小气道功能障碍可能介导体重指数与重度哮喘急性发作之间的关联
2026/06/01
摘要
背景：肥胖与较差的哮喘预后以及急性发作风险的增加有关，但其潜在机制尚未完全明确。小气道功能障碍（SAD）可能是体重超标与不良哮喘预后之间一个关键的机制纽带。
方法：在这项多中心观察性研究中，成年哮喘患者接受了临床特征评估、肺功能检查（spirometry）以及脉冲振荡技术（IOS）检查。SAD的定义采用了一项复合标准，该标准基于周围气道阻力（R5-20）、电抗面积（AX）以及周围气道阻力与总气道阻力的比值（R5-20/R5）。研究使用多变量回归模型评估了体重指数（BMI）、SAD与重度哮喘急性发作之间的关联；使用广义相加模型探索了它们之间的非线性关系；并通过中介分析量化了SAD在肥胖与急性发作关联中的作用占比。
结果：在 1169 例患者中，通过 IOS 定义的 SAD 在 BMI ≥30 kg/m² 的个体中患病率显著更高。BMI 的增加与更差的振荡参数相关（p<0.0001），且呈现非线性模式：当 BMI 值超过约 28-30 kg/m² 时，恶化趋势更为急剧。SAD 与肥胖（调整后 OR：2.11，95% CI：1.56-2.86）以及过去一年的重度哮喘急性发作（调整后 OR：2.01，95% CI：1.53-2.65，两者 p<0.0001）均独立相关。中介分析表明，在肥胖与急性发作风险之间的关联中，有 26%-41% 是由 SAD 介导的（p=0.004 和 0.03）。传统的肺功能测定指标所能提供的额外信息有限。
结论：由振荡技术定义的小气道功能障碍（SAD）代表了一种非线性的功能特征，它是肥胖与重度哮喘急性发作之间存在关联的潜在基础。这一发现支持了 SAD 在肥胖哮喘患者中的临床相关性，并确认了 SAD 可作为一个潜在的“可治疗特征”（treatable trait）。
Small Airway Dysfunction May Mediate the Association Between Body Mass Index and Severe Asthma Exacerbations
Portacci, A., Ventura, L., Menzella, F., Poto, R., Berti, A., Lombardi, C., Comberiati, P., Carpagnano, G. E., Diamant, Z., Adcock, I. M., Lipworth, B., Usmani, O., Cottini, M., & Chan, R.
Abstract
BACKGROUND:Obesity is associated with poorer asthma outcomes and an increased risk of exacerbations, but the underlying mechanisms remain incompletely understood. Small airway dysfunction (SAD) may represent a key mechanistic link between excess body weight and adverse asthma outcomes.
METHODS:In this multicenter observational study, adult patients with asthma underwent clinical characterization, spirometry and impulse oscillometry (IOS). SAD was defined using a composite criterion based on peripheral airway resistance (R5-20), reactance area (AX) and the ratio of peripheral to total airway resistance (R5-20)/R5. Associations between body mass index (BMI), SAD and severe asthma exacerbations were assessed using multivariable regression models. Non-linear relationships were explored using generalized additive models and mediation analyses quantified the contribution of SAD to the obesity-exacerbation association.
RESULTS:Among 1169 patients, IOS-defined SAD was significantly more prevalent in individuals with BMI≥30 kg·m-2. Increasing BMI was associated with worse oscillometric parameters (p<0.0001), following a non-linear pattern with steeper deterioration beyond BMI values of approximately 28-30 kg·m-2. SAD was independently associated with obesity (adjusted OR 2.11, 95% CI 1.56-2.86) and with severe asthma exacerbations in the previous year (adjusted OR 2.01, 95% CI 1.53-2.65, both p<0.0001). Mediation analyses showed that SAD accounted for 26%-41% of the association between obesity and exacerbation risk (p=0.004 and 0.03). Spirometric indices provided limited additional information.
CONCLUSION:Oscillometry-defined small airways dysfunction (SAD) represents a non-linear functional trait underlying the association between obesity and severe asthma exacerbations, supporting its clinical relevance in obese patients with asthma and identifying SAD as a potential treatable trait.
背景：肥胖与较差的哮喘预后以及急性发作风险的增加有关，但其潜在机制尚未完全明确。小气道功能障碍（SAD）可能是体重超标与不良哮喘预后之间一个关键的机制纽带。
方法：在这项多中心观察性研究中，成年哮喘患者接受了临床特征评估、肺功能检查（spirometry）以及脉冲振荡技术（IOS）检查。SAD的定义采用了一项复合标准，该标准基于周围气道阻力（R5-20）、电抗面积（AX）以及周围气道阻力与总气道阻力的比值（R5-20/R5）。研究使用多变量回归模型评估了体重指数（BMI）、SAD与重度哮喘急性发作之间的关联；使用广义相加模型探索了它们之间的非线性关系；并通过中介分析量化了SAD在肥胖与急性发作关联中的作用占比。
结果：在 1169 例患者中，通过 IOS 定义的 SAD 在 BMI ≥30 kg/m² 的个体中患病率显著更高。BMI 的增加与更差的振荡参数相关（p<0.0001），且呈现非线性模式：当 BMI 值超过约 28-30 kg/m² 时，恶化趋势更为急剧。SAD 与肥胖（调整后 OR：2.11，95% CI：1.56-2.86）以及过去一年的重度哮喘急性发作（调整后 OR：2.01，95% CI：1.53-2.65，两者 p<0.0001）均独立相关。中介分析表明，在肥胖与急性发作风险之间的关联中，有 26%-41% 是由 SAD 介导的（p=0.004 和 0.03）。传统的肺功能测定指标所能提供的额外信息有限。
结论：由振荡技术定义的小气道功能障碍（SAD）代表了一种非线性的功能特征，它是肥胖与重度哮喘急性发作之间存在关联的潜在基础。这一发现支持了 SAD 在肥胖哮喘患者中的临床相关性，并确认了 SAD 可作为一个潜在的“可治疗特征”（treatable trait）。
（中日友好医院呼吸与危重症医学科 沈焜路 摘译 林江涛 审校）
（Eur Respir J. 2026 May 21; DOI: 10.1183/13993003.00150-2026）
（Eur Respir J. 2026 May 21; DOI: 10.1183/13993003.00150-2026）
Small Airway Dysfunction May Mediate the Association Between Body Mass Index and Severe Asthma Exacerbations
Portacci, A., Ventura, L., Menzella, F., Poto, R., Berti, A., Lombardi, C., Comberiati, P., Carpagnano, G. E., Diamant, Z., Adcock, I. M., Lipworth, B., Usmani, O., Cottini, M., & Chan, R.
Abstract
BACKGROUND:Obesity is associated with poorer asthma outcomes and an increased risk of exacerbations, but the underlying mechanisms remain incompletely understood. Small airway dysfunction (SAD) may represent a key mechanistic link between excess body weight and adverse asthma outcomes.
METHODS:In this multicenter observational study, adult patients with asthma underwent clinical characterization, spirometry and impulse oscillometry (IOS). SAD was defined using a composite criterion based on peripheral airway resistance (R5-20), reactance area (AX) and the ratio of peripheral to total airway resistance (R5-20)/R5. Associations between body mass index (BMI), SAD and severe asthma exacerbations were assessed using multivariable regression models. Non-linear relationships were explored using generalized additive models and mediation analyses quantified the contribution of SAD to the obesity-exacerbation association.
RESULTS:Among 1169 patients, IOS-defined SAD was significantly more prevalent in individuals with BMI≥30 kg·m-2. Increasing BMI was associated with worse oscillometric parameters (p<0.0001), following a non-linear pattern with steeper deterioration beyond BMI values of approximately 28-30 kg·m-2. SAD was independently associated with obesity (adjusted OR 2.11, 95% CI 1.56-2.86) and with severe asthma exacerbations in the previous year (adjusted OR 2.01, 95% CI 1.53-2.65, both p<0.0001). Mediation analyses showed that SAD accounted for 26%-41% of the association between obesity and exacerbation risk (p=0.004 and 0.03). Spirometric indices provided limited additional information.
CONCLUSION:Oscillometry-defined small airways dysfunction (SAD) represents a non-linear functional trait underlying the association between obesity and severe asthma exacerbations, supporting its clinical relevance in obese patients with asthma and identifying SAD as a potential treatable trait.
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