Serum Serum Surfactant Protein D Research Articles

Novel tools for evaluating COVID-19 at the emergency department: Surfactant protein D level and CHARISMA score

ObjectivesTo investigate the serum surfactant protein D (SP-D) level required to determine the diagnosis and prognosis of coronavirus disease 2019 (COVID-19), and create a new scale for disease prognosis prediction. MethodsThis study was conducted among 64 patients with COVID-19 symptoms and 16 healthy volunteers. The participants were assessed by comparing “Controls/Patients”, “PCR-negative/PCR-positive”, “Simple COVID-19/Acute respiratory distress syndrome (ARDS)-accompanied COVID-19”, “Mild ARDS/Moderate-severe ARDS”, and “Survived/Dead” subgroups. Serum SP-D levels and pulmonary infiltration area (volume and percentage) measurements on CT were compared between the groups. A new scale, the “CHARISMA Score”, was created by logistic regression method for a complete prognosis assessment. This includes confusion, heart rate, age, respiratory rate, percentage of infiltration on CT, serum SP-D level, mean arterial pressure and SaO2. ResultsSerum SP-D levels differed significantly across the groups. There was a strong correlation between SP-D levels and infiltration volumes. CHARISMA scores were higher in the severe than in the mild ARDS group and in patients who died than in survivors. In the receiver operating characteristic curve analysis of the CHARISMA scores, a cutoff value of 4 indicated mortality. ConclusionSerum SP-D levels can be used to determine COVID-19 diagnosis and prognosis, and the CHARISMA score can be used to predict prognosis and mortality risk in patients with COVID-19 pneumonia.

Human Muse cells isolated from preterm- and term-umbilical cord delivered therapeutic effects in rat bleomycin-induced lung injury model without immunosuppressant

BackgroundBleomycin (BLM)-induced lung injury is characterized by mixed histopathologic changes with inflammation and fibrosis, such as observed in human patients with bronchopulmonary dysplasia, idiopathic pulmonary fibrosis, and chronic obstructive pulmonary disease. Although no curative therapies for these lung diseases exist, stem cell therapy has emerged as a potential therapeutic option. Multilineage-differentiating stress-enduring (Muse) cells are endogenous pluripotent- and macrophage-like stem cells distributed in various adult and fetal tissues as stage-specific embryonic antigen-3-positive cells. They selectively home to damaged tissue by sensing sphingosine-1-phosphate and replace the damaged/apoptotic cells by in vivo differentiation. Clinical trials for some human diseases suggest the safety and therapeutic efficacy of intravenously injected human leukocyte antigen-mismatched allogenic Muse cells from adult bone marrow (BM) without immunosuppressant. Here, we evaluated the therapeutic effects of human Muse cells from preterm and term umbilical cord (UC), and adult BM in a rat BLM-induced lung injury model.MethodsRats were endotracheally administered BLM to induce lung injury on day 0. On day 3, human preterm UC-Muse, term UC-Muse, or adult BM-Muse cells were administered intravenously without immunosuppressants, and rats were subjected to histopathologic analysis on day 21. Body weight, serum surfactant protein D (SP-D) levels, and oxygen saturation (SpO2) were monitored. Histopathologic lung injury scoring by the Ashcroft and modified American Thoracic Society document scales, quantitative characterization of engrafted Muse cells, RNA sequencing analysis, and in vitro migration assay of infused Muse cells were performed.ResultsRats administered preterm- and term-UC-Muse cells exhibited a significantly better recovery based on weight loss, serum SP-D levels, SpO2, and histopathologic lung injury scores, and a significantly higher rate of both Muse cell homing to the lung and alveolar marker expression (podoplanin and prosurfactant protein-C) than rats administered BM-Muse cells. Rats receiving preterm-UC-Muse cells showed statistically superior results to those receiving term-UC-Muse cells in many of the measures. These findings are thought to be due to higher expression of genes related to cell migration, lung differentiation, and cell adhesion.ConclusionPreterm UC-Muse cells deliver more efficient therapeutic effects than term UC- and BM-Muse cells for treating BLM-induced lung injury in a rat model.

Exogenous Apelin-13 Administration Ameliorates Cyclophosphamide- Induced Oxidative Stress, Inflammation, and Apoptosis in Rat Lungs.

Apelin-13 is an endogenous adipocytokine known for its antioxidant, antiinflammatory, and antiapoptotic properties. We aimed to investigate the possible protective effects of exogenous Apelin-13 administration on oxidative stress, inflammation, and apoptosis induced by the cytotoxic agent cyclophosphamide (CP) in the lungs. Twenty-four male Wistar albino rats were divided into four groups: Control (saline), CP (200 mg/kg), Apelin-13 (10 μg/kg/day), and CP+Apelin-13. CP was administered as a single dose on the fifth day, and apelin-13 was administered intraperitoneally for five days. Total oxidant status (TOS), total antioxidant status (TAS), and lipid peroxidation were determined with spectrophotometry, TNFα and IL1β were determined with ELISA, APJ, Sirt1, NF-κB, and p53 mRNA expressions were determined with qRT-PCR, cytochrome (Cyt) C and caspase-3 protein expressions were studied with western blotting in lung tissues. The oxidative stress index (OSI) was also calculated. Furthermore, serum surfactant protein-D (SP-D) and Krebs von den Lungen-6 (KL-6) levels were measured with ELISA. Compared to the control group, TOS, OSI, lipid peroxidation, TNFα, IL1β, cyt C, caspase-3, APJ, NF-κB, and p53 were higher, and Sirt1 was lower in the lung tissue of rats in the CP group. Serum KL-6 and SP-D levels were higher in the CP group. Co-administration of CP with Apelin-13 completely reversed the changes induced by CP administration. Exogenous Apelin-13 treatment protected lung tissue against injury by inhibiting cyclophosphamide-induced oxidative stress, inflammation, and apoptosis. This protective effect of apelin-13 was accompanied by upregulation of the Sirt1 and downregulation of NF-κB/p53 in the lungs.

Evaluation of the Relationship Between Surfactant Protein D Levels and COVID-19 Clinical Severity: A Case-Control Study

Purpose: Serum surfactant protein D (SP-D) plays roles in the body such as protection against viral infection, bacterial and fungal clearance, clearance of apoptotic cells and suppression of inflammation. This study aims to examine the relationship between SP-D level and coronavirus disease (COVID-19) severity. 
 Methods: 80 patients (30 with mild disease and 50 with severe/critical COVID-19), and 50 healthy volunteers were enrolled in the study. SP-D levels were analyzed by ELISA in serum samples. 
 Results: The median of SP-D was found to be 2.47 (1.67-7.79) ng/ml in mild disease and 5.65 (3.09-16.55) ng/ml in severe/critical disease groups, while 2.89 (10.8-6.24) ng/ml in the healthy controls. The differences in SP-D levels between the severe/critical disease group compared to both mild disease and control groups were found statistically significant (p=0.007 and 0.001, respectively). ROC analysis showed greater AUC for the serum SP-D levels of the severe/critical COVID-19 patients compared to mild COVID-19 disease patients (AUC=0.691, 95% CI=0.56-0.822; p=0.004). Furthermore, SP-D levels were 86% sensitive and 51.6% specific at 2.44 ng/ml level (p=0.004) to detect severe/critical patients.
 Conclusion: SP-D levels is useful for COVID-19 patients in the prediction of clinical severity and prognosis. SP-D is a valuable biomarker for predicting the clinical severity and prognosis.

Predictive factors for relapse in corticosteroid-treated patients with chronic eosinophilic pneumonia.

Chronic eosinophilic pneumonia (CEP) is an idiopathic disorder characterised by an abnormal and marked accumulation of eosinophils in the interstitium and alveolar spaces of the lungs. Systemic corticosteroid (CS) therapy leads to marked improvement. However, relapse is common in the clinical course, and the predictive factors for relapse of CEP are not well known. This study aimed to investigate predictive factors for relapse in CS-treated cases of CEP. We identified consecutive patients with CEP at our institution between 1999 and 2019. We retrospectively reviewed 36 CS-treated patients with CEP who underwent bronchoalveolar lavage (BAL) and high-resolution computed tomography (CT) at diagnosis. We examined relapse at least 1 year after the initiation of CS treatment. Statistical analysis included univariate and multivariate Cox proportional hazard regression analyses; P<0.05 was considered statistically significant. The median (interquartile range) age at diagnosis was 59.5 years (47.8-70.0 years). This study included 13 men and 23 women. Twenty-five patients (69.4%) were never smokers and 15 (41.7%) had asthma. The peripheral blood eosinophil percentage was 35.0% (15.6-55.8%), and the BAL eosinophil percentage was 40.8% (10.7-68.5%). The median serum surfactant protein-D (SP-D) level was 135 ng/mL (82.2-176.7 ng/mL). High-resolution CT revealed centrilobular opacities in 23 patients (63.9%). Relapse of CEP was observed in 20 patients (55.6%). Higher serum SP-D levels and the presence of centrilobular opacities on high-resolution CT were significant predictors of relapse in multivariate Cox proportional hazard regression analysis (P=0.017 and P=0.028, respectively). Additionally, we devised a relapse prediction model for CS-treated CEP using two categorical parameters: the presence of centrilobular opacities and serum levels of SP-D (>135/≤135 ng/mL). Based on these parameters, cases were scored 2, 1, or 0. Patients with a score of 2 experienced relapses earlier than those with scores of 1 and 0 (log-rank test; P=0.006, P=0.003, respectively). Centrilobular opacities on high-resolution CT and higher serum SP-D levels at diagnosis may be predictive factors for relapse in CS-treated patients with CEP.

Serum Surfactant Protein-D (SP-D) Level: Does it Correlates with Pulmonary Compliance and ARDS in Severe Cases of COVID-19?

Acute Respiratory Distress Syndrome (ARDS) happens to 67% of all severe COVID-19 cases with mortality rate of 50-94%. Main characteristics of ARDS are poor oxygenation and non-compliant lungs. The lungs are like inflatable balloons that are actively inflated by the positive pressure within and/or the negative pressure created in the pleural cavity. Compliance is the ability of the lungs to distend at a certain level of transpulmonary pressure. Surfactant lowers the surface tension of the alveoli so that end-expiratory pulmonary collapse could be prevented and pulmonary compliance could be maintained. Surfactants also play an important role in the host's defense against infection. Surfactants comprise of phospholipids, cholesterol and surfactant proteins (SP) SP-A, -B, -C and –D. Previous study showed that concentration of SP-D was significantly higher in ARDS patients. Higher serum SP-D concentrations were associated with a greater risk of death, fewer ventilator-free days, and fewer organ failure-free days. This review highlights the role of surfactant especially SP-D in pulmonary compliance and ARDS in COVID-19.

Serum surfactant protein D in COVID-19 is elevated and correlated with disease severity

BackgroundThe serum surfactant protein D (SP-D) level is suggested to be a useful biomarker for acute lung injuries and acute respiratory distress syndrome. Whether the serum SP-D level could identify the severity of coronavirus disease 2019 (COVID-19) in the early stage has not been elucidated.MethodsWe performed an observational study on 39 laboratory-confirmed COVID-19 patients from The Fourth People’s Hospital of Yiyang, Hunan, China. Receiver operating characteristic (ROC) curve analysis, correlation analysis, and multivariate logistic regression model analysis were performed.ResultsIn the acute phase, the serum levels of SP-D were elevated significantly in severe COVID-19 patients than in mild cases (mean value ± standard deviation (SD), 449.7 ± 125.8 vs 245.9 ± 90.0 ng/mL, P<0.001), while the serum levels of SP-D in the recovery period were decreased dramatically than that in the acute phase (mean value ± SD, 129.5 ± 51.7 vs 292.9 ± 130.7 ng/ml, P<0.001), and so were for the stratified patients. The chest CT imaging scores were considerably higher in the severe group compared with those in the mild group (median value, 10.0 vs 9.0, P = 0.011), while markedly lower in the recovery period than those in the acute phase (median value, 2.0 vs 9.0, P<0.001), and so were for the stratified patients. ROC curve analysis revealed that areas under the curve of lymphocyte counts (LYM), C-reaction protein (CRP), erythrocyte sedimentation rate (ESR), interleukin-6 (IL-6), and SP-D for severe COVID-19 were 0.719, 0.833, 0.817, 0.837, and 0.922, respectively. Correlation analysis showed that the SP-D levels were negatively correlated with LYM (r = − 0.320, P = 0.047), while positively correlated with CRP (r = 0.658, P<0.001), IL-6 (r = 0.471, P = 0.002), the duration of nucleic acid of throat swab turning negative (r = 0.668, P<0.001), chest CT imaging score on admission (r = 0.695, P<0.001) and length of stay (r = 0.420, P = 0.008). Multivariate logistic regression model analysis showed that age (P = 0.041, OR = 1.093) and SP-D (P = 0.008, OR = 1.018) were risk factors for severe COVID-19.ConclusionsElevated serum SP-D level was a potential biomarker for the severity of COVID-19; this may be useful in identifying patients whose condition worsens at an early stage.

Rapid decrease of serum surfactant protein-D levels predicts the reactivity of rituximab therapy in systemic sclerosis-associated interstitial lung disease.

Systemic sclerosis (SSc) is an autoimmune disorder characterized by vascular damage and excessive fibrosis. SSc-associated interstitial lung disease (ILD) is a leading cause of death in SSc. Several studies have shown the efficacy of rituximab (RTX) in SSc-ILD, but no study has examined the relation between RTX reactivity and change of serum marker levels. In this study we examined the relation between change of serum surfactant protein-D (SP-D) levels and change of percentage forced vital capacity (FVC) in 11 SSc-ILD patients with anti-topoisomerase I antibody treated by RTX. Serum SP-D levels were significantly decreased compared with baseline at 2weeks after first RTX infusion in good responders (P=0.04), while not in poor responders (P=0.77). Moreover, ΔSP-D at 2weeks negatively correlated with Δ%FVC at 24weeks (P=0.001). In conclusion, we suggested that the rapid decrease of SP-D levels may be a predictive marker of RTX effect against SSc-ILD.

Serum Surfactant Protein D is a Potential Biomarker for Chronic Obstructive Pulmonary Disease: a Systematic Review and Meta-analysis.

A number of studies have been conducted to investigate the association between serum surfactant protein D (SP-D) concentration and chronic obstructive pulmonary disease (COPD) risk. However, the results are inconsistent. This systematic review and meta-analysis aim to investigate whether serum SP-D concentration is a potential biomarker for COPD diagnosis. We searched Web of Science, PubMed, China National Knowledge Infrastructure (CNKI), and Wanfang Database from inception through July 18, 2018. The standardized mean difference (SMD) with 95% confidence interval (CI) was used to investigate the effect sizes. Seventeen eligible studies from a total of 4,639 subjects were finally included in this systematic review and meta-analysis. The results indicated that serum SP-D levels in COPD patients were significantly higher than those in controls (SMD = 1.01, 95% CI = 0.62 - 1.41, p < 0.001). We also found that serum SP-D concentration in acute exacerbation of chronic obstructive pulmonary disease (AECOPD) patients was significantly higher than that in stable COPD patients (SMD = 1.50, 95% CI = 0.92 - 2.08, p < 0.001), and serum SP-D concentration was higher in smokers than in nonsmokers in healthy population (SMD = 1.50, 95% CI = 0.35 - 2.64, p = 0.025). The current systematic review and meta-analysis indicates that serum SP-D levels may be a promising biomarker for COPD. In particular, increased serum SP-D levels appear to be associated with acute exacerbation of COPD and smoking in healthy population.

Serum Surfactant Protein D as a Biomarker for Measuring Lung Involvement in Obese Patients With Type 2 Diabetes.

Lung impairment is a new target for late diabetic complications. Biomarkers that could help identify patients requiring functional respiratory tests have not been reported. Our aim was to examine whether serum surfactant protein D (SP-D) and A (SP-A) could be useful biomarkers of lung damage in obese patients with type 2 diabetes (T2D) without known lung disease. A case-control study conducted in an ambulatory obesity unit. Forty-nine obese patients with T2D and 98 subjects without diabetes matched by age, sex, body mass index, and waist circumference were included. Serum SP-D and SP-A levels were measured using enzyme-linked immunosorbent assay. Forced spirometry and static pulmonary volume were assessed. Patients with T2D exhibited higher serum SP-D concentrations than control subjects (P = 0.006). No differences in serum SP-A concentrations were observed. There was an inverse association between forced expiratory volume in 1 second (FEV1) and serum SP-D (r = -0.265; P = 0.029), as well as a significant positive relationship between SP-D concentration and residual volume (r = 0.293; P = 0.043). From receiver operating characteristic analysis, the best SP-D cutoff to identify a FEV1 <80% of predicted was 132.3 ng/mL (area under the curve, 0.725; sensitivity, 77.7%; specificity, 69.4%). Stepwise multivariate regression analysis showed that serum SP-D concentration ≥132.3 ng/mL was independently associated with a FEV1 <80% of predicted (R2 = 0.406). Only the existence of T2D contributed independently to serum SD-P variance among all subjects (R2 = 0.138). Serum SP-D concentration can be a useful biomarker for detecting lung impairment in obese patients with T2D.

Secondhand tobacco smoke and severity in wheezing children: Nasal oxidant stress and inflammation

ABSTRACTObjectives: Prenatal and postnatal smoke exposures are associated with many lung diseases in children due to impaired lung function, increased inflammation, and oxidative stress. We aimed to determine the influence of secondhand tobacco smoke exposure on the levels of nasal glutathione, IL-8, IL-17, MMP-9, and TIMP-1, as well as serum surfactant protein-D (SP-D) in wheezy children. Methods: We enrolled 150 children with recurrent wheezing and recorded wheezing characteristics at enrollment. We measured the levels of serum cotinine, SP-D, nasal glutathione, IL-8, IL-17, MMP-9, and TIMP-1. Serum cotinine levels between 3 and 12 ng/mL, and above 12 ng/mL were defined as lower and higher level secondhand tobacco smoke exposure, respectively. The ANOVA test, Pearson's correlation analysis and multivariate analysis with a linear regression test were used for the statistical analysis. Results: Ninety-one children had been exposed to lower level secondhand tobacco smoke, while 24 children were exposed to higher level secondhand tobacco smoke. Thirty-five children were not exposed to cigarette smoke. Wheezing symptom scores were higher in exposed children (p = 0.03). Levels of other biomarkers showed no significant difference. Conclusions: Secondhand tobacco smoke exposure is associated with more severe respiratory symptoms in wheezing children. However, levels of nasal or serum inflammatory markers fail to explain this association, either because of different mechanical factors in the process or due to low levels of the biomarkers especially in nasal secretions.

Measurement of exhaled nitric oxide and serum surfactant protein D levels for monitoring radiation pneumonitis following thoracic radiotherapy

The present study aimed to examine the role of exhaled nitric oxide (eNO) and serum surfactant protein D (SP-D) level in the determination of radiation pneumonitis (RP) after thoracic radiotherapy (RT). The study included 34 treatments for 33 patients, including 16 three-dimensional conformal and 18 stereotactic body RT treatments. eNO levels were measured prior to RT, immediately subsequent to RT, every week during the RT course and at 1, 3, 6, 9 and 12 months following the treatment. The therapy reduced the eNO from 24.3±12.8 ppb prior to RT to 19.0±10.4 ppb immediately subsequent to RT (P=0.04). A total of 5 patients (14%) developed symptomatic RP of grade 2 or higher 3–5 months later, and exhibited an eNO elevation of 2.1±0.68-fold the minimum value, whereas the RP- group exhibited 1.4±0.6-fold elevation (P=0.02). The sensitivity of a cut-off of a 1.4-fold increase in the eNO ratio at the onset of RP was 100%; however, the specificity was 52%, and no predictive alterations to eNO levels were observed prior to the onset of RP. RT was associated with an elevated serum SP-D level at 3–6 months after RT. There was a statistically significant difference in the initial serum SP-D level between RP+ and RP- patients. In conclusion, obtaining the eNO ratio was a useful RP monitoring tool but did not predict RP occurrence in the present setting, whereas serum SP-D level may be a potential predictor for the detection of RP risk.

Preoperatiove Airway Bacterial Colonization: the Missing Link between Non-small Cell Lung Cancer Following Lobectomy and Postoperative Pneumonia?

背景与目的外科手术是目前治疗肺癌的主要手段，肺癌患者围术期死亡的主要原因仍是术后肺炎。已有的研究结果显示致病性气道定植菌被认为是术后肺部并发症的一个独立危险因素，本研究旨在探讨术前致病性气道定植菌的存在与术后发生肺炎的关系及其危险因素。方法横断面调查2014年5月至2015年1月连续收治于成都市6家三级甲等医院胸外科行手术治疗的125例非小细胞肺癌患者，术前经纤维支气管镜取气管及支气管内液细菌学标本，并检测术前血清肺表面活性蛋白D（surfactant protein D, SP-D）水平，术后肺部相关并发症进行分析。结果肺癌患者术前合并致病性气道定植菌的发生率为15.2%（19/125），以革兰氏阴性菌为主（19/22, 86.36%）；肺癌患者术前合并致病性气道定植菌的高危因素为：高龄（≥75岁）和长期吸烟史（吸烟指数≥400支/年）；术后肺部相关并发症和术后肺炎发生率在肺癌合并致病性气道定植菌组（42.11%, 26.32%）均显著高于非合并组（16.04%, 6.60%）（P=0.021, P=0.019）。术前血清SP-D浓度在肺癌合并致病性气道定植菌（31.25±6.09）显著高于非合并组（28.17±5.23）（P=0.023）。并发术后肺炎患者中气道致病性定值菌发生率为41.67%（5/12），其发生率是无手术后肺炎患者的3.4倍（OR=3.363, 95%CI: 1.467-7.711）。结论肺癌患者合并致病性气道定植菌与术后肺炎发生密切相关，且高危险因素是高龄和长期吸烟史。

Analysis of predictive parameters for the development of radiation-induced pneumonitis.

INTRODUCTION:Prevention and effective treatment of radiation-induced pneumonitis (RP) could facilitate greater use of radiation therapy (RT) for lung cancer. The purpose of this study was to determine clinical parameters useful for early prediction of RP.METHODS:Blood sampling, pulmonary function testing, chest computed tomography, and bronchoalveolar lavage (BAL) were performed in patients with pathologically confirmed lung cancer who had completed ≥60 Gy of RT, at baseline, shortly after RT, and at 1 month posttreatment.RESULTS:By 3 months post-RT, 11 patients developed RP (RP group) and the remaining 11 patients did not (NRP group). RT significantly increased total cell counts and alveolar macrophages in BAL of the NRP group, whereas lymphocyte count was increased in both groups. Matrix metallopeptidase-9 (MMP-9) increased and vascular endothelial growth factor decreased significantly in the BAL fluid (BALF) of the RP group following RT. Serum surfactant protein D (SP-D) increased significantly in the NRP group. SP-D in BALF from the RP group increased significantly with a subsequent increase in serum SP-D. Pulmonary dilution decreased similarly in both groups of patients.CONCLUSIONS:Increased SP-D in BALF, rather than that in serum, could be useful biomarkers in predicting RP. The MMP-9 in BALF might play a role in the pathogenesis of RP. Pulmonary dilution test may not be predictive of the development of RP.

Can Serum Surfactant Protein D Levels be used as an Effective Factor Instead of Clinical Severity Scores of Pneumonia in Pediatric Emergency Departments?

Aim: To investigate whether serum surfactant protein D (SP-D) level is an applicable indicator in differentiating bacterial and viral pneumonia and determining clinical severity in cases with community-acquired pneumonia (CAP). Materials and Methods: A total of 67 subjects were analyzed prospectively; of these, 32 were patients (aged 1 month–18 years) with a diagnosis of CAP and 35 were healthy control subjects. Results: The median age of the patients was 17.5 months (1.5–156 months). The serum SP-D levels of the patient group were significantly higher than those of the control group (p<0.001). Based on the pneumonia clinical severity index, serum SP-D levels in patients with mild (n=7), moderate (n=19), and severe (n=6) pneumonia were significantly higher than those in the control group (p<0.001, respectively). The serum SP-D levels in patients with severe pneumonia were much higher than in those with mild and moderate grades based the clinical severity index (p<0.001 and p<0.001, respectively). Although the serum SP-D levels in the bacterial pneumonia group were higher than those in the viral pneumonia group, the difference was not statistically significant. Conclusion: Although serum SP-D has limited efficacy in differentiating bacterial and viral pneumonia with respect to CAP in children, it can be used as an effective bioindicator for determining the clinical severity of the disease in emergency services. (Eurasian J Emerg Med 2016; 15: 1-6)

Levels and clinical significance of serum SP-D and MBL in infants with cytomegalovirus pneumonia

Objective To investigate the levels of serum surfactant protein D (SP-D) and mannose-binding lectin (MBL) in infants with cytomegalovirus (CMV) pneumonia with the severity of disease. Methods A total of 101 hospitalized infants with CMV pneumonia were enrolled from January 2011 to December 2012.These patients were divided as the severe pneumonia group (n=48) and the mild pneumonia group (n=53) according to physical sign of lung and complication.Another 55 infants who were hospitalized in the same period with non-infectious diseases were used as the control group.Serum levels of SP-D and MBL were detected by enzyme-linked immunosorbent assay.Blood gas analyzer was used to measure arterial partial pressure of oxygen (PaO2) of the blood in severe patients. Results The mean serum SP-D levels in the severe pneumonia group [(150.08±52.59)ng/ml] and the mild pneumonia group [(109.67±31.39)ng/ml] were significantly higher than those in control group [(41.33±16.42)ng/ml] (P 0.05). In severe patients, serum SP-D levels were negatively correlated with PaO2 (r=-0.565, P<0.01). Conclusion Serum SP-D is associated with the severity of CMV pneumonia, but MBL shows no relation.The serum SP-D levels has an important clinical significance in judgment the sererity of infants with CMV pneumonia. Key words: Surfactant protein D; Mannose-binding lectin; Arterial partial pressure of oxygen; Cytomegalovirus pneumonia; Infant

Clinical value of surfactant protein D as a biomarker of pulmonary fibrosis in patients with scleroderma systematica in relation to the presence of gastroesophageal reflux

To study the role of serum surfactant protein D (SP-D) as a biomarker of lung injury in scleroderma systematica (SDS) in relation to the presence of gastroesophageal reflux (GER). Fifty-six patients (mean age 46±14 years) with diffuse and circumscribed SDS were examined and underwent pulmonary functional tests, X-ray and, if lung injury was present, high-resolution computed tomography of the lung, echocardiography, gastroduodenoscopy, and barium X-ray of the esophagus; an enzyme-linked immunosorbent assay was used to determine serum SP-D levels. SP-D concentrations significantly correlate with the presence of lung injury in SDS and are significantly higher in the presence of pulmonary fibrosis and the signs of frosted glass and honeycomb lung patterns. SP-D levels were higher in the patients with lung injury and SDS in the group of those with pulmonary fibrosis and GER than in the group of pulmonary fibrosis patients without the latter. Serum SP-D may be considered in a number of biomarkers for the severity of lung injury in SDS, including GER-associated lung injury.

Genetic Polymorphisms of Surfactant Protein D rs2243639, Interleukin (IL)-1β rs16944 and IL-1RN rs2234663 in Chronic Obstructive Pulmonary Disease, Healthy Smokers, and Non-Smokers

Chronic obstructive pulmonary disease (COPD) is a complex chronic inflammatory disease that involves the activity of various inflammatory cells and mediators. It has been suggested that susceptibility to COPD is, at least in part, genetically determined. The primary aim of this study was to investigate the association between surfactant protein D (SFTPD) rs2243639, interleukin (IL)-1β rs16944 and IL-1 receptor antagonist (IL-1RN) rs2234663 gene polymorphisms and COPD susceptibility, as well as examining the association between the various IL-1RN/IL-1β haplotypes and pulmonary function tests (PFT). Secondly, we aimed to examine the influence of SFTPD rs2243639 polymorphism on serum surfactant protein D (SP-D) level. A total of 114 subjects were recruited in this study and divided into three groups: 63 COPD patients, 25 asymptomatic smokers, and 26 healthy controls. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed for the detection of SFTPD rs2243639 and IL-1β rs16944 polymorphisms. Detection of variable numbers of an 86-bp tandem repeat (VNTR) of IL-1RN was done using PCR. Serum SP-D level was measured using enzyme linked-immunosorbent assay. PFTs were measured by spirometry. Carriers of the SFTPD AG and AA polymorphic genotypes constituted 71.4% of COPD patients versus 48% in asymptomatic smokers, with a statistically significant difference between the two groups (p=0.049). Smokers who were carriers of the polymorphic SFTPD rs2243639 A allele (AG and AA genotypes) have a 2.708 times risk of developing COPD when compared with wild-type GG genotype carriers [odds ratio (OR) 2.708 (95% CI 1.041-7.047)]. Forced expiratory flow (FEF) 25-75% predicted was higher in IL-1RN*1/*1 when compared with *1/*2 (p=0.013). FEF25-75% predicted in carriers of haplotype IL-1RN *1/IL-1β T (49.21±10.26) was statistically significantly higher than in carriers of IL-1RN *2/IL-1β T (39.67±12.64) [p=0.005]. Forced expiratory volume in 1s (FEV1)/forced vital capacity (FVC) in carriers of haplotype IL-1RN *1/IL-1β T (64.09±6.39) was statistically significantly higher than in carriers of IL-1RN *2/IL-1βT (59.44±7.71) [p=0.048]. There was no association between SFTPD rs2243639 genotypes and serum SP-D level. Smokers who are carriers of the SFTPD AG and AA polymorphic genotypes may be at a higher risk of developing COPD when compared with wild-type GG genotype carriers. IL-1RN rs2234663/IL-1β rs16944 haplotypes influence FEF25-75% predicted and FEV1/FVC. SFTPD rs2243639 polymorphism did not influence serum SP-D levels in our group of recruited subjects.

Evaluation of Full-length, Cleaved and Nitrosylated Serum Surfactant Protein D as Biomarkers for COPD

Chronic obstructive pulmonary disease (COPD) is a multicomponent condition that is characterized by partially reversible airflow obstruction. Serum surfactant protein D (SP-D) is synthesized by type II pneumocytes and Clara cells and participates in surfactant homeostasis and pulmonary host defense. Serum levels of SP-D are raised in individuals with COPD but there is no correlation between the serum level of SP-D and the severity of airflow obstruction. Serum SP-D is present in different forms that may have more utility as a biomarker for COPD. We report here the development of new monoclonal antibodies to full length and cleaved SP-D. We have assessed these and existing antibodies in 98 individuals with COPD recruited to the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) cohort. Our data show that neither monoclonal antibodies to full length nor cleaved SP-D provide additional information over that obtained with a polyclonal antibody. Moreover, levels of serum nitrosylated-SP-D did not correlate with serum level of SP-D or any clinical phenotype of COPD. The measurement of modified SP-D is of limited value in characterising individuals with COPD.

Prescreening based on the presence of CT-scan abnormalities and biomarkers (KL-6 and SP-D) may reduce severe radiation pneumonitis after stereotactic radiotherapy

PurposeTo determine the risk factors of severe radiation pneumonitis (RP) after stereotactic body radiation therapy (SBRT) for primary or secondary lung tumors.Materials and methodsFrom January 2003 to March 2009, SBRT was performed on 117 patients (32 patients before 2005 and 85 patients after 2006) with lung tumors (primary = 74 patients and metastatic/recurrent = 43 patients) in our institution. In the current study, the results on cases with severe RP (grades 4-5) were evaluated. Serum Krebs von den Lungen-6 (KL-6) and serum Surfactant protein-D (SP-D) were used to predict the incidence of RP. A shadow of interstitial pneumonitis (IP) on the CT image before performing SBRT was also used as an indicator for RP. Since 2006, patients have been prescreened for biological markers (KL-6 & SP-D) as well as checking for an IP-shadow in CT.ResultsGrades 4-5 RP was observed in nine patients (7.7%) after SBRT and seven of these cases (6.0%) were grade 5 in our institution. A correlation was found between the incidence of RP and higher serum KL-6 & SP-D levels. IP-shadow in patient's CT was also found to correlate well with the severe RP. Severe RP was reduced from 18.8% before 2005 to 3.5% after 2006 (p = 0.042). There was no correlation between the dose volume histogram parameters and these severe RP patients.ConclusionPatients presenting with an IP shadow in the CT and a high value of the serum KL-6 & SP-D before SBRT treatment developed severe radiation pneumonitis at a high rate. The reduction of RP incidence in patients treated after 2006 may have been attributed to prescreening of the patients. Therefore, pre-screening before SBRT for an IP shadow in CT and serum KL-6 & SP-D is recommended in the management and treatment of patients with primary or secondary lung tumors.