The association between systemic inflammation, lung function and respiratory symptoms in the BOLD study in Northern Europe

The role of systemic inflammation in the pathogenesis of respiratory diseases is increasingly recognized, but the relationship between individual inflammatory markers, lung function and respiratory symptoms is not well established. We studied 1,238 adults participating in the first follow-up of the Burden of Obstructive Lung Disease (BOLD) cohort study in Sweden, Norway, Iceland, and Estonia in 2019-2021. Systemic inflammation was assessed using total white blood cell (WBC) count and WBC sub-populations (neutrophils, lymphocytes, monocytes, eosinophils, basophils and neutrophil-to-lymphocyte ratio (NLR)). In regression models adjusted for gender, age, smoking status, body mass index and study site, all WBC sub-populations, except for lymphocytes, were associated with chronic airflow obstruction (CAO) and wheeze. In never smokers, increased neutrophils were associated with reduced lung volumes (FEV₁ β coef. with 95%CI -1.95 (-3.33, -0.57) p = 0.006; FVC - 1.94 (-3.18, -0.69) p = 0.002), but not CAO. Only increased basophils were associated with CAO in never smokers (OR with 95%CI 2.70 (1.28, 5.72) p = 0.009). In former smokers, increased neutrophils, monocytes and eosinophils were significantly associated with reduced FEV₁, reduced FVC, CAO and wheeze. In current smokers, inflammatory markers were associated with cough (neutrophils OR with 95%CI 1.49 (1.10, 2.01) p = 0.010; monocytes 1.24 (0.99, 1.55) p = 0.058; basophils 2.56 (1.12, 5.86) p = 0.026). Systemic inflammation may be related to both obstructive and restrictive respiratory impairment in the general population, with associations that vary by smoking status.