No link between clinical phenotypes and blood eosinophils in preschool wheeze: study

Thursday, 25 Nov 2021

Targeted therapy on the basis of blood eosinophil count or airway bacterial infection did not reduce attacks of preschool wheeze compared to conventional care, a proof-of-concept study has found.

The research, published in Paediatric Allergy Immunology, found no relationship between clinical phenotypes and aero-allergen sensitisation or blood eosinophils in children with preschool wheeze, although there were key limitations in trial design that might have impacted results.

Researchers, led by Professor Sejal Saglani, from the National Heart & Lung Institute at Imperial College London, sought to determine whether a targeted approach to preschool wheeze, as determined by the presence of eosinophilic inflammation or infection, would result in fewer unscheduled healthcare visits (UHCV) compared to standard care.

In the trial, children aged one to five years with moderate to severe wheeze – defined as having needed at least two admissions and/or two short courses of oral steroids for an acute wheeze attack in prior 12 months, with at least one admission and/or course of oral steroids in the last six months – were categorised as having either episodic viral wheeze (EVW) or multiple trigger wheeze (MTW).

Children were randomised into the control or intervention group between September and April each year for three consecutive seasons in 2015-2018. Those in the intervention group were treated with inhaled corticosteroids (ICS) if their blood eosinophil level was 3% or more, or targeted antibiotics if positive culture was shown on a sputum/cough swab. Those in the control group received standard care.

According to the study’s findings, there was no significant difference in UHCV after four months’ treatment between the control (15/30) and intervention (16/30) arm. In fact, “there were no differences in any parameter between those that did and did not have an UHCV,” the authors noted.

Time to first UHCV was 47 days in the control group and 38 days in the intervention group, with no effect observed from atopy status, ICS use, whether EVW or MTW, or eosinophil count.

Also, use of oral corticosteroids were similar, but the authors highlighted a “disappointing level” of adherence to ICS for both groups, (67% for control versus 65% for intervention) “despite weekly phone calls to remind families about taking prescribed therapy”.

Poor adherence to ICS could represent a key limitation in interpretation of the study’s findings, they said, while other limiting factors that would need to be addressed in future research include the trial’s small sample size, time-frame and parental reluctance to clinician-advised treatment.

“Objective assessments of inhaled corticosteroid adherence are essential in preschool wheeze prior to therapy escalation. Future trials of biomarker directed treatment must include assessments of parental acceptability of inhaled corticosteroids,” the authors concluded.

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