Basophil Levels in Childhood Asthma May Indicate Risk for Future Exacerbations

A basophil level that is >0.18% of the circulating peripheral blood mononuclear cell population during an acute respiratory exacerbation is linked with an elevated risk for future exacerbations in children with asthma and/or wheeze, according to the results of a cohort study conducted in Australia and published in The Journal of Allergy and Clinical Immunology.

The investigators sought to define an exacerbation-prone phenotype by dividing the participants into 2 groups: those with a high and those with a low recurrence of exacerbations. A cutoff of 4 prior wheezing or acute asthma exacerbations was used to separate approximately the top quarter of patients with recurrent disease. The 2 patient groups were similar with respect to age at recruitment, gender, atopic status, exacerbation severity, and virus prevalence. Because the age of the participants ranged from 0.6 to 12.3 years and the frequencies of some cell subsets (eg, B cells and CD4⁺ T effector cells) change with increasing age, the researchers used multiple regression to adjust for age in the analyses.

Increased proportions of CD123⁺/CD11c^1o/HLA^– basophils were positively associated with a history of >4 exacerbations. In contrast, elevated proportions of CD3⁺/CD4⁺/CD25⁺/FoxP3^– T effector cells were negatively associated with >4 exacerbations. Additionally, within the basophil subset, CD25 expression was reduced in patients with >4 prior exacerbations. These associations were further confirmed with use of the number of prior exacerbations as a continuous variable: basophils, P =.02; CD4⁺ T effector cells, P =.04.

Once the researchers established that a history of >4 previous exacerbations was linked with altered proportions of basophils and CD4⁺ T effector cells during an acute exacerbation, all patients were stratified into 2 groups based on a median split of these types of cells, with the risk for future exacerbations evaluated within the follow-up period. Based on the plotting of exacerbation-free time, patients with high basophil levels were more likely to experience a subsequent exacerbation, whereas there was no difference observed among those with CD4⁺ T effector cell levels above or below the median (P =.13). This implies that not all changes linked with a history of exacerbations contribute to a recurrent disease phenotype.

To further confirm their findings, the researchers studied an independent set of patients, dividing them into 2 groups based on a median split of basophil levels during an asthma exacerbation. Once again, patients with high basophil levels were more likely than those with low basophil levels to experience additional exacerbations during the follow-up period.

The investigators concluded that the results of this study suggest that patients with a high proportion of basophils within the peripheral blood mononuclear cell preparation (ie, those with many basophils with a density of <1.077 g/mL) were more likely to experience an additional exacerbation during the follow-up period.

These findings require additional confirmation using a larger cohort of patients — in particular, those who are experiencing their first-ever exacerbation. The use of basophil proportion and density as a potential marker of future exacerbations warrants further research.

Reference

Leffler J, Jones AC, Hollams EM, et al. Basophil levels in PBMC population during childhood acute wheeze/asthma are associated with future exacerbations [published online July 20, 2018]. J Allergy Clin Immunol. doi:10.1016/j.jaci.2018.07.003