Quadrupling inhaled glucocorticoids decreased severe asthma exacerbations in adults

A recent study published in The New England Journal of Medicine explored a novel self-management plan to stop asthma exacerbations and reduce the frequency of severe asthma exacerbations among adults and adolescents.

Although self-management plans for asthma have been shown to be effective at improving asthma control, a doubling of the dose of inhaled corticosteroids when asthma control deteriorates has proven ineffective at preventing asthma exacerbations.

Moreover, a 2016 Cochrane Review suggested that increasing the dose of inhaled corticosteroids is unlikely to reduce the chance of systemic glucocorticoid use or hospitalization. This increase also does not cut down on recovery time.

This randomized trial was led by Tricia McKeever, PhD, from the School of Medicine, University of Nottingham, UK.

“We performed an individually randomized, unblinded, pragmatic, multicenter trial involving adults and adolescents to test the hypothesis that a self-management plan that included a temporary increase in the dose of inhaled glucocorticoids by a factor of 4 when asthma control started to deteriorate would reduce the use of oral glucocorticoids or unscheduled health care consultations for asthma as compared with a plan that did not include this step,” the authors wrote.

The researchers included 1,922 participants aged 16 and older (1,871 participants were included in the primary analysis) who were receiving inhaled glucocorticoids either with or without add-on medication. They also had at least one asthma exacerbation that required treatment with systemic corticosteroids during the previous 12 months.

Participants were randomized to one of two self-management plans that were identical except for the temporary quadrupling of inhaled glucocorticoids when asthma control deteriorated. Each group’s plans included 4 zones. Zone 1 (identical in both groups) described well-controlled asthma and the patient’s current treatment. Zone 2 consisted of an increase in bronchodilator medication and a quadrupling of the inhaled glucocorticoids in the quadrupling group, and an increase in bronchodilator use only in the non-quadrupled group. Zones 3 and 4 described when to begin oral glucocorticoids and what to do in the event of a life-threatening exacerbation.

The primary outcome was the time elapsed to a first severe asthma exacerbation that required either treatment with systemic glucocorticoids or an unscheduled health-care visit.

During the year following randomization, 58% of all respondents reached at least Zone 2 in their treatment plans—562 in quadrupling group vs 552 in non-quadrupling group. In the quadrupling group, 420 participants (45%) had a severe asthma exacerbation as compared with 452 participants (52%) in the non-quadrupling group.

Systemic glucocorticoid use and the number of unscheduled asthma-related health care consultations were both lower in the quadrupling group.

On follow-up at 12 months, the estimated mean total dose of inhaled glucocorticoids was 385 mg in the quadrupling group vs 328 mg in the non-quadrupling group. Mean total dose of systemic glucocorticoids was 121 mg and 151 mg, respectively.

Adverse effects were limited and mostly secondary to the local effects of inhaled corticosteroids. They were most likely to affect the quadrupling group.

In this study, the pragmatic design and open-label intervention may have served as a bias and limited the implications of the study data. In other words, because all participants and many physicians were aware of the intervention, the participants may have been more proactive in seeking out medical attention, and physicians may have been more likely to advise treatment with systemic glucocorticoids.

“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,” the authors concluded.

This study was financially supported by the Health Technology Assessment Programme of the National Institute for Health Research in the United Kingdom.

To read more about this study, click here.