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The ratio of Th17/Treg cells as a risk indicator in early acute respiratory distress syndrome.

Yu ZX, Ji MS, Yan J, Cai Y, Liu J, Yang HF, Li Y, Jin ZC, Zheng JX - Crit Care (2015)

Bottom Line: Th17/Treg ratio was positively correlated with APACHE II score, SOFA score, and Lung Injury Score, while negatively correlated with PaO₂/FiO₂.Using a Th17/Treg ratio cutoff value of >0.79 to determine 28-day mortality, the sensitivity was 87.5% with 68.1% specificity.Finally, cumulative survival rates at 28-day follow-up also differed significantly between patients with Th17/Treg ratio >0.79 and ≤0.79 (P <0.001).

View Article: PubMed Central - PubMed

Affiliation: Department of Critical Care Medicine, The Affiliated People's Hospital, Jiangsu University, Zhenjiang, 212002, China. 9yzx@163.com.

ABSTRACT

Introduction: Recent studies have revealed that lung inflammation mediated by CD4+ T cells may contribute to the pathogenesis of acute respiratory distress syndrome (ARDS). The imbalance between CD4 + CD25 + Foxp3 + regulatory T (Treg) cells and T helper (Th)17 cells has been found in a number of different inflammation and autoimmune diseases, while the role of the Th17/Treg balance in ARDS remains largely unknown. The aim of this study was to investigate the Th17/Treg pattern and its impact on disease severity and outcomes in patients with ARDS.

Methods: This prospective, observational study enrolled 79 patients who fulfilled the Berlin definition of ARDS and 26 age- and sex-matched healthy controls. Circulation Th17 and Treg cell frequencies were analyzed by flow cytometry, and the expressions of Th17- and Treg-related cytokines in serum were measured by enzyme-linked immunosorbent assay (ELISA). Acute Physiologic and Chronic Health Evaluation (APACHE) II score, Sequential Organ Failure Assessment (SOFA) score, and the Lung Injury Score were also calculated at enrollment.

Results: Within 24 hours after the onset of ARDS, the changes of peripheral circulating Th17 and Treg cell frequencies gradually increased from mild to severe ARDS. Th17/Treg ratio was positively correlated with APACHE II score, SOFA score, and Lung Injury Score, while negatively correlated with PaO₂/FiO₂. The areas under the receiver operating characteristic (AUC) curves of Th17/Treg ratio for predicting 28-day mortality in ARDS patients was higher than that of APACHE II score, SOFA score, Lung injury score, as well as PaO2/FiO2. Using a Th17/Treg ratio cutoff value of >0.79 to determine 28-day mortality, the sensitivity was 87.5% with 68.1% specificity. Multivariate logistic regression showed Th17/Treg ratio >0.79 (odds ratio = 8.68, P = 0.002) was the independent predictor for 28-day mortality in patients with ARDS. Finally, cumulative survival rates at 28-day follow-up also differed significantly between patients with Th17/Treg ratio >0.79 and ≤0.79 (P <0.001).

Conclusions: The Th17/Treg imbalance favoring a Th17 shift represents a potential therapeutic target to alleviate lung injury and a novel risk indicator in patients with early ARDS.

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Receiver operating characteristic (ROC) curves for the Th17/Treg ratio, acute physiology and chronic health evaluation (APACHE) II, sequential organ failure assessment (SOFA) and lung injury scores, arterial partial pressure of oxygen/inspired oxygen fraction (PaO2/FiO2), and Th17/Treg ratio in combination with APACHE II score for predicting 28-day mortality in patients with acute respiratory distress syndrome (ARDS). The area under the curve (AUC) demonstrates that the Th17/Treg ratio measures 0.824 (95% CI 0.722 to 0.901), the APACHE II score measures 0.791 (95% CI 0.684 to 0.874), the SOFA score measures 0.749 (95% CI 0.639 to 0.840), the lung injury score measures 0.704 (95% CI 0.590 to 0.801), PaO2/FiO2 measures 0.639 (95% CI 0.523 to 0.744) and the Th17/Treg ratio in combination with the APACHE II score measures 0.872 (95% CI 0.790 to 0.954).
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Fig2: Receiver operating characteristic (ROC) curves for the Th17/Treg ratio, acute physiology and chronic health evaluation (APACHE) II, sequential organ failure assessment (SOFA) and lung injury scores, arterial partial pressure of oxygen/inspired oxygen fraction (PaO2/FiO2), and Th17/Treg ratio in combination with APACHE II score for predicting 28-day mortality in patients with acute respiratory distress syndrome (ARDS). The area under the curve (AUC) demonstrates that the Th17/Treg ratio measures 0.824 (95% CI 0.722 to 0.901), the APACHE II score measures 0.791 (95% CI 0.684 to 0.874), the SOFA score measures 0.749 (95% CI 0.639 to 0.840), the lung injury score measures 0.704 (95% CI 0.590 to 0.801), PaO2/FiO2 measures 0.639 (95% CI 0.523 to 0.744) and the Th17/Treg ratio in combination with the APACHE II score measures 0.872 (95% CI 0.790 to 0.954).

Mentions: The ROC curves for Th17/Treg ratio, APACHE II score, SOFA score, lung injury score, PaO2/FiO2 and Th17/Treg ratio in combination with APACHE II score for predicting 28-day mortality in ARDS patients are shown in Figure 2. The area under the ROC curve (AUC) of Th17/Treg ratio for predicting 28-day mortality in ARDS patients was 0.824 (95% CI 0.722 to 0.901), higher than that for the APACHE II score (0.791, 95% CI 0.684 to 0.874), but this was not statistically significant (P = 0.558). Compared to the Th17/Treg ratio, the AUC for the lung injury score (0.704, 95% CI 0.590 to 0.801) was significantly lower (P = 0.011); the AUC for the SOFA score was also lower (0.749, 95% CI 0.639 to 0.840), but this difference did not reach statistical significance (P = 0.257). Moreover, the AUC for PaO2/FiO2 for 28-day mortality was 0.639 (95% CI 0.523 to 0.744) compared to the AUC for the Th17/Treg ratio, APACHE II score, SOFA score, and lung injury score (P = 0.0001, 0.01, 0.132, and 0.063, respectively). The AUC for the Th17/Treg ratio in combination with the APACHE II score was 0.872 (95% CI 0.790 to 0.954), which was significantly higher than that for the APACHE II score alone for predicting 28-day mortality (P = 0.034), and there was no difference for the combination of the Th17/Treg ratio and APACHE II score compared with the Th17/Treg ratio alone (P = 0.171).Figure 2


The ratio of Th17/Treg cells as a risk indicator in early acute respiratory distress syndrome.

Yu ZX, Ji MS, Yan J, Cai Y, Liu J, Yang HF, Li Y, Jin ZC, Zheng JX - Crit Care (2015)

Receiver operating characteristic (ROC) curves for the Th17/Treg ratio, acute physiology and chronic health evaluation (APACHE) II, sequential organ failure assessment (SOFA) and lung injury scores, arterial partial pressure of oxygen/inspired oxygen fraction (PaO2/FiO2), and Th17/Treg ratio in combination with APACHE II score for predicting 28-day mortality in patients with acute respiratory distress syndrome (ARDS). The area under the curve (AUC) demonstrates that the Th17/Treg ratio measures 0.824 (95% CI 0.722 to 0.901), the APACHE II score measures 0.791 (95% CI 0.684 to 0.874), the SOFA score measures 0.749 (95% CI 0.639 to 0.840), the lung injury score measures 0.704 (95% CI 0.590 to 0.801), PaO2/FiO2 measures 0.639 (95% CI 0.523 to 0.744) and the Th17/Treg ratio in combination with the APACHE II score measures 0.872 (95% CI 0.790 to 0.954).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4355972&req=5

Fig2: Receiver operating characteristic (ROC) curves for the Th17/Treg ratio, acute physiology and chronic health evaluation (APACHE) II, sequential organ failure assessment (SOFA) and lung injury scores, arterial partial pressure of oxygen/inspired oxygen fraction (PaO2/FiO2), and Th17/Treg ratio in combination with APACHE II score for predicting 28-day mortality in patients with acute respiratory distress syndrome (ARDS). The area under the curve (AUC) demonstrates that the Th17/Treg ratio measures 0.824 (95% CI 0.722 to 0.901), the APACHE II score measures 0.791 (95% CI 0.684 to 0.874), the SOFA score measures 0.749 (95% CI 0.639 to 0.840), the lung injury score measures 0.704 (95% CI 0.590 to 0.801), PaO2/FiO2 measures 0.639 (95% CI 0.523 to 0.744) and the Th17/Treg ratio in combination with the APACHE II score measures 0.872 (95% CI 0.790 to 0.954).
Mentions: The ROC curves for Th17/Treg ratio, APACHE II score, SOFA score, lung injury score, PaO2/FiO2 and Th17/Treg ratio in combination with APACHE II score for predicting 28-day mortality in ARDS patients are shown in Figure 2. The area under the ROC curve (AUC) of Th17/Treg ratio for predicting 28-day mortality in ARDS patients was 0.824 (95% CI 0.722 to 0.901), higher than that for the APACHE II score (0.791, 95% CI 0.684 to 0.874), but this was not statistically significant (P = 0.558). Compared to the Th17/Treg ratio, the AUC for the lung injury score (0.704, 95% CI 0.590 to 0.801) was significantly lower (P = 0.011); the AUC for the SOFA score was also lower (0.749, 95% CI 0.639 to 0.840), but this difference did not reach statistical significance (P = 0.257). Moreover, the AUC for PaO2/FiO2 for 28-day mortality was 0.639 (95% CI 0.523 to 0.744) compared to the AUC for the Th17/Treg ratio, APACHE II score, SOFA score, and lung injury score (P = 0.0001, 0.01, 0.132, and 0.063, respectively). The AUC for the Th17/Treg ratio in combination with the APACHE II score was 0.872 (95% CI 0.790 to 0.954), which was significantly higher than that for the APACHE II score alone for predicting 28-day mortality (P = 0.034), and there was no difference for the combination of the Th17/Treg ratio and APACHE II score compared with the Th17/Treg ratio alone (P = 0.171).Figure 2

Bottom Line: Th17/Treg ratio was positively correlated with APACHE II score, SOFA score, and Lung Injury Score, while negatively correlated with PaO₂/FiO₂.Using a Th17/Treg ratio cutoff value of >0.79 to determine 28-day mortality, the sensitivity was 87.5% with 68.1% specificity.Finally, cumulative survival rates at 28-day follow-up also differed significantly between patients with Th17/Treg ratio >0.79 and ≤0.79 (P <0.001).

View Article: PubMed Central - PubMed

Affiliation: Department of Critical Care Medicine, The Affiliated People's Hospital, Jiangsu University, Zhenjiang, 212002, China. 9yzx@163.com.

ABSTRACT

Introduction: Recent studies have revealed that lung inflammation mediated by CD4+ T cells may contribute to the pathogenesis of acute respiratory distress syndrome (ARDS). The imbalance between CD4 + CD25 + Foxp3 + regulatory T (Treg) cells and T helper (Th)17 cells has been found in a number of different inflammation and autoimmune diseases, while the role of the Th17/Treg balance in ARDS remains largely unknown. The aim of this study was to investigate the Th17/Treg pattern and its impact on disease severity and outcomes in patients with ARDS.

Methods: This prospective, observational study enrolled 79 patients who fulfilled the Berlin definition of ARDS and 26 age- and sex-matched healthy controls. Circulation Th17 and Treg cell frequencies were analyzed by flow cytometry, and the expressions of Th17- and Treg-related cytokines in serum were measured by enzyme-linked immunosorbent assay (ELISA). Acute Physiologic and Chronic Health Evaluation (APACHE) II score, Sequential Organ Failure Assessment (SOFA) score, and the Lung Injury Score were also calculated at enrollment.

Results: Within 24 hours after the onset of ARDS, the changes of peripheral circulating Th17 and Treg cell frequencies gradually increased from mild to severe ARDS. Th17/Treg ratio was positively correlated with APACHE II score, SOFA score, and Lung Injury Score, while negatively correlated with PaO₂/FiO₂. The areas under the receiver operating characteristic (AUC) curves of Th17/Treg ratio for predicting 28-day mortality in ARDS patients was higher than that of APACHE II score, SOFA score, Lung injury score, as well as PaO2/FiO2. Using a Th17/Treg ratio cutoff value of >0.79 to determine 28-day mortality, the sensitivity was 87.5% with 68.1% specificity. Multivariate logistic regression showed Th17/Treg ratio >0.79 (odds ratio = 8.68, P = 0.002) was the independent predictor for 28-day mortality in patients with ARDS. Finally, cumulative survival rates at 28-day follow-up also differed significantly between patients with Th17/Treg ratio >0.79 and ≤0.79 (P <0.001).

Conclusions: The Th17/Treg imbalance favoring a Th17 shift represents a potential therapeutic target to alleviate lung injury and a novel risk indicator in patients with early ARDS.

Show MeSH
Related in: MedlinePlus