Sputum‐to‐serum hydrogen sulphide ratio as a novel biomarker of predicting future risks of asthma exacerbation

Summary Background Increased level of hydrogen sulphide (H2S) in sputum is reported to be a new biomarker of neutrophilic airway inflammation in chronic airway disorders. However, the relationship between H2S and disease activity remains unclear. Objective We investigated whether H2S levels could vary during different conditions in asthma. Method H2S levels in sputum and serum were measured using a sulphide‐sensitive electrode in 47 stable asthmatic subjects (S‐BA), 21 uncontrolled asthmatic subjects (UC‐BA), 26 asthmatic subjects with acute exacerbation (AE‐BA) and 15 healthy subjects. Of these, H2S levels during stable, as well as exacerbation states, were obtained in 13 asthmatic subjects. Results Sputum H2S levels were significantly higher in the AE‐BA subjects compared to the UC‐BA and healthy subjects (P < .05). However, serum H2S levels in the AE‐BA subjects were lower than in the S‐BA subjects (P < .001) and similar to those in healthy subjects. Thus, the sputum‐to‐serum ratio of H2S (H2S ratio) in the AE‐BA subjects was significantly higher than in the S‐BA, UC‐BA and healthy subjects (P < .05). Among all subjects, sputum H2S levels showed a trend to decrease with FEV1 %predicted and significantly positive correlations with sputum neutrophils (%), sputum IL‐8 and serum IL‐8. A multiple linear regression analysis showed that sputum H2S was independently associated with increased sputum neutrophils (%) and decreased FEV1 %predicted (P < .05). The cut‐off level of H2S ratio to indicate an exacerbation was ≥0.34 (area under the curve; 0.88, with a sensitivity of 81.8% and specificity of 72.7%, P < .001). Furthermore, half of the asthmatic subjects with H2S ratios higher than the cut‐off level experienced asthma exacerbations over the following 3 months after enrolment. Conclusions The H2S ratio may provide useful information on predicting future risks of asthma exacerbation, as well as on obstructive neutrophilic airway inflammation as one of the non‐Th2 biomarkers, in asthma.