预测哮喘急性发作未来风险的新型生物标志物-痰液与血清硫化氢比值
2018/06/20
摘要
背景:痰液中硫化氢（hydrogen sulfide，H2S）水平的升高是慢性气道疾病中中性粒细胞气道炎症的新型生物标志物。然而，H2S与疾病活动的关系尚不清楚。
目的:我们研究了哮喘不同状态下的H2S水平是否会发生变化。
方法:在47例稳定哮喘受试者(S-BA)、21例未控制哮喘受试者(UC-BA)、26例急性发作哮喘受试者(AE-BA)和15例健康受试者中，使用硫化物敏感电极测量痰液和血清中的H2S水平。其中，13例哮喘受试者在稳定期和急性发作期均测定H2S水平。
结果:与UC-BA组和健康组相比，AE-BA组的痰液H2S水平显著升高(p<0.05)。然而，AE-BA受试者的血清H2S水平低于S-BA受试者(p<0.001)，与健康受试者相似。因此，AE-BA组的痰液-血清H2S (H2S比值)明显高于S-BA组、UC-BA组和健康组(p<0.05)。所有受试者中，痰液H2S水平呈现随FEV1%实预比下降的趋势，且与痰中性粒细胞(%)、痰IL-8、血清IL-8水平呈显著正相关关系。多元线性回归分析表明，痰液H2S与痰中性粒细胞(%)的增加和FEV1%实预比下降独立相关(p < 0.05)。H2S比值用于预测哮喘急性发作的截点值为≥0.34 (曲线下的面积；0.88，敏感性81.8%，特异性72.7%，p<0.001)。此外，H2S比值高于截点值水平的一半哮喘受试者在入组后的3个月内出现哮喘急性发作。
结论:H2S比值可以为预测哮喘急性发作未来风险提供有用信息，并可作为哮喘阻塞性中性粒细胞气道炎症中非Th2生物标志物之一。
Sputum-to-serum hydrogen sulfide ratio as a novel biomarker of predicting
future risks of asthma exacerbation
Suzuki Y, Saito J, Kikuchi M, Uematsu M, Fukuhara A, Sato S, Munakata M.
Clinical Experimental Allergy.2018 May 14.Doi:10.1111/cea.13173
Abstract
BACKGROUND: Increased level of hydrogen sulfide (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 sulfide-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<0.05). However, serum H2S levels in the AE-BA subjects were lower than in the S-BA subjects (p<0.001) 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<0.05). 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<0.05) .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<0.001). Furthermore, half of the asthmatic subjects with H2S ratios higher than the cutoff level experienced asthma exacerbations over the following 3 months after enrollment.
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.
背景:痰液中硫化氢（hydrogen sulfide，H2S）水平的升高是慢性气道疾病中中性粒细胞气道炎症的新型生物标志物。然而，H2S与疾病活动的关系尚不清楚。
目的:我们研究了哮喘不同状态下的H2S水平是否会发生变化。
方法:在47例稳定哮喘受试者(S-BA)、21例未控制哮喘受试者(UC-BA)、26例急性发作哮喘受试者(AE-BA)和15例健康受试者中，使用硫化物敏感电极测量痰液和血清中的H2S水平。其中，13例哮喘受试者在稳定期和急性发作期均测定H2S水平。
结果:与UC-BA组和健康组相比，AE-BA组的痰液H2S水平显著升高(p<0.05)。然而，AE-BA受试者的血清H2S水平低于S-BA受试者(p<0.001)，与健康受试者相似。因此，AE-BA组的痰液-血清H2S (H2S比值)明显高于S-BA组、UC-BA组和健康组(p<0.05)。所有受试者中，痰液H2S水平呈现随FEV1%实预比下降的趋势，且与痰中性粒细胞(%)、痰IL-8、血清IL-8水平呈显著正相关关系。多元线性回归分析表明，痰液H2S与痰中性粒细胞(%)的增加和FEV1%实预比下降独立相关(p < 0.05)。H2S比值用于预测哮喘急性发作的截点值为≥0.34 (曲线下的面积；0.88，敏感性81.8%，特异性72.7%，p<0.001)。此外，H2S比值高于截点值水平的一半哮喘受试者在入组后的3个月内出现哮喘急性发作。
结论:H2S比值可以为预测哮喘急性发作未来风险提供有用信息，并可作为哮喘阻塞性中性粒细胞气道炎症中非Th2生物标志物之一。
（黄丹 张红萍 王刚 四川大学华西医院中西医结合科呼吸组）
（Clinical Experimental Allergy.2018 May 14.Doi:10.1111/cea.13173）
（Clinical Experimental Allergy.2018 May 14.Doi:10.1111/cea.13173）
Sputum-to-serum hydrogen sulfide ratio as a novel biomarker of predicting
future risks of asthma exacerbation
Suzuki Y, Saito J, Kikuchi M, Uematsu M, Fukuhara A, Sato S, Munakata M.
Clinical Experimental Allergy.2018 May 14.Doi:10.1111/cea.13173
Abstract
BACKGROUND: Increased level of hydrogen sulfide (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 sulfide-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<0.05). However, serum H2S levels in the AE-BA subjects were lower than in the S-BA subjects (p<0.001) 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<0.05). 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<0.05) .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<0.001). Furthermore, half of the asthmatic subjects with H2S ratios higher than the cutoff level experienced asthma exacerbations over the following 3 months after enrollment.
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.
