Plasma surfactant protein-D as a diagnostic biomarker for acute respiratory distress syndrome: validation in US and Korean cohorts

Jinkyeong Park, Maria Pabon, Augustine M K Choi, Ilias I Siempos, Laura E Fredenburgh, Rebecca M Baron, Kyeongman Jeon, Chi Ryang Chung, Jeong Hoon Yang, Chi-Min Park, Gee Young Suh, Jinkyeong Park, Maria Pabon, Augustine M K Choi, Ilias I Siempos, Laura E Fredenburgh, Rebecca M Baron, Kyeongman Jeon, Chi Ryang Chung, Jeong Hoon Yang, Chi-Min Park, Gee Young Suh

Abstract

Background: Acute respiratory distress syndrome (ARDS) is potentially underrecognized by clinicians. Early recognition and subsequent optimal treatment of patients with ARDS may be facilitated by usage of biomarkers. Surfactant protein D (SP-D), a marker of alveolar epithelial injury, has been proposed as a potentially useful biomarker for diagnosis of ARDS in a few studies. We tried to validate the performance of plasma SP-D levels for diagnosis of ARDS.

Methods: We conducted a retrospective analysis using data from three (two in USA and one in Korea) prospective biobank cohorts involving 407 critically ill patients admitted to medical intensive care unit (ICU). A propensity score matched analysis (patients with versus without ARDS, matched 1:1) was carried out using significant variables from multiple logistic regression. The diagnostic accuracy of plasma SP-D as a diagnostic marker of ARDS was assessed by receiver operating characteristic curve analysis.

Results: Out of the 407 subjects included in this study, 39 (10%) patients fulfilled ARDS criteria. Patients with ARDS had higher SP-D levels in plasma (p < 0.01) and higher hospital-mortality (p < 0.001) than those without ARDS. Thirty eight subjects with ARDS (cases) were successfully matched for propensity for ARDS with 38 subjects without ARDS (controls). Plasma levels of SP-D were higher in cases with ARDS compared to their matched controls without ARDS [median 20.8 ng/mL (interquartile range, 12.7-38.4) versus 7.9 (4.1-17.0); p = 0.001]. The area under the receiver operating characteristic curve for SP-D for the diagnosis of ARDS was 0.71 (95% confidence intervals, 0.60-0.83). A cut-off point of 12.7 ng/mL for SP-D yielded sensitivity of 74% and specificity of 63%.

Conclusions: High levels of SP-D within 48 h after ICU admission might serve as a diagnostic marker for ARDS in patients hospitalized in medical ICU. Further prospective trials are required to validate the diagnostic role of SP-D in ARDS, and if its usefulness is greater in direct than in indirect ARDS, as well as across different strata of severity of ARDS.

Keywords: Acute lung injury; Critical illness; Pulmonary surfactant-associated protein D; Respiratory distress syndrome.

Conflict of interest statement

Authors’ information

No additional information is provided.

Ethics approval and consent to participate

The study protocol was approved by Institutional Review Board of SMC (2012–12-033), NYPH-WCMC (1405015116A005), and BWH (2008-P-000495). Informed consent was obtained in all study sites.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Receiver operating characteristic (ROC) curve of plasma Surfactant Protein D (SP-D) for discriminating patients with ARDS (n = 38) versus patients without ARDS (n = 38). The area under the ROC curve (AUC) for SP-D was 0.71 (95% confidence intervals, 0.60–0.83). A cut-off point of 12.7 ng/mL for SP-D yielded sensitivity of 74% and specificity of 63%

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