Surfactant Protein D Levels Research Articles

Serum MMP-9, SP-D, and VEGF levels reflect the severity of connective tissue disease-associated interstitial lung diseases

BackgroundInterstitial lung disease (ILD) is a common pulmonary complication of connective tissue disease (CTD). This study aims to evaluate the clinical diagnostic value of matrix metalloproteinase-9 (MMP-9), surfactant protein-D (SP-D), and vascular endothelial growth factor (VEGF) as potential biomarkers for CTD-ILD.MethodsThis research included 33 CTD-ILD patients, 31 CTD patients without ILD, and 24 healthy control subjects. Then, the value of biomarkers for the diagnosis and evaluation of CTD-ILD was assessed through high-resolution computed tomography (HRCT) findings and pulmonary function test (PFT) parameters.ResultsThe serum MMP-9, SP-D, and VEGF levels in the CTD-ILD group were higher than those in the CTD-NILD group and healthy group. The ROC curve indicates that VEGF has good to excellent diagnostic performance in diagnosing CTD-ILD, the cut-off that best optimizes sensitivity and specificity in diagnosing CTD-ILD is 277.60 pg/ml (sensitivity, 87.9%; specificity, 83.6%), with an area under the curve (AUC) of 0.905 (95% confidence interval (CI) 0.842–0.968); The ROC curve for MMP-9 suggests this biomarker is fair for diagnosis of CTD-ILD(sensitivity, 81.8%; specificity, 81.8%), with an AUC of 0.867 (95% CI 0.784–0.950), but SP-D only provided lower specificity with higher sensitivity in diagnosing CTD-ILD(sensitivity, 90.9%; specificity, 40.0%). The different serum biomarkers are more specific and sensitive when combined to diagnose ILD. The semiquantitative score for the degree of ILD severity on HRCT was positively correlated with SP-D and VEGF levels (r = 0.461, P = 0.007; r = 0.362, P = 0.039), and serum MMP-9 levels were elevated in the UIP subgroup compared to the non-UIP subgroup. The percentage of diffusing capacity of the lung for carbon monoxide (DLco) (% predicted) had a negative correlation with the SP-D level (r = − 0.407, P = 0.044) and a statistically negative correlation between MMP-9 and the forced vital capacity (FVC) (r = − 0.451, P = 0.024).ConclusionsSerum MMP-9, SP-D, and VEGF levels may have clinical value in screening and evaluating the severity of CTD-ILD.

Serial Measurements of Protein Biomarkers in Sepsis-Induced Acute Respiratory Distress Syndrome.

IMPORTANCE:The role of early, serial measurements of protein biomarkers in sepsis-induced acute respiratory distress syndrome (ARDS) is not clear.OBJECTIVES:To determine the differences in soluble receptor for advanced glycation end-products (sRAGEs), angiopoietin-2, and surfactant protein-D (SP-D) levels and their changes over time between sepsis patients with and without ARDS.DESIGN, SETTING, AND PARTICIPANTS:Prospective observational cohort study of adult patients admitted to the medical ICU at Grady Memorial Hospital within 72 hours of sepsis diagnosis.MAIN OUTCOMES AND MEASURES:Plasma sRAGE, angiopoietin-2, and SP-D levels were measured for 3 consecutive days after enrollment. The primary outcome was ARDS development, and the secondary outcome of 28-day mortality. The biomarker levels and their changes over time were compared between ARDS and non-ARDS patients and between nonsurvivors and survivors.RESULTS:We enrolled 111 patients, and 21 patients (18.9%) developed ARDS. The three biomarker levels were not significantly different between ARDS and non-ARDS patients on all 3 days of measurement. Nonsurvivors had higher levels of all three biomarkers than did survivors on multiple days. The changes of the biomarker levels over time were not different between the outcome groups. Logistic regression analyses showed association between day 1 SP-D level and mortality (odds ratio, 1.52; 95% CI, 1.03–2.24; p = 0.03), and generalized estimating equation analyses showed association between angiopoietin-2 levels and mortality (estimate 0.0002; se 0.0001; p = 0.04).CONCLUSIONS AND RELEVANCE:Among critically ill patients with sepsis, sRAGE, angiopoietin-2, and SP-D levels were not significantly different between ARDS and non-ARDS patients but were higher in nonsurvivors compared with survivors. The trend toward higher levels of sRAGE and SP-D, but not of angiopoietin-2, in ARDS patients may indicate the importance of epithelial injury in sepsis-induced ARDS. Changes of the biomarker levels over time were not different between the outcome groups.

Correlation between serum surfactant protein-D level with respiratory compliance and acute respiratory distress syndrome in critically ill COVID-19 Patients: A retrospective observational study.

Acute respiratory distress syndrome (ARDS) is one of the manifestations of severe coronavirus disease 2019 (COVID-19) with low respiratory compliance and poor oxygenation as main characteristics and mortality rate of 50%-94%. Surfactants, including surfactant protein D (SP-D), have a role in maintaining respiratory compliance. This study aimed to analyze the relationship between serum SP-D levels with respiratory compliance and ARDS in patients with critically ill COVID-19 pneumonia. This study was a cross-sectional study. Subjects were adult reverse transcription-polymerase chain reaction-confirmed COVID-19 patients who had ARDS treated with invasive mechanical ventilation. All data were obtained from medical records. Statistical analysis was done using Spearman test, Mann-Whitney test, and receiver operating characteristic curve. Serum level of SP-D was significantly correlated with static respiratory compliance (P = 0.009; correlation coefficient [rs] = 0.467). Serum SP-D levels correlated with ARDS severity (P < 0.001). SP-D levels had a very strong diagnostic value for ARDS severity, with an optimal cutoff value of 44.24 ng/mL (sensitivity 92.3%; specificity 94.1%). ARDS severity also correlated significantly with respiratory compliance (P = 0.005; correlation coefficient 0.496). Higher serum SP-D levels were associated with lower respiratory compliance, ARDS severity, and may be utilized diagnostically to identify patients with severe ARDS.

Surfactant Protein D Level in Cement Workers

Background: Pneumoconiosis occurs almost all in entire worldwide. Pneumoconiosis had threatened cement workers. Serologic abnormalities had found in pneumoconiosis. Surfactant Protein D (SP-D) levels increased in silica exposed workers. Surfactant Protein D (SP-D) may be useful biomarkers for early diagnosis of pneumoconiosis but it has not yet been studied in Indonesia.Method: This is a cross-sectional study and was done by consecutive sampling. The total subject was 61, consisting of 44 cement exposed workers and 17 control from September 2017–March 2018. Serum level of SP-D was measured by ELISA method. Cement exposed workers are a worker in the production area in workers in quarry areas.Results: This study found that total characteristic subjects were male 100% and mean of age was 42.5 years old, the youngest and oldest subject was 21 and 55 years old, respectively. Normal weight group's greatest number was found in 21 subjects (47.7%), followed by overweight 12 subjects (22.3%), obese 8 subjects (18.2%), and underweight 1 subject (2.3%). Based on a history of smoking, this study found that 26 subjects (59.1%) had never smoked, 12 subjects (27.3%) as smokers, and 6 subjects (13.6%) as former smokers. Duration of exposure &lt;10 years was found in 9 subjects (20.5%) and duration of exposure ≥10 years was found in 35 subjects (79.5%) with using self-respiratory safety instrument as good categorical 5 subjects (11.4%), moderate categorical 36 subjects (81.8%) and poor in quality categorical 3 subjects were found (6.8%). Mean of serum SP-D levels in exposed group was found that 111.027 ng/ml and mean of serum SP-D levels in control group was found that 67.648 ng/ml. Levels of serum SP-D were significantly higher in exposed group than control group (p-value=0.014).Conclusion: Comparison serum SP-D levels between exposed group and control group statistically higher in exposed group than control group.

Dysregulated serum and seminal plasma levels of surfactant protein D and MCP-1 in men with genital tract infection/inflammation.

Surfactant protein D (SP-D), a multimeric collectin expressed by testicular mucosal epithelia and is positively regulated by testosterone. It exerts antimicrobial effects, modulates inflammation and rescued spermatogenesis in a murine model. Various cytokines and chemokines, including MCP-1, play a key role in regulating the inflammation in rat and human testis. The study aimed to investigate the role of SP-D and involvement of chemokines and cytokines in the male infertility associated with urogenital infections or inflammation. The cross-sectional study evaluated levels of SP-D, testosterone, estradiol and the cytokines/chemokines including MCP-1 in the serum and semen samples of fertile and infertile Indian men with and without urogenital infections/inflammation (n=76). Both fertile and infertile males with urogenital infection/inflammation had significantly lower levels of SP-D and higher levels of the chemokine, Monocyte chemoattractant protein 1 (MCP-1) in the serum and seminal plasma. Seminal plasma of these males exhibited significantly higher proportion of proteolytically degraded forms of SP-D. The serum SP-D levels positively correlated with testosterone/estradiol (TE) ratio. There was no significant correlation between the SP-D levels in seminal plasma and sperm count/motility. With a significant area under the Receiver Operating Characteristic curves, the serum and seminal plasma SP-D levels exhibited significant potential to predict infertility with high sensitivity and specificity in men with genital infections/inflammation. The circulating and seminal plasma SP-D levels were decreased in men with urogenital infection and inflammation. This could be due to their engagement at the site of infection, dysregulated expression owing to the altered hormonal profile and increased proteolytic degradation.

Correlation of Surfactant Protein-D (SP-D) Serum Levels with ARDS Severity and Mortality in Covid-19 Patients in Indonesia.

The purpose of this research was to investigate the correlation between serum levels of surfactant protein-D (SPD) with acute respiratory distress syndrome (ARDS) severity and mortality in COVID-19. This was a prospective cohort research study that included 76 patients in the period from July to October 2020. SP-D serum levels were taken upon admission to the hospital, the diagnosis of ARDS and its grade were confirmed according to the WHO criteria, and then patients were observed for 28-day mortality. The mean SP-D serum levels from 76 patients were 39.33 ng/ml (SD±31.884 ng/ml). The statistical analysis showed that there was a significant correlation between SP-D serum levels and the severity of ARDS upon admission to the hospital (P=0.04, Spearman's rank correlation coefficient (rs)=0.26), but the correlation between serum levels of SP-D and mortality was not statistically significant (P=0.89; rs=-0.016). SP-D serum levels had a significant but weak correlation with ARDS severity, but were not significant for mortality.

Immunomodulatory effect of pachymaran on cyclosporine A (CsA)-induced lung injury in mice

ObjectiveTo investigate the immunomodulatory effect of pachymaran on cyclosporine A (CsA)-induced lung injury in mice. Methods(i) Fifty male BALB/c mice were randomly divided into five groups (10 mice in each group): normal control (NC) group, 30, 45, and 60 mg/kg CsA groups, and lipopolysaccharide (LPS) group. Except for the NC group, other groups underwent CsA modeling. The NC group was treated with phosphate-buffered saline (PBS), the LPS group with 10 mg/kg LPS eight hours before mice euthanized, and the 30, 45, and 60 mg/kg CsA groups with corresponding doses of CsA for seven consecutive days. After treatment, the body and organ mass of each group were weighed, and the lung, thymus, and spleen indexes were calculated. Hematoxylin-Eosin (HE) staining was performed to observe histopathological changes in the lungs of the mice. The protein expression levels of interleukin (IL)-2 and IL-1β in the blood were detected using enzyme-linked immunosorbent assay (ELISA), and those of surfactant protein D (SP-D), IL-2, and IL-6 in lung tissues were detected by immunohistochemistry (IHC). The mRNA expression levels of SP-D, IL-1β, IL-6, and myeloperoxidase (MPO) in the lung tissues were detected by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). (ii) Another 60 BALB/c mice were divided into six groups (10 mice in each group) : NC group, model control (MC) group, 50, 100, and 200 mg/kg pachymaran groups, and polyinosinic-polycytidylic acid [poly(I:C)] group. Except for the NC group, other groups underwent 45 mg/kg CsA modeling. The NC and MC groups were treated with distilled water, the pachymaran groups with corresponding doses pachymaran, and the poly(I:C) group with 0.1 mg/kg poly(I:C) for seven days.The mice were euthanized to obtain tissues and serum for detection. Detection methods were identical to those described in (i) above. Results(i) CsA (30 mg/kg) increased the lung index of mice (P < 0.001), and decreased the spleen index (P < 0.01), thymus index (P < 0.05), and the serum level of IL-2 (P < 0.05). CsA (45 mg/kg) decreased the spleen, thymus indexes, and the serum level of IL-2 (P < 0.01) in mice, and increased the serum level of IL-1β (P < 0.05) and the protein level of lung SP-D (P <0.001). CsA (60 mg/kg) increased the lung index of mice (P < 0.01), the serum level of IL-1β (P < 0.05), the protein level of lung SP-D (P < 0.01), and the mRNA levels of lung MPO and SP-D ( P < 0.05), and decreased the thymus index of mice (P < 0.01). HE staining showed that 30, 45, and 60 mg/kg CsA, and LPS caused pathological changes in the lung tissue of mice. (ii) After pachymaran intervention in MC mice, the spleen and thymus indexes (P < 0.05) were increased in the 100 and 200 mg/kg pachymaran groups, and the lung index was decreased (P < 0.05). Moreover, 50 mg/kg pachymaran increased the thymus index (P < 0.05) and decreased the lung index (P < 0.01) in MC group. Pachymaran (50, 100, and 200 mg/kg) improved lung tissue injury, reduced the serum level of IL-1β (P < 0.001), and the mRNA levels of MPO and SP-D in lung tissues (P < 0.05) of mice. Pachymaran (100 mg/kg) increased the protein level of lung IL-2 (P < 0.01), decreased the protein level of lung SP-D (P < 0.01), and the mRNA level of IL-1β (P < 0.001) in the lung tissues of mice. Pachymaran (200 mg/kg) increased the serum level of IL-2 (P < 0.01) and lung IL-6 of mice (P < 0.05). Pachymaran (50 and 200 mg/kg) increased the mRNA level of IL-6 in the lung tissues of mice (P < 0.05). ConclusionWhile the immune function of mice was suppressed by CsA, the lung tissue was also damaged. Pachymaran can improve the immunosuppression induced by CsA and improve the lung tissue injury in immunosuppressed mice.

Role of serum surfactant protein-D as a prognostic predictor in fibrotic hypersensitivity pneumonitis.

Serum Krebs von den Lungen-6 (KL-6) and surfactant protein-D (SP-D) are candidate diagnostic and activity markers for fibrotic hypersensitivity pneumonitis (HP), although their correlation with prognosis remains unclear. We aimed to evaluate the prognostic usefulness of serum KL-6 and SP-D in patients with fibrotic HP. This was a retrospective medical record review of 185 patients with fibrotic HP at a single center from 2005 to 2019. The baseline and minimum serum KL-6 and SP-D levels over two years were recorded. The contribution of KL-6 and SP-D levels to the incidence of progressive fibrosing interstitial lung disease (PF-ILD) and mortality were evaluated using multivariate analysis. The respective baseline and minimum levels were 1441 and 808 U/ml for KL-6 and 254 and 132ng/mL for SP-D. A high minimum SP-D level was significantly associated with a high incidence of PF-ILD by logistic regression, independent of baseline forced vital capacity and honeycombing. Similarly, a high minimum SP-D level was significantly associated with high mortality by Cox proportional hazard model analysis. The stratified minimum SP-D levels of <100, 100-200, and >200 revealed significantly distinct groups in the entire cohort, with PF-ILD incidence rates of 28%, 48%, and 74% and median survival times of 120, 74, and 45 months, respectively. High minimum SP-D levels over two years were correlated with an unfavorable prognosis in our cohort. Patient with consistently high SP-D levels during the clinical course may have a poor prognosis and be a candidate for early treatment intensification.

The Surfactant Protein D (SP-D) Serum Levels in Limestone Mining Worker

Background: Limestone is sedimentation rocks consist of minerals calcite and aragonite, often contains silica, and fossils, commonly used in building materials. Limestone mining workers are at high risk to pneumoconiosis. Surfactant protein D(SP-D) is part of collectin family, and served as innate immune system of pathogen recognition receptor (PRR). SP-D level were usually increased in fibrotic lung disease. In this study, we sought the serum level of SP-D as marker for early pneumoconiosis in limestone worker in Indonesia.Method: This study was cross-sectional observational study. Participant of the study were 65 limestone workers, willing to participate in this study by signing informed consent, were questionnaire, and blood sample were collected to measure SP-D level by ELISA.Results: This study found that characteristic subjects dominated by male with the median of age was 42 years old and last education mostly elementary school. Majority duration of working &lt;6 years and time working in a day &gt;8 hours per day. The limestone mining workers mostly did not wear mask and had normal weight group. Majority limestone mining workers ever smoker, mean SP-D level in limestone workers was (66.3±5.5ng/mL), slightly higher than normal subject. Smoking status, gender, working hour were correlated with higher SP-D level.Conclusion: Although not statistically significant, the SP-D serum levels in limestone mining workers might be used as monitoring for early screening for pneumoconiosis in limestone workers.

Surfactant protein D: A useful biomarker for distinguishing COVID-19 pneumonia from COVID-19 pneumonia-like diseases.

IntroductionComputed tomography is useful for the diagnosis of coronavirus disease (COVID‐19) pneumonia. However, many types of interstitial lung diseases and even bacterial pneumonia can show abnormal chest shadows that are indistinguishable from those observed in COVID‐19 pneumonia. Thus, it is necessary to identify useful biomarkers that can efficiently distinguish COVID‐19 pneumonia from COVID‐19 pneumonia‐like diseases. Herein, we investigated the usefulness of serum Krebs von den Lungen 6 (KL‐6) and surfactant protein D (SP‐D) for identifying patients with COVID‐19 pneumonia among patients with abnormal chest shadows consistent with COVID‐19 pneumonia.MethodThis was a retrospective cohort study of consecutive patients who underwent evaluation of serum KL‐6 and SP‐D at a single center from February 2019 to December 2020. A total of 54 patients with COVID‐19 pneumonia and 65 patients with COVID‐19 pneumonia‐like diseases were enrolled in this study from the source population. Serum KL‐6 and SP‐D levels in both groups were analyzed.ResultThe serum levels of KL‐6 and SP‐D in patients with COVID‐19 pneumonia were significantly lower than those in patients with COVID‐19 pneumonia‐like disease (median [interquartile range]: 208.5 [157.5–368.5] U/ml vs. 430 [284.5–768.5] U/ml, p < 0.0001 and 24.7 [8.6–51.0] ng/ml vs. 141 [63.7–243.5] ng/ml, p < 0.0001, respectively). According to receiver operating characteristic (ROC) analysis, the areas under the ROC curves (95% confidence intervals) of serum KL‐6 and SP‐D levels for distinguishing COVID‐19 pneumonia from COVID‐19 pneumonia‐like diseases were 0.761 (0.675–0.847) and 0.874 (0.812–0.936), respectively. The area under the ROC curve of serum SP‐D was significantly larger than that of serum KL‐6 (p = 0.0213), suggesting that serum SP‐D can more efficiently distinguish COVID‐19 pneumonia from COVID‐19 pneumonia‐like diseases.ConclusionSerum SP‐D is a promising biomarker for distinguishing COVID‐19 pneumonia from COVID‐19 pneumonia‐like diseases. Serum SP‐D can be useful for the management of patients with abnormal chest shadow mimicking COVID‐19 pneumonia.

Increased Serum SP-D Level, Neutrophils and Lymphocytes Sputum in Malang Splendid Bird Market Workers

Background: Workers in the bird market have a high risk of exposure in the form of air pollution, pollutant particles including debris / organic dust, loose feathers, insects/ticks, aerosol particles in food, bird excreta (ammonia), various kinds of gram bacteria, fungi and virus. Exposure to particles will stimulate the immune system against harmful pathogens in the form of inflammatory response. An infection or injury will stimulate the secretion of Surfactant protein-D (SP-D) which is a group of collectin (collagen-lectin) with subgroups of the C-type lectin superfamily, together with bovine coglutinin, mannose-binding lectin (MBL), and CL43 protein. This aim of this study was to determine serum SP-D and neutrophil and sputum lymphocyte levels in workers at splendid bird market.Methods: A cross sectional analytic observational study on 35 subjects, analyzed the characteristics of the workers, calculated neutrophil types, lymphocytes on induced sputum and serum SP-D levels using sandwich ELISA.Results: Mean SP-D serum levels in workers in the bird market environment increased (mean SD: 81.39 + 47.656 ng/ml) from normal levels (60 ± 3 ng/ml). There was a significant positive correlation between length of exposure and serum SP-D levels (r: 0.693; p &lt;0.001). There was an average increase in the percentage of neutrophils and sputum lymphocytes (90.71% + 4.04% and 9.17% + 4.42%) compared to normal limit (50.3% + 23.5% and 2.6% + 5.2%).Conclusion: Inhalation exposure in the Bird Market environment can cause an increase in the percentage of neutrophils, sputum lymphocytes and serum SP-D levels in workers that indicate an airway inflammation process, as well as an alleged increase in alveolar wall permeability, damage and regeneration of alveolar epithelial cell type II cells (AEC type II).

Surfactant protein D is a biomarker of influenza-related pediatric lung injury.

Biomarkers that can risk-stratify children with influenza virus lower respiratory infection may identify patients for targeted intervention. Early elevation of alveolar-related proteins in the bloodstream in these patients could indicate more severe lung damage portending worse outcomes. We used a mouse model of human influenza infection and evaluated relationships between lung pathophysiology and surfactant protein D (SP-D), SP-A, and Club cell protein 16 (CC16). We then measured SP-A, SP-D, and CC16 levels in plasma samples from 94 children with influenza-associated acute respiratory failure (PICFLU cohort), excluding children with underlying conditions explaining disease severity. We tested for associations between levels of circulating proteins and disease severity including the diagnosis of acute respiratory distress syndrome (ARDS), mechanical ventilator, intensive care unit and hospital days, and hospital mortality. Circulating SP-D showed a greater increase than SP-A and CC16 in mice with increased alveolar-vascular permeability following influenza infection. In the PICFLU cohort, SP-D was associated with moderate-severe ARDS diagnosis (p = 0.01) and with mechanical ventilator (r = 0.45, p = 0.002), ICU (r = 0.44, p = 0.002), and hospital days (r = 0.37, p = 0.001) in influenza-infected children without bacterial coinfection. Levels of SP-D were lower in children with secondary bacterial pneumonia (p = 0.01) and not associated with outcomes. CC16 and SP-A levels did not differ with bacterial coinfection and were not consistently associated with severe outcomes. SP-D has potential as an early circulating biomarker reflecting a degree of lung damage caused directly by influenza virus infection in children. Secondary bacterial pneumonia alters SP-D biomarker performance.

Association of serum surfactant protein D and SFTPD gene variants with asthma in Danish children, adolescents, and young adults.

BackgroundSurfactant Protein D (SP‐D) is a pattern recognition molecule belonging to the family of collectins expressed in multiple human organ systems, including the lungs. Previous studies have shown that SP‐D levels in bronchoalveolar lavage samples decrease and serum levels increase in patients suffering from asthma, possibly due to a combination of induced SP‐D synthesis and decreased air–blood barrier integrity. The aims of this study were to investigate whether serum levels of SP‐D and common variants in the SP‐D gene were associated with asthma in adolescents and young adults.MethodsProspective observational study including 449 adolescents and young adults (age 11–27 years) previously diagnosed with asthma during a 2‐year period from 2003 to 2005 (0–16 years). At follow‐up from 2016 to 2017, 314 healthy controls with no history of asthma were recruited. Serum SP‐D was analyzed on samples obtained at baseline as well as samples obtained at follow‐up. SP‐D genotyping was performed for rs721917, rs2243639, and rs3088308.ResultsNo differences were found in mean levels of sSP‐D and SFTPD genotype among subjects with current asthma, no current asthma, and controls. Serum SP‐D and SFTPD genotype were not associated with any clinical parameters of asthma. Furthermore, baseline sSP‐D was not associated with asthma at follow‐up.ConclusionSerum surfactant protein D and common SP‐D gene variants were not associated with asthma in Danish adolescents and young adults with mild to moderate asthma. Serum surfactant protein D did not demonstrate any value as a clinical biomarker of asthma.

Surfactant protein D concentration in a pediatric population with suspected sleep disorder.

Obstructive sleep apnea (OSA) affects between 2% and 4% in children and there is a search for new biomarkers that can be useful both in the diagnosis and in the evolution of the disease. The surfactant protein D (SP-D) is a collection that is part of the innate immune system exerting an anti-inflammatory and antimicrobial effect. Thus, the objective of this study was to evaluate the concentration of SP-D in the suspect OSA pediatric population. A total of 178 children were recruited in this prospective study. Blood samples, sleep parameters, feeding habits, anthropometric, sociodemographic, and family data were collected. Specific biochemical determinations were made, and the plasmatic concentrations of SP-D were measured by enzyme-linked immunosorbent assay. We found no statistical correlation between the SP-D concentration and the apnea-hypopnea index (AHI) from the data. Nevertheless, the changes in SP-D levels could be correlated to a large extent by the arousals that often go along with hypopneas (r = -0.258, p = 0.011 unadjusted; r = -0.258, p = 0.014 adjusted by age and body mass inded [BMI] Z-score). Intermittent hypoxia was correlated with C-reactive protein levels (r = 0.547, p < 0.001 unadjusted; r = 0.542, p < 0.001 adjusted by age and BMI Z-score). Although AHI and SP-D did not appear to correlate, a secondary analysis suggests that sleep fragmentation, which is produced by arousals, may do, and further research is needed to determine the mechanisms by which changes in SP-D occur in OSA.

The potential role of SP-D as an early biomarker of severity of asthma

Surfactant decreases the surface tension of peripheral airways and modulates the immunological responses of the lung. The alterations of surfactant due to the airway inflammation suggest a role in the pathogenesis of asthma. We aim to test the hypothesis that serum levels of SP-A (Surfactant Protein A) and SP-D (Surfactant Protein-D) are altered in patients with mild asthma compared to healthy controls and those alterations are related to functional abnormalities of peripheral airways, which are an early marker of progression of asthma. In this pilot study, we recruited 20 mild asthmatics and 10 healthy controls. We measured serum SP-A and SP-D and all subjects underwent clinical, lung functional and biological assessments. Serum SP-D was significantly higher in asthmatics compared to healthy controls (mean (SD) values: 7.9(4.65) vs 3.31(1.71) ng ml−1, p-value: 0.008). In the asthmatic group, serum SP-D was significantly correlated to CalvNO (alveolar NO concentration) (R-squared: 0.26; p-value: 0.014). These preliminary findings suggest that serum SP-D could be used as a lung-specific biomarker of small airways damage thus predicting the progression to the most severe forms of asthma.

Serial Measurements of Circulating KL-6, SP-D, MMP-7, CA19-9, CA-125, CCL18, and Periostin in Patients with Idiopathic Pulmonary Fibrosis Receiving Antifibrotic Therapy: An Exploratory Study.

Idiopathic pulmonary fibrosis (IPF) is a progressive and inevitably fatal disease with a heterogeneous clinical course. This study aimed to evaluate the usefulness of circulating biomarkers in routine IPF clinical practice. We conducted an exploratory study in a cohort of 28 IPF subjects qualified for anti-fibrotic therapy with up to 24 months serial measurements of seven IPF biomarkers, including those that are well-established, Krebs von den Lungen-6 (KL-6), surfactant protein D (SP-D), matrix metalloproteinase 7 (MMP-7), and more recently introduced ones, cancer antigen 19-9 (CA19-9), cancer antigen 125 (CA-125), chemokine (C-C motif) ligand 18 (CCL18), and periostin. Among studied biomarkers, SP-D had the highest diagnostic accuracy to differentiate IPF subjects from controls, followed by MMP-7 and KL-6. At each study timepoint, KL-6 levels correlated inversely with forced vital capacity % predicted (FVC% pred.), and transfer factor of the lung for carbon monoxide % predicted (TL,CO% pred.), while SP-D levels correlated inversely with FVC% pred. and TL,CO% pred. at 24 months of anti-fibrotic therapy. Baseline KL-6 and CA19-9 concentrations were significantly elevated in patients with progressive disease in comparison to patients with stable disease. In addition, in the progressors subgroup CA19-9 concentrations significantly increased over the second year of study follow-up. In patients with progressive disease, we observed a significant inverse correlation between a change in SP-D levels and a change in FVC% pred. in the first year of treatment, whereas in the second year a significant inverse correlation between a change in KL-6 levels and a change in FVC% pred. was noted. Our study findings support the view that both well-established IPF biomarkers, including KL-6, SP-D, and MMP-7, and more recently introduced ones, like CA19-9, have the potential to support clinical practice in IPF.

Expression of Surfactant Protein D Distinguishes Severe Pandemic Influenza A(H1N1) from Coronavirus Disease 2019.

The differentiation between influenza and coronavirus disease 2019 (COVID-19) could constitute a diagnostic challenge during the ongoing winter owing to their clinical similitude. Thus, novel biomarkers are required to enable making this distinction. Here, we evaluated whether the surfactant protein D (SP-D), a collectin produced at the alveolar epithelium with known immune properties, was useful to differentiate pandemic influenza A(H1N1) from COVID-19 in critically ill patients. Our results revealed high serum SP-D levels in patients with severe pandemic influenza but not those with COVID-19. This finding was validated in a separate cohort of mechanically ventilated patients with COVID-19 who also showed low plasma SP-D levels. However, plasma SP-D levels did not distinguish seasonal influenza from COVID-19 in mild-to-moderate disease. Finally, we found that high serum SP-D levels were associated with death and renal failure among severe pandemic influenza cases. Thus, our studies have identified SP-D as a unique biomarker expressed during severe pandemic influenza but not COVID-19.

A community study of the risk for obstructive sleep apnea and respiratory inflammation in an adult Chinese population

ABSTRACT Objectives: We aimed to investigate the relationship between obstructive sleep apnea (OSA) risk and respiratory inflammation evaluated by the exhaled breath condensate (EBC) interleukin-6 (IL-6) and plasma surfactant protein-D (SP-D), based on the Berlin questionnaire (BQ) screening values in an adult, urban community in Beijing, China. Methods: Volunteers aged >40 years were recruited from the Shichahai community of central Beijing (Registration number: NCT04832711). Their general information and disease history were recorded. OSA risk was assessed using the BQ. IL-6 in EBC and plasma SP-D were d etected by enzyme-linked immunoassay through specimens collected while fasting. The differences in IL-6 and SP-D values between high-risk and low-risk groups for OSA were compared, and the factors affecting their values were analyzed. Results: Among 1,239 participants, 18.8% of participants were in the high-risk group. There were more participants with higher body mass index, chronic hypertension, coronary heart disease, and diabetes in the high-risk group than in the low-risk group (P < 0.05). There were no significant differences in EBC IL-6 and plasma SP-D between the high- and low-OSA risk groups (p > 0.05). After adjustment for age, sex and chronic comorbidities, multivariate logistic regression showed that there was no correlation between risk of OSA and IL-6 in EBC. However, the risk of OSA (odds ratio [OR] [95% CI]: 1.69 [1.15,2.48]; β = 0.522) and BMI (OR [95%CI]: 0.94 [0.91,0.98]; β = −0.061) were independently associated with plasma SP-D level (p < 0.05 for both). Stratification analysis showed that OSA risk were independently associated with plasma SP-D levels in participants <65 years, or men, or participants with BMI<25. Conclusion: This study showed that plasma SP-D, an inflammation biomarker, was associated with risk of OSA and BMI in a Chinese central urban community. The relationship between the risk of OSA and respiratory inflammation in community populations needs to be further evaluated.

Surfactant protein D: a predictor for severity of community-acquired pneumonia in children.

BackgroundSurfactant protein D (SP-D) is a promising biomarker proposed for the prediction of community-acquired pneumonia (CAP) severity. Therefore, we aimed to assess the role of SP-D in the prediction of CAP severity in pediatric patients.MethodsA prospective cohort study was carried out at the Pediatric Intensive Care Unit (PICU) and wards of Menoufia University Hospital. We recruited 112 children admitted into wards with pneumonia (simple pneumonia) and 68 children admitted into PICU with severe pneumonia (PICU admitted). World Health Organization (WHO) classification and mortality predictive scores were calculated to determine the severity of pneumonia for the two groups, including the Pediatric Respiratory Severity Score (PRESS) and the Predisposition, Insult, Response, and Organ dysfunction modified Score (PIROm). SP-D was measured at admission.ResultsThe SP-D level was significantly lower in patients with simple pneumonia than in patients with severe pneumonia (P < 0.001). SP-D was significantly higher among children with severe pneumonia, as determined by WHO, PRESS, and PIROm (P = 0.001). SP-D was significantly higher among children with mechanical ventilation, shock, hypoxia, sepsis, and mortality. Receiver operating characteristic curve analysis for SP-D showed that the area under the curve was 0.741 (P value < 0.001), with a sensitivity of 85.3% and a specificity of 44.6%.ConclusionsSerum SP-D level has a predictive value for the detection of community-acquired pneumonia severity in children.Impact SP-D is a good predictor for the detection of CAP severity in hospitalized children. SP-D was correlated with severity scores and was associated with indicators of CAP severity, including mechanical ventilation, shock, hypoxia, sepsis, and mortality.

Extra Virgin Olive Oil Nanoemulsion Attenuated Inflammatory Response in Lipopolysaccharide-Induced Sepsis

The provision of nutritional components in critical illness such as sepsis remains a big issue in clinical application, particularly through oral route due to intestinal integrity damaged-associated absorption problem. The aim of this research was to develop Extra Virgin Olive Oil (EVOO) nanoemulsion as a nutrient carrier to improve its permeability while maintaining the intestinal mucosa integrity in mouse model of lipopolysaccharide-induced sepsis. EVOO nanoemulsion was prepared by using ultrasonication-mild agitation method. EVOO nanoemulsion (1.5 mL) was administered to the mice through orogastric tube. The effect of EVOO nanoemulsion was evaluated by assessing the histopathological alterations in lung, measuring the activation of NFκB-p65 by immunohistochemistry of lung tissue, the levels of circulating Surfactant Protein-D (SP-D), tumor necrosis factor-alpha, interleukin (IL)-8, and IL-10. The main result, EVOO nanoemulsion decreased circulating SP-D level after 24 h. In conclusion, EVOO nanoemulsion is a promising carrier to improve nutrition absorption and decrease circulating SP-D as organ injury biomarker.