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

Abstract

BackgroundAcute 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.MethodsWe 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.ResultsOut 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%.ConclusionsHigh 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.

Are Serum Interleukin 6 and Surfactant Protein D Levels Associated with the Clinical Course of COVID-19?

“…In vitro studies with SP-D showed that it modulates antigen presentation to class II T cells in a dose-dependent manner and plays a role in the clearance of influenza A and HIV viruses [18,19]. Studies related to SARS-CoV demonstrated a strong relationship between mutations in the MBL gene and poor prognosis and clinical course [6,20]. In studies evaluating the relationship between SP-D level and respiratory and non-respiratory diseases, higher levels were observed with chronic airway diseases and smoking.…”

“…These proteins mainly target alveolar macrophages, dendritic cells, and T cells and play an important role in agglutination, opsonization, and modulation. Studies have shown that SP-D levels increase with disease severity and IgG level in patients infected with SARS-CoV, a similar coronavirus responsible for severe acute respiratory syndrome (SARS) [5,6].…”

Circulating cell death biomarker TRAIL is associated with increased organ dysfunction in sepsis

“…The primary cohort was derived from the WC-BOCI at the NYP/WMC, and the validation cohorts were drawn from the ASAN prospective Registry of Critical Illness and the BWH-RoCI. Protocols for recruitment, data collection, and sample processing have been described previously (22,(34)(35)(36), and further detail can be found in the Supplemental Methods. Briefly, both the WC-BOCI and BWH-RoCI cohorts recruited any patient admitted to the medical ICU, with exclusion for the lack of the ability to provide or the lack of a surrogate to provide informed consent and moribund state.…”

Biomarker profiles of coagulopathy and alveolar epithelial injury in acute respiratory distress syndrome with idiopathic/immune-related disease or common direct risk factors

“…SP-D and KL-6 are also known to be elevated in ARDS patients [14, 36], but no published reports have compared the biomarker levels according to different ARDS etiologies. Using data from Korea and the USA, Park et al showed that plasma SP-D levels were elevated (median, 20.8 ng/mL; interquartile range, 12.7–38.4 ng/mL) in patients with ARDS mostly due to pneumonia (87.2% of the study population) [37]. Ohnishi et al compared SP-D and KL-6 levels in patients with ILD (including IPF and CVD-associated interstitial pneumonia) with those in patients with bacterial pneumonia and healthy subjects [13].…”