The positive association identified between type 2 biomarkers and severe exacerbations of severe refractory asthma may not extend to mild to moderate asthma, according to a study published by the Journal of Allergy and Clinical Immunology: In Practice.

Researchers recruited 230 participants from 2 adult asthma cohorts. Baseline measurements of blood eosinophils, fractional exhaled nitric oxide (FENO), serum periostin, and serum immunoglobulin E (IgE) were compared with results obtained at least 12 months (median time, 3.8 years) later to assess the association between time to exacerbation and type 2 biomarkers and levels of blood eosinophils, FENO, serum periostin, and serum IgE in a broad population of adults with asthma.

It was hypothesized that individuals with higher blood levels of eosinophils, FENO, serum periostin, and serum IgE would be more likely to have severe asthma exacerbations, resulting in a significant decrease in lung function over the course of time.

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A total of 67 of 212 individuals experienced at least 1 severe exacerbation, with a total of 189 severe exacerbations, representing a rate of 0.29 severe exacerbations per patient-year in those with well-controlled mild to moderately severe asthma. 

No significant association was found between baseline blood eosinophil count or serum periostin level and time to severe exacerbation (P =.17 and P =.1, respectively). However, the adjusted hazard ratios (HR) for baseline FENO (adjusted HR, 0.65 [95% CI, 0.52-0.81] per 0.693 log FENO increase, P <.001) and IgE (adjusted HR, 0.89 [95% CI, 0.80-1.00] per 0.693 log IgE increase, P =.05) to time of severe exacerbation were statistically significant. There was also strong evidence of an association between inhaled corticosteroid use at baseline and time to severe exacerbation (adjusted HR, 3.66; 95% CI, 1.65-8.08).

There was no evidence of an association between baseline FENO, serum periostin, or serum IgE levels and forced expiratory volume in 1 second (FEV1); however, there was strong evidence of an association between FEV1 changes and blood eosinophil counts at baseline in a multivariate model after adjusting for age, sex, inhaled corticosteroid use, and smoking status (P <.001).

Researchers concluded that there was a statistically significant association between high FENO and serum IgE levels at baseline and lower risk for a severe exacerbation in adults with predominately intermittent mild to moderately severe asthma. In addition, a baseline eosinophil count of <0.21 x 109/L was associated with a decline in FEV1. Researchers suggested that, “the positive results for FENO and IgE and negative results for eosinophils might indicate that the exacerbations in our population could be driven by [interleukin]-13 rather than [interleukin]-5.”

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Clinicians should keep in mind that the positive association observed between type 2 biomarkers and risk for severe asthma exacerbations in individuals with severe refractory asthma may not extend to mild to moderate asthma and therefore should use these biomarkers with caution in those patients.


Semprini R, Williams M, Semprini A, et al. Type 2 biomarkers and prediction of future exacerbations and lung function decline in adult asthma [published online March 30, 2018]. J Allergy Clin Immunol Pract. doi:10.1016/j.jaip.2018.03.004