Sputum-to-serum hydrogen sulfide ratio in COPD

Objectives: Hydrogen sulfide (H₂S) is a gas produced by respiratory cells including smooth muscle cells and may play a role as a cellular gasotransmitter. We evaluated 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 sulfide-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 stable COPD, healthy smoking and non-smoking subjects (p<0.001). In 14 COPD subjects whose H₂S ratios were measured during and after an exacerbation, the mean ratio was increased during exacerbation (p<0.05). H₂S ratio was positively correlated with St. George's Respiratory Questionnaire score, sputum neutrophils and IL-6 and IL-8 levels in sputum and serum (p<0.01) but inversely correlated with sputum macrophages (%), FEV₁%predicted and FEV₁/FVC (p<0.01). The cut-off level of H₂S ratio to indicate an exacerbation was ≥0.44 (sensitivity of 93.1% and specificity of 84.5%).

Conclusions: The ratio of sputum-to-serum levels of H₂S may provide a useful marker of COPD indicative of obstructive neutrophilic inflammation and of potential ongoing exacerbation.