High dose, low impact: why we need to rethink ICS asthma strategy

Escalating doses of inhaled corticosteroids in an effort to head off impending asthma exacerbations is unsuccessful in children and of limited value in adults.

US research showed increasing the regular dose of inhaled steroids by a factor of five at the first signs of deterioration in children did not prevent severe asthma exacerbations requiring systemic glucocorticoids.

Time to treatment with systemic therapy did not differ between the two groups and emergency department (ED) or other urgent healthcare visits for asthma were also similar.

Instead of benefit, children given the higher dose of inhaled treatment had a 16% greater exposure to steroids overall and a lower linear growth rate per year than other children.

In a similar but ‘real world’ UK study in adolescents and adults – previously reported in the limbic – quadrupling regular inhaled glucocorticoids on deterioration resulted in a significant reduction in severe asthma exacerbations from 52% to 45%.

Patients in the higher dose group used less systemic glucocorticoids and had fewer unscheduled asthma consultations than other patients.

The study calculated the number of patients who needed to be treated with the higher dose to prevent one severe asthma exacerbation was 15.

“Given the potential benefits 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,” the researchers concluded.

Debatable benefit

Commenting on the two studies in the NEJM, Professor Philip Bardin, from the Monash Lung and Sleep Unit and Hudson Institute of Medical Research, said the degree of benefit was ‘debatable’.

“Evidence indicates that substantial escalation of regularly used inhaled glucocorticoids, even by a factor of 4 or 5, fails to prevent most asthma exacerbations,” he wrote.

He told the limbic one of the issues may be whether the inhaled steroids were actually getting to where the trouble was when a patient’s chest really tightened up.

“And in children with small airways, that may be even more of a problem whereas in adults, especially at the early stage, they may get some uptake of the treatment into the lung. Maybe that’s why in adults, there is an effect in a small group of people but in the children’s study, I think it’s pretty clear that it doesn’t work.”

Professor Bardin said with new scientific and molecular tools at our disposal, it should be possible to get a better understanding of the heterogeneity of exacerbations.

“Currently there is a fairly broad approach to exacerbations in assuming they are all the same. But although they clinically look similar – for example wheezy – the causes are quite varied and it’s important to try and understand better why people are getting exacerbations.”

He said the rapid identification of respiratory viruses triggering an exacerbation was one potential way forward.

“In the past, we suspected particular viruses but couldn’t identify them early and treatments weren’t available but that is changing. So we have anti-viral treatments – for example, some new drugs are being developed for respiratory syncytial virus and the science is starting to have an impact on rhinoviruses.”

“It’s early days but my editorial raises the issue of using new knowledge to treat people in a more personalised fashion. We need to think outside the square.”

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