Association of the Tyrosine/Nitrotyrosine pathway with death or ICU admission within 30 days for patients with community acquired pneumonia
Abstract Background Oxidative stress is a modifiable risk-factor in infection causing damage to human cells. As an adaptive response, cells catabolize Tyrosine to 3-Nitrotyrosine (Tyr-NO2) by nitrosylation. We investigated whether a more efficient reduction in oxidative stress, mirrored by a lowerin...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2018-08-01
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| Series: | BMC Infectious Diseases |
| Online Access: | http://link.springer.com/article/10.1186/s12879-018-3335-y |
| _version_ | 1819157543396573184 |
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| author | Thomas Baumgartner Giedré Zurauskaité Yannick Wirz Marc Meier Christian Steuer Luca Bernasconi Andreas Huber Mirjam Christ-Crain Christoph Henzen Claus Hoess Robert Thomann Werner Zimmerli Beat Mueller Philipp Schuetz |
| author_facet | Thomas Baumgartner Giedré Zurauskaité Yannick Wirz Marc Meier Christian Steuer Luca Bernasconi Andreas Huber Mirjam Christ-Crain Christoph Henzen Claus Hoess Robert Thomann Werner Zimmerli Beat Mueller Philipp Schuetz |
| author_sort | Thomas Baumgartner |
| collection | DOAJ |
| description | Abstract Background Oxidative stress is a modifiable risk-factor in infection causing damage to human cells. As an adaptive response, cells catabolize Tyrosine to 3-Nitrotyrosine (Tyr-NO2) by nitrosylation. We investigated whether a more efficient reduction in oxidative stress, mirrored by a lowering of Tyrosine, and an increase in Tyr-NO2 and the Tyrosine/Tyr-NO2 ratio was associated with better clinical outcomes in patients with community-acquired pneumonia (CAP). Methods We measured Tyrosine and Tyr-NO2 in CAP patients from a previous randomized Swiss multicenter trial. The primary endpoint was adverse outcome defined as death or ICU admission within 30-days; the secondary endpoint was 6-year mortality. Results Of 278 included CAP patients, 10.4% experienced an adverse outcome within 30 days and 45.0% died within 6 years. After adjusting for the pneumonia Severity Index [PSI], BMI and comorbidities, Tyrosine nitrosylation was associated with a lower risk for short-term adverse outcome and an adjusted OR of 0.44 (95% CI 0.20 to 0.96, p = 0.039) for Tyr-NO2 and 0.98 (95% CI 0.98 to 0.99, p = 0.043) for the Tyrosine/Tyr-NO2 ratio. There were no significant associations for long-term mortality over six-years for Tyr-NO2 levels (adjusted hazard ratio 0.81, 95% CI 0.60 to 1.11, p = 0.181) and Tyrosine/Tyr-NO2 ratio (adjusted hazard ratio 1.00, 95% CI 0.99 to 1.00, p = 0.216). Conclusions Tyrosine nitrosylation in our cohort was associated with better clinical outcomes of CAP patients at short-term, but not at long term. Whether therapeutic modulation of the Tyrosine/Tyr-NO2 pathway has beneficial effects should be evaluated in future studies. Trial registration ISRCTN95122877. Registered 31 July 2006. |
| first_indexed | 2024-12-22T16:10:26Z |
| format | Article |
| id | doaj.art-f65bdb1f0f2e47119e5b5fe381100e17 |
| institution | Directory Open Access Journal |
| issn | 1471-2334 |
| language | English |
| last_indexed | 2024-12-22T16:10:26Z |
| publishDate | 2018-08-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Infectious Diseases |
| spelling | doaj.art-f65bdb1f0f2e47119e5b5fe381100e172022-12-21T18:20:31ZengBMCBMC Infectious Diseases1471-23342018-08-011811810.1186/s12879-018-3335-yAssociation of the Tyrosine/Nitrotyrosine pathway with death or ICU admission within 30 days for patients with community acquired pneumoniaThomas Baumgartner0Giedré Zurauskaité1Yannick Wirz2Marc Meier3Christian Steuer4Luca Bernasconi5Andreas Huber6Mirjam Christ-Crain7Christoph Henzen8Claus Hoess9Robert Thomann10Werner Zimmerli11Beat Mueller12Philipp Schuetz13Division of Endocrinology, Diabetology and Metabolism, Kantonsspital Aarau, Medical University DepartmentDivision of Endocrinology, Diabetology and Metabolism, Kantonsspital Aarau, Medical University DepartmentDivision of Endocrinology, Diabetology and Metabolism, Kantonsspital Aarau, Medical University DepartmentDivision of Endocrinology, Diabetology and Metabolism, Kantonsspital Aarau, Medical University DepartmentDepartment of Laboratory Medicine Kantonsspital AarauDepartment of Laboratory Medicine Kantonsspital AarauDepartment of Laboratory Medicine Kantonsspital AarauEndocrinology, Diabetology and Metabolism, University Hospital BaselDepartment of Internal Medicine, Kantonsspital LuzernDepartment of Internal Medicine, Kantonsspital MünsterlingenDepartment of Internal Medicine, Bürgerspital SolothurnDepartment of Internal Medicine, Kantonsspital LiestalDivision of Endocrinology, Diabetology and Metabolism, Kantonsspital Aarau, Medical University DepartmentDivision of Endocrinology, Diabetology and Metabolism, Kantonsspital Aarau, Medical University DepartmentAbstract Background Oxidative stress is a modifiable risk-factor in infection causing damage to human cells. As an adaptive response, cells catabolize Tyrosine to 3-Nitrotyrosine (Tyr-NO2) by nitrosylation. We investigated whether a more efficient reduction in oxidative stress, mirrored by a lowering of Tyrosine, and an increase in Tyr-NO2 and the Tyrosine/Tyr-NO2 ratio was associated with better clinical outcomes in patients with community-acquired pneumonia (CAP). Methods We measured Tyrosine and Tyr-NO2 in CAP patients from a previous randomized Swiss multicenter trial. The primary endpoint was adverse outcome defined as death or ICU admission within 30-days; the secondary endpoint was 6-year mortality. Results Of 278 included CAP patients, 10.4% experienced an adverse outcome within 30 days and 45.0% died within 6 years. After adjusting for the pneumonia Severity Index [PSI], BMI and comorbidities, Tyrosine nitrosylation was associated with a lower risk for short-term adverse outcome and an adjusted OR of 0.44 (95% CI 0.20 to 0.96, p = 0.039) for Tyr-NO2 and 0.98 (95% CI 0.98 to 0.99, p = 0.043) for the Tyrosine/Tyr-NO2 ratio. There were no significant associations for long-term mortality over six-years for Tyr-NO2 levels (adjusted hazard ratio 0.81, 95% CI 0.60 to 1.11, p = 0.181) and Tyrosine/Tyr-NO2 ratio (adjusted hazard ratio 1.00, 95% CI 0.99 to 1.00, p = 0.216). Conclusions Tyrosine nitrosylation in our cohort was associated with better clinical outcomes of CAP patients at short-term, but not at long term. Whether therapeutic modulation of the Tyrosine/Tyr-NO2 pathway has beneficial effects should be evaluated in future studies. Trial registration ISRCTN95122877. Registered 31 July 2006.http://link.springer.com/article/10.1186/s12879-018-3335-y |
| spellingShingle | Thomas Baumgartner Giedré Zurauskaité Yannick Wirz Marc Meier Christian Steuer Luca Bernasconi Andreas Huber Mirjam Christ-Crain Christoph Henzen Claus Hoess Robert Thomann Werner Zimmerli Beat Mueller Philipp Schuetz Association of the Tyrosine/Nitrotyrosine pathway with death or ICU admission within 30 days for patients with community acquired pneumonia BMC Infectious Diseases |
| title | Association of the Tyrosine/Nitrotyrosine pathway with death or ICU admission within 30 days for patients with community acquired pneumonia |
| title_full | Association of the Tyrosine/Nitrotyrosine pathway with death or ICU admission within 30 days for patients with community acquired pneumonia |
| title_fullStr | Association of the Tyrosine/Nitrotyrosine pathway with death or ICU admission within 30 days for patients with community acquired pneumonia |
| title_full_unstemmed | Association of the Tyrosine/Nitrotyrosine pathway with death or ICU admission within 30 days for patients with community acquired pneumonia |
| title_short | Association of the Tyrosine/Nitrotyrosine pathway with death or ICU admission within 30 days for patients with community acquired pneumonia |
| title_sort | association of the tyrosine nitrotyrosine pathway with death or icu admission within 30 days for patients with community acquired pneumonia |
| url | http://link.springer.com/article/10.1186/s12879-018-3335-y |
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