Type 2 Biomarkers and Prediction of Future Exacerbations and Lung Function Decline in Adult Asthma

Abstract

Background: Type 2 biomarkers that predict both likelihood of future severe exacerbations and response to mAb therapy in asthma would be useful clinically in identifying patients both at greater risk of hospitalization and most likely to benefit from mAb therapy.

Objective: To describe the association between type 2 biomarkers, blood eosinophils, fractional exhaled nitric oxide (Feno), serum periostin, and serum IgE, and time to severe exacerbation in a broad asthma population.

Methods: Participants from 2 adult asthma cohorts with baseline measurements of blood eosinophils, Feno, serum periostin, and serum IgE were reviewed after at least 12 months to obtain an exacerbation history, corroborated with general practitioner and hospital medical records. The association between baseline type 2 biomarkers and time to exacerbation was described by Cox proportional hazard ratios (HRs) using multivariate models.

Results: A total of 212 participants were followed for a median (range) 3.8 (1.1-5.3) years; 67 of 212 (32%) had at least 1 severe exacerbation. The HRs (95% CI) of baseline type 2 biomarkers and time to exacerbation were as follows: blood eosinophils per 0.1 × 10⁹/L increase, 0.89 (0.76-1.05), P = .17; log Feno per 0.693 increase, 0.65 (0.52-0.81), P < .001; log serum periostin per 0.693 increase, 0.62 (0.35-1.09), P = .10; log serum IgE per 0.693 increase, 0.89 (0.80-1.00), P = .05.

Conclusions: The positive association between type 2 biomarkers and risk of severe exacerbations in populations with severe refractory asthma does not extend to mild and moderate asthma. Non-type 2 asthma may represent a phenotype associated with an increased risk of severe exacerbations in a broad asthma population.

Keywords: Asthma; Exacerbation; Noneosinophilic asthma; Type 2 biomarkers.