A Metabolic Basis for Inflammation in COPD Suggests a New Therapeutic Target

The clinical features of systemic inflammation in chronic obstructive pulmonary disease (COPD) are well recognized, but little is understood about the molecular mechanisms underlying this inflammation, which is thought to be a result of overabundance of inflammatory mediators from the lungs or the entry of noxious particles into systemic circulation.

A recent study examined the metabolic state of human peripheral blood mononuclear cells (PBMCs), including monocytes, lymphocytes, and natural killer cells, after long-term exposure to tobacco in smokers with preserved lung function and in patients with COPD, and it found a potential metabolic basis for the inflammatory response in COPD.

The study, funded by the Chest Research Foundation and published in Respiratory Research, used PBMCs isolated from 16 healthy nonsmokers, 13 healthy smokers, and 14 patients with COPD and a history of smoking. The cells were cultured and analyzed for plasma levels of inflammatory cytokines. Cells were also exposed to cigarette smoke condensate.

The PBMCs from patients with COPD showed a significant decrease in extracellular acidification rate while using glucose—the principle substrate used by effector cells to generate energy—compared with cells from healthy nonsmokers. During mitochondrial respiration while using palmitate or pyruvate—which anti-inflammatory immune cells predominantly use to generate energy—mitochondrial oxygen consumption rates were also significantly lower in patients with COPD compared with healthy smokers.

Additionally, plasma levels of inflammatory cytokines were significantly elevated in patients with COPD versus healthy nonsmokers. Healthy smokers also showed a significant increase in most cytokines measured when compared with healthy nonsmokers.

“In this study, we report for the first time that circulating mononuclear cells of subjects with COPD have a reduced ability to utilize glucose, pyruvate, or fatty acids at baseline,” the authors wrote. These findings could explain the reason for frequent exacerbations in patients with COPD and “could be explored as a potential target to delay the onset of disease.”

Reference

Agarwal AR, Kadam S, Brahme A, et al. Systemic immuno-metabolic alterations in chronic obstructive pulmonary disease (COPD). Respir Res. 2019;20:171. doi: 10.1186/s12931-019-1139-2.