Rationale: Small airway dysfunction (SAD) is a frequent feature of asthma that has been linked to disease severity and poor symptom control. However, little is known about the role of SAD in nocturnal asthma.
Objective: To study the association between the severity of SAD and frequency of nocturnal symptoms compared to conventional lung function testing.
Methods: We assessed the frequency of self-reported nocturnal symptoms through the asthma control test. We studied the impact of nocturnal asthma using the Asthma Quality of Life Questionnaire (AQLQ) and the Multidimensional Fatigue Inventory (MFI-20). We assessed the lung function using spirometry, body plethysmography, impulse oscillometry, single and multiple inert gas washout and measured markers of T2-inflammation (blood and sputum eosinophils; fractional exhaled nitric oxide (FeNo)). We stratified the patients according to the presence and frequency of nocturnal asthma.
Results: A total of 166 asthma patients were enrolled in the analysis. Eighty-seven patients (52%) reported to have nocturnal symptoms at least once in the last four weeks. The odds ratio of nocturnal asthma correlated with the severity of all non-spirometric measures of SAD, yet neither with airflow obstruction (FEV1 and FEV/FVC) nor with large airway resistance (R20). Patients with frequent nocturnal asthma (n = 29) had a numerical increase of T2 markers and more severe SAD, as indicated by all non-spirometric measures of SAD (all p-values < 0.05), worse overall asthma control, increased fatigue and reduced quality of life (all p-values < 0.01) compared to patients with infrequent nocturnal asthma (n = 58) or patients without nocturnal asthma (n = 79). We identified 63 patients without airflow obstruction, nearly 43% of them (n = 27) had nocturnal asthma. In this subgroup, only markers of air trapping and ventilation heterogeneity were significantly elevated and correlated with the frequency of nocturnal symptoms: LCI (Spearman’s coefficient = − 0.42, p < 0.001), RV% (− 0.32, p = 0.02).
Conclusion: SAD is closely associated to asthma with nocturnal symptoms. Spirometry might underestimate the broad spectrum of distal lung function impairments in this population of patients.

Keywords: small airway dysfunction, nocturnal asthma, ventilation heterogeneity, air trapping


中文翻译：

---

小气道功能障碍与夜间症状哮喘的相关性

理由：小气道功能障碍 (SAD) 是哮喘的常见特征，与疾病严重程度和症状控制不佳有关。然而，关于 SAD 在夜间哮喘中的作用知之甚少。
目的：与常规肺功能检测相比，研究 SAD 的严重程度与夜间症状频率之间的关系。
方法：我们通过哮喘控制测试评估了自我报告的夜间症状的频率。我们使用哮喘生活质量问卷 (AQLQ) 和多维疲劳量表 (MFI-20) 研究了夜间哮喘的影响。我们使用肺活量计、身体体积描记法、脉冲示波法、单次和多次惰性气体冲洗以及测量的 T2 炎症标志物（血液和痰嗜酸性粒细胞；呼出气一氧化氮分数 (FeNo)）评估了肺功能。我们根据夜间哮喘的存在和频率对患者进行分层。
结果：共有 166 名哮喘患者参与了分析。87 名患者 (52%) 报告在过去 4 周内至少有一次夜间症状。夜间哮喘的优势比与所有非肺活量测量 SAD 的严重程度相关，但与气流阻塞（FEV1 和 FEV/FVC）或大气道阻力（R20）均无关。频繁夜间哮喘患者（n = 29）的 T2 标志物数量增加和更严重的 SAD，如所有 SAD 的非肺活量测量（所有 p 值 < 0.05）所示，总体哮喘控制更差，疲劳增加和减少与罕见夜间哮喘患者（n = 58）或无夜间哮喘患者（n = 79）相比，生活质量（所有 p 值 < 0.01）。我们确定了 63 名没有气流阻塞的患者，其中近 43%（n = 27）患有夜间哮喘。在该亚组中，只有空气滞留和通气异质性标志物显着升高并与夜间症状的频率相关：LCI（Spearman 系数 = - 0.42，p < 0.001），RV%（- 0.32，p = 0.02）。
结论： SAD与伴有夜间症状的哮喘密切相关。肺活量测定法可能低估了该患者人群中广泛的远端肺功能损害。

关键词：小气道功能障碍，夜间哮喘，通气异质性，空气滞留