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April 26, 2022
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High use of short-acting beta 2 agonists may be ‘danger signal’ of more severe asthma

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Although infrequent, high use of short-acting beta 2 agonists was associated with more severe asthma, according to a study published in The Journal of Allergy and Clinical Immunology: In Practice.

Also, obesity and higher symptom scores at diagnosis can predict this higher long-term use of short-acting beta 2 agonists (SABAs), the researchers wrote, adding that high SABA users should be identified in clinical practice so providers can intervene.

Asthma patients with high SABA use used 49 canisters over 12 years, while patients with low SABA use used 6.
Data were derived from Vähätalo I, et al. J Allergy Clin Immunol Pract. 2022;doi:10.1016.j.jaip.2022.03.027.

“Short-term studies have associated high use of SABAs to poor outcomes of asthma, but no studies existed on long-term SABA use among patients with clinically confirmed adult-onset asthma, which is the aim of the current study,” Iida Vähätalo, MScPharm, a PhD student in the faculty of medicine and health technology’s respiratory research group at Tampere University and the department of respiratory medicine at Seinäjoki Central Hospital, both in Finland, told Healio.

Iida Vähätalo

“In addition, studies on this topic often lack information of disease control and patients’ adherence to controller treatment, such as inhaled corticosteroids (ICS), both affecting the need of SABA. We were able to evaluate these factors in this study,” Vähätalo said.

The study’s design

The prospective, 12-year follow-up study examined 203 patients (58% female; mean age at asthma onset, 46 years; standard deviation, 14) aged 15 years and older diagnosed with new-onset adult asthma between 1999 and 2002, as well as data on dispensed SABA and ICS.

Researchers determined SABA use by the numbers of canisters collected annually and cumulatively for the 12-year period — with high SABA use considered as 36 or more SABA canisters in 12 years — and they tallied ICS use by numbers of 150-dose canisters.

The researchers also stratified SABA over-reliance into three categories: high SABA use no dispensed ICS canisters during follow-up; high SABA use and less than 36 dispensed canisters of ICS; and high SABA use with fewer ICS canisters than SABA canisters dispensed.

Patients completed the Airways Questionnaire 20 (AQ20) during their baseline visit. During the follow-up visit, clinicians used the AQ20 and the Asthma Control Test to measure symptoms and the Global Initiative for Asthma 2010 report to classify patients by asthma control.

Patients were diagnosed with noncontrolled asthma — which was defined as partially controlled or uncontrolled asthma — if they had asthma symptoms or needed rescue treatment more than twice a week, had decreased lung function of less than 80% predicted or limited activities due to their asthma.

The study’s results

During the 12-year study period, patients overall received a median of six (interquartile range [IQR], 3-6) SABA canisters and 48 (IQR, 18-67) ICS canisters, corresponding to using a median of two (IQR, 1-4) SABA and 11 (IQR, 5-16) ICS puffs per week.

On average per year, 60% of patients used three or more ICS canisters, and 88% of patients used less than two SABA canisters. Cumulatively, 58% used less than 10 SABA canisters and 59% used 40 or more ICS canisters during the study period.

“High use and over-reliance on SABA were infrequent in patients with confirmed adult-onset asthma as only 10% of the patients were classified as high SABA users during the 12-year study period, and none of the patients was fully over-reliant on SABA, ie, not using ICS at all,” Vähätalo said.

“Patients with high SABA use also had better 12-year adherence to ICS than patients with low SABA use, indicating that these patients had more severe asthma and higher demand of SABA compared with low SABA users,” Vähätalo said.

High SABA users received a median of 49 (IQR, 39-69) SABA canisters during the 12-year study period, with 12 (IQR, 9-16) puffs per week. Those with low SABA use received a median of six (IQR, 3-12) canisters in total, with one (IQR 1-3) puff per week.

Five of the patients classified as high SABA users received more SABA canisters than ICS canisters. Also, the researchers considered two patients undertreated because they were high SABA users but did not receive ICS with long-acting beta 2 agonists or long-acting muscarinic antagonists.

“Patients with high use of SABA had more symptoms, a higher number of ED visits and more oral corticosteroid and antibiotic courses vs. low SABA users,” Vähätalo said.

“In addition, 86% of high SABA users had noncontrolled asthma, and over one-quarter of the patients had severe asthma according to European Respiratory Society/American Thoracic Society criteria,” Vähätalo said.

Further, patients who were characterized with high SABA use had higher BMI and poorer quality of life based on AQ20 at diagnosis compared with the patients who used less SABA, leading the researchers to consider BMI of 30 kg/m2 or greater and higher AQ20 scores at diagnosis significant predictors for higher long-term SABA use.

High SABA users additionally had fewer years of education and more comorbidities compared with patients who reported low SABA use, in addition to more contacts with health care services related to asthma.

The next steps

By over-relying on SABA, the researchers said, airway inflammation is not treated, and the downregulation of beta 2 receptors is not reversed, increasing the risk for negative outcomes with asthma. Also, the researchers continued, patients often poorly understand these interactions.

“As high SABA use was associated with more severe asthma, these patients should be recognized in clinical practice. However, based on our results, rather than being dangerous as such, we consider high use of SABA as a danger signal indicating more severe and/or uncontrolled asthma needing further therapeutic intervention,” Vähätalo said.

Considering these findings, the researchers called for the inclusion of weight-management strategies and consideration of socioeconomic status in treatment. They also recommended research into the mechanisms of non-type 2 asthma, asthma control independent of SABA use and the role of other diseases, lifestyle and socioeconomics in asthma control.

“To ensure the generality of the results, more studies on this topic are needed with a larger number of patients who have clinically confirmed asthma diagnosis and reliable knowledge of the dispensed medication,” Vähätalo said. “In addition, future studies should standardize the evaluation of SABA use to enable better comparison of the results.

For more information:

Iida Vähätalo, MScPharm, can be reached at iida.vahatalo@epshp.fi.