Preschoolers' exclusion detection and empathy: the mediating role of moral evaluation.

Persistent low or rapidly declining lung function trajectories are not only observed in patients with chronic obstructive pulmonary disease (COPD) but also in healthy adults with chronic or intermittent productive cough []. Interest in identifying the specific trajectory that leads to COPD and the factors associated with worsening lung function trajectories is growing. This is attributable to the association of rapid decline in lung function with adverse outcomes, including increased number of exacerbations, deteriorating quality of life, and increased frequency of cardiovascular events [, ]. The number of exacerbations is a well-established factor associated with lung function decline in COPD, and this has already been proven in randomized controlled trials [–]. Age, smoking status, existence and extent of emphysema, socioeconomic status, body mass index (BMI), and degree of dyspnea have also been identified as risk factors that contribute to the accelerated decline of lung function [, ]. Although several blood-based biomarkers for COPD have been investigated, their clinical utility differs substantially. Peripheral blood eosinophil count is currently the most established blood-based biomarker for COPD, serving as a surrogate marker associated with exacerbation risk, lung function decline, and response to inhaled corticosteroids or type 2 inflammation–targeted therapies [, ]. In contrast, other blood-based markers such as C-reactive protein (CRP), fibrinogen, or interleukin-6 lack sufficient specificity, consistency, or clinical relevance and are not routinely recommended for individual risk stratification or treatment decision-making [–]. Recent studies have effectively established associations of blood biomarkers with treatable traits in subjects with risk factors in early phase studies involving large prospective cohorts, including COPDGene and SPIROMICS []. Smoking is a significant risk factor for COPD. Approximately 20% of smokers develop the disease [], but a substantial proportion of COPD cases occurs in never smokers, suggesting factors beyond smoking exposure contribute to the disease’s pathogenesis []. Although the genes analyzed vary from study to study, several studies have shown that genetic variation in individuals influences differential susceptibility to COPD []. However, reliable blood-based markers that can predict COPD development or rapid lung function decline in both smokers and never smokers remain limited. Cigarette smoke exposure induces oxidative stress, which plays a crucial role in the pathogenesis of COPD [, ]. The imbalance between oxidants and antioxidants triggered by smoking leads to chronic lung inflammation and contributes to COPD development and progression []. Oxidative stress has also been linked to red blood cell (RBC) aggregation associated with increased blood viscosity [–]. Previous studies have shown that increased blood viscosity impairs pulmonary blood flow in the general population []. However, the specific role of blood viscosity in COPD—particularly in differentiating the effects of the disease from those of smoking—remains poorly characterized. Furthermore, the impact of viscosity on longitudinal lung function decline has not been explored in smoking or non-smoking COPD populations. Therefore, we aimed to evaluate whether blood viscosity was independently associated with COPD and lung function decline independently of the effects of smoking exposure.