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 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.