Late Breaking Abstract - Phenotyping Mepolizumab EXacerbations in severe eosinophilic asthma (MEX)

<b>Background:</b> 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. <b>Methods:</b> Observational study in mepolizumab treated patients (n=145) at 4 UK Severe Asthma Specialist clinics. Patients attended study centre for exacerbation assessment pre-treatment. <b>Results:</b> 172 exacerbations with 96 assessed pre-treatment; peak flow &amp; symptoms diaries showed no difference in assessed &amp; missed exacerbations. At initial exacerbation/participant, 45/69 (65%) produced sputum of whom 47% were sputum eosinophil (SE) high ≥2% &amp; 53% were SE low &lt;2%. SE≥2% were FeNO high (57[30,111] vs 24[16,45] ppb, p&lt;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&lt;0.001) and median SE 10%[5,21] vs 0.4%[0.2, 0.8], p&lt;0.001. In contrast, SE&lt;2% exacerbations were FeNO low, CRP high (15[5,24] vs 2.3[2,5] mg/L, p &lt;0.001), with sputum neutrophilia (90%[72, 95] vs 37%[29,54], p&lt;0.001) and 50% receiving antibiotics (v 19% in SE≥2%, p0.03). FeNO (&lt;20 or ≥50ppb) was a useful discriminator. <b>Conclusion:</b> Exacerbations on mepolizumab are 2 distinct entities; non-eosinophilic events are driven by infection &amp; FeNO low, while eosinophilic exacerbations can be differentiated by high FENO.