嗜酸性粒细胞和呼出气一氧化氮与哮喘、慢性阻塞性肺疾病（COPD）及哮喘合并COPD患者病情加重的关联：NOVELTY研究
2026/04/28
摘要
背景：血液嗜酸性粒细胞（EOS）和呼出气一氧化氮分数（FeNO）是哮喘和慢性阻塞性肺疾病（COPD）疾病进展和治疗反应的潜在生物标志物。我们研究了它们与哮喘、COPD以及哮喘合并COPD急性加重的关联。
方法：NOVEL观察性纵向研究是一项针对医生诊断为哮喘、COPD以及哮喘合并COPD患者的多国家前瞻性研究。分别和联合分析基线EOS/FeNO与疾病诊断以及不同急性加重亚型（所有类型、仅使用抗生素、仅使用口服皮质类固醇[OCS]）之间的关系，采用负二项回归和逻辑回归分析。
结果：较高的基线EOS与哮喘患者所有类型急性加重风险增加显著相关（发病率比[IRR] 1.09，95%置信区间[CI] 1.01 - 1.18，p = 0.033），在COPD患者中有增加趋势（IRR 1.09，95% CI 1.00 - 1.19，p = 0.069），但在哮喘合并COPD中患者无此关联。较高的基线FeNO与COPD患者所有类型急性加重风险降低显著相关（IRR 0.91，95% CI 0.84 - 0.99，p = 0.025），与哮喘（比值比[OR] 1.16，95% CI 1.04 - 1.92，p = 0.006）和哮喘合并COPD（OR 1.55，95% CI 1.22 - 1.97，p < 0.001）患者仅使用OCS治疗的急性加重风险增加显著相关。在哮喘患者急性加重风险方面（IRR 1.14，95% CI 1.05 - 1.24，p = 0.003），而在COPD患者中，较高的 EOS（IRR 1.12，95% CI 1.02 - 1.24，p = 0.033）和较低的FeNO（IRR 0.87，95% CI 0.78 - 0.96， =p 0.009）均独立与急性加重风险相关。
结论：较高的EOS可预测哮喘和COPD患者的急性加重，而FeNO显示出异质性关联，尤其是对于仅使用OCS治疗的急性加重。评估急性加重亚型可能改善个体化管理。本研究的解读受医生诊断、潜在的吸入性皮质类固醇（ICS）混杂因素和回忆偏倚的限制。
Association of blood eosinophils and exhaled nitric oxide with exacerbations in patients with asthma, COPD and asthma+COPD: the NOVELTY study
Susan Muiser, Hana Müllerová, Laura Belton, Nifasha Rusibamayila, Clement Erhard, Alvar Agusti, Rosa Faner, Ian Pavord, Simon Couillard, Hiromasa Inoue, David B Price, Jose Maria Olaguibel, Huib A M Kerstjens, Maarten van den Berge 12; NOVELTY Scientific Community; NOVELTY study investigators
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.
背景：血液嗜酸性粒细胞（EOS）和呼出气一氧化氮分数（FeNO）是哮喘和慢性阻塞性肺疾病（COPD）疾病进展和治疗反应的潜在生物标志物。我们研究了它们与哮喘、COPD以及哮喘合并COPD急性加重的关联。
方法：NOVEL观察性纵向研究是一项针对医生诊断为哮喘、COPD以及哮喘合并COPD患者的多国家前瞻性研究。分别和联合分析基线EOS/FeNO与疾病诊断以及不同急性加重亚型（所有类型、仅使用抗生素、仅使用口服皮质类固醇[OCS]）之间的关系，采用负二项回归和逻辑回归分析。
结果：较高的基线EOS与哮喘患者所有类型急性加重风险增加显著相关（发病率比[IRR] 1.09，95%置信区间[CI] 1.01 - 1.18，p = 0.033），在COPD患者中有增加趋势（IRR 1.09，95% CI 1.00 - 1.19，p = 0.069），但在哮喘合并COPD中患者无此关联。较高的基线FeNO与COPD患者所有类型急性加重风险降低显著相关（IRR 0.91，95% CI 0.84 - 0.99，p = 0.025），与哮喘（比值比[OR] 1.16，95% CI 1.04 - 1.92，p = 0.006）和哮喘合并COPD（OR 1.55，95% CI 1.22 - 1.97，p < 0.001）患者仅使用OCS治疗的急性加重风险增加显著相关。在哮喘患者急性加重风险方面（IRR 1.14，95% CI 1.05 - 1.24，p = 0.003），而在COPD患者中，较高的 EOS（IRR 1.12，95% CI 1.02 - 1.24，p = 0.033）和较低的FeNO（IRR 0.87，95% CI 0.78 - 0.96， =p 0.009）均独立与急性加重风险相关。
结论：较高的EOS可预测哮喘和COPD患者的急性加重，而FeNO显示出异质性关联，尤其是对于仅使用OCS治疗的急性加重。评估急性加重亚型可能改善个体化管理。本研究的解读受医生诊断、潜在的吸入性皮质类固醇（ICS）混杂因素和回忆偏倚的限制。
（中日友好医院呼吸与危重症医学科 李红雯 摘译 林江涛 审校）
（Thorax. 2026 Apr 21:thorax-2025-223646. doi: 10.1136/thorax-2025-223646.）
（Thorax. 2026 Apr 21:thorax-2025-223646. doi: 10.1136/thorax-2025-223646.）
Association of blood eosinophils and exhaled nitric oxide with exacerbations in patients with asthma, COPD and asthma+COPD: the NOVELTY study
Susan Muiser, Hana Müllerová, Laura Belton, Nifasha Rusibamayila, Clement Erhard, Alvar Agusti, Rosa Faner, Ian Pavord, Simon Couillard, Hiromasa Inoue, David B Price, Jose Maria Olaguibel, Huib A M Kerstjens, Maarten van den Berge 12; NOVELTY Scientific Community; NOVELTY study investigators
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.
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度普利尤单抗可降低哮喘患者痰液的放射密度并减少新痰栓形成
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犬类过敏原与内毒素对肺功能及哮喘的保护作用
