Evidence for Exacerbation-Prone Asthma and Predictive Biomarkers of Exacerbation Frequency.

BACKGROUND Cross-sectional studies suggest an exacerbation-prone asthma (EPA) phenotype and the utility of blood eosinophils and plasma interleukin 6 (IL-6) as predictive biomarkers. OBJECTIVE To prospectively test for EPA phenotype and utility of baseline blood measures of eosinophils and IL6 as predictive biomarkers. METHODS Three-year asthma exacerbation data were analyzed in 406 adults in the Severe Asthma Research Program-3. Transition models were used to assess uninformed and informed probabilities of exacerbation in year 3. Binomial regression models were used to assess eosinophils and IL6 as predictive biomarkers. RESULTS 83 participants (21%) had > 1 exacerbation in each year (EPA) and 168 participants (41%) had no exacerbation in any year (exacerbation-resistant asthma [ERA]). The uninformed probability of an exacerbation in year 3 was 40%, but the informed probability increased to 63% with an exacerbation in year 2 and 82% with an exacerbation in years 1 and 2. The probability of a year 3 exacerbation with no year 1 or 2 exacerbations was 13%. Compared to ERA, EPA was characterized by lower FEV1, and a higher prevalence of obesity, hypertension and diabetes. High plasma IL6 occurred in EPA, and the incident rate ratio (IRR) for exacerbation increased 10% for each 1 pg/uL increase in baseline IL6 level. Although high blood eosinophils did not occur in EPA, the IRR for exacerbations increased 9% for each 100 cell/uL increase in baseline eosinophil number. CONCLUSIONS Longitudinal analysis confirms an EPA phenotype characterized by features of metabolic dysfunction. Blood measures of IL-6, but not eosinophils, were significantly associated with EPA, and IL-6 and eosinophils predicted exacerbations in the sample as a whole.

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