Small airway dysfunction across alpha-1 antitrypsin deficiency genotypes with preserved spirometry

Alpha-1 antitrypsin deficiency (AATD) is a genetic disorder that generally predisposes to pulmonary emphysema with or without chronic obstructive pulmonary disease (COPD). Despite the lack of spirometric obstruction, early Small Airways Dysfunction (SAD) may occur in AATD patients preceding lung damage.

We conducted a retrospective, single-center study on 60 AATD patients without airflow obstruction (FEV₁/FVC ≥ 0.70). SAD was defined as: reduced spirometric flows (≥2 of FEF25-75, FEF50, FEF75 <65% predicted) and/or IOS R5-R20 value greater than 0.07 kPa•s•L⁻¹. Correlation and agreement between spirometry and IOS were assessed, as well as associations with Modified Medical Research Council (mMRC) dyspnea scores.

SAD was detected in 23% of patients by spirometry, 10% by IOS, and 13% by both methods. A slight agreement was found between spirometric and IOS criteria (κ = 0.22). Only IOS-defined SAD was significantly associated with dyspnea (mMRC ≥2; p = 0.05), and R5-R20 values correlated with mMRC scores (r = 0.38, p = 0.003). No association was observed between spirometry-defined SAD and symptoms.

These findings support IOS as a partially complementary tool for the early detection of peripheral airway impairment in AATD. Moreover, IOS but not spirometry criteria were related to breathlessness perception in AATD patients without airflow obstruction, with IOS proving to be a clinically more sensitive measure.