SE<2% exacerbations were FeNO low, CRP high (15[5,24] vs 2.3[2,5] mg/L, p <0.001), with sputum neutrophilia (90%[72, 95] vs 37%[29,54], p<0.001) and 50% receiving antibiotics (v 19% in SE≥2%, p0.03). FeNO (<20 or ≥50ppb) was a useful discriminator.Conclusion: Exacerbations on mepolizumab are 2 distinct entities; non-eosinophilic events are driven by infection & FeNO low, while eosinophilic exacerbations can be differentiated by high FENO. FootnotesCite this article as: European Respiratory Journal 2020; 56: Suppl. 64, 2250.This abstract was presented at the 2020 ERS International Congress, in session “Respiratory viruses in the "pre COVID-19" era”.This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).