Serum sphingosine-1-phosphate levels and Sphingosine-1-Phosphate gene polymorphisms in acute respiratory distress syndrome: a multicenter prospective study.
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SUBMITTER: Zhao J
PROVIDER: S-EPMC7137241 | biostudies-literature | 2020 Apr
REPOSITORIES: biostudies-literature
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Serum sphingosine-1-phosphate levels and Sphingosine-1-Phosphate gene polymorphisms in acute respiratory distress syndrome: a multicenter prospective study.
Zhao Jiangnan J Tan Yan Y Wang Li L Su Xin X Shi Yi Y
Journal of translational medicine 20200406 1
<h4>Background</h4>Sphingosine-1-phosphate (S1P) is a signaling phospholipid involved in pathophysiologic progression of acute respiratory distress syndrome (ARDS) through its roles in endothelial barrier function and immune modulation. We hypothesized that decreased serum S1P level is associated with the clinical outcomes of ARDS and polymorphisms in the S1P gene are associated with serum S1P levels.<h4>Methods</h4>This multicenter prospective study includes ARDS patients and healthy blood dono ...[more]
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Project description:ImportanceAcute respiratory distress syndrome (ARDS) confers high mortality risk among critically ill patients. Identification of biomarkers associated with ARDS risk may guide clinical diagnosis and prognosis.ObjectiveTo systematically evaluate the association of blood metabolites with ARDS risk and survival.Design, setting, and participantsIn this cohort study, data from the Molecular Epidemiology of ARDS (MEARDS) study, a prospective cohort of 403 patients with ARDS and 1227 non-ARDS controls, were analyzed. Patients were recruited in intensive care units (ICUs) at Massachusetts General Hospital and Beth Israel Deaconess Medical Center, both in Boston, Massachusetts, from January 1, 1998, to December 31, 2014. Data analysis was performed from December 9, 2018, to January 4, 2019.Main outcomes and measuresParticipants were followed up daily for ARDS development defined by Berlin criteria, requiring fulfillment of chest radiograph and oxygenation criteria on the same calendar day during invasive ventilatory assistance. A 2-stage study design was used to explore novel metabolites associated with ARDS risk and survival.ResultsOf the 1630 participants from MEARDS who were admitted to the ICU , 403 (24.7%) were diagnosed with ARDS (mean [SD] age, 63.0 [17.0] years; 251 [62.3%] male) and 1227 (75.3%) were at-risk but did not have ARDS (mean [SD] age, 62.3 [16.9] years; 753 [61.4%] male). Mendelian randomization suggested that genetically regulated serum mannose was associated with ARDS risk (odds ratio [OR], 0.64; 95% CI, 0.53-0.78; P = 7.46 × 10-6) in the discovery stage. In the functional validation stage incorporating 83 participants with ARDS and matched at-risk participants in the control group from the ICU, the protective association of mannose with ARDS risk was validated (OR, 0.67; 95% CI, 0.46-0.97; P = .03). Furthermore, serum mannose was associated with 28-day (OR, 0.25; 95% CI, 0.11-0.56; P = 6.95 × 10-4) and 60-day (OR, 0.36; 95% CI, 0.19-0.71; P = 3.12 × 10-3) mortality and 28-day (hazard ratio, 0.49; 95% CI, 0.32-0.74; P = 6.41 × 10-4) and 60-day (hazard ratio, 0.55; 95% CI, 0.37-0.80; P = 2.11 × 10-3) survival.Conclusions and relevanceIn this study, genetically regulated serum mannose appeared to be associated with ARDS risk and outcome, and increased serum mannose at admission was associated with reduced ARDS risk and better survival. These findings could inform prevention and clinical intervention in ARDS cases, which have increased with the expansion of the coronavirus disease 2019 pandemic.
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Project description:BACKGROUND:Acute respiratory distress syndrome (ARDS) is caused by rapid-onset (within hours) acute inflammatory processes in lung tissue, and it is a life-threatening condition with high mortality. The treatment of ARDS to date is focused on the prevention of further iatrogenic damage of the lung rather than the treatment of the initial inflammatory process. Several preclinical studies have revealed a beneficial effect of iloprost on the control of pulmonary inflammation, and in a small number of patients with ARDS, iloprost treatment resulted in improved oxygenation. Therefore, we plan to conduct a large multicenter trial to evaluate the effect of iloprost on ARDS. METHODS:The Therapeutic Iloprost during ARDS trial (ThIlo trial) is a multicenter, randomized, single blinded, clinical phase II trial assessing the efficacy of inhaled iloprost for the prevention of the development and progression of ARDS in critically ill patients. One hundred fifty critically ill patients suffering from acute ARDS will be treated either by nebulized iloprost or NaCl 0.9% for 5?days. Blood samples will be drawn at defined time points to elucidate the serum levels of iloprost and inflammatory markers during treatment. Mechanical ventilation will be standardized. In follow-up visits at days 28 and 90 as well as 6?months after enrollment, functional status according to the Barthel Index and a health care-related questionnaire, and frailty (Vulnerable Elders Survey) will be evaluated. The primary endpoint is the improvement of oxygenation, defined as the ratio of PaO2/FiO2. Secondary endpoints include 90-day all-cause mortality, Sequential Organ Failure Assessment scores during the study period up to day 90, the duration of mechanical ventilation, the length of intensive care unit (ICU) stay, ventilator-associated pneumonia, delirium, ICU-acquired weakness, and discharge localization. The study will be conducted in three university ARDS centers in Germany. DISCUSSION:The results of the ThIlo trial will highlight the anti-inflammatory effect of iloprost on early inflammatory processes during ARDS, resulting in the improvement of outcome parameters in patients with ARDS. TRIAL REGISTRATION:EUDRA-CT: 2016-003168-37. Registered on 12 April 2017. ClinicalTrials.gov: NCT03111212. Registered on 4 June 2017.
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Project description:BACKGROUND:Inflammatory response is activated during cardiopulmonary bypass (CPB), which may lead to acute respiratory distress syndrome (ARDS) and procalcitonin (PCT) increases during this inflammatory response. The objective of the study was to validate whether patients with higher serum PCT concentrations have a higher incidence of ARDS. METHODS:The study was a prospective, single-center, observational cohort study. All patients who received cardiac surgery with CPB were screened for study eligibility. Patients were assigned to the PCT-elevated cohort or the control cohort according to serum PCT concentration on the first postoperative day with a cut-off value of 7.0 ng/mL. Patients were followed up until the 7th postoperative day. The primary endpoint was the incidence of ARDS, which was diagnosed according to the Berlin definition. RESULTS:A total of 296 patients were enrolled, 64 patients were assigned to the PCT-elevated cohort and 232 patients were assigned to the control cohort. PCT concentration was 16.23?±?5.9 ng/mL in the PCT-elevated cohort, and 2.70?±?1.43 ng/mL in the control cohort (p?<?0.001). The incidence of ARDS was significantly higher in the PCT-elevated cohort than in the control cohort (21.9% versus 5.6%, p?<?0.001). The incidence of moderate-to-severe ARDS was also significantly higher in the PCT-elevated cohort than in the control cohort (10.9% versus 0.4%, p?<?0.001). The hazard ratio of ARDS at 7 days in the PCT-elevated cohort, as compared with the control cohort, was 6.8 (95% confidence interval 2.7 to 17.4). The hazard ratio of moderate-to-severe ARDS in the PCT-elevated cohort was 57.3 (95% confidence interval 10.4 to 316.3). The positive predictive value of PCT for ARDS and moderate-to-severe ARDS were 0.242 and 0.121, respectively; the negative predictive value of PCT for ARDS and moderate-to-severe ARDS were 0.952 and 1.0, respectively. CONCLUSION:Cardiac surgical patients with elevated PCT concentration have a higher incidence of ARDS. Elevated PCT may serve as a warning signal of postoperative ARDS in patients undergoing cardiac surgery with CPB. Study registration Chinese Clinical Trial Registry (ChiCTR-OCH-14005076).
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