Inflammation and endothelial activation in early adulthood are associated with future emphysema: the CARDIA Lung Study

Abstract

Chronic obstructive pulmonary disease (COPD) is a heterogeneous syndrome that is characterised by inflammation, airflow limitation and emphysema [1]. Systemic inflammation is associated with decreased lung function and an accelerated decline in lung function over time [2-4], and it has been postulated that chronic inflammation accelerates pulmonary structural damage. In addition to systemic inflammation, differences in cell adhesion molecules, which are markers of endothelial activation, have been tied to accelerated progression of emphysema on computed tomography (CT) in a large community population [5]. However, whether endothelial activation or systemic inflammation predicts the development of emphysema remains unclear. We hypothesised that elevated circulating levels of high-sensitivity C-reactive protein (hs-CRP), fibrinogen, and the cellular adhesion molecules intercellular adhesion molecule (ICAM)-1 and P-selectin, measured in early adulthood, are associated with emphysema on CT in middle age in a general population-based sample.

Acute exacerbations of COPD are associated with a prothrombotic state through platelet-monocyte complexes, endothelial activation and increased thrombin generation

“…This is in line with our observation of increased VWF:Ag but stable VWFpp, which suggests chronic, rather than acute, endothelial activation [20]. Chronic endothelial activation in early adulthood has been associated with future emphysema development [33]. Moreover, we report significantly higher platelet reactivity during the index exacerbation in patients who later suffer from a recurrent exacerbation.…”

The presence of emphysema on chest imaging and mid-life cognition

“…Such knowledge is important to determine the potential long-term clinical impact of emphysema on cognitive function. In addition, chest CT scans were acquired with cardiac gating, which prevented quantitative measures of emphysema [ 40 ] and we did not assess emphysema distribution or for the presence of coexisting interstitial lung abnormalities. Further characterisation and quantification of emphysema and other associated CT findings may help better determine how cognition and emphysema are related.…”

What every clinician should know about inflammation in COPD

“…Low-grade systemic inflammation is evidenced by elevated circulating concentrations of inflammatory markers (e.g., C-reactive protein [CRP], fibrinogen, and TNFα) and circulating leukocytes [101]. Interestingly, systemic elevations in markers of inflammation and endothelial activation have been shown to predict future development of emphysema in healthy young adults [102].…”