Diagnostic and Prognostic Values of Serum Activin-A Levels in Patients With Acute Respiratory Distress Syndrome

Jee-min Kim; Jung-Kyu Lee; Sun Mi Choi; Jinwoo Lee; Young Sik Park; Chang-Hoon Lee; Jae-Joon Yim; Chul-Gyu Yoo; Young Whan Kim; Sung Koo Han; Sang-Min Lee


BMC Pulm Med. 2019;19(115) 

In This Article

Abstract and Introduction


Background: We aimed to evaluate whether serum activin-A levels are elevated and have any value in predicting severity and prognosis in acute respiratory distress syndrome (ARDS).

Methods: Retrospective cohort study was performed with patients who were admitted to MICU with diagnosis of ARDS and have serum samples stored within 48 h of Intensive care unit (ICU) admission between March 2013 and December 2016 at a single tertiary referral hospital. Serum activin-A levels were measured with ELISA kit, and were compared with those of normal healthy control and non-ARDS sepsis patients.

Results: Total 97 ARDS patients were included for the study. Levels of Activin-A were elevated in ARDS patients compared to those of healthy controls (Log-transformed activin-A levels 2.89 ± 0.36 vs. 2.34 ± 0.11, p < 0.001, absolute activin-A levels 1525.6 ± 1060.98 vs. 225.9 ± 30.1, p = 0.016) and non-ARDS sepsis patients (Log-transformed activin-A levels 2.89 ± 0.36 vs. 2.73 ± 0.34, p = 0.002, Absolute activin-A levels 1525.6 ± 1060.98 vs. 754.8 ± 123.5 pg/mL, p = 0.036). When excluding five outliers with extremely high activin-A levels, activin-A showed statistically significant correlation with in-hospital mortalities (In-hospital survivors 676.2 ± 407 vs. non-survivors 897.9 ± 561.9 pg/mL, p = 0.047). In predicting in-hospital mortality, serum activin-A concentrations showed superior area under curve compared to that of Acute physiologic and chronic health evaluation II scores (0.653; 95% CI [0541, 0.765] vs. 0.591, 95% CI [0.471, 0.710]). With cut-off level of 708 pg/mL, those with high serum activin-A levels had more than twofold increased risk of in-hospital mortalities. However, those relations were missing when outliers were in.

Conclusions: Serum activin-A levels in ARDS patients are elevated. However, its levels are weakly associated with ARDS outcomes.


Acute Respiratory Distress Syndrome (ARDS), characterized by diffuse inflammation and increased pulmonary vascular permeability with widespread fibrosis later on, continues to be a major healthcare burden with a mortality of 27–45% depending on reports.[1] Several scoring systems have been proposed for early identification of patients at risk of developing ARDS and prediction of survival in ARDS patients. Those tools include Lung Injury Prediction Score (LIPS), Early Acute Lung Injury (EALI) score, and Surgical Lung Injury Prediction (SLIP), but their use is limited in real clinical world for they have low positive predictive value and some of these scoring systems are only for pre-operative patients.[2–4] For evaluating severity and predicting prognosis of ARDS patients, Acute Physiology and Chronic Health Evaluation (APACHE II) and Sequential Organ Failure Assessment (SOFA) scores are widely used, but these instruments have shortcomings in that they are complex, time-consuming to calculate, and they are not specifically designed for ARDS patients.[5,6]

For these reasons, there have been increasing needs for biomarker which could reflect severity or prognosis of ARDS patients. Serum activin-A, a member of transforming growth factor (TGF-ß) superfamily, is a pleiotrophic regulator of cell development and function and its level is elevated in both acute and chronic inflammation.[7,8] It has already been studied that serum activin-A has a prognostic role in sepsis.[9] Furthermore, there are increasing evidence that activin-A plays an important role in several lung diseases including ARDS. In murine model, selective overexpression of activin-A in airway caused pulmonary pathology which was similar to acute lung injury(ALI)/ARDS. In human, it has been reported that patients with ARDS have increased level of activin-A levels in broncho-alveolar lavage(BAL) fluid.[10] However, levels of activin-A in serum, which is more convenient to measure than performing BAL in clinical practice, in ARDS patients has not been elucidated. Moreover, its relationship with ARDS severity or prognosis is rarely known. We aimed to study whether serum activin-A concentration has any diagnostic or prognostic value for critically ill patients with ARDS.