@article {McDowell2250, author = {Pamela Jane McDowell and Sarah Diver and Jieqiong Freda Yang and Catherine Borg and John Busby and Vanessa Brown and Rahul Shrimanker and Ciara Cox and Christopher Brightling and Rekha Chaudhuri and Ian Pavord and Liam Heaney}, title = {Late Breaking Abstract - Phenotyping Mepolizumab EXacerbations in severe eosinophilic asthma (MEX)}, volume = {56}, number = {suppl 64}, elocation-id = {2250}, year = {2020}, doi = {10.1183/13993003.congress-2020.2250}, publisher = {European Respiratory Society}, abstract = {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/{\textmu}L, 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 {\textquotedblleft}Respiratory viruses in the "pre COVID-19" era{\textquotedblright}.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).}, issn = {0903-1936}, URL = {https://erj.ersjournals.com/content/56/suppl_64/2250}, eprint = {https://erj.ersjournals.com/content}, journal = {European Respiratory Journal} }