Differentiating metabolomic signatures of airway and pulmonary vascular abnormalities in COPD

Abstract

<b>Background:</b> Small airways disease and pulmonary vascular pruning are risk factors for emphysema progression. <b>Aim:</b> Determine metabolomics disturbances associated with these abnormalities. <b>Methods:</b> Plasma metabolites (Metabolon, Morrisville, NC, USA) and chest CT metrics (volume of pulmonary arteries &lt; 5 mm2 (BV5a), total lung volume (TLV), extent of functional small airways disease (fSAD)) were measured in COPDGene participants. Among 472 participants in the highest and lowest tertiles of fSAD and BV5a/TLV (lower ratio indicates more vascular pruning), we selected differentiating metabolites at a 10% false discovery rate based on logistic regression of high vascular pruning/low fSAD vs. high fSAD/low vascular pruning after adjusting for age, sex, BMI, smoking, diabetes and site. <b>Results:</b> Mean age was 67.2±8.9 years, mean FEV1 73.9±27.9 % predicted, and 55.7% were women. The high vascular pruning/low fSAD group was associated with higher concentrations of specific phospholipids (including glycerophosphocholines), while the high fSAD/low vascular pruning group displayed higher concentrations of specific sphingolipids (including sphingomyelins) and lower concentrations of certain amino acids (including histidine and tryptophan) (Figure). <b>Conclusion:</b> Alterations in plasma lipids and amino acids distinguished fSAD and pulmonary vascular pruning, lending insights into mechanistic processes underlying these COPD phenotypes.