Exacerbation Profile and Risk Factors in a T2-Low Severe Asthma Population

P Jane McDowell, John Busby, Catherine E Hanratty, Ratko Djukanovic, Ashley Woodcock, Samantha Walker, Timothy Colin Hardman, Joseph R Arron, David F Choy, Peter Bradding, Chris E Brightling, Rekha Chaudhuri, Douglas Cowan, Adel H Mansur, Stephen J Fowler, Sarah E Diver, Peter Howarth, James Lordan, Andrew Menzies-Gow, Timothy HarrisonDouglas S Robinson, Cecile T J Holweg, John G Matthews, Ian D Pavord, Liam G Heaney

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Abstract

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.

Original languageEnglish
JournalAmerican Journal of Respiratory and Critical Care Medicine
Early online date12 May 2022
DOIs
Publication statusEarly online date - 12 May 2022

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