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Does boosting inhaled glucocorticoids avoid asthma exacerbations?

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Possible subgroup benefit from high-dose inhaled steroids

These two trials address the important question of whether substantial escalation of regularly used inhaled glucocorticoids prevents exacerbations if started at the first sign of deterioration, as this so-called yellow zone has long been thought the perfect time to initiate more aggressive care. However glucocorticoids have serious side effects, and there is some preclinical evidence that they may enhance viral replication

One trial shows that escalating dose in this yellow zone does not prevent exacerbations in children with the early signs of asthma instability. The second trial is more complex and more controversial, as the open-label design may have biased the outcome, and the degree of benefit is debatable.

Together, these studies suggest that high doses of inhaled glucocorticoids either do not prevent exacerbations or only do so in a small subgroup of patients with as-yet-undefined baseline and exacerbation characteristics.

Philip G. Bardin, PhD, is from the Monash Lung and Sleep Unit at the Monash University Medical Centre in Melbourne, Australia. These comments are taken from an accompanying editorial (N Engl J Med. 2018 Mar 3. doi: 10.1056/NEJMe1800152). Dr. Bardin reported personal fees from GlaxoSmithKline outside the submitted work.



“Given the potential benefit with respect to preventing exacerbations and in view of the toxic effects of inhaled glucocorticoids and the biases that may have been introduced by the absence of blinding, individual practitioners, patients, and guideline committees will need to consider whether the magnitude of the reduction achieved is clinically meaningful,” wrote Tricia McKeever, PhD, from the department of epidemiology and public health at the University of Nottingham (United Kingdom) and her coauthors.

The second study, which was double blinded, investigated whether quintupling the dose of inhaled glucocorticoids might avoid exacerbations in children. They randomized 254 children who had mild-moderate persistent asthma and had had at least one exacerbation treated with systemic glucocorticoids in the previous year to manage “yellow zone” early warning signs with either normal dose or five times their usual dose of inhaled glucocorticoids.

The rate of severe asthma exacerbations did not differ significantly between the quintuple-dose and normal-dose groups at the 1-year follow-up (0.48 vs. 0.37; P = 0.3), nor did the time to the first severe exacerbation or the rate of emergency department or urgent care visits.

The four hospitalizations for asthma all occurred in the high-dose group. However, there was a lower growth rate seen in children in the high-dose group than in the low-dose group (5.43 cm/yr vs. 5.65 cm/yr; P = .06). There were no significant differences between the two groups in other adverse events.

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