小气道功能障碍作为接受生物制剂治疗的重度哮喘患者肺功能定义临床缓解的功能性障碍

文献信息

中文摘要

背景与目的： 小气道功能障碍（SAD）是重度哮喘中常见但未被充分认识的特征，可能影响治疗结局和缓解。本研究评估了使用脉冲振荡（IOS）和肺功能检测的SAD患病率及其对生物制剂治疗临床缓解的影响。
方法： 通过IOS、肺功能检测和联合方式评估重度哮喘患者的SAD。比较有和无SAD患者的基线特征、生物标志物和临床结局。分析生物制剂治疗1年后的变化，并评估SAD与临床缓解标准（CR）之间的关联。
结果： SAD最常通过IOS检测到（66.9%），其次为肺功能检测（54.9%）。SAD患者年龄显著更大，且过敏性鼻炎、糖尿病和高血压发生率更高（均P < 0.05）。基线肺功能显示SAD组气流受限和外周气道阻力更严重（P < 0.001）。生物制剂治疗显著改善哮喘控制、减少急性发作并提高FEV1（P < 0.001）。血嗜酸性粒细胞计数（BEC）的平均值和中位数均显著下降，而FeNO和IgE总体上未显示显著变化。然而，分类分析显示所有3种生物标志物均发生显著变化，其中BEC改善最大。尽管有这些获益，仅17.3%的患者达到CR，并且在SAD患者中显著更少见（P ≤ 0.01）。在通过肺功能检测或联合方式定义SAD的患者中，生物制剂治疗后BEC水平显著更低。
结论： SAD在重度哮喘中常见，并与年龄较大、代谢和过敏性合并症以及更差的基线肺功能相关。虽然生物制剂治疗带来显著的临床和功能改善，但SAD持续存在预示CR可能性更低以及独特的生物标志物动态变化，强调了在个体化哮喘管理中评估小气道功能的重要性。

英文摘要

BACKGROUND AND OBJECTIVE: Small airway dysfunction (SAD) is a frequent yet underrecognized feature of severe asthma that may influence treatment outcomes and remission. This study evaluated the prevalence of SAD using impulse oscillometry (IOS) and spirometry, and its impact on clinical remission on biologic therapy.
METHODS: Severe asthma patients were assessed for SAD by IOS, spirometry, and combined modalities. Baseline characteristics, biomarkers, and clinical outcomes were compared between patients with and without SAD. Changes after 1 year of biologic therapy were analyzed, and associations between SAD and clinical remission criteria (CR) were evaluated.
RESULTS: SAD was most frequently detected by IOS (66.9%), followed by spirometry (54.9%). Patients with SAD were significantly older and had higher rates of allergic rhinitis, diabetes, and hypertension (all P < 0.05). Baseline pulmonary function showed greater airflow limitation and peripheral airway resistance in the SAD group (P < 0.001). Biologic therapy significantly improved asthma control, reduced exacerbations, and enhanced FEV1 (P < 0.001). Blood eosinophil count (BEC) decreased significantly in both mean and median values, whereas FeNO and IgE did not show significant overall change. However, categorical analysis revealed significant shifts in all 3 biomarkers, with the greatest improvement in BEC. Despite these benefits, CR was achieved in only 17.3% of patients and was significantly less frequent among those with SAD (P ≤ 0.01). Post-biologic BEC levels were significantly lower in patients with SAD defined by spirometry or combined modalities.
CONCLUSION: SAD is common in severe asthma and is associated with older age, metabolic and allergic comorbidities, and worse baseline lung function. While biologic therapy yields substantial clinical and functional improvement, the persistence of SAD predicts a lower likelihood of CR and distinct biomarker dynamics, underscoring the importance of assessing small airway function in personalized asthma management.