小气道功能障碍介导FeNO与哮喘控制之间的关系
2025/08/18
摘要
背景：生理状态下，呼出气一氧化氮（FeNO）主要在小气道产生，但目前关于FeNO与哮喘小气道功能障碍（SAD）关系的研究仍较少。
目的：探讨哮喘控制水平、FeNO随支气管舒张试验（BD）前后的变化（ΔFeNO）与SAD之间的关联。
方法：对连续接受社区规范治疗的成年哮喘患者进行基线常规肺功能、脉冲振荡及FeNO（BD前后，吸入沙丁胺醇400µg）测定。按照ΔFeNO将受试者分为FeNO“应答者”（BD后FeNO较基线增加>10%）和“非应答者”（增幅≤10%）。
结果：在BD后FeNO＞25 ppb 的患者比例较基础评估额外增加31.5%。纳入的92例患者中，61%为FeNO“应答者”，39%为“非应答者”。ΔFeNO与SAD的功能指标R5–R20呈显著中度至强度正相关（R=0.52，P<0.0001），而与常规肺功能指标的相关性不显著（P>0.05）。R5–R20和ΔFeNO均与哮喘控制水平呈负相关（P<0.0001）。因果中介分析显示，哮喘控制对ΔFeNO的影响主要通过SAD介导，哮喘控制通过SAD对ΔFeNO的间接效应显著（β=−7.04，95%CI：−11.80～−3.53，P<0.0001），而直接效应不显著（β=−4.96，95%CI：−9.15～0.11，P=0.056）。
结论：比较BD前后FeNO的变化有助于识别“TH2高”哮喘表型。ΔFeNO与哮喘控制之间的关系主要由SAD介导，提示小气道损伤在哮喘控制中具有重要作用。
关键词：小气道功能障碍；FeNO；哮喘控制；脉冲振荡
背景：生理状态下，呼出气一氧化氮（FeNO）主要在小气道产生，但目前关于FeNO与哮喘小气道功能障碍（SAD）关系的研究仍较少。
目的：探讨哮喘控制水平、FeNO随支气管舒张试验（BD）前后的变化（ΔFeNO）与SAD之间的关联。
方法：对连续接受社区规范治疗的成年哮喘患者进行基线常规肺功能、脉冲振荡及FeNO（BD前后，吸入沙丁胺醇400µg）测定。按照ΔFeNO将受试者分为FeNO“应答者”（BD后FeNO较基线增加>10%）和“非应答者”（增幅≤10%）。
结果：在BD后FeNO＞25 ppb 的患者比例较基础评估额外增加31.5%。纳入的92例患者中，61%为FeNO“应答者”，39%为“非应答者”。ΔFeNO与SAD的功能指标R5–R20呈显著中度至强度正相关（R=0.52，P<0.0001），而与常规肺功能指标的相关性不显著（P>0.05）。R5–R20和ΔFeNO均与哮喘控制水平呈负相关（P<0.0001）。因果中介分析显示，哮喘控制对ΔFeNO的影响主要通过SAD介导，哮喘控制通过SAD对ΔFeNO的间接效应显著（β=−7.04，95%CI：−11.80～−3.53，P<0.0001），而直接效应不显著（β=−4.96，95%CI：−9.15～0.11，P=0.056）。
结论：比较BD前后FeNO的变化有助于识别“TH2高”哮喘表型。ΔFeNO与哮喘控制之间的关系主要由SAD介导，提示小气道损伤在哮喘控制中具有重要作用。
关键词：小气道功能障碍；FeNO；哮喘控制；脉冲振荡
（南方医科大学南方医院 胡玉玲 龚钊乾 赵文驱 赵海金）
（Cottini M, Ventura L, Lombardi C, Landi M, Imeri G, Di Marco F, Comberiati P, Berti A. Small airway dysfunction mediates the relationship between Fractional Exhaled Nitric Oxide and asthma control. Ann Allergy Asthma Immunol. 2025 May;134(5):548-555.e4. doi: 10.1016/j.anai.2025.01.003. Epub 2025 Jan 16. PMID: 39826900.）
Abstract
Background：Most physiological production of Fractional exhaled Nitric Oxide (FeNO) occurs in the small airways, but studies on the relationship between FeNO and small airway dysfunction (SAD) in asthma are scant.
Objective：To investigate the relationship between asthma control, changes of FeNO in relation to airway bronchodilation (BD), and SAD.
Methods：Baseline conventional spirometry, impulse oscillometry, and FeNO pre- and post-BD (salbutamol 400 μg) were tested on consecutive community-treated adult patients with asthma. Results were stratified by FeNO response (change in FeNO [ΔFeNO]), being FeNO “responder” if the increase is greater than 10% post-BD compared with the basal values and “nonresponder” if less than or equal to 10%.
Results：When measured, post-BD FeNO greater than 25 parts per billion was found in an additional 31.5% of patients. Of the 92 patients included, 61% were classified as FeNO “responders” and 39% as “nonresponders.” A significant moderate-to-strong correlation was observed between ΔFeNO and R5R20, a functional marker of SAD (R = 0.52,P< .0001), whereas the correlations between spirometry markers and ΔFeNO were not significant (P> .05). Both R5R20 and ΔFeNO inversely correlated with asthma control (P< .0001). Using causal mediation analysis modeling, the effect of asthma control on ΔFeNO was mediated by SAD, with a strong indirect effect of asthma control on ΔFeNO mediated by SAD (β value: −7.04, 95% CI: −11.80 to −3.53,P< .0001), without a significant direct effect (β value: −4.96, 95% CI: −9.15 to 0.11,P= .056).
Conclusion：Changes in FeNO values pre-/post-BD can improve the identification of patients with “TH2 high” asthma. The relationship between ΔFeNO and asthma control is mainly mediated by SAD, highlighting its contribution to asthma control.
Keywords: Small Airway Dysfunction; Fractional Exhaled Nitric Oxide; Asthma Control; Impulse Oscillometry.
Abstract
Background：Most physiological production of Fractional exhaled Nitric Oxide (FeNO) occurs in the small airways, but studies on the relationship between FeNO and small airway dysfunction (SAD) in asthma are scant.
Objective：To investigate the relationship between asthma control, changes of FeNO in relation to airway bronchodilation (BD), and SAD.
Methods：Baseline conventional spirometry, impulse oscillometry, and FeNO pre- and post-BD (salbutamol 400 μg) were tested on consecutive community-treated adult patients with asthma. Results were stratified by FeNO response (change in FeNO [ΔFeNO]), being FeNO “responder” if the increase is greater than 10% post-BD compared with the basal values and “nonresponder” if less than or equal to 10%.
Results：When measured, post-BD FeNO greater than 25 parts per billion was found in an additional 31.5% of patients. Of the 92 patients included, 61% were classified as FeNO “responders” and 39% as “nonresponders.” A significant moderate-to-strong correlation was observed between ΔFeNO and R5R20, a functional marker of SAD (R = 0.52,P< .0001), whereas the correlations between spirometry markers and ΔFeNO were not significant (P> .05). Both R5R20 and ΔFeNO inversely correlated with asthma control (P< .0001). Using causal mediation analysis modeling, the effect of asthma control on ΔFeNO was mediated by SAD, with a strong indirect effect of asthma control on ΔFeNO mediated by SAD (β value: −7.04, 95% CI: −11.80 to −3.53,P< .0001), without a significant direct effect (β value: −4.96, 95% CI: −9.15 to 0.11,P= .056).
Conclusion：Changes in FeNO values pre-/post-BD can improve the identification of patients with “TH2 high” asthma. The relationship between ΔFeNO and asthma control is mainly mediated by SAD, highlighting its contribution to asthma control.
Keywords: Small Airway Dysfunction; Fractional Exhaled Nitric Oxide; Asthma Control; Impulse Oscillometry.
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