Sputum Biomarkers Predictive of Exacerbations, Disease Severity in COPD

sputum culture
A better understanding of the physiologic pathways affected by COPD may lead to new biomarkers for predicting exacerbations and new therapeutic targets.

Therapies that target pathways involved in mucus hydration, adenosine metabolism, methionine salvage, and oxidative stress may be of benefit in the treatment of chronic obstructive pulmonary disease (COPD), and a simple model adding sputum-soluble phase biomarkers can improve prediction of pulmonary exacerbations, according results of the SPIROMICS study (Clinical Trial Registration: NCT01969344) published in CHEST.

Improved understanding of the pathways associated with COPD pathogenesis may help to provide new predictive biomarkers of pulmonary exacerbations and novel therapeutic targets. In the SPIROMICS trial, researchers sought to assess the relevance of these biomarkers by applying a previously developed mass spectrometric panel of metabolomic biomarkers related to mucus hydration and inflammation to sputa collected through an observational longitudinal cohort of 980 subjects (77 healthy nonsmokers, 341 smokers with preserved spirometry, and 562 COPD subjects).

The investigators found that biomarkers from multiple pathways were elevated in COPD and were associated with sputum neutrophil counts. The most significant analytes included sialic acid, hypoxanthine, xanthine, methylthioadenosine, adenine, and glutathione. The researchers also noted that sialic acid and hypoxanthine were strongly associated with measures of disease severity, and elevation of these biomarkers was associated with shorter time to exacerbation and improved prediction models of future exacerbations.

“We identified several physiological pathways altered in the airways of subjects with COPD and associated with markers of disease severity, with the strongest relationships to metabolite biomarkers of mucus hydration and adenosine metabolism,” the researchers concluded. They added, “Although further validation is required, measurement of these sputum metabolites could provide a straightforward means to assess disease severity, identify those at risk for future exacerbations, and measure the impact of novel therapeutics.”

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. 


Esther CR Jr., O’Neal WK, Anderson WH, et al; SPIROMICS research group. Identification of sputum biomarkers predictive of pulmonary exacerbations in chronic obstructive pulmonary disease. CHEST. Published online October 29, 2021. doi:10.1016/j.chest.2021.10.049