From the Journals

Does boosting inhaled glucocorticoids avoid asthma exacerbations?


Key clinical point: Escalating the dose of inhaled glucocorticoids at the first early warnings of an asthma exacerbation may not significantly reduce the likelihood of the exacerbation occurring.

Major finding: Fifteen individuals would need to quadruple their dose of inhaled glucocorticoids to avoid one asthma exacerbation.

Data source: Two randomized, controlled trials in 1,992 adolescents and adults and 254 children with asthma.

Disclosures: The first study was supported by the National Institute for Health Research. Six authors declared grants, personal fees, and other funding and support from the pharmaceutical industry outside the submitted work. The second study was supported by the National Heart, Lung, and Blood Institute. Fifteen authors declared grants, personal fees, and other funding from the pharmaceutical industry, as well as other private industry, outside the submitted work. Several also declared grants from organizations including the National Institutes of Health. No other conflicts of interest were declared.

Sources: McKeeve T et al. N Engl J Med. 2018 Mar 3. doi: 10.1056/NEJMoa1714257; Jackson DJ et al. N Engl J Med. 2018 Mar 3. doi: 10.1056/NEJM0a1710988.

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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.



Significantly escalating the dose of inhaled glucocorticoids at the first sign of an imminent asthma exacerbation has had mixed results in preventing the exacerbation from occurring, according to the results of two trials in adults and children.

Presented at the joint congress of the American Academy of Allergy, Asthma, and Immunology and the World Asthma Organization and simultaneously published in the March 3 online edition of the New England Journal of Medicine, one study explored the effect of quadrupling the inhaled glucocorticoid dose in adults and adolescents with asthma, while the other looked at quintupling the dose in children.

The first study involved 1,922 participants who were aged 16 years or above, who were receiving inhaled glucocorticoids, and had experienced at least one asthma exacerbation in the previous year. They were randomized to a self-management plan that instructed them to either take quadruple their usual dose of inhaled glucocorticoids at the first sign of worsening asthma – more use of reliever inhaler, difficult sleeping, or reduced peak flow – or continue using their usual dose of inhaled glucocorticoids.

At 1 year, there was a significantly lower incidence of severe asthma exacerbations in the group who used the higher dose of inhaled glucocorticoids (45% vs. 52%; hazard ratio, 0.80; P = .001) after adjusting for age, sex, and peak flow measures at randomization.


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