WHAT IS ALREADY KNOWN ON THIS TOPIC

  • CT density gradient (CTDG) is associated with chronic obstructive pulmonary disease (COPD) severity and clinical outcomes, but its biological significance in non-obstructed smokers is not well established.

  • WHAT THIS STUDY ADDS

  • CTDG was associated with distinct blood transcriptomic and immune-cell profiles in non-obstructed smokers, involving inflammatory, immune-regulatory and metabolic pathways, suggesting that CTDG captures biological abnormalities that may precede airflow obstruction.

  • HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY

  • CTDG may complement spirometry as an imaging marker of early COPD-related changes and provide a useful phenotype for studying disease initiation and progression.

  • Introduction

    Chronic obstructive pulmonary disease (COPD) often develops silently, with pathophysiological changes occurring long before the onset of clinically detectable airflow obstruction.1 2 Prolonged exposure to cigarette smoke and other environmental pollutants initiates a cascade of biological and structural alterations in the lung, including oxidative stress, epithelial injury,…