Extrafine ICS/LABA Versus As-Needed SABA for Small Airway Dysfunction in Symptomatic Patients With Preserved Spirometry

Yi-Han Hsiao93 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Eligibility

Sex: ALLMin age: 20 Years

Medical Language ↔ Plain English

Inclusion Criteria: * 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 Exclusion Criteria: * 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

Outcomes

Primary Outcomes

Change in Impulse Oscillometry (IOS) Parameters After 4 Weeks of Treatment

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.

Time frame: Baseline (Visit 1) and Week 4 (Visit 2)

Secondary Outcomes

Change in Asthma Control Test (ACT) Score

Time frame: Baseline and Week 4

Change in Fractional Exhaled Nitric Oxide (FeNO)

Time frame: Baseline and Week 4

Change in Spirometric Parameters (FEV1, FVC)

Time frame: Baseline and Week 4

Change in Type 2 Inflammatory Biomarkers (Blood Eosinophil Count, Serum Total IgE)

Time frame: Baseline and Week 4

Frequency of Rescue SABA Use

Puffs of salbutamol per day, number of days requiring rescue medication, and number of weeks with SABA use ≥2 puffs/week during the 4-week treatment period.

Time frame: 4 weeks

Extrafine ICS/LABA Versus As-Needed SABA for Small Airway Dysfunction in Symptomatic Patients With Preserved Spirometry

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes