Serum Surfactant Protein D Concentrations Research Articles

Lipidomic analysis of surfactant and plasma from horses with asthma and age-matched healthy horses.

To perform lipidomic analysis of surfactant and plasma from asthmatic and healthy horses. 30 horses with clinical signs of asthma and 30 age-matched control horses. Detailed history, physical examination, CBC, and bronchoalveolar lavage fluid (BALF) cytologies were obtained. Asthmatic horses were grouped based on their BALF inflammatory profile: severe equine asthma (SEA), mild equine asthma with neutrophilic airway inflammation (MEA-N), or mild equine asthma with eosinophilic airway inflammation (MEA-E). Each asthma group was assigned its own age-matched control group. Lipidomic analysis was completed on surfactant and plasma. Surfactant protein D (SP-D) concentrations were measured in serum and BALF. SEA surfactant was characterized by a phospholipid deficit and altered composition (increased ceramides, decreased phosphatidylglycerol, and increased cyclic phosphatidic acid [cPA]). In comparison, MEA-N surfactant only had a decrease in select phosphatidylglycerol species and increased cPA levels. The plasma lipidomic profile was significantly different in all asthma groups compared to controls. Specifically, all groups had increased plasma phytoceramide. SEA horses had increased plasma cPA and diacylglycerol whereas MEA-N horses only had increased cPA. MEA-E horses had increases in select ceramides and dihydrocermides. Only SEA horses had significantly increased serum SP-D concentrations. The most significant surfactant alterations were present in SEA (altered phospholipid content and composition); only mild changes were observed in MEA-N horses. The plasma lipidomic profile was significantly altered in all groups of asthmatic horses and differed among groups. Data from a larger population of asthmatic horses are needed to assess implications for diagnosis, prognosis, and treatment.

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.

Refractory ceramic fibers induced changes in serum Clara cell protein 16 and surfactant protein D levels in rats

Objective: To explore the effect of refractory ceramic fibers (RCFs) on the serum Clara cell protein 16 (CC16) and surfactant protein D (SP-D) levels in Wistar rats. Methods: In October 2020, 96 healthy adult male Wistar rats were randomly divided into control group (equal volume of normal saline) , low-dose group (5 mg/ml RCFs) , medium-dose group (10 mg/ml RCFs) and high-dose group (20 mg/ml RCFs) , and subjected to non-exposure tracheal instillation. After intraperitoneal anesthesia, the rats were instilled with 200 μl of RCFs suspension or normal saline, once every 3 days for a total of 4 times. At 7, 14, 28, and 90 days after exposure, 6 rats were sacrificed by blood sampling through the abdominal aorta. The organs were separated, histopathological changes of lungs were observed and lung injury scores were performed. The contents of serum CC16 and SP-D were determined by enzyme-linked immunosorbent assay (ELISA) . Results: RCFs could cause inflammatory cells in rat lung tissues, widening of the lung septum and destruction of alveolar structure. 7 days after exposure, the lung injury scores of rats in each dose group were higher than control group, and the lung injury score of the high-dose group was higher than low-dose group (P<0.05) . 14 and 90 days after exposure, the lung injury scores of the medium-dose and high-dose groups were higher than control group (P<0.05) . 28 days after exposure, the lung injury score of the high-dose group was higher than control group (P<0.05) . 7 days after exposure, the serum CC16 and SP-D concentrations of rats in the medium-dose and high-dose groups were significantly higher than control and low-dose groups (P<0.05) . 28 days after exposure, the serum CC16 concentrations of rats in the low-dose and medium-dose groups were significantly lower than those of the control and high-dose groups (P<0.05) . After 90 days of exposure, the serum CC16 concentrations of rats decreased with the increase of the exposure dose (F=28.853, P<0.01) , and the concentrations of SP-D increased with the increase of the exposure dose (F=25.636, P<0.01) . Conclusion: RCFs exposure may cause certain damage to rat Clara cells and alveolar-capillary barrier. The severity of lung injury can be indirectly understood through the dynamic changes of serum CC16 and SP-D.

Surfactant protein D concentrations in serum and bronchoalveolar lavage fluid from young healthy horses on pasture and in a barn environment.

To evaluate surfactant protein D (SP-D) concentrations in serum and bronchoalveolar lavage fluid (BALF) from young healthy horses on pasture or housed in a typical barn. 20 young healthy horses. Horses were randomly assigned to 1 of 2 groups (pasture, n = 10; barn, 10), and serum and BALF samples were collected for SP-D determination at baseline (all horses on pasture) and 2 weeks and 4 weeks after the barn group of horses was relocated from the pasture to the barn. Other evaluations included physical and tracheoscopic examinations. Findings were compared within and between groups. Physical and tracheoscopic examinations, CBC, and serum biochemical analysis did not reveal evidence of respiratory disease, and no significant differences were present within and between groups. Serum SP-D concentrations did not significantly differ within and between groups, but BALF SP-D concentrations were significantly lower for the barn group at 2 weeks but not at 4 weeks, compared with baseline. The BALF SP-D concentration-to-BALF total protein concentration ratio was < 1.5 and did not significantly differ within and between groups. A mild decrease was evident in the concentration of SP-D in the BALF collected from young healthy horses after 2 weeks of exposure to a barn environment. The clinical importance of this finding remains to be determined.

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 concentrations of Krebs von den Lungen-6, surfactant protein D, and matrix metalloproteinase-2 as diagnostic biomarkers in patients with asbestosis and silicosis: a case\u2013control study

BackgroundAsbestosis and silicosis are progressive pneumoconioses characterized by interstitial fibrosis following exposure to asbestos or silica dust. We evaluated the potential diagnostic biomarkers for these diseases.MethodsThe serum concentrations of Krebs von den Lungen-6 (KL-6), surfactant protein D (SP-D), and matrix metalloproteinase-2 (MMP-2), MMP-7, and MMP-9 were measured in 43 patients with asbestosis, 45 patients with silicosis, 40 dust-exposed workers (DEWs) without pneumoconiosis, and 45 healthy controls (HCs). Chest high-resolution computed tomography (HRCT) images were reviewed by experts blinded to the clinical data. According to the receiver operating characteristic (ROC) curve, the ideal level of each biomarker and its diagnostic sensitivity were obtained.ResultsThe serum KL-6 and MMP-2 concentrations were highest in patients with asbestosis, particularly in comparison with those in DEWs and HCs (P<0.05). The serum SP-D concentration was significantly higher in patients with asbestosis than in patients with silicosis, DEWs, and HCs (P<0.01), whereas no significant difference was noted among patients with silicosis, DEWs, and HCs. No significant difference in the serum MMP-7 or -9 concentration was found among patients with asbestosis, patients with silicosis, DEWs, or HCs. Among patients with asbestosis, the serum KL-6 concentration was significantly correlated with the lung fibrosis scores on HRCT and negatively correlated with the forced vital capacity (FVC) % predicted and diffusing capacity of the lung for carbon monoxide (DLCO) % predicted. The serum SP-D and MMP-2 concentrations were negatively correlated with the DLCO % predicted (all P<0.05). The order of diagnostic accuracy according to the ROC curve was KL-6, SP-D, and MMP-2 in patients with asbestosis alone and in the combination of both patients with asbestosis and those with silicosis. The combination of all three biomarkers may increase the possibility of diagnosing asbestosis (sensitivity, 93%; specificity, 57%) and both asbestosis and silicosis (sensitivity, 83%; specificity, 62%).ConclusionsKL-6, SP-D, and MMP-2 are available biomarkers for the adjuvant diagnosis of asbestosis and silicosis. The combination of all three biomarkers may improve the diagnostic sensitivity for asbestosis and silicosis.

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.

The role of serum surfactant protein D as a biomarker of exacerbation of chronic obstructive pulmonary disease.

Background: The exacerbation of chronic obstructive pulmonary disease (COPD) is a major factor for the high mortality associated with the disease. There is a paucity in the lung-specific biomarkers which diagnose these exacerbations. Surfactant protein D (SP-D) is a promising biomarker in predicting clinical outcomes for patients with COPD, is lung-specific and can be detected in serum. However, the profile in which serum concentrations of SP-D change during acute exacerbation is still unclear. This study aims to estimate and compare the concentrations of serum SP-D in patients with stable disease and during the exacerbation. Methods: A cross-sectional study was conducted which composed of apparently healthy individuals (n = 28), which included 14 smokers and 14 nonsmokers, patients with stable COPD (n = 28), and patients experiencing acute exacerbations (n = 28). Pulmonary functions were performed for all groups. Serum SP-D concentrations were measured using enzyme-linked immunosorbent assay (ELISA). These concentrations were compared by analysis of variance. Results: Serum SP-D levels were significantly elevated in patients with acute exacerbations (508.733 ± 102.813 ng/ml) compared to patients with stable COPD (337.916 ± 86.265 ng/ml) and healthy subjects (177.313 ± 46.998 ng/ml; p < 0.001). Serum SP-D levels correlated inversely with lung function parameters including FEV1%pred, FVC%pred and FEV1/FVC. Conclusion: Serum SP-D levels are raised early on during acute exacerbations of COPD, which could be a potential early diagnostic biomarker for COPD exacerbations.

Fucosylated surfactant protein-D is a biomarker candidate for the development of chronic obstructive pulmonary disease

We previously reported that knockout mice for α1,6-fucosyltransferase (Fut8), which catalyzes the biosynthesis of core-fucose in N-glycans, develop emphysema and that Fut8 heterozygous knockout mice are more sensitive to cigarette smoke-induced emphysema than wild-type mice. Moreover, a lower FUT8 activity was found to be associated with a faster decline in lung function among chronic obstructive pulmonary disease (COPD) patients. These results led us to hypothesize that core-fucosylation levels in a glycoprotein could be used as a biomarker for COPD. We focused on a lung-specific glycoprotein, surfactant protein D (SP-D), which plays a role in immune responses and is present in the distal airways, alveoli, and blood circulation. The results of a glycomic analysis reported herein demonstrate the presence of a core-fucose in an N-glycan on enriched SP-D from pooled human sera. We developed an antibody–lectin enzyme immunoassay (EIA) for assessing fucosylation (core-fucose and α1,3/4 fucose) in COPD patients. The results indicate that fucosylation levels in serum SP-D are significantly higher in COPD patients than in non-COPD smokers. The severity of emphysema was positively associated with fucosylation levels in serum SP-D in smokers. Our findings suggest that increased fucosylation levels in serum SP-D are associated with the development of COPD. Biological significanceIt has been proposed that serum SP-D concentrations are predictive of COPD pathogenesis, but distinguishing between COPD patients and healthy individuals to establish a clear cut-off value is difficult because smoking status highly affects circulating SP-D levels. Herein, we focused on N-glycosylation in SP-D and examined whether or not N-glycosylation patterns in SP-D are associated with the pathogenesis of COPD. We performed an N-glycomic analysis of human serum SP-D and the results show that a core-fucose is present in its N-glycan. We also found that the N-glycosylation in serum SP-D was indeed altered in COPD, that is, fucosylation levels including core-fucosylation are significantly increased in COPD patients compared with non-COPD smokers. The severity of emphysema was positively associated with fucosylation levels in serum SP-D in smokers. Our findings shed new light on the discovery and/or development of a useful biomarker based on glycosylation changes for diagnosing COPD.This article is part of a Special Issue entitled: HUPO 2014.

Serum concentration of surfactant protein D in horses with lower airway inflammation

Surfactant protein D (SP-D), mainly synthesised by alveolar type II cells and nonciliated bronchiolar cells, is one important component of innate pulmonary immunity. In man, circulating concentrations of SP-D are routinely used as biomarkers for pulmonary injury. To date, serum SP-D levels have only been investigated in horses in an experimental model of bacterial airway infection. To compare serum SP-D concentrations at rest and after exercise in horses with and without inflammatory airway disease (IAD). Venous blood samples were collected from 42 Standardbred racehorses at rest and 60 min after performing a standardised treadmill exercise test. Tracheal wash and bronchoalveolar lavage fluid (BALF) samples were collected after exercise. Based on BALF cytology, 22 horses were defined as IAD-affected and 20 classified as controls. Serum SP-D concentrations were assessed using a commercially available ELISA kit and statistically compared between groups of horses and sampling times. Serum concentrations of SP-D in IAD-affected horses were significantly higher than those of control horses, both at rest and after exercise. Within the IAD-affected group, no significant correlation was found between serum SP-D concentrations and BALF cytology. Within each group of horses (IAD and control), no significant influence of exercise was found on serum SP-D levels. This is the first study determining serum SP-D concentrations in a noninfectious, naturally occurring form of lower airway inflammation in horses. The results highlight that IAD is associated with a detectable, though moderate, increase of circulating SP-D levels. Serum concentration of surfactant protein D could represent a potentially valuable and readily accessible blood biomarker of equine lower airway inflammation.

The Effect of Intrauterine Growth Restriction on Circulating Surfactant Protein D Concentrations in the Perinatal Period

The aim of this study was to investigate possible alterations in circulating concentrations of surfactant protein D (SP-D)-an important component of the innate immune system that is upregulated in pulmonary diseases-in appropriate for gestational age (AGA) and intrauterine growth-restricted (IUGR) pregnancies, because the latter are characterized by structural lung immaturity, impaired immunocompetence, and increased risk of respiratory infections and chronic obstructive lung disease in later life. Serum SP-D concentrations were determined in 40 mothers and their 20 IUGR and 20 AGA full-term fetuses-neonates on postnatal day 1 (N1) and 4 (N4). Fetal SP-D concentrations were higher in the IUGR group (b = 18.16, 95% CI: 6.86-29.47, P = .002) and negatively correlated with infants' customized centiles and gestational age (r = -.326, P = .04, and r = -.446, P = .004, respectively). In both groups, fetal SP-D concentrations were lower than N1 and N4 ones (P <or= .015 in all cases). In the IUGR group, N1 SP-D concentrations were higher in vaginal deliveries (P = .032). Higher SP-D concentrations in IUGR fetuses may reflect structural lung immaturity, leading to increased alveolar-vascular permeability and protein leakage into the circulation. Alternatively, SP-D production may be increased due to intrauterine glucocorticoid exposure, leading to accelerated lung maturation. Surfactant protein D concentrations postnatally increase and are higher in neonates born vaginally, probably as a consequence of lung liquid reabsorption, concomitant with initiation of breathing and delivery stress. A progressive decrease in placental function may result in downregulated SP-D production, accounting for the negative correlation between fetal SP-D concentrations and gestational age.

Polymorphisms in Surfactant Protein–D Are Associated with Chronic Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease (COPD) is characterized by alveolar destruction and abnormal inflammatory responses to noxious stimuli. Surfactant protein-D (SFTPD) is immunomodulatory and essential to host defense. We hypothesized that polymorphisms in SFTPD could influence the susceptibility to COPD. We genotyped six single-nucleotide polymorphisms (SNPs) in surfactant protein D in 389 patients with COPD in the National Emphysema Treatment Trial (NETT) and 472 smoking control subjects from the Normative Aging Study (NAS). Case-control association analysis was performed using Cochran-Armitage trend tests and multivariate logistic regression. The replication of significant associations was attempted in the Boston Early-Onset COPD Study, the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) Study, and the Bergen Cohort. We also correlated SFTPD genotypes with serum concentrations of surfactant protein-D (SP-D) in the ECLIPSE Study. In the NETT-NAS case-control analysis, four SFTPD SNPs were associated with susceptibility to COPD: rs2245121 (P = 0.01), rs911887 (P = 0.006), rs6413520 (P = 0.004), and rs721917 (P = 0.006). In the family-based analysis of the Boston Early-Onset COPD Study, rs911887 was associated with prebronchodilator and postbronchodilator FEV(1) (P = 0.003 and P = 0.02, respectively). An intronic SNP in SFTPD, rs7078012, was associated with COPD in the ECLIPSE Study and the Bergen Cohort. Multiple SFTPD SNPs were associated with serum SP-D concentrations in the ECLIPSE Study. We demonstrated an association of polymorphisms in SFTPD with COPD in multiple populations. We demonstrated a correlation between SFTPD SNPs and SP-D protein concentrations. The SNPs associated with COPD and SP-D concentrations differed, suggesting distinct genetic influences on susceptibility to COPD and SP-D concentrations.

Surfactant Protein D, a Marker of Lung Innate Immunity, Is Positively Associated With Insulin Sensitivity

OBJECTIVEImpaired lung function and innate immunity have both attracted growing interest as a potentially novel risk factor for glucose intolerance, insulin resistance, and type 2 diabetes. We aimed to evaluate whether surfactant protein D (SP-D), a lung-derived innate immune protein, was behind these associations.RESEARCH DESIGN AND METHODSSerum SP-D was evaluated in four different cohorts. The cross-sectional associations between SP-D and metabolic and inflammatory parameters were evaluated in two cohorts, the cross-sectional relationship with lung function in one cohort, and the longitudinal effects of weight loss on fasting and circadian rhythm of serum SP-D and cortisol concentrations in one prospective cohort.RESULTSIn the cross-sectional studies, serum SP-D concentration was significantly decreased in subjects with obesity and type 2 diabetes (P = 0.005) and was negatively associated with fasting and postload serum glucose. SP-D was also associated with A1C, serum lipids, insulin sensitivity, inflammatory parameters, and plasma insulinase activity. Smoking subjects with normal glucose tolerance, but not smoking patients with type 2 diabetes, showed significantly higher serum SP-D concentration than nonsmokers. Serum SP-D concentration correlated positively with end-tidal carbon dioxide tension (r = 0.54, P = 0.034). In the longitudinal study, fasting serum SP-D concentration decreased significantly after weight loss (P = 0.02). Moreover, the main components of cortisol and SP-D rhythms became synchronous after weight loss.CONCLUSIONSThese findings suggest that lung innate immunity, as inferred from circulating SP-D concentrations, is at the cross-roads of inflammation, obesity, and insulin resistance.

Roles of Serum Clara Cell Protein 16 and Surfactant Protein-D in the Early Diagnosis and Progression of Silicosis

To study roles of Clara cell protein 16 (CC16) and surfactant protein-D (SP-D) as serum biomarkers in the early diagnosis and the pathogenesis of silicosis. Thirty healthy volunteers, 30 silica-exposed workers, and 30 workers with suspected silicosis and phase I silicosis were included. Serum CC16 and SP-D concentrations were determined using enzyme-linked immunosorbent assay. Serum CC16 concentrations decreased in silica-exposed workers when compared with in controls, but serum SP-D levels increased, and this trend was obvious in phase 0 and I groups. Discriminant analysis showed that the accuracies of classifying group membership into control, phase 0, phase 0, and phase I were 86.7%, 46.7%, 66.7%, and 70%, respectively, and the total classification accuracy rate was 67.5%. Serum CC16 and SP-D may be useful biomarkers for early diagnosis, and serum SP-D concentration may associate with the pathogenesis of silicosis.

Serum surfactant protein D is correlated to development of dementia and augmented mortality

Development of dementia, including Alzheimer’s disease (AD), is associated with lipid dysregulation and inflammation. As the host defense lectin surfactant protein D (SP-D) has multiple effects in lipid homeostasis and inflammation, the correlation between SP-D concentrations and development of dementia was investigated. A total of 418 non-demented persons were included in the study and cognitively re-examined after 3 years, while survival was followed for 11 years. Serum SP-D concentrations were measured at baseline. Logistic regression analysis controlling for age, gender, smoking status, and CRP showed that Odds Ratio for developing dementia was 2.62 (1.12–6.15) with an SP-D concentration in the highest quartile compared to the other quartiles. The risk of AD was 2.55 (0.95–6.90). Cox regression controlling for the same variables showed that hazard ratio of death was 1.43 (1.06–1.92) in the highest quartile. SP-D concentration thus correlates to development of dementia as well as to augmented mortality.

Plasma surfactant D in patients following acute paraquat intoxication

Free radical-induced lung injury is a major problem that occurs because of paraquat intoxication. Serum surfactant protein D (SP-D) reflects the severity of various lung diseases. The purpose of this study is to investigate the changes in plasma SP-D concentrations and to correlate disease severity with SP-D concentrations in patients with acute paraqaut intoxication. Twelve paraquat-intoxicated patients participated in this study. Their paraquat exposure was assessed by their plasma's paraquat level. Serial plasma SP-Ds were measured by ELISA. SP-D was decreased two and three days after the initial measurement within 2 to 72 hours of ingestion. There was no difference in initial SP-D levels between survivors and non-survivors. The SP-D test revealed a significant positive correlation between the SP-D level and PaO2 (r = 0.384, p = 0.003, N = 57). SP-D did not predict the likelihood of survival, but it was positively correlated with PaO2. This finding suggests that low concentrations of plasma SP-D could reflect hypoxia due to free radical-induced injury.

Therapeutic effects for hypersensitivity pneumonitis induced by Japanese mushroom (Bunashimeji)

Bunashimeji-related hypersensitivity pneumonitis is found among workers who cultivate the mushroom in indoor facilities. An evaluation of protective measures was initiated using the outcomes of clinical, immunological, and radiological findings. Twenty-two patients presented with symptoms of HP; all were employed cultivating Bunashimeji mushrooms in indoor facilities. After hospitalization, 6 of 22 patients quit their job to avoid exposure to spores (Avoidance group). Sixteen patients continued to work used a mask for 3 months, and were then divided into two subgroups: Mask alone (seven patients) and mask plus oral prednisolone (Mask + PSL) (nine patients). The erythrocyte sedimentation rate (ESR), serum Krebs von der Lungen-6 (KL-6), surfactant protein-D (SP-D), lymphocyte stimulation test (LST), ground-glass scores in chest high-resolution computed tomography (HRCT), and bronchoalveolar lavage (BAL) were assessed before and after treatment. Complete avoidance resulted in a significant decrease in LST. There was a significant decrease after PSL treatment in serum KL-6, SP-D, and total cell counts in the BAL fluid in the Mask + PSL group. In the Mask alone group, serum KL-6, SP-D, ground-glass scores in chest HRCT and total cell counts in BAL fluid showed high levels compared with the other two groups. Complete cessation was the best treatment for hypersensitivity pneumonitis. The use of a mask was ineffective for patients with a high serum KL-6 and SP-D concentration and severe ground-glass opacity on chest HRCT. Initial treatment with PSL is recommended for these patients with high levels of total cell counts in BAL fluid.

Genetic and environmental influences of surfactant protein D serum levels

The collectin surfactant protein D (SP-D) is an important component of the pulmonary innate immune system, but SP-D is also present on extrapulmonary epithelial surfaces and in serum, where it has been used as a biomarker for pulmonary disease states. In this study, we investigate the mechanisms defining the constitutional serum level of SP-D and determine the magnitude of the genetic contribution to serum SP-D in the adult population. Recent studies have demonstrated that serum SP-D concentrations in children are genetically determined and that a single nucleotide polymorphism (SNP) located in the NH(2)-terminal region (Met11Thr) of the mature protein is significantly associated with the serum SP-D levels. A classic twin study was performed on a twin population including 1,476 self-reported healthy adults. The serum SP-D levels increased with male sex, age, and smoking status. The intraclass correlation was significantly higher for monozygotic (MZ) twin pairs than for dizygotic (DZ) twin pairs. Serum SP-D variance was influenced by nonshared environmental effects and additive genetic effects. Multivariate analysis of MZ and DZ covariance matrixes showed significant genetic correlation among serum SP-D and metabolic variables. The Met11Thr variant explained a significant part of the heritability indicating that serum SP-D variance could be decomposed into non-shared environmental effects (e(2) = 0.19), additive genetic effects (h(2) = 0.42), and the effect of the Met11Thr variations (q(2) = 0.39).

Host defence lectins in preterm neonates

Deficiency in collectins is discussed as a risk factor for pulmonary and systemic infections in children and adults. The objective of this study was to determine serum concentrations of surfactant protein D (SP-D) and mannose-binding lectin (MBL) in preterm and term infants at birth. 47 preterm infants below 32 wk gestational age (GA) and 19 healthy, term newborn infants at birth have been included in the study, and SP-D as well as MBL concentrations have been determined in umbilical cord blood samples using sandwich ELISA technique. In addition, SP-D concentrations were assessed in tracheal aspirates (TA) of 24 mechanically ventilated preterms and in infants without pulmonary complications before elective surgery. MBL serum concentrations were significantly lower in preterms <32 wk GA (756.7 ng/ml; 14.6-11 184 ng/ml) compared to term newborns (3168.9 ng/ml; 282.3-7679.5 ng/ml; p=0.005; median and range, respectively). Serum SP-D concentrations were significantly decreased in preterms between 28 and 32 wk GA (1.4 ng/ml; 0-4.6 ng/ml; n=26) compared to term infants (2.2 ng/ml; 1.2-3.3 ng/ml; p=0.05) and were found to positively correlate with history of antenatal corticosteroids and chorioamnionitis. SP-D concentrations in TA were increased in preterm infants between 28 and 32 wk GA with respiratory distress syndrome (RDS) (25.0 ng/ml; 0.9-44.7 ng/ml; n=12) compared to control subjects (6.6 ng/ml; 0.5-30.4 ng/ml; n=12) in contrast to extremely immature infants <28 wk GA suffering from RDS (4.4 ng/ml; 0.8-78.4 ng/ml; n=12). In preterm infants, significant changes occur in collectin umbilical cord blood concentrations and pulmonary SP-D levels. Functional aspects of these findings need to be addressed further.

Serum surfactant protein D is increased in acute and chronic inflammation in mice

Surfactant protein A (SP-A) and surfactant protein D (SP-D) are important components of innate immunity that can modify the inflammatory response. However, alterations and regulation of SP-A and SP-D in acute and chronic inflammation are not well defined. In addition, serum SP-D may serve as a biomarker of lung inflammation. We determined the expression of SP-A and SP-D in murine models. To study acute inflammation, we instilled bleomycin intrabronchially. To study chronic lung inflammation, we used a transgenic mouse that overexpresses tumor necrosis factor (TNF)-α under the control of the SP-C promoter. These mice have a chronic mononuclear cell infiltration, airspace enlargement, pulmonary hypertension, and focal pulmonary fibrosis. In acute inflammation model, levels of mRNA for all surfactant proteins were reduced after bleomycin administration. However, serum SP-D was increased from days 7 to 28 after instillation. In chronic inflammation model, SP-D mRNA expression was increased, whereas the expression of SP-A, SP-B and SP-C was reduced. Both serum and lung SP-D concentrations were increased in chronic lung inflammation. These data clarified profile of SP-A and SP-D in acute and chronic inflammation and indicated that serum SP-D can serve as a biomarker of lung inflammation in both acute and chronic lung injury in mice.