Background: Emerging evidence has indicated that small airway dysfunction (SAD) contributes to the clinical expression of asthma. Objectives: The aim of the study was to explore the relationships of SAD assessed by forced expiratory flow between 25 and 75% (FEF25-75%), with clinical and inflammatory profile and treatment responsiveness in asthma. Method: In study I, dyspnea intensity (Borg scale), chest tightness, wheezing and cough (visual analog scales, VASs), and pre- and post-methacholine challenge testing (MCT) were analyzed in asthma patients with SAD and non-SAD. In study II, asthma subjects with SAD and non-SAD underwent sputum induction, and inflammatory mediators in sputum were detected. Asthma patients with SAD and non-SAD receiving fixed treatments were prospectively followed up for 4 weeks in study III. Spirometry, Asthma Control Questionnaire (ACQ), and Asthma Control Test (ACT) were carried out to define treatment responsiveness. Results: SAD subjects had more elevated Delta VAS for dyspnea (p = 0.027) and chest tightness (p = 0.032) after MCT. Asthma patients with SAD had significantly elevated interferon (IFN)-gamma in sputum (p < 0.05), and Spearman partial correlation found FEF25-75% significantly related to IFN-gamma and interleukin-8 (both having p < 0.05). Furthermore, multivariable regression analysis indicated SAD was significantly associated with worse treatment responses (decrease in ACQ >= 0.5 and increase in ACT >= 3) (p = 0.022 and p = 0.032). Conclusions: This study indicates that SAD in asthma predisposes patients to greater dyspnea intensity and chest tightness during bronchoconstriction. SAD patients with asthma are characterized by non-type 2 inflammation that may account for poor responsiveness to therapy.
基金：
National Key Development Plan for Precision Medicine Research [2017YFC091004]; National Natural Science Foundation of China [81670023, 81570023, 81870027, 81920108002]; Science and Technology Foundation of Sichuan Province [2018SZ0167]; 1.3.5 project for disciplines of excellence Clinical Research Incubation Project, West China Hospital, Sichuan University [2018HXFH016]
第一作者单位：[1]Sichuan Univ, West China Hosp, Dept Integrated Tradit Chinese & Western Med, Pneumol Grp,State Key Lab Biotherapy, Chengdu, Peoples R China[2]Collaborat Innovat Ctr Biotherapy, Chengdu, Peoples R China[3]Sichuan Univ, West China Hosp, Dept Integrated Tradit Chinese & Western Med, Pneumol Grp, Chengdu, Peoples R China
通讯作者：
推荐引用方式(GB/T 7714)：
Liu Ying,Zhang Li,Li Hong Lin,et al.Small Airway Dysfunction in Asthma Is Associated with Perceived Respiratory Symptoms, Non-Type 2 Airway Inflammation, and Poor Responses to Therapy[J].RESPIRATION.2021,100(8):767-779.doi:10.1159/000515328.
APA：
Liu, Ying,Zhang, Li,Li, Hong Lin,Liang, Bin Miao,Wang, Ji...&Oliver, Brian G..(2021).Small Airway Dysfunction in Asthma Is Associated with Perceived Respiratory Symptoms, Non-Type 2 Airway Inflammation, and Poor Responses to Therapy.RESPIRATION,100,(8)
MLA：
Liu, Ying,et al."Small Airway Dysfunction in Asthma Is Associated with Perceived Respiratory Symptoms, Non-Type 2 Airway Inflammation, and Poor Responses to Therapy".RESPIRATION 100..8(2021):767-779
