Effects of Extrafine Inhaled Corticosteroid/Long-Acting β2-Agonist Therapy on Small Airway Dysfunction and Type 2 Inflammatory Biomarkers in Symptomatic Patients With Preserved Spirometry
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 93
- 试验地点
- 1
- 主要终点
- Change in Airway Resistance Difference (R5-R20) After 4 Weeks of Treatment
研究概览
简要总结
This study evaluates whether 4 weeks of extrafine inhaled corticosteroid/long-acting β2-agonist (beclomethasone dipropionate/formoterol fumarate, BDP/FOR) therapy improves clinical, physiological, and type 2 inflammatory outcomes compared with as-needed short-acting β2-agonist (SABA, salbutamol) alone in symptomatic patients who have preserved conventional spirometry but impulse oscillometry (IOS)-defined small airway dysfunction (SAD) and small airway reversibility (SAR) after bronchodilator inhalation. Participants were randomized 1:1 to receive extrafine BDP/FOR plus as-needed salbutamol, or as-needed salbutamol alone, for 4 weeks. Symptom score (Asthma Control Test), spirometry, IOS parameters, type 2 inflammatory biomarkers (FeNO, blood eosinophils, IgE), and rescue medication use were assessed before and after treatment.
详细描述
Symptomatic patients with asthma-like respiratory symptoms may have preserved conventional spirometry (FEV1/FVC ≥ 0.7, FVC ≥ 80% predicted, negative bronchodilator reversibility) yet still exhibit small airway dysfunction detectable only by impulse oscillometry (IOS). This prospective, single-center, open-label, randomized controlled trial enrolled adult patients (≥20 years) with chronic respiratory symptoms ≥8 weeks, preserved spirometry, IOS-defined SAD, and small airway reversibility (SAR), defined as AX > 0.44 kPa/L with a post-bronchodilator reduction in AX ≥35% after salbutamol 400 µg. Eligible participants were randomized 1:1 to receive either extrafine beclomethasone dipropionate/formoterol fumarate (100 mcg/6 mcg, 1 puff twice daily) plus as-needed salbutamol, or as-needed salbutamol alone (100 mcg, up to 200 mcg per use, maximum 4 times daily), for 4 weeks. Outcomes assessed before and after treatment included Asthma Control Test (ACT) score, spirometry (FEV1, FVC), IOS parameters (R5-R20, resonant frequency [Fres], reactance at 5Hz [X5], reactance area [AX]) with pre/post-bronchodilator change, fractional exhaled nitric oxide (FeNO), blood eosinophil count, serum total IgE, and frequency of rescue SABA use. The primary endpoint was the between-group difference in change of IOS parameters after 4 weeks of treatment; secondary endpoints included changes in symptom score, conventional spirometry, and inflammatory biomarkers, as well as treatment safety and tolerability.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
盲法说明
Open-label design; participants and investigators were not blinded to treatment allocation due to differing inhaler devices.
入排标准
- 年龄范围
- 20 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥20 years
- •Chronic respiratory symptoms (cough, sputum, chest tightness, dyspnea, or wheezing) for ≥8 weeks
- •Preserved spirometry: FEV1/FVC ≥0.7, FVC ≥80% predicted, and negative bronchodilator reversibility (increase in FEV1 or FVC <12% and <200 mL after salbutamol)
- •IOS-defined small airway dysfunction and small airway reversibility (SAR): AX >0.44 kPa/L with post-bronchodilator reduction in AX ≥35% after salbutamol inhalation
排除标准
- •Age <20 years
- •Impaired spirometry (FEV1/FVC <0.7, FVC ≤80% predicted, or positive bronchodilator reversibility)
- •Absence of SAD or lack of significant SAR
- •Respiratory symptoms absent or <8 weeks
- •Acute respiratory condition within 4 weeks before enrollment (upper/lower respiratory tract infection, acute exacerbation, pneumonia requiring antibiotics, ED visit or hospitalization)
- •Current diagnosis of COPD, chronic respiratory infection, or structural lung disease (active/prior tuberculosis, bronchiectasis, interstitial/restrictive lung disease, arteriovenous malformation, or prior pulmonary surgery)
- •Use of any bronchodilator (oral/inhaled), theophylline, steroid (inhaled/oral/IV), or beta-blocker within 4 weeks before enrollment
- •Known hypersensitivity to beclomethasone dipropionate/formoterol fumarate or salbutamol
- •Contraindication to pulmonary function testing or venous blood sampling (severe/unstable cardiovascular disease, recent major thoracic/abdominal surgery, unresolved pneumothorax, uncontrolled bronchospasm or hemoptysis, need for FiO2 >50%, impaired consciousness or dementia)
- •Other physician-assessed unsuitability for pulmonary function testing or blood sampling
- •Incomplete informed consent
- •Known HIV/AIDS infection
- •Pregnant or breastfeeding women
研究组 & 干预措施
Extrafine BDP/FOR + as-needed SABA
Extrafine beclomethasone dipropionate 100 mcg/formoterol fumarate dihydrate 6 mcg (Foster®), 1 inhalation twice daily for 4 weeks, plus salbutamol 100 mcg as needed (max 200 mcg/use, max 4 times/day).
Assigned Intervention: Drug: Beclomethasone dipropionate/formoterol fumarate (extrafine)
干预措施: Beclomethasone dipropionate/formoterol fumarate (extrafine) (Drug)
As-needed SABA alone
Salbutamol 100 mcg as needed (max 200 mcg/use, max 4 times/day) for 4 weeks, without ICS/LABA.
Assigned Intervention: Drug: Salbutamol
干预措施: Salbutamol (Drug)
Extrafine BDP/FOR + as-needed SABA
Extrafine beclomethasone dipropionate 100 mcg/formoterol fumarate dihydrate 6 mcg (Foster®), 1 inhalation twice daily for 4 weeks, plus salbutamol 100 mcg as needed (max 200 mcg/use, max 4 times/day).
Assigned Intervention: Drug: Beclomethasone dipropionate/formoterol fumarate (extrafine)
干预措施: Salbutamol (Drug)
结局指标
主要结局
Change in Airway Resistance Difference (R5-R20) After 4 Weeks of Treatment
时间窗: Baseline (Visit 1) and Week 4 (Visit 2)
Between-group difference in change from baseline in the difference between resistance at 5 Hz and resistance at 20 Hz (R5-R20), measured by impulse oscillometry. Unit of measure: kPa/(L/s).
Change in Resonant Frequency (Fres) After 4 Weeks of Treatment
时间窗: Baseline (Visit 1) and Week 4 (Visit 2)
Between-group difference in change from baseline in resonant frequency (Fres), measured by impulse oscillometry. Unit of measure: Hz.
Change in Reactance at 5 Hz (X5) After 4 Weeks of Treatment
时间窗: Baseline (Visit 1) and Week 4 (Visit 2)
Between-group difference in change from baseline in reactance at 5 Hz (X5), measured by impulse oscillometry. Unit of measure: kPa/(L/s).
Change in Reactance Area (AX) After 4 Weeks of Treatment
时间窗: Baseline (Visit 1) and Week 4 (Visit 2)
Between-group difference in change from baseline in reactance area (AX), measured by impulse oscillometry. Unit of measure: kPa/L.
Change in Impulse Oscillometry (IOS) Parameters After 4 Weeks of Treatment
时间窗: Baseline (Visit 1) and Week 4 (Visit 2)
Between-group difference in change from baseline (R5-R20, resonant frequency \[Fres\], reactance at 5 Hz \[X5\], and reactance area \[AX\]) at end of the 4-week treatment period.
次要结局
- Change in Asthma Control Test (ACT) Score(Baseline and Week 4)
- Change in Fractional Exhaled Nitric Oxide (FeNO)(Baseline and Week 4)
- Change in Spirometric Parameters (FEV1, FVC)(Baseline and Week 4)
- Change in Type 2 Inflammatory Biomarkers (Blood Eosinophil Count, Serum Total IgE)(Baseline and Week 4)
- Frequency of Rescue SABA Use(4 weeks)
研究者
Yi-Han Hsiao
Physician
Taipei Veterans General Hospital, Taiwan