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A novel asthma burden score that incorporated asthma exacerbations and healthcare utilization better reflected disease severity and predicted asthma remission with high sensitivity and specificity, according to an analysis of prospective data from two longitudinal cohorts.

Higher burden scores correlated with worse lung function, asthma control, and quality of life, and a burden score of 0.15 or lower predicted asthma remission with sensitivity greater than 91% and a specificity of 99%, Joe Zein, MD, PhD, of Mayo Clinic Arizona in Scottsdale, and colleagues reported in .

In 34% of participants in one cohort and 19% in a second with severe asthma, the burden score was below the median cutoff of 1.29 per patient-year. The score was above the median value in 28% and 27%, respectively, of participants in the two cohorts with non-severe asthma.

"This study challenges the value of treatment-based severity scores, which do not consider specifically other important factors such as asthma control, recurrent exacerbations, and coexistent functional limitations," study authors wrote in their conclusion. "We propose a different approach to assess asthma severity based on an asthma burden score. This personalized score represents patient-centered data encompassing factors that reflect patients' responses to real-world asthma morbidity in daily life."

Severe asthma is currently defined by European Respiratory Society (ERS) and American Thoracic Society (ATS) consensus guidelines as the need for high-dose inhaled corticosteroids plus a second controller, or as asthma that remains uncontrolled despite this therapy. But this definition is based on the level of prescribed therapy and does not capture frequency of symptoms, exacerbations, or functional limitations. "These definitions might not have the required precision to be used in pathobiology studies to understand the basis of disease progression and severity," the authors wrote.

Compared to current classifications, "the proposed score better reflects the burden of disease, in terms of asthma control and the need for healthcare utilization," Jean Bousquet, MD, PhD, of the Fraunhofer Institute for Translational Medicine and Pharmacology, Immunology & Allergology in Berlin, and colleagues wrote in an . "It also independently predicts asthma remission. Interestingly, both cohorts showed similar results, pointing to the robustness of the findings."

Bousquet and co-authors also highlighted the score's use of utilities, which quantitatively measure patients' preferences for certain health states, writing, "by weighting health states based on their respective utilities, the authors incorporated patients' perspectives into the burden score." However, they noted that the utilities were not obtained from a systemic review but from individual studies.

Using clinical and biological data from two longitudinal asthma cohorts -- the in the U.S. (SARP III) and from 11 European countries (U-BIOPRED) -- researchers created a composite burden score based on the number of asthma exacerbations, emergency department visits, asthma-related hospital admissions, and admissions to the intensive care unit.

This score was modified to include the use of short-acting beta agonist (SABA) rescue medications as a measure of asthma symptom burden, and weighted with disability-adjusted life-years to capture the relative health burden of various asthma exacerbations, healthcare utilization events, and SABA use in an effort to reflect actual asthma burden on quality of life.

SARP III included 528 adult participants with asthma who were followed for a mean of 4.4 years. According to the ERS-ATS guidelines, 59% of them had severe asthma. U-BIOPRED included 509 adult participants with asthma who were followed for up to 1 year; 83% had severe asthma.

Researchers also found that high blood neutrophil counts were correlated with high burden score, while "traditional" type 2 (T2) asthma biomarkers like blood eosinophil counts and fractional exhaled nitric oxide were not in either cohort, "suggesting a role for non-T2 mechanisms responsible for symptomatic asthma that include [interleukin 6] endotypes," they wrote.

"Consistent with previous studies, increased asthma burden was associated with the activation of inflammatory pathways -- an important response to the viral infections that cause the exacerbations," according to Bousquet and colleagues. When it comes to remission, however, they questioned whether daily assessment of asthma control status might be more useful than the proposed burden score.

Study limitations included differences between the two cohorts, including a large number of African-American participants in SARP III and largely white Europeans in U-BIOPRED. Children and adolescents were excluded, and adults in these cohorts had high rates of severe asthma, so more information is needed on a wider group of patients and varying levels of severity. Data on exacerbations prior to the studies were not available, and medication adherence was assessed with self-reports and RNA sequencing data, but not with pharmacy data. Also, the study did not account for complications related to chronic corticosteroid use.

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