Hydrogen sulfide (H2S) in sputum and serum as a novel biomarker of COPD

Objectives: Hydrogen sulphide (H2S) is a gas produced by respiratory cells including smooth muscle cells and may play a role as a cellular gasotransmitter. The aim of the study is to evaluate whether H2S levels in serum or sputum could represent a new biomarker of COPD in a cross-sectional study. Methods: H2S levels in sputum and serum samples were measured using a sulphide sensitive electrode in 64 patients with stable COPD (S-COPD), 29 COPD subjects during acute exacerbation (AE-COPD), 14 healthy smokers, and 21 healthy non-smokers. Results: Sputum H2S levels in AE-COPD subjects were higher than those in S-COPD, healthy smoking and non-smoking subjects (p<0.001), but serum H2S levels in AE-COPD were lower than those in S-COPD (p<0.001). Thus, the sputum-to-serum ratio of H2S (H2S ratio) in AE-COPD subjects were higher than those in S-COPD, healthy smoking and non-smoking subjects (p<0.001). In 14 COPD subjects where concomitant sputum and serum H2S levels were measured at baseline and during an exacerbation, the mean ratio was increased during exacerbation (p<0.01). Both sputum and serum H2S levels correlated inversely with the degree of airflow obstruction measured as FEV1 %predicted and FEV1/FVC. Additionally, there were positive relationships between sputum neutrophils and H2S levels in sputum as well as serum (p<0.01). Finally, the optimal cut-off level of H2S ratio to predict an exacerbation was ≥0.44 (sensitivity of 93.1%, and specificity of 84.5%). Conclusion: The ratio of sputum-to-serum levels of H2S may provide a useful marker of COPD indicative of obstructive neutrophilic inflammation and of potential future risk of exacerbation.