血EOS、FENO与哮喘、慢阻肺及ACO患者急性加重的关联：NOVELTY 研究
2026/06/03
摘要
研究目标：探究血嗜酸性粒细胞（EOS）和呼出气一氧化氮（FeNO）单独及联合使用时，与哮喘、慢性阻塞性肺疾病（COPD）及哮喘合并COPD（ACO）患者1年内急性加重风险的关联，同时分析不同加重亚型[仅口服糖皮质激素（OCS）或仅抗生素治疗]的差异，评估二者作为生物标志物的预测价值。
研究方法：基于NOVELTY研究队列，纳入来自19个国家，由医生确诊的哮喘、COPD和ACO三类患者；采集基线EOS、FeNO水平，随访1年记录所有急性加重，以及仅需OCS治疗加重或仅抗生素治疗加重的发生情况。采用负二项回归与逻辑回归，校正年龄、性别、吸烟状态，并根据模型类型差异化校正吸入性糖皮质激素（ICS）使用情况，分析两项标志物与急性加重风险的关联。
主要结果：1.EOS与加重风险：在哮喘患者中，基线EOS水平越高，总体急性加重风险显著增加（IRR=1.09，p=0.033）；在COPD患者中，EOS水平越高，总体急性加重风险呈升高趋势（IRR=1.09，p=0.069）；在ACO患者中，EOS与急性加重风险无显著关联。
2.FeNO与加重风险：在哮喘患者中，基线FeNO越高，仅 需OCS 治疗的急性加重风险越高（OR=1.16，p=0.006），仅抗生素治疗加重风险越低（OR=0.75，p=0.001）；在COPD患者中，FeNO越高，总体急性加重风险显著降低（IRR=0.91，p=0.025），但该关联在校正ICS使用后减弱，无统计学意义（p=0.072）；在ACO患者中，FeNO 越高，仅需OCS治疗加重风险显著升高（OR=1.55，p<0.001）。
3.EOS与FeNO联合分析：在哮喘患者中，仅高EOS可独立升高总体急性加重风险（IRR= 1.14）；在COPD患者中，高EOS（IRR =1.12）与低FeNO（IRR= 0.87）分别独立升高总体急性加重风险；在ACO患者中，仅高FeNO可独立升高仅需OCS治疗急性加重风险（OR =1.46）。
研究结论：EOS是预测哮喘和COPD患者急性加重风险的有效生物标志物，其预测作用较为稳定，基线水平升高提示加重风险增加；FeNO的预测价值具有疾病与亚型特异性，其高基线水平可识别哮喘及ACO患者中仅需OCS治疗的加重风险，但在COPD中作为预测指标的价值有限；二者联合检测并未较单一标志物显著提升预测价值。
Muiser S, Müllerová H, Belton L,et al.Association of blood eosinophils and exhaled nitric oxide with exacerbations in patients with asthma, COPD and asthma+COPD: the NOVELTY study. Thorax. 2026 Apr 21:thorax-2025-223646.
Abstract
Background: Blood eosinophils (EOS) and fractional exhaled nitric oxide (FeNO) are potential biomarkers for disease progression and treatment response in asthma and chronic obstructive pulmonary disease (COPD). We investigated their association with exacerbations in asthma, COPD and asthma+COPD.
Methods: NOVEL observational longiTudinal studY is a multicountry prospective study of patients with physician-assigned asthma, COPD and asthma+COPD. Negative binomial and logistic regression analyses were performed for baseline EOS/FeNO (separately and combined), by diagnosis, and for different exacerbation subtypes (all, antibiotics-only, oral corticosteroids (OCS)-only).
Results: Higher baseline EOS was significantly associated with increased risk of all exacerbations in asthma (incidence rate ratio (IRR) 1.09, 95% CI 1.01 to 1.18, p=0.033), with a trend increase with COPD (IRR 1.09, 95% CI 1.00 to 1.19, p=0.069) but not asthma+COPD. Higher baseline FeNO was significantly associated with decreased risk of all exacerbations in COPD (IRR 0.91, 95% CI 0.84 to 0.99, p=0.025) and increased risk of OCS-only exacerbations in asthma (OR 1.16, 95% CI 1.04 to 1.29, p=0.006) and asthma+COPD (OR 1.55, 95% CI 1.22 to 1.97, p<0.001). In exacerbation risk in asthma (IRR 1.14, 95% CI 1.05 to 1.24, p=0.003), while in COPD, both higher EOS (IRR 1.12, 95% CI 1.02 to 1.24, p=0.033) and lower FeNO (IRR 0.87, 95% CI 0.78 to 0.96, p=0.009) were independently associated with exacerbation risk.
Conclusions: Higher EOS predicted exacerbations in asthma and COPD, while FeNO showed heterogeneous associations, particularly for OCS-only treated exacerbations. Assessment of exacerbation subtype might improve personalised management. Interpretation is limited by physician-assigned diagnoses, potential ICS confounding and recall bias.
Keywords: Asthma; COPD Exacerbations; Eosinophil Biology; Exhaled Airway Markers.
研究目标：探究血嗜酸性粒细胞（EOS）和呼出气一氧化氮（FeNO）单独及联合使用时，与哮喘、慢性阻塞性肺疾病（COPD）及哮喘合并COPD（ACO）患者1年内急性加重风险的关联，同时分析不同加重亚型[仅口服糖皮质激素（OCS）或仅抗生素治疗]的差异，评估二者作为生物标志物的预测价值。
研究方法：基于NOVELTY研究队列，纳入来自19个国家，由医生确诊的哮喘、COPD和ACO三类患者；采集基线EOS、FeNO水平，随访1年记录所有急性加重，以及仅需OCS治疗加重或仅抗生素治疗加重的发生情况。采用负二项回归与逻辑回归，校正年龄、性别、吸烟状态，并根据模型类型差异化校正吸入性糖皮质激素（ICS）使用情况，分析两项标志物与急性加重风险的关联。
主要结果：1.EOS与加重风险：在哮喘患者中，基线EOS水平越高，总体急性加重风险显著增加（IRR=1.09，p=0.033）；在COPD患者中，EOS水平越高，总体急性加重风险呈升高趋势（IRR=1.09，p=0.069）；在ACO患者中，EOS与急性加重风险无显著关联。
2.FeNO与加重风险：在哮喘患者中，基线FeNO越高，仅 需OCS 治疗的急性加重风险越高（OR=1.16，p=0.006），仅抗生素治疗加重风险越低（OR=0.75，p=0.001）；在COPD患者中，FeNO越高，总体急性加重风险显著降低（IRR=0.91，p=0.025），但该关联在校正ICS使用后减弱，无统计学意义（p=0.072）；在ACO患者中，FeNO 越高，仅需OCS治疗加重风险显著升高（OR=1.55，p<0.001）。
3.EOS与FeNO联合分析：在哮喘患者中，仅高EOS可独立升高总体急性加重风险（IRR= 1.14）；在COPD患者中，高EOS（IRR =1.12）与低FeNO（IRR= 0.87）分别独立升高总体急性加重风险；在ACO患者中，仅高FeNO可独立升高仅需OCS治疗急性加重风险（OR =1.46）。
研究结论：EOS是预测哮喘和COPD患者急性加重风险的有效生物标志物，其预测作用较为稳定，基线水平升高提示加重风险增加；FeNO的预测价值具有疾病与亚型特异性，其高基线水平可识别哮喘及ACO患者中仅需OCS治疗的加重风险，但在COPD中作为预测指标的价值有限；二者联合检测并未较单一标志物显著提升预测价值。
（南方医科大学南方医院 石宇萱 杨跞予 赵海金）
Muiser S, Müllerová H, Belton L,et al.Association of blood eosinophils and exhaled nitric oxide with exacerbations in patients with asthma, COPD and asthma+COPD: the NOVELTY study. Thorax. 2026 Apr 21:thorax-2025-223646.
Abstract
Background: Blood eosinophils (EOS) and fractional exhaled nitric oxide (FeNO) are potential biomarkers for disease progression and treatment response in asthma and chronic obstructive pulmonary disease (COPD). We investigated their association with exacerbations in asthma, COPD and asthma+COPD.
Methods: NOVEL observational longiTudinal studY is a multicountry prospective study of patients with physician-assigned asthma, COPD and asthma+COPD. Negative binomial and logistic regression analyses were performed for baseline EOS/FeNO (separately and combined), by diagnosis, and for different exacerbation subtypes (all, antibiotics-only, oral corticosteroids (OCS)-only).
Results: Higher baseline EOS was significantly associated with increased risk of all exacerbations in asthma (incidence rate ratio (IRR) 1.09, 95% CI 1.01 to 1.18, p=0.033), with a trend increase with COPD (IRR 1.09, 95% CI 1.00 to 1.19, p=0.069) but not asthma+COPD. Higher baseline FeNO was significantly associated with decreased risk of all exacerbations in COPD (IRR 0.91, 95% CI 0.84 to 0.99, p=0.025) and increased risk of OCS-only exacerbations in asthma (OR 1.16, 95% CI 1.04 to 1.29, p=0.006) and asthma+COPD (OR 1.55, 95% CI 1.22 to 1.97, p<0.001). In exacerbation risk in asthma (IRR 1.14, 95% CI 1.05 to 1.24, p=0.003), while in COPD, both higher EOS (IRR 1.12, 95% CI 1.02 to 1.24, p=0.033) and lower FeNO (IRR 0.87, 95% CI 0.78 to 0.96, p=0.009) were independently associated with exacerbation risk.
Conclusions: Higher EOS predicted exacerbations in asthma and COPD, while FeNO showed heterogeneous associations, particularly for OCS-only treated exacerbations. Assessment of exacerbation subtype might improve personalised management. Interpretation is limited by physician-assigned diagnoses, potential ICS confounding and recall bias.
Keywords: Asthma; COPD Exacerbations; Eosinophil Biology; Exhaled Airway Markers.
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