Surfactant Protein D Levels Research Articles

Plasma CC16 levels are associated with development of ALI/ARDS in patients with ventilator-associated pneumonia: a retrospective observational study

BackgroundDespite consensus criteria, diagnosing acute lung injury, or its more severe form acute respiratory distress syndrome (ALI/ARDS) remains challenging. Adding objective measures, such as plasma levels of biological markers could facilitate recognition of ALI/ARDS. This study was designed to assess and compare the diagnostic accuracy of biological markers for ALI/ARDS with ventilator-associated pneumonia (VAP).MethodsWe performed serial measurements of Clara cell protein (CC16), soluble receptor for advanced glycation end products (sRAGE), surfactant protein D (SP-D) and Krebs von den Lungen (KL-6) in plasma of patients with VAP and mechanically ventilated control patients without VAP. ALI/ARDS was diagnosed using the criteria of the North-American European consensus conference.ResultsThirty-seven patients were enrolled - 22 patients with VAP and 15 control patients. Ten patients with pneumonia met the ALI/ARDS consensus criteria. Control patients never met these criteria. Plasma CC16 had a good diagnostic capacity for ALI/ARDS as shown by the receiver operating characteristic curve with an area under the curve of 0.91 (95% confidence interval (CI) 0.79 - 1.00; p < 0.001). Identification of ALI/ARDS patients by sudden increases in plasma CC16 of 30% or more yielded a sensitivity of 90% and a specificity of 92%. Of note, levels of CC16 increased 2 days before ALI/ARDS diagnosis. A cut-off level of 50 ng/ml SP-D yielded a specificity of 100% while the sensitivity was 70%. The area under the curve for SP-D was 0.80 (95% CI 0.58 - 1.00; p = 0.02). The diagnostic accuracies of KL-6 and sRAGE were low.ConclusionPlasma CC16 seems a potential biological marker for ALI/ARDS in patients with VAP. Plasma levels of sRAGE, SP-D and KL-6 have limited discriminative power for diagnosing ALI/ARDS in VAP.

Circulating Surfactant Protein D Is Decreased in Systemic Lupus Erythematosus

Deficiencies of innate immune molecules like mannan binding lectin (MBL) have been implicated in the pathogenesis of systemic lupus erythematosus (SLE). Surfactant protein D (SP-D) and MBL belong to the same family of innate immune molecules - the collectins, which share important structural and functional properties. We aimed to compare concentrations of serum SP-D in patients with SLE and in healthy controls, and to investigate if SP-D is associated with selected disease indicators. We investigated the possible association of the Met11Thr polymorphism with disease, since this polymorphism is an important determinant for serum level, oligomerization pattern, and function of SP-D. Serum SP-D was measured using a 5-layer ELISA in 70 SLE patients and 1476 healthy subjects. DNA was genotyped for the Met11Thr variant. Median SP-D level in serum was 911 ng/ml (95% CI 776-1118) in patients and 1068 ng/ml (95% CI 901-1246) in controls (p = 0.0004). Circulating SP-D did not differ significantly in patients with high, intermediate, or low SLE disease activity. Similarly, SP-D did not correlate with C-reactive protein, erythrocyte sedimentation rate, and anti-dsDNA seropositivity. Genetic analysis did not support an association of the Met11Thr genotype with SLE. These findings suggest that low SP-D, unrelated to conventional disease indicators, represents an aspect of SLE etiopathogenesis.

Prospective randomized controlled study on the effects of perioperative administration of a neutrophil elastase inhibitor to patients undergoing video-assisted thoracoscopic surgery for thoracic esophageal cancer

Sivelestat sodium hydrate (Ono Pharmaceutical Co., Osaka, Japan) is a selective inhibitor of neutrophil elastase (NE) and is effective in reducing acute lung injury associated with systemic inflammatory response syndrome (SIRS). We conducted a prospective randomized controlled study to investigate the efficacy of perioperative administration of sivelestat sodium hydrate to prevent postoperative acute lung injury in patients undergoing thoracoscopic esophagectomy and radical lymphadenectomy. Twenty-two patients with thoracic esophageal cancer underwent video-assisted thoracoscopic esophagectomy with extended lymph node dissection in our institution between April 2007 and November 2008. Using a double-blinded method, these patients were randomly assigned to one of two groups preoperatively. The active treatment group received sivelestat sodium hydrate intravenously for 72 hours starting at the beginning of surgery (sivelestat-treated group; n= 11), while the other group received saline (control group; n= 11). All patients were given methylprednisolone immediately before surgery. Postoperative clinical course was compared between the two groups. Two patients (one in each group) were discontinued from the study during the postoperative period because of surgery-related complications. Of the remaining 20 patients, 2 patients who developed pneumonia within a week after surgery were excluded from some laboratory analyses, so data from 18 patients (9 patients in each group) were analyzed based on the arterial oxygen pressure/fraction of inspired oxygen ratio, white blood cell count, serum C-reactive protein level, plasma cytokine levels, plasma NE level, and markers of alveolar type II epithelial cells. In the current study, the incidence of postoperative morbidity did not differ between the two groups. The median duration of SIRS in the sivelestat-treated group was significantly shorter than that in the control group: 17 (range 9-36) hours versus 49 (15-60) hours, respectively (P= 0.009). Concerning the parameters used for the diagnosis of SIRS, the median heart rates on postoperative day (POD) 2 were significantly lower in the sivelestat-treated group than in the control group (P= 0.007). The median arterial oxygen pressure/fraction of inspired oxygen ratio of the sivelestat-treated group were significantly higher than those of the control group on POD 1 and POD 7 (POD 1: 372.0 [range 284.0-475.0] vs 322.5 [243.5-380.0], respectively, P= 0.040; POD 7: 377.2 [339.5-430.0] vs 357.6 [240.0-392.8], P= 0.031). Postoperative white blood cell counts, serum C-reactive protein levels, plasma interleukin-1beta, tumor necrosis factor-alpha levels, and plasma NE levels did not differ significantly between the two groups at any point during the postoperative course, nor did serum Krebs von den Lungen 6, surfactant protein-A, or surfactant protein-D levels, which were used as markers of alveolar type II epithelial cells to evaluate the severity of lung injury. Plasma interleukin-8 levels were significantly lower in the sivelestat-treated group than in the control group on POD 3 (P= 0.040). In conclusion, perioperative administration of sivelestat sodium hydrate (starting at the beginning of surgery) mitigated postoperative hypoxia, partially suppressed postoperative hypercytokinemia, shortened the duration of SIRS, and stabilized postoperative circulatory status after thoracoscopic esophagectomy.

Long-term stability and circadian variation in circulating levels of surfactant protein D

Surfactant protein D (SP-D) is an oligomeric calcium-dependent lectin with important roles in innate host defence against infectious microorganisms. Several studies have shown that patients with inflammatory lung disease have elevated levels of circulating SP-D, and serum SP-D has been suggested to be used as a biomarker for disease e.g. in COPD. We aimed to investigate the variation of circulating SP-D in healthy individuals in and between days for 6 months. In addition, we studied the SP-D response to a standardized physical exercise programme. SP-D was measured in serum using a 5-layered ELISA technique. We found that circulating SP-D remained constant over a 6-month period. However, during the course of one day SP-D varied significantly. Median SP-D peaked at 10 a.m. at 1009 ng/ml (95% CI: 803-1497), subsequently decreasing to nadir at 10 p.m. at 867 ng/ml (95% CI: 650-1148)(P<0.00005). Median pre-exercise level of SP-D was 746 ng/ml (95% CI: 384-2035), and immediately after cessation of physical activity the median SP-D level was 767 ng/ml (95% CI: 367-1885) (P=0.248). Our findings underscore the importance of standardized blood sampling conditions in future studies on the potential role of SP-D as a biomarker. Importantly, stable measures of systemic SP-D over a prolonged period support that SP-D is suitable for biomarker studies.

Surfactant Protein D and KL-6 as Serum Biomarkers of Interstitial Lung Disease in Patients with Scleroderma

To assess whether serum concentrations of surfactant protein D (SP-D) and Krebs von den Lungen-6 (KL-6), glycoproteins expressed by type II pneumocytes, correlate with the presence of "alveolitis" and measures of lung function in patients enrolled in the Scleroderma Lung Study (SLS). Serum obtained at baseline screening of patients with systemic sclerosis (SSc, scleroderma) in the SLS was assayed. "Alveolitis" was defined by either bronchoalveolar lavage or thoracic high-resolution computed tomography (HRCT) by SLS criteria. SP-D and KL-6 levels were measured by ELISA in 66 SSc patients (44 with "alveolitis," 22 without "alveolitis") and in 10 healthy controls. These were compared to clinical measures of lung disease and "alveolitis" in the SLS patients. SP-D levels were 300+/-214 ng/ml (mean+/-SD) in the SSc patients compared to 40+/-51 ng/ml in controls (p<0.0001). KL-6 levels were 1225+/-984 U/ml in the SSc patients and 333+/-294 U/ml in controls (p<0.0001). SSc patients with "alveolitis" had higher levels of both SP-D and KL-6 than those without "alveolitis." The level of SP-D was 353+/-219 ng/ml in patients with "alveolitis" and 161+/-143 ng/ml without "alveolitis" (p=0.0002). The level of KL-6 was 1458+/-1070 U/ml in patients with "alveolitis" and 640+/-487 U/ml without "alveolitis" (p=0.0001). Receiver operator characteristic curve analysis demonstrated high sensitivity and specificity of both SP-D and KL-6 for the determination of "alveolitis." KL-6 and SP-D were positively correlated with maximum fibrosis scores, but not with maximum ground-glass opacities, on HRCT. Serum levels of SP-D and KL-6 appear to be indicative of "alveolitis" in SSc patients as defined by the SLS, and are significantly higher than in SSc patients without "alveolitis." Serum SP-D and KL-6 may serve as noninvasive serological means of assessing interstitial lung disease in patients with SSc.

Elevation of Serum KL-6 Glycoprotein or Surfactant Protein-D in Adult T-cell Leukemia with Distinct Pulmonary Complications

Patients with hematological malignancies frequently suffer from lung diseases as a complication. However, it is difficult to discriminate leukemic invasion into the lung from infectious pulmonary complications. The serum level of Krebs von den Lungen-6 (KL-6), which is a mucin-like glycoprotein, is increased in more than 70% of patients with interstitial pneumonia. Surfactant protein-D (SP-D) is produced mainly in the lung by alveolar type II and bronchiolar epithelial cells and is a useful serum marker for interstitial pneumonia. We therefore measured the levels of KL-6 and SP-D in sera from 128 patients (76 males and 52 females, mean age: 59 years) with hematological malignancies, including adult T-cell leukemia (ATL). Overall, the increase in KL-6 or SP-D, above each cut-off value (500 U/ml for KL-6 and 110 ng/ml for SP-D), was detected in 11 patients (8.6%) or 10 patients (7.8%), respectively. In contrast, among 67 ATL patients, 15 patients had high serum levels of KL-6 and/or SP-D; both were elevated in 2 patients, only KL-6 was elevated in 6 patients and only SP-D was elevated in 7 patients. Thus, serum KL-6 and SP-D appear to be elevated in a mutually exclusive manner in ATL. Indeed, high serum levels of KL-6 were closely related to the stage of ATL, while the serum SP-D was elevated in ATL patients with pulmonary infection. In conclusion, the combined measurement of KL-6 and SP-D in ATL may become a useful means to discriminate leukemic pulmonary lesions from infectious pulmonary complications.

Serum surfactant protein D during acute exacerbations of chronic obstructive pulmonary disease.

Background: There is a paucity of lung specific biomarkers to diagnose exacerbations of chronic obstructive pulmonary disease (COPD) and to track their progression. Surfactant protein D (SP-D) is a pulmonary collectin regulating the innate immunity of the lung and its serum expression is perturbed in COPD. However, it is not known whether serum levels change during exacerbations. We sought to determine whether serum SP-D levels are raised in COPD exacerbations. Objectives: To determine whether or not patients with exacerbations have elevated serum SP-D levels compared with asymptomatic controls, stable disease. Study design: case control study. Methods: We measured serum SP-D levels from patients with stable COPD (n = 14), patients experiencing acute exacerbations (n = 13) and in control subjects (n = 54) using a specific immunoassay and compared the levels using analysis of variance. Results: Serum SP-D levels were significantly increased in patients who experienced an acute exacerbation (227 ± 120 ng/mL) compared to patients with stable disease (151 ± 83 ng/mL) or control subjects (128 ± 65 ng/mL; p = 0.003). Serum SP-D levels were also found to be inversely related to various lung function parameters including FEV1/FVC% predicted. Conclusions: Our study suggests that serum SP-D levels are increased in patients during exacerbations and may be a potential diagnostic biomarker for COPD exacerbations.

Serum Surfactant Protein D during Acute Exacerbations of Chronic Obstructive Pulmonary Disease

Background: There is a paucity of lung specific biomarkers to diagnose exacerbations of chronic obstructive pulmonary disease (COPD) and to track their progression. Surfactant protein D (SP-D) is a pulmonary collectin regulating the innate immunity of the lung and its serum expression is perturbed in COPD. However, it is not known whether serum levels change during exacerbations. We sought to determine whether serum SP-D levels are raised in COPD exacerbations.Objectives: To determine whether or not patients with exacerbations have elevated serum SP-D levels compared with asymptomatic controls, stable disease.Study design: case control study.Methods: We measured serum SP-D levels from patients with stable COPD (n= 14), patients experiencing acute exacerbations (n= 13) and in control subjects (n= 54) using a specific immunoassay and compared the levels using analysis of variance.Results: Serum SP-D levels were significantly increased in patients who experienced an acute exacerbation (227 ± 120 ng/mL) compared to patients with stable disease (151 ± 83 ng/mL) or control subjects (128 ± 65 ng/mL;p= 0.003). Serum SP-D levels were also found to be inversely related to various lung function parameters including FEV1/FVC% predicted.Conclusions: Our study suggests that serum SP-D levels are increased in patients during exacerbations and may be a potential diagnostic biomarker for COPD exacerbations.

Children with absent surfactant protein D in bronchoalveolar lavage have more frequently pneumonia

Surfactant protein D (SP-D) is an important component of the pulmonary host defense system. We hypothesized that bronchoalveolar lavage (BAL) SP-D levels are lower in children presenting with recurrent bronchitis, providing evidence for a role of SP-D in human respiratory diseases. SP-D levels in BAL were measured in 45 children, who suffered from recurrent bronchitis for an average of 2-3 yr. Clinical outcome was assessed 2 yr after BAL. For comparison, BAL fluids from 15 control children without respiratory symptoms were evaluated. Among the 45 children with recurrent bronchitis, 12 had no SP-D in their BAL at the time of investigation. These SP-D-deficient patients had more frequently pneumonias and their long-term outcome was worse than that of the children with detectable SP-D. No genetic cause could be identified for the SP-D deficiency. Among the children with recurrent bronchitis and SP-D clearly detectable in BAL, those with the diagnosis of allergic asthma had threefold elevated levels compared with controls. In accordance with animal and in vitro data, elevated SP-D concentrations in BAL may represent an up-regulation due to allergic airway inflammation. In contrast, SP-D deficiency due to consumption or failure to up-regulate SP-D may be linked to pulmonary morbidity in children.

Surfactant Protein D and Bronchial Dysplasia in Smokers at High Risk of Lung Cancer

Surfactant dysfunction has been implicated in both lung cancer and COPD. This study evaluated the relationship between surfactant protein D (SP-D) and the progression of bronchial dysplasia in heavy smokers. SP-D and oxidized glutathione levels were determined in samples of BAL fluid from 71 ex-smokers and current heavy smokers who participated in a lung cancer chemoprevention study with inhaled budesonide therapy. Bronchoscopy with biopsies was performed at baseline and was repeated at 6 months. The primary end point was the progression of bronchial dysplasia over 6 months. Log-normalized SP-D levels in BAL fluid were significantly associated with the progression of bronchial dysplasia. A 1-U decrease in log-normalized SP-D levels at baseline was associated with a 3.2-fold increase (95% confidence interval, 1.24 to 8.26) in the risk for progression. Reduced FEV(1) also predicted the progression of bronchial dysplasia (p < 0.05). Additional reductions in BAL fluid SP-D levels over the 6 months further increased the risk of progression (odds ratio, 1.76 for a 1-U decrease in log-normalized SP-D levels in BAL fluid; p = 0.023). Thirty-seven percent of the variation in SP-D levels in BAL fluid was related positively to the subject's FEV(1)/FVC ratio, and inversely to their plasma C-reactive protein levels and number of pack-years of smoking. Reduced SP-D expression in BAL fluid was associated with the progression of bronchial dysplasia. SP-D levels in BAL fluid may serve as a potential biomarker to identify smokers who are at risk of early lung cancer.

Enhanced expression of murine β-defensins (MBD-1, -2,- 3, and -4) in upper and lower airway mucosa of influenza virus infected mice

Although defensins are known to inhibit the replication of human influenza A virus (IAV) in vitro, their in vivo expression during IAV infection is not known. Here we investigated mRNA and protein expression of several β-defensins in the airways of IAV infected mice. Expression of murine β-defensin (MBD)-3 and -4 was enhanced (3 to 5-fold, p < 0.01) in infected lungs, trachea and sinonasal mucosa. MBD-3 and -4 expressions were correlated with the time course of acute IAV infection suggesting their induction by IAV infection. Infected mice also showed increased levels of surfactant protein-D especially in the sinonasal mucosa. MBD-3 and -4 were localized to the conducting airway epithelial cells but not the alveolar tissue. We conclude that IAV infection upregulated the expression of inducible β-defensins in both the upper and lower airways. These novel findings suggest that β-defensins might contribute to innate and adaptive immune responses targeted against IAV infection.

Dynamic changes of surfactant protein-D and Clara cell protein expressions in lung tissue and bronchoalveolar lavage fluid of silica-treated rats

To investigate the dynamic changes of surfactant protein-D (SP-D) and Clara cell protein (CC16) expressions in lung tissue and bronchoalveolar lavage fluid (BALF) of silica-treated rats. 80 rats were randomly divided into the control group and the silica group. The silicotic animal model was established by direct tracheal instillation of silica suspension into rat lungs surgically. On 7, 14, 21, 28 and 60 d after establishment of the animal model, eight rats in each group were sacrificed and lung tissue and BALF were collected. Lung tissue chip microarray was made in different time points after the silica was injected. Expressions of SP-D and CC16 on tissue microarray were detected with immunohistochemistry and quantified by Image-Pro Plus Version 4.5 for Windows(TM); The SP-D and CC16 levels of BALF were detected with western blot and quantified by Quantity One Version 4.6.2. SP-D expressed very little in alveolar type II and Clara cell intracytoplasmic of control group while its expression significantly increased after 7 d in silica group (P < 0.01) and it reached the peak on the 14 d, after this SP-D expression decreased gradually. CC16 was expressed strongly in intracytoplasmic and it expressed little in nucleus of Clara cell by bronchioles of control while it significantly decreased after 7 d in silica group (P < 0.01), and CC16 expression decreased gradually with the exposed silica time, which was correlated negatively among them (r(s) = -0.967, P < 0.01). On 7 d and 28 d, the SP-D levels of BALF in silica group were significantly higher than control (P < 0.01). Furthermore the SP-D levels of BALF on 28 d was significantly elevated than that on 7 d in silica group (P < 0.01). On 7 d and 28 d, the CC16 levels of BALF in silica group were significantly lower than control (P < 0.01). Moreover, CC16 levels of BALF on 28 d was significantly decreased than that on 7 d in silica group (P < 0.01). The dynamic changes of SP-D and CC16 protein expressed in lung tissue and bronchoalveolar lavage fluid could be induced by silica exposure and are related with the silica exposure time.

Effects of leukoreduced blood on acute lung injury after trauma: A randomized controlled trial*

The requirement for a blood transfusion after trauma is associated with an increased risk of acute lung injury. Residual leukocytes contaminating red cells are potential mediators of this syndrome. The goal of this trial was to test our hypothesis that prestorage leukoreduction of blood would reduce rates of posttraumatic lung injury. Double blind, randomized, controlled clinical trial. University-affiliated level I trauma center in King County, Seattle, WA. Two hundred sixty-eight injured patients requiring red blood cell transfusion within 24 hrs of injury. Prestorage leukoreduced vs. standard allogeneic blood transfusions. We compared the incidence of acute lung injury and acute respiratory distress syndrome at early (< or = 72 hrs) and late (> 72 hrs) time points after injury. In a subset, we compared plasma levels of surfactant protein-D and von Willebrand factor antigen between intervention arms. Rates of acute lung injury (relative risk [RR] 1.06, 95% confidence interval [CI] .69-1.640) and acute respiratory distress syndrome (RR .96, 95% CI 0.48-1.91) were not statistically different between intervention arms early after injury. Similarly, no statistically significant effect of leukoreduced transfusion on rates of acute lung injury (RR .88, 95% CI .54-1.44) or acute respiratory distress syndrome (RR .95, 95% CI .58-1.57) was observed to occur late after injury. There was no significant difference in the number of ventilator-free days or in other ventilator parameters between intervention arms. No statistically significant effect of leukoreduced blood on plasma levels of surfactant protein-D or von Willebrand factor antigen was identified. Prestorage leukoreduction had no effect on the incidence or timing of lung injury or on plasma measures of systemic alveolar and endothelial inflammation in a population of trauma patients requiring transfusion. The relationship between transfusion and lung injury is not obviously explained by mechanistic pathways involving the presence of transfused leukocytes.

The Effects of Fluticasone with or without Salmeterol on Systemic Biomarkers of Inflammation in Chronic Obstructive Pulmonary Disease

Small studies have suggested that inhaled corticosteroids can suppress systemic inflammation in chronic obstructive pulmonary disease (COPD). To determine the effect of inhaled corticosteroids with or without long-acting beta(2)-adrenergic agonist on systemic biomarkers of inflammation. We conducted a double-blind randomized placebo-controlled trial across 11 centers (n = 289 patients with FEV(1) of 47.8 +/- 16.2% of predicted) to compare the effects of inhaled fluticasone alone or in combination with salmeterol against placebo on circulating biomarkers of systemic inflammation over 4 weeks. The primary endpoint was C-reactive protein (CRP) level. Secondary molecules of interest were IL-6 and surfactant protein D (SP-D). Neither fluticasone nor the combination of fluticasone/salmeterol had a significant effect on CRP or IL-6 levels. There was, however, a significant reduction in SP-D levels with fluticasone and fluticasone/salmeterol compared with placebo (P = 0.002). Health status also improved significantly in both the fluticasone and fluticasone/salmeterol groups compared with placebo, driven mostly by improvements in the symptom scores. Changes in the circulating SP-D levels were related to changes in health status scores. FEV(1) improved significantly only in the fluticasone/salmeterol group compared with placebo. ICS in conjunction with long-acting beta(2)-adrenergic agonist do not reduce CRP or IL-6 levels in serum of patients with COPD over 4 weeks. They do, however, significantly reduce serum SP-D levels. These data suggest that these drugs reduce lung-specific but not generalized biomarkers of systemic inflammation in COPD.

Chronic obstructive pulmonary disease and inhaled steroids alter surfactant protein D (SP-D) levels: a cross-sectional study

BackgroundSurfactant protein D (SP-D), an innate immune molecule, plays an important protective role during airway inflammation. Deficiency of this molecule induces emphysematous changes in murine lungs, but its significance in human COPD remains unclear.MethodsWe collected bronchoalveolar lavage fluid from 20 subjects with varying degrees of COPD (8 former smokers and 12 current smokers) and 15 asymptomatic healthy control subjects (5 never smokers, 3 remote former smokers, and 7 current smokers). All subjects underwent a complete medical history and pulmonary function testing. SP-D was measured by Enzyme-Linked ImmunoSorbent Assay. Statistical analysis was performed using nonparametric methods and multivariable linear regression for control of confounding. The effect of corticosteroid treatment on SP-D synthesis was studied in vitro using an established model of isolated type II alveolar epithelial cell culture.ResultsAmong former smokers, those with COPD had significantly lower SP-D levels than healthy subjects (median 502 and 1067 ng/mL, respectively, p = 0.01). In a multivariable linear regression model controlling for age, sex, race, and pack-years of tobacco, COPD was independently associated with lower SP-D levels (model coefficient -539, p = 0.04) and inhaled corticosteroid use was independently associated with higher SP-D levels (398, p = 0.046). To support the hypothesis that corticosteroids increase SP-D production we used type II alveolar epithelial cells isolated from adult rat lungs. These cells responded to dexamethasone treatment by a significant increase of SP-D mRNA (p = 0.041) and protein (p = 0.037) production after 4 days of culture.ConclusionAmong former smokers, COPD is associated with lower levels of SP-D and inhaled corticosteroid use is associated with higher levels of SP-D in the lung. Dexamethasone induced SP-D mRNA and protein expression in isolated epithelial cells in vitro. Given the importance of this molecule as a modulator of innate immunity and inflammation in the lung, low levels may play a role in the pathogenesis and/or progression of COPD. Further, we speculate that inhaled steroids may induce SP-D expression and that this mechanism may contribute to their beneficial effects in COPD. Larger, prospective studies are warranted to further elucidate the role of surfactant protein D in modulating pulmonary inflammation and COPD pathogenesis.

Circulating Surfactant Protein D is Decreased in Early Rheumatoid Arthritis: A 1‐year Prospective Study

Innate immune system abnormalities, e.g., mannan-binding lectin (MBL) genotype variants, have been demonstrated to modify the disease course of rheumatoid arthritis (RA). Surfactant protein D (SP-D) shares important structural and functional properties with MBL suggesting that SP-D may be an additional RA disease modifier. The Met11Thr polymorphism in the N-terminal part of SP-D is an important determinant for the SP-D serum level, but this polymorphism is also essential to the function and assembly into oligomers. We aimed to compare the serum levels of SP-D in a cohort of newly diagnosed untreated RA patients with healthy matched controls, and to investigate if there was an association to core measures of disease activity within the first year after disease onset. Secondly, we aimed to investigate whether the Met11Thr polymorphism was associated with RA. Serum SP-D was significantly lower in DMARD naive RA patients compared with healthy controls (P = 0.016). Median SP-D concentration at inclusion was 878 ng/ml (95% CI: 730-1033) and 1164 ng/ml (95% CI: 1093-1366) in RA patients and matched controls, respectively. SP-D increased during Methotrexate treatment (P < 0.0001), and at 1-year follow-up median SP-D was 1032 ng/ml (95% CI: 777-1255). SP-D levels did not correlate with traditional disease activity measures. The Thr11/Thr11 genotype and the Thr11 allele tended to be more frequent in RA patients. In conclusion, the low serum level of SP-D and the lack of correlation with traditional disease activity measures indicate that SP-D reflects a distinctive aspect in the RA pathogenesis.

Circulating surfactant protein D as a potential lung-specific biomarker of health outcomes in COPD: a pilot study

BackgroundThere is a paucity of surrogate lung-specific biological markers that can be used to track disease progression and predict clinical outcomes in chronic obstructive pulmonary disease (COPD). The principal aim of this pilot study was to determine whether circulating surfactant protein D (SPD) or Clara Cell protein-16 (CC16) levels are associated with lung function or health status in patients with severe COPD.MethodsWe studied 23 patients with advanced COPD. Lung function measurements, Chronic Respiratory Disease Questionnaire (CRQ) scores, and serum levels of SPD, CC16, and C-reactive protein (CRP) were determined at baseline and at 3 months.ResultsAt baseline, FEV1 was inversely associated with serum SPD levels (P = 0.045) but not with CC16 (P = 0.675) or CRP levels (P = 0.549). Over a 3 month period, changes in SPD levels correlated significantly with changes in CRQ scores (adjusted P = 0.008) such that patients who had the largest declines in serum SPD levels experienced the largest gains in health status. The association was particularly notable between circulating SPD level and the dyspnea domain of the CRQ score (P = 0.018). Changes in CC16 or CRP levels did not correlate with changes in CRQ scores.ConclusionChanges in serum SPD levels tracked well with changes in health status over a 3 month period in patients with severe COPD. These data suggest that circulating SPD levels may be useful biomarkers to track health outcomes of COPD patients.

Regulation of surfactant protein D in the mouse female reproductive tract in vivo

Surfactant protein D (SP-D) plays a role in innate immunity in the lung and is expressed at many other mucosal surfaces throughout the human body. In this study, we show that SP-D mRNA and protein are present in the murine female reproductive tract; i.e. in the vagina, cervix, uterus and oviduct. SP-D protein is primarily localized to epithelial cells lining the genital tract and is also present in secretory material within the lumen of the uterus and cervix. The levels of SP-D mRNA in the uterus vary by a factor of 10 during the estrous cycle with peak levels present at estrus and the lowest levels at diestrus. In contrast, SP-D mRNA levels in the lung do not change during the estrous cycle. Since SP-D is an innate host defense protein present in the mouse reproductive tract, we studied the influence of infection on SP-D levels in vivo. We found that Chlamydia muridarum infection caused an increase in the SP-D protein content of reproductive tract epithelial cells. These data are suggestive that SP-D may play a role in innate immunity in the female reproductive tract in vivo.

Impact of neutrophils on antiviral activity of human bronchoalveolar lavage fluid

Surfactant protein D (SP-D) and neutrophils participate in the early innate immune response to influenza A virus (IAV) infection. SP-D increases neutrophil uptake of IAV and modulates neutrophil respiratory burst responses to IAV; however, neutrophil proteases have been shown to degrade SP-D, and human neutrophil peptide defensins bind to SP-D and can cause precipitation of SP-D from bronchoalveolar lavage fluid (BALF). BALF has significant antiviral activity against IAV. We first added neutrophils to BALF during incubation with IAV. Addition of neutrophils to BALF caused significantly greater clearance of IAV from culture supernatants than from BALF alone, and this effect was significantly more pronounced when neutrophils were activated during incubation with the virus. In contrast, if activated neutrophils were incubated with BALF before addition of virus, they reduced antiviral activity of BALF. This effect correlated with depletion of SP-D from BALF. Activation of neutrophils with agonists that induce primary granule release (including release of human neutrophil peptide defensins) caused SP-D depletion, but activation with PMA, which causes only secondary granule release, did not. The ability of activated neutrophils to deplete SP-D from BALF was partially, but not fully, corrected with protease inhibitors but was unaffected by inhibition of neutrophil respiratory burst responses. These results suggest that chronic neutrophilic inflammation (e.g., as in chronic smoking or cystic fibrosis) may reduce SP-D levels and predispose to IAV infection. In contrast, acute inflammation, as occurs in the early phase of IAV infection, may promote neutrophil-mediated viral clearance.

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.