Serum Surfactant Protein D Levels Research Articles

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

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

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

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

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.

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

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

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

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

SP-D Serum Levels Reveal Distinct Epithelial Damage in Direct Human ARDS.

Acute respiratory distress syndrome (ARDS) is a heterogeneous syndrome with multiple underlying diseases. Particularly epithelial damage results from direct (e.g., pneumonia) rather than indirect lung injury (e.g., nonpulmonary sepsis), which is more likely associated with endothelial damage. Hence, targeting ARDS patients based on their molecular phenotypes is a promising approach to improve outcome. With regard to distinct inflammatory responses and subsequent lung damage in direct ARDS due to the causing pathogen, we quantified markers of epithelial and endothelial damage and pro-inflammatory cytokines in patients with ARDS triggered by bacterial, viral, and atypical pathogen pneumonia or indirect ARDS. The serum levels of interleukin-6 (IL-6) and interleukin-8 (IL-8), lung epithelial injury markers surfactant protein D (SP-D), and soluble receptor for advanced glycation end-products (sRAGE) as well as endothelial injury marker angiopoietin-2 (Ang-2) from 49 patients with distinct types of ARDS were analyzed by multiplex immunoassay. Epithelial damage marker SP-D was significantly higher in direct ARDS caused by viral and atypical pathogens in contrast to ARDS caused by typical bacterial pneumonia and nonpulmonary sepsis. In contrast, sRAGE levels did not differ due to the causing pathogen. Patients with atypical pathogen pneumonia related ARDS showed significantly lower Ang-2 levels compared to patients with viral and indirect ARDS. Patients with viral and atypical pneumonia related ARDS possessed significantly lower serum IL-6 levels compared to bacterial pneumonia related ARDS and IL-6 levels in atypical pneumonia related ARDS were significantly lower than in indirect ARDS. Current findings report a potential difference in ARDS biomarkers due to the underlying disease and pathogen.

Serum Levels of Collectins Are Sustained During Pregnancy: Surfactant Protein D Levels Are Dysregulated Prior to Missed Abortion.

About 15% of pregnant women undergo missed abortion (MA), wherein women do not experience cramping and vaginal bleeding. Dysregulation of the immune molecules and steroid hormones contribute to early pregnancy loss. Collectins- surfactant protein A (SP-A), surfactant protein D (SP-D), and mannose-binding lectin (MBL) are a group of innate immune molecules regulated by the steroid hormones. Reduced levels of SP-A and SP-D during the early gestation exhibited a significant association with the severe early onset preeclampsia. In order to determine the serum profile of collectins throughout the normal pregnancy and explore their predictive potential during the 8-12weeks of gestation for MA, we examined a prospective cohort of pregnant women (n = 221). The serum levels of SP-A and SP-D were significantly downregulated in the normal pregnant women in all the three trimesters (n = 30) compared with the non-pregnant women (n = 20) and were not significantly different across the three trimesters. Fourteen of the women from the cohort underwent MA during the 14-20weeks of gestation and exhibited a significant downregulation in the serum levels of SP-D during 8-12weeks of gestation. A significant inhibition of the HTR-8/SVneo cell proliferation and migration in the presence of a recombinant fragment of human SP-D suggested the relevance of SP-D in placental development. We report here that the serum levels of SP-A, SP-D, and MBL are consistently maintained during pregnancy in the Indian cohort. Dysregulated serum levels of SP-D and P4/E2 ratio during the early first trimester may predict occurrence of MA.

Identification of Subclinical Lung Involvement in ACPA-Positive Subjects through Functional Assessment and Serum Biomarkers.

Lung involvement is related to the natural history of anti-citrullinated proteins antibodies (ACPA)-positive rheumatoid arthritis (RA), both during the pathogenesis of the disease and as a site of disease-related injury. Increasing evidence suggests that there is a subclinical, early lung involvement during the course of the disease, even before the onset of articular manifestations, which can potentially progress to a symptomatic interstitial lung disease. To date, reliable, non-invasive markers of subclinical lung involvement are still lacking in clinical practice. The aim of this study is to evaluate the diagnostic potential of functional assessment and serum biomarkers in the identification of subclinical lung involvement in ACPA-positive subjects. Fifty ACPA-positive subjects with or without confirmed diagnosis of RA (2010 ARC-EULAR criteria) were consecutively enrolled. Each subject underwent clinical evaluation, pulmonary function testing (PFT) with assessment of diffusion lung capacity for carbon monoxide (DLCO), cardiopulmonary exercise testing (CPET), surfactant protein D (SPD) serum levels dosage and high-resolution computed tomography (HRCT) of the chest. The cohort was composed of 21 ACPA-positive subjects without arthritis (ND), 10 early (disease duration < 6 months, treatment-naïve) RA (ERA) and 17 long-standing (disease duration < 36 months, on treatment) RA (LSRA). LSRA patients had a significantly higher frequency of overall HRCT abnormalities compared to the other groups (p = 0.001). SPD serum levels were significantly higher in ACPA-positive subjects compared with healthy controls (158.5 ± 132.3 ng/mL vs 61.27 ± 34.11 ng/mL; p < 0.0001) and showed an increasing trend from ND subjects to LSRD patients (p = 0.004). Patients with HRCT abnormalities showed significantly lower values of DLCO (74.19 ± 13.2% pred. vs 131.7 ± 93% pred.; p = 0.009), evidence of ventilatory inefficiency at CPET and significantly higher SPD serum levels compared with subjects with no HRCT abnormalities (213.5 ± 157.2 ng/mL vs 117.7 ± 157.3 ng/mL; p = 0.018). Abnormal CPET responses and higher SPD levels were also associated with specific radiological findings. Impaired DLCO and increased SPD serum levels were independently associated with the presence of HRCT abnormalities. Subclinical lung abnormalities occur early in RA-associated autoimmunity. The presence of subclinical HRCT abnormalities is associated with several functional abnormalities and increased SPD serum levels of SPD. Functional evaluation through PFT and CPET, together with SPD assessment, may have a diagnostic potential in ACPA-positive subjects, contributing to the identification of those patients to be referred to HRCT scan.

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.

The effect of physical preparedness levels on serum levels of CC16, SP-D and lung function in endurance runners

Summary Objectives Endurance runners are exposed to respiratory damages due to extreme endurance exercises. Increasing CC16 and SP-D in the bloodstream is a sign of respiratory tract damage. The purpose of this pilot study was to investigate the effect of physical preparedness levels on serum CC16 and SP-D levels and lung function. Equipment and methods Ten healthy male elite runners and ten healthy male recreational runners were recruited based on the inclusion and exclusion criteria. Lung permeability [Surfactant protein D (SP-D), the Clara cell secretory protein (CC16) in serum and CC16/SP-D ratio] and lung function (FEV1, FVC and FEV1/FVC ratio) were measured before and after endurance session of running with an intensity of 80% to 85% maximum heart rate for 30 minutes. Comparisons were performed by RM-ANCOVA. Results Serum CC-16 and SP-D levels, and CC16/SP-D ratio increased significantly with time (P = 0.05). However, FEV1, FVC, FEV1/FVC ratio decreased significantly with time (P ≤ 0.05). Also, the interaction of group × time and between group changes was not significant for FEV1, FVC, FEV1/FVC ratio (P > 0.05). Based on the results of this study, physical preparedness levels have no effect on the release of CC16, SP-D, CC16/SP-D ratio and lung function. Further large-scale studies are needed to confirm these findings.

Serial changes in biomarkers in pulmonary and extrapulmonary acute respiratory distress syndrome

Objective: To compare the serial changes of circulating angiopoietin-2 (Ang-2), surfactant protein D (SP-D) and soluble receptor for advanced glycation end product (sRAGE) in patients with pulmonary acute respiratory distress syndrome (ARDS) and extrapulmonary ARDS. Methods: A total of 36 eligible patients with ARDS were included from the Department of Respiratory Intensive Care Unit(RCU) and Department of Intensive Care Unit (ICU), the Central Hospital of Wuhan, during April 2017 to February 2018, and divided into pulmonary ARDS group (n=20) and extrapulmonary ARDS group (n=16) according to primary causes. The levels of Ang-2, SP-D and sRAGE in serum of each group were measured on Day 1, 4 and 7 after diagnosis. Results: The serum level of Ang-2 in extrapulmonary ARDS group declined gradually during the course. The serum level of Ang-2 on Day 1 was significantly higher than that on Day 7 [2 801 (1 386, 7 526) vs 1 461 (737, 2 135) ng/L, P<0.05]. There was no significant difference in serum levels of Ang-2 on Day 1, 4, 7 in pulmonary ARDS group [1 462 (545, 3 715) vs 1 353 (659, 5 847) vs1 616 (754, 3 460) ng/L, all P>0.05]. There was no significant difference in serum levels of SP-D on Day 1,4, 7 in each group [pulmonary ARDS group: 5.6(1.8, 14.0) vs 5.7(1.8, 14.5) vs 7.9(3.0, 16.8) mg/L, all P>0.05; extrapulmonary ARDS group: 3.4(0.5, 9.1) vs 1.6(0.6, 6.3) vs 1.6(0.7, 7.9)mg/L, all P>0.05]. The serum level of sRAGE in each group declined gradually during the course. The serum level of sRAGE on Day 1 in each group was significantly higher than that on Day 7 [pulmonary ARDS group: 328(107, 595) vs 66 (50,171) ng/L, extrapulmonary ARDS group: 237 (98, 410) vs 81 (38, 154) ng/L, all P<0.05]. Conclusion: The serum level of Ang-2 in extrapulmonary ARDS declines significantly in the early stage of disease, while there is no significant difference in that of pulmonary ARDS.

Evaluation of Lung Injury in Infants with Congenital Diaphragmatic Hernia

Background/PurposeThe presence of lung injury and the factors that contribute to it in infants with congenital diaphragmatic hernia (CDH) have not been objectively measured during their clinical course. In adults with acute respiratory distress syndrome, higher serum levels of surfactant protein D (SP-D) are linked to lung injury and worse outcomes. We hypothesized that serum SP-D levels would be elevated in CDH infants and that the levels would correlate to the amount of lung injury present. MethodsIn this retrospective cohort study, serum SP-D levels were analyzed in 37 CDH infants and 5 control infants using a commercially available enzyme-linked immunosorbent assay kit. ResultsInfants with more severe CDH had a statistically significant increase (p < 0.001) in serum SP-D over their first month of life. SP-D levels in CDH infants were similar to control infants while on extracorporeal membrane oxygenation (ECMO) but were 2.5-fold higher (p = 0.03) than controls following ECMO termination. SP-D levels increased 1.6-fold following surgical repair of the diaphragm and were significantly higher in the second week following surgery when compared to pre-operative levels (p < 0.03). ConclusionsThese results demonstrate that CDH infants experience lung injury during the first week of life, around the time of surgery, and at the time of ECMO termination.Level II prognosis study.

Plasma surfactant protein-D as a potential biomarker in idiopathic pulmonary fibrosis

ObjectivesIdiopathic pulmonary fibrosis (IPF) is a disease of an increasing burden. Its diagnosis is based on definite high-resolution computed tomography pattern and is associated with the histopathological and/or radiological pattern of usual interstitial pneumonia with exclusion of other causes of interstitial pneumonia. The surfactant protein-D (SP-D) level in the serum is measured in several lung diseases, including IPF.Aim of studyThe aim of the current study is to assess the serum level of SP-D as a potential biomarker to distinguish between IPF and other idiopathic interstitial pneumonia patients.Patients and methodsThis study was conducted in the Chest Department, Kasr Al Ainy Hospitals, Cairo University. The study population included 20 healthy controls, 20 IPF patients, and 18 other idiopathic interstitial pneumonia patients. All were subjected to full history taking, clinical examination, high-resolution computed tomography chest, spirometry, arterial blood gases, blood samples for measuring SP-D by enzyme-linked immunosorbent assay.ResultsThere was no statistical significance between the serum level of SP-D in IPF and non-IPF patients, however, there was a significant increase in the serum level of SP-D in IPF patients diagnosed at a late stage compared with those diagnosed at an early stage and those on anti-fibrotic therapy. Also, there was a statistical significance between the degree of clubbing and gastroesophageal reflux disease and the serum level of SP-D with a P value of 0.005 and 0.029, respectively. Serum SP-D level had a negative correlation with more severe form of the disease regarding the duration of illness, forced vital capacity percent, and it had a significant negative correlation with oxygen saturation and 6 min walk distance with a P value of 0.023 and 0.005, respectively.ConclusionThe level of serum SP-D level in IPF patients correlate well with the severity of the disease and could be a possible marker to use for the follow up of patients on anti-fibrotic drugs.

Performance of Candidate Serum Biomarkers for Systemic Sclerosis-Associated Interstitial Lung Disease.

Interstitial lung disease (ILD) in systemic sclerosis (SSc) runs a highly variable course, and prediction tools are highly desired. The aim of this study was to assess the diagnostic and prognostic performance of 4 candidate serum biomarkers for SSc-associated ILD. Serum samples from a combined cohort of SSc patients (from Paris, France and Oslo, Norway; n = 427) were analyzed by enzyme-linked immunosorbent assay for concentrations of lung epithelial-derived surfactant protein D (SP-D), Krebs von den Lungen 6 glycoprotein (KL-6), CCL18, and OX40 ligand (OX40L). Lung fibrosis was measured by high-resolution computed tomography and pulmonary function tests. Associations of these candidate biomarkers with baseline disease involvement and prediction of disease progression over time (mean ± SD follow-up 3.2 ± 4.4 years) were investigated. In SSc patients at baseline, serum levels of KL-6 correlated with the forced vital capacity (FVC) (r = -0.317, P < 0.001), diffusing capacity for carbon monoxide (r = -0.335, P < 0.001), and extent of lung fibrosis (r = 0.551, P < 0.001). In multivariate analyses, serum levels of KL-6 and SP-D, but not CCL18 and OX40L, were associated with lung fibrosis (odds ratio [OR] 2.41, 95% confidence interval [95% CI] 1.43-4.07 [P = 0.001] and OR 3.15, 95% CI 1.81-5.48 [P < 0.001], respectively). In SSc patients with ILD at baseline, longitudinal, multivariate analyses showed that CCL18 serum levels were an independent predictor of a >10% decrease in the FVC (hazard ratio [HR] 2.90, 95% CI 1.25-6.73; P = 0.014) and de novo development of extensive disease (HR 3.71, 95% CI 1.02-13.52; P = 0.048). Matrix-based logistic regression models for the diagnosis and prognosis of SSc-associated ILD were constructed, and these models discriminated 3 groups of risk (mild, moderate, or high) for the diagnosis or worsening of lung fibrosis according to the serum levels of SP-D (for diagnosis) and serum levels of CCL18 (for progression of disease). These results show that SP-D is a relevant diagnostic biomarker for SSc-associated ILD, whereas KL-6 could be used to assess the severity of lung fibrosis. CCL18 appears to be a potential predictive marker for progression of ILD in SSc.

Evaluation of changes in the serum levels of Krebs von den Lungen-6 and surfactant protein-D over time as important biomarkers in idiopathic fibrotic nonspecific interstitial pneumonia.

Some cases of idiopathic fibrotic nonspecific interstitial pneumonia (f-NSIP) show a progressive course that is similar to that of idiopathic pulmonary fibrosis. However, it is difficult to predict poor patient outcomes. This study aimed to evaluate whether serial changes in serum levels of Krebs von den Lungen-6 (KL-6) and surfactant protein-D (SP-D) can predict disease progression. We retrospectively analyzed the medical records of 75 patients with idiopathic f-NSIP. Disease behavior was categorized into two groups depending on long-term change of pulmonary function: progressive type (≥5%/year relative decline in the slope of forced vital capacity [FVC] and/or ≥7.5%/year relative decline in the slope of %diffusing capacity of the lung for carbon monoxide [%DLCO]) and stable type. Levels of KL-6 and SP-D and results of pulmonary function tests, which were performed parallelly, were reviewed and analyzed using a linear mixed-effects model. The study subjects comprised 62 patients with stable type and 13 patients with progressive type disease behavior. Among these subjects, 50 patients fulfilled the diagnostic criteria of interstitial pneumonia with autoimmune features (IPAF). Serum levels of both KL-6 and SP-D at baseline showed a negative correlation with %DLCO, but not with FVC, and these biomarkers were not related to disease progression. Persistently high levels of KL-6 and SP-D correlated with progressive type disease behavior in idiopathic (non-IPAF) f-NSIP. Changes in serum KL-6 and SP-D levels over time may provide useful predictive information on disease behavior during treatment in patients with idiopathic f-NSIP and especially in those with non-IPAF f-NSIP.

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.

Clinical Significance of Serum Hemeoxygenase-1 as a New Biomarker for the Patients with Interstitial Pneumonia.

Background Serum hemeoxygenase-1 (HO-1) has been proposed to be a biomarker of lung disease activity and prognosis. The present study aimed at evaluating whether HO-1 could be a useful marker for evaluating disease activity and predicting prognosis in patients with interstitial pneumonia (IP). Materials and Methods Serum HO-1 levels of newly diagnosed or untreated patients with IP were measured at hospitalization. We evaluated the relationships between serum HO-1 and other serum biomarkers, high resolution CT (HRCT) findings, and hospital mortality. Results Twenty-eight patients with IP, including 14 having an acute exacerbation (AE) and 14 not having an AE, were evaluated. The patients having an AE had significantly higher HO-1 levels than those not having an AE (53.5 ng/mL vs. 24.1 ng/mL; p < 0.001), and the best cut-off level to discriminate between having an AE or not having an AE was 41.6 ng/mL. Serum HO-1 levels were positively correlated with serum levels of surfactant protein-D (r=0.66, p < 0.001) and the ground glass opacity score (calculated from HRCT; r=0.40, p=0.036). Patients who subsequently died in hospital had presented with significantly higher HO-1 levels than those who did not die in hospital (64.8 ng/mL vs. 32.0 ng/mL; p=0.009). Conclusion Serum HO-1 may serve as a useful biomarker for detecting AE or predicting hospital mortality in patients with IP.

Surfactant protein D alleviates eosinophil-mediated airway inflammation and remodeling in patients with aspirin-exacerbated respiratory disease.

Surfactant protein D (SPD) is a member of the collectin family that lines the airway epithelial cells with host defense. However, the role of SPD in the pathogenesis of aspirin-exacerbated respiratory disease (AERD) is still unclear. The serum SPD level was measured in patients with AERD (n=336), those with aspirin-tolerant asthma (ATA, n=442), and healthy controls (HC, n=104). Polymorphisms of SFTPD in the study subjects were analyzed. The effect of LTE4 on SPD production through eosinophil infiltration was investigated in BALB/c mice. The protective function of SPD against eosinophils inducing inflammation and remodeling was assessed invitro/vivo. The potential efficacy of nintedanib against airway remodeling through the production of SPD was evaluated. The serum SPD level was significantly lower (P<.001) in AERD compared with ATA patients, and negatively correlated with fall in FEV1 (%) after lysine-aspirin bronchoprovocation test and/or the urinary LTE4 level. In addition, polymorphism of SFTPD at rs721917 was significantly different in the study subjects (odds ratio, 1.310; 95% confidence intervals, 2.124-3.446; P=.002). LTE4-exposed mice showed an increased eosinophil count with a decreased SPD level in bronchoalveolar lavage fluid. Eosinophils increased α-smooth muscle actin expression in airway epithelial cells, which was attenuated by SPD treatment. Furthermore, nintedanib protected the airway epithelial cells against eosinophils by enhancing the production of SPD. The decreased level of SPD in AERD was associated with airway inflammation/remodeling under the eosinophilic condition, suggesting that modulation of SPD may provide a potential benefit in AERD.

Prediction of therapeutic response before and during i.v. cyclophosphamide pulse therapy for interstitial lung disease in systemic sclerosis: A longitudinal observational study.

There have been no established parameters to predict responsiveness to i.v. cyclophosphamide (IVCY) pulse therapy in combination with corticosteroids in patients with interstitial lung disease (ILD) related to systemic sclerosis (SSc). This retrospective study was conducted to determine predictive factors for efficacy of IVCY at the time of before and during the treatment. Thirty-two Japanese SSc patients, ever treated for ILD with IVCY in combination with prednisolone, were analyzed retrospectively. We performed detailed time-course analyses of parameters derived from blood samples and pulmonary function tests. With the exclusion of eight unclassified patients, 24 patients were classified into 14 good responders (GR) or 10 poor responders (PR) on the basis of changes in percent predicted diffusing capacity for carbon monoxide (DLco). Pretreatment percent predicted DLco was significantly reduced in PR compared with GR. In addition, serum parameters such as Krebs von den Lungen-6 (KL-6), surfactant protein D (SP-D) and C-reactive protein were significantly higher in PR than in GR. Furthermore, our time-course analyses revealed a transient increase in serum KL-6 levels with a peak at 3 months after the first infusion of cyclophosphamide, which showed no relation to therapeutic efficacy. Moreover, continuously high serum KL-6 levels (>2000 U/mL) and rapid decrease in SP-D levels (<200 ng/mL) during IVCY were remarkably characteristic of PR and GR, respectively. ILD severity/activity before treatment and variability of serum KL-6 and SP-D levels during treatment may be useful to predict therapeutic effects of IVCY on SSc-ILD.

Serum concentration of surfactant protein D in patients with systemic sclerosis: The potential marker of the interstitial lung disease severity.

Pulmonary involvement is a severe manifestation of systemic sclerosis (SSc). The study was designed to determine the serum level of surfactant protein D (SP-D) in patients with SSc in relation to clinical and laboratory parameters as well as to analyze dynamics of changes of these indices within one year of observation. SP-D was assayed in 41 patients with SSc and 15 healthy controls. Additionally, pulmonary function tests, chest high-resolution computed tomography (HRCT), and inflammatory markers were assessed. All tests were performed twice: at entry and repeated after one year of observation. The serum level of SP-D was significantly higher in patients with SSc than in healthy controls. Serum concentration of SP-D was significantly higher in patients with systemic sclerosis-related interstitial lung disease (SSc-ILD) than in those without SSc-ILD. SP-D was found to correlate with lung involvement evaluated with the Medsger score (diffusing capacity of the lung for carbon monoxide (DLCO), forced vital capacity, radiological changes, and estimated pressure in the pulmonary artery in echocardiography). SP-D correlated with the honeycombing and/or reticular pattern in HRCT and ground glass opacification pattern. Serum concentration of SP-D was elevated in patients with a decreased DLCO. Furthermore, SP-D was higher in patients with diffuse cutaneous type (dcSSc) of the disease than in those with SSc limited type (lcSSc). Because of the small size of the group, it was not possible to perform a statistical analysis for patients who had different results in HRCT, VC, and Medsger score between the first and the second evaluation. SP-D seems to be an index for assessing lung involvement. It reflects the state of pulmonary fibrosis but not the dynamics of the pulmonary fibrosis progression. Further studies are needed to evaluate clinical application of the index, and currently, there is no evidence for the recommendation of the application of SP-D in routine evaluation of patients with SSc.