Stenberg Henning, Chan Rory, Abd-Elaziz Khalid, Pelgröm Arjen, Lammering Karin, Kuijper-De Haan Gerda, Weersink Els, Lutter René, Zwinderman Aeilko H, de Jongh Frans, Diamant Zuzana
Center for Primary Health Care Research, Department of Clinical Sciences, Malmö, Lund University, 21428 Malmö, Sweden.
University Clinic Primary Care Skåne, 29189 Kristianstad, Region Skåne, Sweden.
J Clin Med. 2025 Jan 30;14(3):906. doi: 10.3390/jcm14030906.
: Small airway dysfunction (SAD) is associated with impaired asthma control, but small airway physiology is not routinely assessed in clinical practice. Previously, we demonstrated impulse oscillometry (IOS)-defined small airway dysfunction (SAD) in dual responders (DRs) upon bronchoprovocation with various allergens. : To compare lung physiology using spirometry and IOS following bronchoprovocation with methacholine (M) and inhaled house dust mite (HDM) extract in corticosteroid-naïve asthmatic subjects. : Non-smoking, clinically stable HDM-allergic asthmatic subjects (18-55 years, FEV > 70% of pred.) underwent an M and inhaled HDM challenge on two separate days. Airway response was measured by IOS and spirometry, until a drop in FEV ≥ 20% (PC) from post-diluent baseline (M), and up to 8 h post-allergen (HDM). Early (EAR) and late asthmatic response (LAR) to HDM were defined as ≥20% and ≥15% fall in FEV from post-diluent baseline during 0-3 h and 3-8 h post-challenge, respectively. IOS parameters (Rrs5, Rrs20, Rrs5-20, Xrs5, AX, Fres) were compared between mono-responders (MRs: EAR only) and dual responders (EAR + LAR). Correlations between maximal % change from baseline after the two airway challenges were calculated for both FEV and IOS parameters. : A total of 47 subjects were included (11 MRs; 36 DRs). FEV % predicted did not differ between MR and DR at baseline, but DR had lower median PCM (0.84 (range 0.07-7.51) vs. MR (2.15 (0.53-11.29)); = 0.036). During the LAR, DRs had higher IOS values than MRs. For IOS parameters (but not for FEV), the maximal % change from baseline following M and HDM challenge were correlated. PCM was inversely correlated with the % change in FEV and the % change in Xrs5 during the LAR (r= -0.443; = 0.0018 and r= -0.389; = 0.0075, respectively). : During HDM-induced LAR, changes in small airway physiology can be non-invasively detected with IOS and are associated with increased airway hyperresponsiveness and changes in small airway physiology during methacholine challenge. DRs have a small airways phenotype, which reflects a more advanced airway disease.
小气道功能障碍（SAD）与哮喘控制不佳相关，但在临床实践中，小气道生理功能并非常规评估项目。此前，我们证实在使用各种过敏原进行支气管激发试验时，双重反应者（DRs）中存在脉冲振荡法（IOS）定义的小气道功能障碍（SAD）。
比较初治哮喘患者在使用乙酰甲胆碱（M）和吸入屋尘螨（HDM）提取物进行支气管激发试验后，使用肺量计和IOS测量的肺生理功能。
非吸烟、临床稳定的HDM过敏哮喘患者（18 - 55岁，FEV>预计值的70%）在两个不同日期分别接受M和吸入HDM激发试验。通过IOS和肺量计测量气道反应，直至FEV较稀释后基线下降≥20%（PC）（M激发试验），以及过敏原（HDM）激发试验后长达8小时。HDM的早期哮喘反应（EAR）和迟发哮喘反应（LAR）分别定义为激发试验后0 - 3小时和3 - 8小时内FEV较稀释后基线下降≥20%和≥15%。比较单重反应者（MRs：仅EAR）和双重反应者（EAR + LAR）之间的IOS参数（Rrs5、Rrs20、Rrs5 - 20、Xrs5、AX、Fres）。计算两次气道激发试验后相对于基线的最大百分比变化之间FEV和IOS参数的相关性。
共纳入47名受试者（11名MRs；36名DRs）。基线时，MR和DR的FEV%预计值无差异，但DR的PCM中位数较低（0.84（范围0.07 - 7.51）vs. MR（2.15（0.53 - 11.29））；P = 0.036）。在LAR期间，DRs的IOS值高于MRs。对于IOS参数（但FEV参数不适用），M和HDM激发试验后相对于基线的最大百分比变化具有相关性。PCM与LAR期间FEV的百分比变化以及Xrs5的百分比变化呈负相关（r = -0.443；P = 0.0018和r = -0.389；P = 0.0075）。
在HDM诱导的LAR期间，小气道生理功能的变化可以通过IOS进行无创检测，并且与气道高反应性增加以及乙酰甲胆碱激发试验期间小气道生理功能的变化相关。DRs具有小气道表型，这反映了更严重的气道疾病。
