Ηeparan sulphate elevated in acute exacerbations of COPD

Circulating levels of heparan sulphate (HS) are higher in patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD), a study has found. This increase appears to be associated with the aetiology of AECOPD.

A total of 1,189 patients with COPD, GOLD grade II‒IV, from a discovery cohort (n=638) and a validation cohort (n=551) participated in this study. The researchers measured HS and heparinase (HSPE-1) longitudinally in plasma at stable state, at AECOPD, and at 4 weeks follow-up.

Patients with COPD had higher plasma HS than non-COPD controls. In addition, plasma HS was markedly elevated at AECOPD as compared with stable state (p<0.001) in both discovery and validation cohorts. [Respirology 2023;28:767-774]

In the validation cohort, four distinct exacerbation groups were classified based on aetiology: no infection, bacterial infection, viral infection, and bacterial and viral coinfection. The increase in HS from stable state to AECOPD correlated with the aetiology of exacerbation and was higher in patients with bacterial and viral coinfections.

HSPE-1 was also significantly elevated at AECOPD, but HSPE-1 levels showed no association with the aetiology of these events.

Moreover, the likelihood of having an infection at AECOPD elevated as HS levels rose from stable state to AECOPD. Such odds were much higher for those with bacterial infections than viral infections.

The most common causes for AECOPD are respiratory viral and bacterial infections, said the researchers. Many pathogens, such as bacteria, viruses, and parasites, bind glycosaminoglycans (GAGs) as receptors to recognize and interact with host cells. [Cold Spring Harb Perspect Biol 2011;3:a004952; Cold Spring Harb Perspect Biol 2011;3:a004952; Cold Spring Harb Perspect Biol 2011;3:a004952]

Furthermore, HS contributes to the adherence of bacteria on the surface of lung epithelial cells, while the enzymatic digestion of HS reduces bacterial adhesion on lung cells. [BMC Infect Dis 2017;17:319]

“The current analysis provides new insights into the pathophysiology of AECOPD from the novel perspective of glycan polymers. HS is the most abundant sulphated GAG in the lung parenchyma,” the researchers said.

“Its ability to sequester water provides HS the capacity to serve as a structural component of the lungs, whereas its ability to bind positively charged soluble ligands and cell surface receptors characterizes HS as a regulator of signaling pathways,” they added. [Intensive Care Med 2008;34:610-618; Cold Spring Harb Perspect Biol 2011;3:a004952; Anat Rec 2010;293:955-967]

Biomarkers of COPD severity

Previous studies suggested the use of a group of biomarkers that reflect different pathophysiological pathways and comorbidities would be useful in predicting the severity and outcome of COPD. [Expert Rev Respir Med 2013;7:57-64; Chest 2007;131:1058-1067; Chest 2007;131:1058-1067]

One study further suggested that concurrently elevated levels of adrenomedullin, arginine vasopressin, and atrial natriuretic peptide in patients with stable COPD were associated with a higher risk of death. [Chest 2007;131:1058-1067]

“In the present study, we show that HS is significantly correlated with inflammatory serum biomarkers such as copeptin, procalcitonin, atrial natriuretic peptide, and adrenomedullin,” the researchers said.

“It remains to be elucidated if concomitant measurements of plasma HS together with well-established and cheaper inflammatory markers such as C-reactive protein, would increase the accuracy of the prediction of disease severity and outcome, as well as of the aetiology of AECOPD,” they added.