Elevated AbsΔX5 Identifies a Distinct COPD Phenotype with Peripheral Airway Dysfunction and Longitudinal Improvement in Oscillometric Parameters

BACKGROUND: Impulse oscillometry (IOS) is increasingly used to assess small airway dysfunction (SAD) in chronic obstructive pulmonary disease (COPD). However, the physiological significance of the absolute inspiratory-expiratory reactance difference (AbsΔX5) remains unclear. We investigated whether elevated AbsΔX5 identifies a distinct COPD phenotype associated with baseline physiological abnormalities and longitudinal physiological changes. METHODS: We retrospectively analyzed patients with COPD who underwent serial IOS and spirometry between January 2023 and February 2025. COPD was defined as a post-bronchodilator FEV₁/FVC <0.70, and SAD as R5-R20 >0.07 kPa/L/s and/or AX >0.33 kPa/L. Patients were classified into COPD without SAD, SAD+/AbsΔX5 <0.10, and SAD+/AbsΔX5 ≥0.10. The 0.10 cutoff was determined by an exploratory threshold analysis. Baseline characteristics and longitudinal changes in IOS and post-bronchodilator spirometric parameters were compared. RESULTS: Among 710 patients who underwent both IOS and spirometry, 112 met the diagnostic criteria for COPD. Patients were classified into COPD without SAD (n=36), SAD+/AbsΔX5 <0.10 (n=46), and SAD+/AbsΔX5 ≥0.10 (n=30). Baseline IOS abnormalities progressively worsened across the groups. Patients with SAD+/AbsΔX5 ≥0.10 had significantly higher R5-R20, AX, and Fres values and more negative X5 than the other groups. During follow-up, they showed greater improvements in R5, R5-R20, and AX, whereas spirometric changes were modest, except for a greater increase in FVC than in COPD without SAD. Conclusions: Elevated AbsΔX5 was most clinically informative in patients with IOS-defined SAD, identifying a distinct COPD phenotype characterized by more severe baseline peripheral airway dysfunction and greater longitudinal improvement in IOS parameters.