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

Small airway dysfunction (SAD) is a key feature of COPD and might present in tobacco-exposed adults with normal spirometry. So far, the role of oscillometry-defined SAD in this population is largely unexplored. To investigate the prevalence of oscillometry-defined SAD and its associations with airway structural changes, quality of life (QoL), metabolic and cardiovascular disease (CVD) in tobacco-exposed adults with impaired or preserved airflow. In a sub-cohort (n=1628) nested within a lung cancer screening trial, we assessed airway disease using preBD-spirometry, oscillometry, and AI-powered CT. Impaired airflow included airflow obstruction (AFO) and preserved ratio impaired spirometry (PRISm). Subjects with preserved airflow (PA), defined as FEV1 and FEV1/FVC > LLN, were further stratified as PA with SAD (PA-SAD) or normal lung function. SAD was defined as the frequency dependence of resistance (R5-19) or reactance area (AX) > ULN. CT biomarkers included airway wall thickness (AWT-Pi10), lumen diameter, branch count, and emphysema. QoL was measured using the EQ-5D-5L. 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 impaired airflow, subjects with PA-SAD had lower EQ-5D-5L score, greater AWT-Pi10, narrower lumen, lower branch count, and higher rate of metabolic and CVD than those with normal lung function, (all p-values <0.01). 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, OR: 1.91 (95% CI: 1.55 - 2.36), even after adjusting for confounders and metabolic disease. SAD is highly prevalent among tobacco-exposed adults and is associated with airway structural changes, impaired QoL, and increased rate of CVD, even in those with PA. PA-SAD is distinct from AFO by its preserved airway count and minimal emphysema. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).