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High-dose inhaled corticosteroids may not avert asthma exacerbations

By Bianca Nogrady
Significantly boosting the dose of inhaled corticosteroids at the first signs of an impending asthma exacerbation does not appear to avert it.

Two studies – both published in The New England Journal of Medicine – tested the hypothesis that taking a much higher dose of inhaled corticosteroids in the so-called ‘yellow zone’ could stop an exacerbation in its tracks. In both studies, all participants had had at least one asthma exacerbation in the previous 12 months, and all were taking low-dose inhaled corticosteroids.

The first nonblinded randomised study examined the effect of quadrupling the inhaled corticosteroid dose compared with usual treatment when asthma control started to deteriorate, in 1922 adults and adolescents with asthma.

At one year, there was a significant 20% lower hazard ratio in the time to the first severe asthma exacerbation in the group who used the higher dose of inhaled corticosteroids after adjusting for age, sex and peak flow measures.

Researchers also saw a lower percentage of participants using systemic corticosteroids in the quadruple-dose group compared with the normal-dose group (33% vs 40%, respectively), and the quadruple-dose group also showed a 14% lower incidence of unscheduled healthcare consultations. But the incidence of oral candidiasis and dysphonia – both potentially treatment related – was significantly higher in the quadruple-dose group.

In the second study, 254 children aged 5 to 11 years with mild-to-moderate persistent asthma were randomised to either a quintupling of their usual inhaled corticosteroid dose or a normal dose at the early signs of loss of asthma control.

This study found that the rate of severe asthma exacerbations did not differ significantly between the quintuple-dose and normal-dose groups at the one-year follow up, nor did the time to the first severe exacerbation or the rate of emergency department or urgent care visits.

However, all four hospitalisations for asthma occurred in the high-dose group, and the children in the high-dose group showed a reduced growth rate compared with those in the low-dose group (5.43 cm/year vs 5.65 cm/year).

Commenting on the studies, Professor Philip Bardin, Head of Respiratory and Lung Research at the Hudson Institute of Medical Research, Melbourne, said the results were not entirely surprising, as previous studies of doubling the dose of inhaled corticosteroids had shown no effect.

‘The other thing we wonder about is, because children’s airways are very small, whether inhaled therapy doesn’t penetrate to where the inflammation is located in the lung,’ he said.

In an accompanying editorial, Professor Bardin noted that the effect in adults was below what the authors benchmarked as a worthwhile effect but raised the possibility there might be subgroups of patients that could still benefit from taking a higher dose of inhaled corticosteroid at the early sign of an exacerbation.

‘I wonder whether the atopic eosinophil group may have benefited but it’s not entirely clear from the [adult] study whether they are the people who did best,’ he told Medicine Today.

He also pointed out that exacerbations had different causes, and this might also influence the likelihood of responding to the higher corticosteroid dose.
NEJM 2018; doi: 10.1056/NEJMoa1714257.
NEJM 2018; doi: 10.1056/NEJMoa1710988.
NEJM 2018; doi:10.1056/NEJMe1800152.