Tang Francesca S M, Rutting Sandra, Farrow Catherine E, Tonga Katrina O, Watts Joanna, Dame-Carrol Jessica R, Bertolin Amy, King Gregory G, Thamrin Cindy, Chapman David G
Department of Respiratory Medicine, Royal North Shore Hospital, Sydney, NSW, Australia.
Airway Physiology and Imaging Group, The Woolcock Institute of Medical Research, The University of Sydney, Sydney, NSW, Australia.
Respirology. 2020 Aug;25(8):827-835. doi: 10.1111/resp.13772. Epub 2020 Feb 5.
Abnormal peripheral airway function is an important feature of asthma and relates to asthma symptoms and poor asthma control. We aimed to determine whether peripheral airway function, as measured by forced oscillatory impedance and multiple-breath nitrogen washout (MBNW), relates to symptom improvement in asthmatic participants with uncontrolled asthma, after stepping up to high-dose ICS/LABA treatment.
A total of 19 subjects (14 females, mean age: 29.9 ± 13.6 years) with uncontrolled asthma, as defined by an ACQ5 > 1.5, taking 500 μg/day fluticasone equivalent or less, underwent spirometry, plethysmography, fractional exhaled FeNO, forced oscillatory resistance (Rrs ) and reactance (Xrs ), and indices of MBNW ventilation heterogeneity (lung clearance index (LCI), diffusion-convection-dependent (Sacin) and convection-dependent (Scond)). Measurements were made before and after 8 weeks of treatment with fluticasone/formoterol combination inhaler 250/10 μg, 2 puffs twice daily.
Treatment improved ACQ5 (P = 0.0002), FEV (P = 0.02), FVC (P = 0.04), FeNO (P = 0.0008), Xrs (P = 0.01), LCI (P = 0.0002), Sacin (P = 0.006) and Scond (P = 0.01). At baseline, ACQ5 correlated with Xrs (r = 0.52, P = 0.03) and Rrs (r = 0.55, P = 0.02). The improvement in ACQ5 was predicted by more abnormal baseline LCI (P = 0.03), Scond (P = 0.02) and Rrs (P = 0.006). Baseline Scond was the best predictor of a clinically meaningful improvement in asthma control (ΔACQ > 0.5, ROC-AUC = 0.91, P = 0.007).
Step-up to high-dose combination treatment in uncontrolled asthma is associated with improved peripheral airway function as measured by Xrs and MBNW. Baseline MBNW and FOT parameters correlated with the improvement in symptoms and may predict a positive response to up-titration in uncontrolled asthmatic patients.
外周气道功能异常是哮喘的一个重要特征，与哮喘症状及哮喘控制不佳相关。我们旨在确定，在升级至高剂量吸入性糖皮质激素/长效β2受体激动剂（ICS/LABA）治疗后，通过强迫振荡阻抗和多次呼吸氮冲洗（MBNW）测量的外周气道功能是否与未控制哮喘的参与者的症状改善相关。
共有19名未控制哮喘的受试者（14名女性，平均年龄：29.9±13.6岁），其哮喘控制问卷（ACQ）评分>1.5，每日服用氟替卡松当量500μg或更少，接受了肺量计检查、体积描记法、呼出一氧化氮分数（FeNO）、强迫振荡阻力（Rrs）和电抗（Xrs）以及MBNW通气异质性指标（肺清除指数（LCI）、扩散对流依赖性（Sacin）和对流依赖性（Scond））的测量。在使用氟替卡松/福莫特罗联合吸入器250/10μg，每日两次，每次2喷，治疗8周前后进行测量。
治疗后ACQ评分（P = 0.0002）、第一秒用力呼气容积（FEV）（P = 0.02）、用力肺活量（FVC）（P = 0.04）、FeNO（P = 0.0008）、Xrs（P = 0.01）、LCI（P = 0.0002）、Sacin（P = 0.006）和Scond（P = 0.01）均有所改善。基线时，ACQ评分与Xrs（r = 0.52，P = 0.03）和Rrs（r = 0.55，P = 0.02）相关。基线LCI（P = 0.03）、Scond（P = 0.02）和Rrs（P = 0.006）越异常，ACQ评分改善越明显。基线Scond是哮喘控制临床有意义改善（ΔACQ>0.5）的最佳预测指标（受试者工作特征曲线下面积（ROC-AUC）= 0.91，P = 0.007）。
未控制哮喘升级至高剂量联合治疗与通过Xrs和MBNW测量的外周气道功能改善相关联。基线MBNW和强迫振荡技术（FOT）参数与症状改善相关，可能预测未控制哮喘患者上调治疗的阳性反应。
