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

Clin Exp Allergy. 2018 Sep;48(9):1155-1163. doi: 10.1111/cea.13173. Epub 2018 Jun 6.

Abstract

Background: Increased level of hydrogen sulphide (H2 S) in sputum is reported to be a new biomarker of neutrophilic airway inflammation in chronic airway disorders. However, the relationship between H2 S and disease activity remains unclear.

Objective: We investigated whether H2 S levels could vary during different conditions in asthma.

Method: H2 S 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, H2 S levels during stable, as well as exacerbation states, were obtained in 13 asthmatic subjects.

Results: Sputum H2 S levels were significantly higher in the AE-BA subjects compared to the UC-BA and healthy subjects (P < .05). However, serum H2 S 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 H2 S (H2 S 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 H2 S 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 H2 S was independently associated with increased sputum neutrophils (%) and decreased FEV1 %predicted (P < .05). The cut-off level of H2 S 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 H2 S ratios higher than the cut-off level experienced asthma exacerbations over the following 3 months after enrolment.

Conclusions: The H2 S 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.

Keywords: airway inflammation; asthma; exacerbation; hydrogen sulphide; neutrophils.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Asthma / diagnosis
  • Asthma / immunology*
  • Asthma / metabolism*
  • Biomarkers*
  • Cross-Sectional Studies
  • Cytokines / metabolism
  • Disease Progression
  • Female
  • Humans
  • Hydrogen Sulfide / blood
  • Hydrogen Sulfide / metabolism*
  • Male
  • Middle Aged
  • Neutrophils / immunology
  • Neutrophils / metabolism
  • Prognosis
  • ROC Curve
  • Respiratory Function Tests
  • Sputum / metabolism*
  • Th1 Cells / immunology
  • Th1 Cells / metabolism
  • Th2 Cells / immunology
  • Th2 Cells / metabolism

Substances

  • Biomarkers
  • Cytokines
  • Hydrogen Sulfide