Evidence for Exacerbation-Prone Asthma and Predictive Biomarkers of Exacerbation Frequency
Evidence for Exacerbation-Prone Asthma and Predictive Biomarkers of Exacerbation Frequency
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DOI：
10.1164/rccm.201909-1813oc
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发表时间：
2020-10-01
影响因子：
24.7
通讯作者：
Denlinger, Loren C.
中科院分区：
文献类型：
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作者：
Peters, Michael C.;Mauger, David;Denlinger, Loren C.
理论基础：横断面研究表明易加重哮喘(EPA)表型和血嗜酸性粒细胞和血浆IL-6作为预测生物标志物的有效性。目的：前瞻性测试EPA表型和基础血液指标嗜酸性粒细胞和IL-6作为预测生物标志物的有效性。方法：分析重症哮喘研究计划-3中406名成人的三年哮喘恶化数据。过渡模型被用来评估第3年病情恶化的不知情和知情概率。二项回归模型被用来评估嗜酸性粒细胞和IL-6作为预测生物标志物。测量和主要结果：83名参与者(21%)每年有1次病情恶化(EPA)，168名参与者(41%)在任何一年都没有恶化(病情抵抗型哮喘)。第3年恶化的不知情概率为40%，但第2年恶化的知情概率增加到63%，第1年和第2年恶化的知情概率增加到82%。第3年恶化而第1年或第2年没有恶化的概率为13%。与难治性哮喘相比，EPA的特点是FEV1较低，肥胖症、高血压和糖尿病的患病率较高。EPA患者血浆IL-6水平升高，基线IL-6水平每升高1-pg/亩L，病情恶化发生率增加10%。虽然EPA中未出现高嗜酸性粒细胞，但L基础嗜酸性粒细胞每增加100个/亩，病情加重的发生率增加9%。结论：纵向分析证实了EPA具有代谢紊乱特征的表型。血液中的IL-6，而不是嗜酸性粒细胞，与EPA显著相关，而IL-6和嗜酸性粒细胞预测了整个样本的恶化。
Rationale: Cross-sectional studies suggest an exacerbation-prone asthma (EPA) phenotype and the utility of blood eosinophils and plasma IL-6 as predictive biomarkers.Objectives: To prospectively test for EPA phenotype and utility of baseline blood measures of eosinophils and IL-6 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 IL-6 as predictive biomarkers.Measurements and Main Results: Eighty-three participants (21%) had >= 1 exacerbation in each year (EPA) and 168 participants (41%) had no exacerbation in any year (exacerbation-resistant asthma). 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 with exacerbation-resistant asthma, EPA was characterized by lower FEV1 and a higher prevalence of obesity, hypertension, and diabetes. High-plasma IL-6 occurred in EPA, and the incident rate ratio for exacerbation increased 10% for each 1-pg/mu l increase in baseline IL-6 level. Although high blood eosinophils did not occur in EPA, the incident rate ratio for exacerbations increased 9% for each 100-cell/mu l 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.