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

Area of Science:

• Pulmonary Medicine
• Genetics
• Respiratory Physiology

Background:

• Alpha-1 antitrypsin deficiency (AATD) is a genetic disorder linked to pulmonary emphysema and COPD.
• Early Small Airways Dysfunction (SAD) can precede lung damage in AATD, even without spirometric obstruction.

Purpose of the Study:

• To investigate the early detection of SAD in AATD patients lacking airflow obstruction.
• To compare the utility of spirometry and Impulse Oscillometry (IOS) in identifying SAD.
• To assess the association between SAD, spirometry, IOS, and patient-reported dyspnea.

Main Methods:

• Retrospective study of 60 AATD patients with normal spirometry (FEV₁/FVC ≥ 0.70).
• SAD defined by reduced spirometric flows (FEF25-75, FEF50, FEF75 <65% predicted) and/or IOS R5-R20 > 0.07 kPa•s•L⁻¹.
• Correlation and agreement between spirometry and IOS assessed; association with mMRC dyspnea scores analyzed.

Main Results:

• SAD detected in 23% by spirometry, 10% by IOS, and 13% by both; slight agreement (κ = 0.22).
• Only IOS-defined SAD significantly associated with dyspnea (mMRC ≥2; p = 0.05).
• IOS R5-R20 values correlated with mMRC scores (r = 0.38, p = 0.003); spirometry-defined SAD showed no symptom association.

Conclusions:

• IOS is a valuable complementary tool for early detection of peripheral airway impairment in AATD.
• IOS criteria, unlike spirometry, relate to breathlessness perception in AATD patients without airflow obstruction.
• IOS demonstrates greater clinical sensitivity for detecting early airway dysfunction and its symptomatic impact in AATD.