Exacerbation Profile and Risk Factors in a T2-Low Severe Asthma Population.
McDowell PJ., Busby J., Hanratty CE., Djukanovic R., Woodcock A., Walker S., Hardman TC., Arron JR., Choy DF., Bradding P., Brightling CE., Chaudhuri R., Cowan D., Mansur AH., Fowler SJ., Diver SE., Howarth P., Lordan J., Menzies-Gow A., Harrison T., Robinson DS., Holweg CTJ., Matthews JG., Pavord ID., Heaney LG., investigators for the MRC Refractory Asthma Stratification Program None.
Although present in a minority of severe asthmatics, very little is known about the mechanisms underlying T2-low asthma, making it a significant unmet need in asthma research. METHODS: Exacerbation assessment was a pre-specified secondary analysis of data from a RCT comparing the use of biomarkers & symptoms to adjust steroid treatment in a T2-low severe asthma-enriched cohort. Participants were phenotyped as T2LOW(fractional exhaled nitric oxide [FeNO] ≤20 ppb & blood eosinophil count [PBE] ≤150 cells/µL) or T2HIGH ( FeNO>20 or PBE>150) at study enrolment & at each exacerbation. We report comparison of exacerbators & non-exacerbators, physiological changes at exacerbation in T2LOW & T2HIGH ,& stability of inflammatory phenotypes. RESULTS: 60.8% (183/301) ≥1 self-reported exacerbations (total of 390). Exacerbators were more likely to be female, have a higher BMI & more exacerbations requiring oral corticosteroid (OCS) & unscheduled primary care attendances for exacerbations. At enrolment, 23.6% (71/301) were T2LOW, & 76.4% (230/301) T2HIGH. The T2LOW group had more asthma primary care attendances, were more likely to have a previous admission to HDU/ICU & to be receiving maintenance OCS. At exacerbation the T2LOW events were indistinguishable from T2HIGH exacerbations in terms of lung function & symptom increase, with no increase in T2 biomarkers from stable to exacerbation state in the T2LOW exacerbations. CONCLUSION: Asthma exacerbations demonstrating a T2LOW phenotype were physiologically & symptomatically similar to T2HIGHexacerbations. The clinically significant T2LOW exacerbations highlights the unmet & pressing need to further understand the mechanisms at play in non-T2 asthma.