Diffusing capacity for carbon monoxide is significantly associated with plasma proteins independently of obstruction

<bold>Introduction:</bold> There is a known association between plasma proteins and measures of spirometry. Diffusing capacity (D_LCO) measures gas exchange that can be impaired both by lung and heart diseases. Our aim was to study the associations between D_LCO and cardiovascular-linked plasma proteins in the Roll Of Low Lung Function Study (ROLLS) in Sweden. <bold>Methods:</bold> A total of 89 proteins were analysed (OLINK CVD I panel, proximity extension assay method) in 450 individuals. D_LCO%predicted (European Coal & Steel Community) was used as the independent variable and proteins were used as the dependent variables. Analyses were adjusted for age, gender, height, weight, smoking status and pack years and cardiovascular morbidity (carotid plaques, hypertension and cardiac medication). A sensitivity analysis was carried out after excluding subjects with an FEV₁/VC ratio of <0.70 (n=318). <bold>Results:</bold> Twenty seven proteins were associated with DLCO%predicted after adjusting for confounders, and after adjusting for the multiplying tests to control the false discovery rate under level 5%. After excluding subjects with FEV₁/VC <0.70, 12 proteins remained associated with D_LCO%predicted (GDF-15, IL-6, FGF-23, RAGE, MMP-12, CCL-20, AM, IL-1ra, U-PAR, FABP4, ECP and IL-8). All proteins except RAGE were negatively associated with DLCO%predicted. <bold>Conclusion:</bold> Several cardiovascular-linked plasma proteins were associated with D_LCO. Interestingly, the majority of these associations were consistent in subjects without airflow obstruction and after adjustments for known cardiovascular morbidity. These proteins might potentially signal for early disease mechanisms leading to impaired gas exchange.