Oscillometry-defined Small Airway Dysfunction in Tobacco-exposed Adults with Impaired or Preserved Airflow

Rationale: Small airway dysfunction (SAD) is a key feature of chronic obstructive pulmonary disease and might present in tobacco-exposed adults with normal spirometry. So far, the role of oscillometry-defined SAD in this population is largely unexplored. Objective: To investigate the prevalence of oscillometry-defined SAD and its associations with airway structural changes, quality of life (QoL), metabolic disease, and cardiovascular disease (CVD) in tobacco-exposed adults with impaired airflow or preserved airflow (PA). Methods: In a subcohort (n = 1,628) nested within a lung cancer screening trial, we assessed airway disease using pre-bronchodilator spirometry, oscillometry, and artificial intelligence-powered computed tomography. Impaired airflow included airflow obstruction (AFO) and preserved ratio impaired spirometry (PRISm). Subjects with PA, defined as FEV₁ and FEV₁:FVC greater than the lower limit of normal, were further stratified as PA with SAD (PA-SAD) or normal lung function. SAD was defined as the frequency dependence of resistance or reactance area greater than the upper limit of normal. Computed tomography biomarkers included airway wall thickness, luminal diameter, branch count, and emphysema. QoL was measured using the euroqol 5-dimension 5-level (EQ-5D-5L). Measurements and Main Results: The overall prevalence of SAD was 39%. SAD was present in 26% of subjects with PA and in 60% of those with impaired airflow. The frequency of AFO, PRISm, and PA-SAD was 21%, 15%, and 16%, respectively. Similar to those with impaired airflow, subjects with PA-SAD had lower EQ-5D-5L scores, greater airway wall thickness, narrower lumen, lower branch count, and higher rate of metabolic disease and CVD than those with normal lung function (P < 0.01 for all). However, they had minimal emphysema and significantly higher branch count than those with AFO. Subjects with AFO or PRISm and concurrent SAD had greater structural changes and more frequent CVD than those with AFO or PRISm alone. SAD was associated with CVD (odds ratio, 1.91 [95% confidence interval, 1.55-2.36]), even after adjusting for confounders and metabolic disease. Conclusions: SAD is highly prevalent among tobacco-exposed adults and is associated with airway structural changes, impaired QoL, and an increased rate of CVD, even among those with PA. PA-SAD is distinct from AFO by its preserved airway count and minimal emphysema.