{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T00:52:20Z","timestamp":1783471940649,"version":"3.55.0"},"reference-count":38,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2018,6,6]],"date-time":"2018-06-06T00:00:00Z","timestamp":1528243200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["15K09182"],"award-info":[{"award-number":["15K09182"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Experimental Allergy"],"published-print":{"date-parts":[[2018,9]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Increased level of hydrogen sulphide (H<jats:sub>2<\/jats:sub>S) in sputum is reported to be a new biomarker of neutrophilic airway inflammation in chronic airway disorders. However, the relationship between H<jats:sub>2<\/jats:sub>S and disease activity remains unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>We investigated whether H<jats:sub>2<\/jats:sub>S levels could vary during different conditions in asthma.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>H<jats:sub>2<\/jats:sub>S levels in sputum and serum were measured using a sulphide\u2010sensitive electrode in 47 stable asthmatic subjects (S\u2010<jats:styled-content style=\"fixed-case\">BA<\/jats:styled-content>), 21 uncontrolled asthmatic subjects (<jats:styled-content style=\"fixed-case\">UC<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">BA<\/jats:styled-content>), 26 asthmatic subjects with acute exacerbation (<jats:styled-content style=\"fixed-case\">AE<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">BA<\/jats:styled-content>) and 15 healthy subjects. Of these, H<jats:sub>2<\/jats:sub>S levels during stable, as well as exacerbation states, were obtained in 13 asthmatic subjects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Sputum H<jats:sub>2<\/jats:sub>S levels were significantly higher in the <jats:styled-content style=\"fixed-case\">AE<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">BA<\/jats:styled-content> subjects compared to the <jats:styled-content style=\"fixed-case\">UC<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">BA<\/jats:styled-content> and healthy subjects (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.05). However, serum H<jats:sub>2<\/jats:sub>S levels in the <jats:styled-content style=\"fixed-case\">AE<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">BA<\/jats:styled-content> subjects were lower than in the S\u2010<jats:styled-content style=\"fixed-case\">BA<\/jats:styled-content> subjects (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.001) and similar to those in healthy subjects. Thus, the sputum\u2010to\u2010serum ratio of H<jats:sub>2<\/jats:sub>S (H<jats:sub>2<\/jats:sub>S ratio) in the <jats:styled-content style=\"fixed-case\">AE<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">BA<\/jats:styled-content> subjects was significantly higher than in the S\u2010<jats:styled-content style=\"fixed-case\">BA<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\"> UC<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">BA<\/jats:styled-content> and healthy subjects (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.05). Among all subjects, sputum H<jats:sub>2<\/jats:sub>S levels showed a trend to decrease with <jats:styled-content style=\"fixed-case\">FEV<\/jats:styled-content><jats:sub>1<\/jats:sub> %predicted and significantly positive correlations with sputum neutrophils (%), sputum <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20108 and serum <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20108. A multiple linear regression analysis showed that sputum H<jats:sub>2<\/jats:sub>S was independently associated with increased sputum neutrophils (%) and decreased <jats:styled-content style=\"fixed-case\">FEV<\/jats:styled-content><jats:sub>1<\/jats:sub> %predicted (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.05). The cut\u2010off level of H<jats:sub>2<\/jats:sub>S ratio to indicate an exacerbation was \u22650.34 (area under the curve; 0.88, with a sensitivity of 81.8% and specificity of 72.7%, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.001). Furthermore, half of the asthmatic subjects with H<jats:sub>2<\/jats:sub>S ratios higher than the cut\u2010off level experienced asthma exacerbations over the following 3\u00a0months after enrolment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The H<jats:sub>2<\/jats:sub>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\u2010Th2 biomarkers, in asthma.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cea.13173","type":"journal-article","created":{"date-parts":[[2018,5,14]],"date-time":"2018-05-14T17:34:52Z","timestamp":1526319292000},"page":"1155-1163","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Sputum\u2010to\u2010serum hydrogen sulphide ratio as a novel biomarker of predicting future risks of asthma exacerbation"],"prefix":"10.1111","volume":"48","author":[{"given":"Y.","family":"Suzuki","sequence":"first","affiliation":[{"name":"Department of Pulmonary Medicine School of Medicine Fukushima Medical University Fukushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9876-1160","authenticated-orcid":false,"given":"J.","family":"Saito","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine School of Medicine Fukushima Medical University Fukushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Kikuchi","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine School of Medicine Fukushima Medical University Fukushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Uematsu","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine School of Medicine Fukushima Medical University Fukushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Fukuhara","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine School of Medicine Fukushima Medical University Fukushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine School of Medicine Fukushima Medical University Fukushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Munakata","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine School of Medicine Fukushima Medical University Fukushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,6,6]]},"reference":[{"key":"e_1_2_8_2_1","unstructured":"Global Initiative for Asthma.Global strategy for asthma management and prevention. 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