Serum SP-D Levels Research Articles

Outcomes and prognosis of progressive pulmonary fibrosis in patients with antineutrophil cytoplasmic antibody-positive interstitial lung disease

Approximately one-third of fibrosing interstitial lung diseases exhibit progressive pulmonary fibrosis (PPF), a clinicopathological condition distinct yet resembling idiopathic pulmonary fibrosis (IPF). PPF in ANCA-positive ILD (ANCA-ILD) is poorly documented. To clarify incidence, predictors of PPF in ANCA-ILD, and their prognostic impact, 56 patients with ANCA-ILD were followed for ≥ 1 year (April 2004 to April 2021). PPF was defined per ATS/ERS/JRS/ALAT PPF 2022 guideline. We compared PPF and non-PPF in 38 patients with pulmonary function tests and ≥ 1 year follow up. ANCA-ILD (19 male, 19 female; mean age 72 years) comprised 21 patients with microscopic polyangiitis ILD (MPA-ILD) and 17 with ANCA-positive IP without systemic vasculitis (ANCA-IP). PPF occurred in 15/38 (39.5%) overall, and 27% of patients with MPA-ILD and 53% with ANCA-IP. Patient characteristics did not differ between PPF and non-PPF, however, the survival was significantly worse in patients with PPF than those with non-PPF. On multivariate regression analysis, higher age, higher serum SP-D level, and lower baseline %FVC were associated with PPF. In ANCA-ILD, 39.5% of patients demonstrated PPF, which is associated with increased mortality. Predictors of PPF were older age, higher SP-D, and lower baseline %FVC.

The Soluble Lectin Families as Novel Biomarkers for COVID-19 Pneumonia.

The lung-specific soluble lectins, SP-A and SP-D have been clinically used to diagnose interstitial lung disease, but their clinical significance in COVID-19 remains controversial. This study was undertaken to determine their association with other lectins (MBL and FCN1), disease severity, and radiographs in COVID-19 patients. A total of 131 patients with COVID-19 admitted in the Sapporo Medical University Hospital between May 22 and September 19, 2021, were enrolled in the study. Data including demographics, medical history, symptoms, signs, laboratory findings, and radiological images were collected from the patients' medical records. Chest computed tomography (CT) scanning was performed at admission. Serum levels of surfactant protein A and D (SP-A and SP-D), mannose-binding lectin (MBL) and ficolin1 (FCN1) were measured using enzyme-linked immunosorbent assay (ELISA) kits. Compared to the control group, the COVID-19 group had significantly higher serum SP-A and FCN1 levels on admission (SP-A: 59.60±38.89 vs. 35.61±11.22 ng/ml; p<0.01, FCN1: 542.45±506.04 vs. 250.6±161.1 ng/ml; p<0.01). The severe group in COVID-19 had significantly higher serum SP-D and lower MBL levels than the non-severe group (SP-D: 141.7±155.7 vs. 61.41±54.54 ng/ml; p<0.01, MBL: 1,670±1,240 vs. 2,170±1,140 ng/ml; p<0.05). SP-D strongly reflected the degree of imaging findings, whereas SP-A showed a significant correlation, albeit slightly weaker than SP-D. Conversely, MBL and FNC1 were not significantly correlated with imaging findings. Among soluble serum lectins, SP-A and SP-D may be more sensitive to CT findings than reported disease biomarkers such as IL-6, LDH, and CRP due to their lung-specific characteristics.

Comparison of frailty in patients with nontuberculous mycobacterial lung disease and bronchiectasis: a prospective cohort study

BackgroundThe incidence of nontuberculous mycobacterial lung disease (NTM-LD) peaks in middle- and old age groups, coinciding with senescence; thus, chronic infectious diseases can accelerate frailty and worsen mental health in the elderly. In this study, we aimed to compare the prevalence of physical and psychiatric frailty between patients with NTM-LD and bronchiectasis (BE).MethodsThe Kihon Checklist Questionnaire (KCQ) was used to assess physical and psychiatric frailties and identify those at risk of requiring care among patients with newly diagnosed NTM-LD and BE. Additionally, the Hospital Anxiety and Depression Scale (HADS) scores and chronic inflammatory biomarkers of the alveolar region (surfactant protein [SP]-A, SP-D, and human cationic antibacterial protein [hCAP]/LL-37) were assessed and compared between NTM-LD and BE patients.ResultsThere were no significant differences in the background characteristics between the 33 NTM and 36 BE patients recruited. The KCQ revealed that the proportion of frail NTM patients at diagnosis was higher than that of frail BE patients (48.5% vs. 22.2%, p = 0.026). HADS scores were significantly higher in the NTM group than in the BE group (p < 0.01). Bronchoalveolar lavage fluid (BALF) hCAP/LL-37 and SP-D levels were significantly higher (p = 0.001), but serum hCAP/LL-37 levels were significantly lower in the NTM group than in the BE group (p = 0.023). However, there were no significant differences in the BALF and serum SP-D levels between the two groups.ConclusionsThe number of frail NTM patients at diagnosis was significantly higher than that of frail BE patients. Biomarker analysis suggested that the former had more localized lung inflammation than the latter.Trial registrationThis trial was prospectively registered in the Clinical Trials Registry (UMIN 000027652).

Coronavirus disease 2019 (COVID-19) in patients before, during, or after lung irradiation, and serum SP-A and SP-D levels.

BackgroundThe correlation between COVID‐19 and RT has not been determined to date and remains a clinical question. The aim of this study was to evaluate coronavirus disease 2019 (COVID‐19) pneumonia before, during, and after radiation therapy (RT) regarding the radiation doses, radiation pneumonitis, and surfactant protein levels.MethodsWe evaluated patients diagnosed with COVID‐19 before, during, or after RT for the lung between August 2020 and April 2022. In patients with breast cancer, the RT dose to the ipsilateral lung was determined. In all other patients, bilateral lung RT doses were determined. Patients diagnosed with COVID‐19 after RT were evaluated to determine whether radiation pneumonitis had worsened compared with before RT. The serum levels of the surfactant proteins SP‐A and SP‐D were measured before, during, and after RT.ResultsThe patients included in the study comprised three men (27.3%) and eight women (72.7%). The primary cancer sites were the breast (n = 7; 63.7%), lung (n = 2; 18.1%), esophagus (n = 1; 9.1%), and tongue (9.1%). COVID‐19 was diagnosed before RT in four patients, during RT in two patients, and after RT in five patients. Six (54.5%) patients developed COVID‐19 pneumonia. Radiation pneumonitis grade ≥2 was not identified in any patient, and radiation pneumonitis did not worsen after RT in any patient. No rapid increases or decreases in SP‐A and SP‐D levels occurred after the diagnosis of COVID‐19 in all patients regardless of RT timing.ConclusionsCOVID‐19 did not appear to result in lung toxicity and surfactant protein levels did not change dramatically.

Serum C-X-C Chemokine Ligand 1 Levels in Patients with Systemic Sclerosis: Relationship of Clinical and Laboratory Observations to Anti-CD20 Monoclonal Antibody Administration.

Objectives: To determine whether C-X-C chemokine ligand 1 (CXCL1), which is a potent neutrophil chemoattractant and activator that plays important role in inflammation, is elevated in patients with systemic sclerosis (SSc) and whether it is associated with the clinical features and disease activity of patients with SSc. In addition, to determine whether the changes in serum CXCL1 levels before and after treatment correlate with changes in disease activity in SSc patients who received an anti-CD20 monoclonal antibody drug. Patients and method: We examined patient serum collected in the DesiReS trial, which was a double-blind, parallel-group, randomized, placebo-controlled, multicenter, phase II clinical trial. In the trial, patients were randomly allocated to the drug or placebo group and received 375 mg/m2 of an anti-CD20 antibody, rituximab, or placebo once a week for four weeks. We obtained serum samples from 47 patients administered at our hospital, including 3 males and 44 females, the median age of 48 years, range 27–71 years, with 42 diffuse cutaneous SSc and 5 with limited cutaneous SSc. Serum CXCL1 levels were measured using multiplex immunoassay in patient serum before and 24 weeks after administration and also in serum from 33 healthy controls. Results: Serum CXCL1 levels were significantly higher in SSc patients (mean 25.70 ng/mL; 95% confidence interval (CI) 18.35–33.05 ng/mL) than in the healthy controls (15.61 ng/mL; 95% CI 9.73–21.51 ng/mL). In addition, SSc patients with elevated CXCL1 levels had a significantly higher percentage of area occupied with interstitial shadows (p < 0.05), increased serum levels of surfactant protein (SP)-A (p < 0.05), SP-D (p < 0.05), Krebs von den Lungen-6 (p < 0.01), and C-reactive protein (p < 0.05) compared to those with normal levels. Furthermore, defining Δ as the value after rituximab administration minus the value before rituximab administration, baseline serum CXCL1 levels correlated with Δ percent predicted diffusing capacity for carbon monoxide (p < 0.01). In addition, ΔCXCL1 correlated with ΔSP-A (p < 0.05). Similarly, serum CXCL1 levels after rituximab administration correlated with percent predicted forced vital capacity (p < 0.05) and serum SP-D levels (p < 0.05) after rituximab. Conclusions: Our results suggest that serum CXCL1 is associated with the disease activity of SSc-ILD, and high serum CXCL1 levels are one of the predictors of improvement in SSc-ILD with rituximab.

Association of surfactant protein D gene polymorphism with susceptibility to gestational diabetes mellitus: a case\u2013control study

BackgroundSurfactant protein D (SP-D) is a critical component of the innate immune system intrinsically linked to energy metabolism. However, the relationship of SP-D gene polymorphisms and gestational diabetes mellitus (GDM) remains unclear. In this study, we analyzed SP-D gene polymorphisms in GDM patients and nondiabetic controls and then determined the association of SP-D gene polymorphisms with GDM.MethodsWe examined a common genetic polymorphism located in the SP-D coding region (rs721917, Met31Thr) in GDM patients (n = 147) and healthy pregnant controls (n = 97) by using a cleaved amplification polymorphism sequence-tagged sites (PCR–RFLP) technique. The level of SP-D protein in the serum of GDM patients and nondiabetic controls was determined by ELISA. The gene and allele frequencies of SP-D and their association with GDM as well as SP-D protein levels were analyzed and expressed as odds ratios (ORs) with 95% confidence intervals (95% CIs).ResultsWe found that there was a significant association of the SP-D polymorphism (rs721917) with GDM. The SP-D (T/T) genotype was found in 11.6% and 21.6% of GDM patients and matched healthy controls, respectively (odds ratio, 0.473; 95% confidence interval, 0.235–0.952; P = 0.033), indicating that women with the (T/T) genotype had a lower prevalence of GDM (OR = 0.473). Women with the T/C genotype showed an increased risk of GDM (odds ratio, 2.440; 95% confidence interval, 1.162–5.123; P = 0.017). We did not observe corrections between glucose homeostasis markers and SP-D genotypes in women with GDM. Furthermore, serum SP-D levels were higher in GDM patients than in matched healthy controls.ConclusionsThis study found the first evidence that an SP-D gene polymorphism (rs721917) was associated with GDM, which may provide the basis for further study on how SP-D plays a regulatory role in GDM.

The interaction effect of aerobic exercise and vitamin D supplementation on inflammatory factors, anti-inflammatory proteins, and lung function in male smokers: a randomized controlled trial

BackgroundThis study aimed to investigate the interaction effect of aerobic exercise and vitamin D supplementation on inflammation (TNF-α, IL-6, CC16, SP-D, and CC16/SP-D ratio) and lung function (FEV1, FVC, and FEV1/FVC ratio) in male smokers.MethodsAfter applying inclusion criteria, a total of 40 healthy male smokers were recruited in this study. The participants were randomly divided into four groups as follows: Aerobic Exercise + vitamin D Supplementation (AE + VitD, n = 10), Aerobic Exercise (AE, n = 10), vitamin D Supplementation (VitD, n = 10), and Control (C, n = 10). The participants in the AE + VitD and AE groups performed aerobic exercise training (running) up to 50% of the maximum heart rate, three times a week for four weeks. Participants in AE + VitD and VitD groups received 6000 IU/w vitamin D3 for four weeks. The participants in control group did not receive any intervention. Serum tumor necrosis factor (TNF)-α, interleukin (IL)-6, Clara cell protein (CC16), surfactant protein (SP)-D, CC16/SP-D ratio, and lung function (FEV1, FVC, and FEV1/FVC ratio) were measured before and after four weeks of intervention.ResultsSerum levels of TNF-α, IL-6, and CC16 decreased significantly in AE + VitD, VitD, and AE groups after four weeks (P < 0.05). Serum SP-D level decreased significantly only in the AE + VitD group (P = 0.011). In addition, FEV1 and FVC increased significantly (P < 0.05) in AE + VitD and AE groups after four weeks of intervention. However, the interventions did not have a significant effect on CC16/SP-D ratio and FEV1/FVC ratio (P > 0.05). Furthermore, serum levels of 1,25-dihydroxyvitamin D increased significantly in AE + VitD and VitD groups (P < 0.05) after four weeks of intervention. However, except for TNF-α, between-group comparisons showed no significant differences in levels of IL-6, CC16, SP-D, CC16/SP-D ratio, FEV1, FVC, FEV1/FVC, and 1,25-dihydroxyvitamin D (P > 0.05).ConclusionsThe results of present study were that aerobic exercise combined with vitamin D supplementation can reduce serum inflammatory factors and anti-inflammatory proteins and improve lung function after four weeks of intervention. Further trials with larger sample size and longer duration are suggested to confirm these results.Trial registration Retrospectively registered. IRCT20180513039637N4. Registration date: 2020/10/20. URL: https://www.irct.ir/search/result?query=IRCT20180513039637N4

The role of angiopoietin-2 and surfactant protein-D levels in SARS-CoV-2-related lung injury: A prospective, observational, cohort study.

IntroductionCoronavirus disease‐2019 (COVID‐19) is a respiratory disease whose clinical manifestation ranges from asymptomatic to severe respiratory failure. The purpose of this study was to investigate the place of serum surfactant‐D (SP‐D) and angiopoetin‐2 (Ang‐2) levels in predicting severity of disease in patients diagnosed with COVID‐19.MethodsSixty‐four patients diagnosed with COVID‐19 between September 2020 and February 2021, 50 patients diagnosed with community‐acquired pneumonia and a 50‐member healthy control group were included in the study. Plasma samples and clinical data were collected within 72 h after admission, during hospital stay. Serum SP‐D and Ang‐2 concentrations were measured using the enzyme‐linked immunosorbent assay.ResultsSP‐D and Ang‐2 levels were significantly higher in the mild–moderate pneumonia and severe/critical patient groups compared to the asymptomatic and noncomplicated COVID‐19 patients (p < 0.001 for all groups). Serum SP‐D and Ang‐2 levels of severe‐critical COVID‐19 patients were significantly higher than CAP patients (p < 0.001). Powerful correlation was present between clinical severity of COVID‐19 and SP‐D and Ang‐2 levels (r = 0.885 p < 0.001 and r = 0.913 p < 0.001, respectively). Cut‐off values of 37.7 ng/ml (AUC = 0.763, p < 0.001, 95% confidence interval [CI] = 0.667–0.860) for SP‐D and 4208.3 pg/ml (AUC = 0.659, p = 0.004, 95% CI = 0.554–0.763) for Ang‐2 were identified as predictors of COVID‐19 disease at receiver operating characteristic curve analysis.ConclusionSP‐D and Ang‐2 are predictive factors in differentiating COVID‐19 patients and determining severity of disease. These data may be important for the initiation of treatment in the early stage of the disease in patients with COVID‐19.

Human Surfactant Protein D Binds Spike Protein and Acts as an Entry Inhibitor of SARS-CoV-2 Pseudotyped Viral Particles.

Human SP-D is a potent innate immune molecule whose presence at pulmonary mucosal surfaces allows its role in immune surveillance against pathogens. Higher levels of serum SP-D have been reported in the patients with severe acute respiratory syndrome coronavirus (SARS-CoV). Studies have suggested the ability of human SP-D to recognise spike glycoprotein of SARS-CoV; its interaction with HCoV-229E strain leads to viral inhibition in human bronchial epithelial (16HBE) cells. Previous studies have reported that a recombinant fragment of human SP-D (rfhSP-D) composed of 8 Gly-X-Y repeats, neck and CRD region, can act against a range of viral pathogens including influenza A Virus and Respiratory Syncytial Virus in vitro, in vivo and ex vivo. In this context, this study was aimed at examining the likely protective role of rfhSP-D against SARS-CoV-2 infection. rfhSP-D showed a dose-responsive binding to S1 spike protein of SARS-CoV-2 and its receptor binding domain. Importantly, rfhSP-D inhibited interaction of S1 protein with the HEK293T cells overexpressing human angiotensin converting enzyme 2 (hACE2). The protective role of rfhSP-D against SARS-CoV-2 infection as an entry inhibitor was further validated by the use of pseudotyped lentiviral particles expressing SARS-CoV-2 S1 protein; ~0.5 RLU fold reduction in viral entry was seen following treatment with rfhSP-D (10 µg/ml). These results highlight the therapeutic potential of rfhSP-D in SARS-CoV-2 infection and merit pre-clinical studies in animal models.

Surfactant protein A as a biomarker of outcomes of anti-fibrotic drug therapy in patients with idiopathic pulmonary fibrosis

BackgroundIdiopathic pulmonary fibrosis (IPF) is a progressive and fibrosing lung disease with poor prognosis. Pirfenidone and nintedanib are anti-fibrotic drugs used for patients with IPF. These drugs reduce the rate of decline in forced vital capacity (FVC). Serum surfactant protein (SP)-A, SP-D, and Krebs von den Lungen-6 (KL-6) are monitoring and prognostic biomarkers in patients with IPF; however, their relationship with the therapeutic outcomes of anti-fibrotic drugs has not been investigated. We aim to clarify whether serum SP-A, SP-D, and KL-6 reflect therapeutic outcomes of pirfenidone and nintedanib administration in patients with IPF.MethodsWe retrospectively investigated patients with IPF who were initiated on pirfenidone or nintedanib administration between January 2014 and June 2018 at our hospital. Changes in clinical parameters and serum SP-A, SP-D, and KL-6 levels were evaluated. Patients with ≥10% decline in FVC or ≥ 15% decline in diffusing capacity of the lung for carbon monoxide (DLco) from baseline to 6 months were classified as progression group, while the other patients were classified as stable group.ResultsForty-nine patients were included (pirfenidone, 23; nintedanib, 26). Stable group comprised 32 patients, while progression group comprised 17 patients. In the stable group, changes in SP-A and KL-6 from baseline to 3 and 6 months significantly decreased compared with the progression group (SP-A: 3 months − 6.0% vs 16.7%, 6 months − 10.2% vs 20.2%, KL-6: 3 months − 9.2% vs 6.7%, 6 months − 15.0% vs 12.1%, p < 0.05). Changes in SP-A and SP-D levels showed significant negative correlations with the change in %FVC (r = − 0.46 and r = − 0.39, p < 0.01, respectively) and %DLco (r = − 0.67 and r = − 0.54, p < 0.01, respectively). Similar results were also seen in subgroup analysis for both pirfenidone and nintedanib groups. On logistic regression analysis, decrease in SP-A from baseline to 3 months and 6 months was found to predict the outcomes at 6 months (odds ratios: 0.89 and 0.88, respectively).ConclusionsChanges in serum SP-A reflected the outcomes of anti-fibrotic drug therapy. Serum SP-A has a potential as a biomarker of therapeutic outcomes of anti-fibrotic drugs.

Inhalation of titanium dioxide (P25) nanoparticles to rats and changes in surfactant protein (SP-D) levels in bronchoalveolar lavage fluid and serum

Titanium dioxide (TiO2) nanoparticles are typical and widely used nanomaterials, and there are many studies on the inflammatory responses induced by their inhalation. In this study, we conducted a 4-week inhalation exposure study of aerosolized TiO2> nanoparticles (P25) to male Wistar rats. The mean aerosol concentration measured at each day was 4.1 mg/m3 by dry powder dispersion of TiO2 nanoparticles. Control and exposure groups of rats were killed at 3 and 30 days after the termination of exposure, and bronchoalveolar lavage fluid (BALF) and serum were collected for analysis of total cell count, neutrophil count, and surfactant protein (SP-D) in BALF and SP-D in serum, as well as other serum biomarkers. SP-D is a component of lung surfactants produced in type II alveolar epithelial cells and Clara cells and secreted into the alveolar space and blood. The neutrophil count in the BALF was significantly elevated at 3 and 30 days. The levels of SP-D in the BALF were also elevated at 3 and 30 days, while the serum SP-D levels were elevated at 3 days only. We determined the amounts of TiO2 in the rat lungs in the exposure group at 3, 30, and 73 days to analyze the lung deposition fraction (10.2%) and the biological half-life time (72.4 days) of inhaled TiO2 nanoparticles. Histopathological analysis revealed mild pulmonary inflammation in lung tissue at 3 days. Serum SP-D was found to be a potential biomarker for exposure to TiO2 nanoparticles in this study.

The relationship between serum levels of surfactant protein D in COPD exacerbation severity and mortality

Background/aim Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality. In COPD patients, various inflammatory markers such as cytokines and acute phase proteins, which show systemic inflammation in the circulation, increase during exacerbations. In our study, we aimed to determine the relationship between serum SP-D levels and exacerbation severity, clinical course of the disease, and early mortality after discharge.Materials and methods Fifty hospitalized patients with COPD acute exacerbation (46 male and 4 female) were recruited in this study. Thirty-three of the subjects (31 male and 2 female) were reevaluated after discharge. Venous blood samples were taken from all patients and followed up for exacerbation frequency, hospital admission, and mortality for 12 months.Results Serum SP-D levels in the stable period of the patients were lower than exacerbation (P < 0.001). The median exacerbation period SP-D level of the patients admitted to emergency department in the first month was statistically significantly higher than that of the patients who were not admitted (P < 0.05) after discharge. There was a correlation between the rate of emergency admission and serum SP-D levels during the 12-month period after discharge (P = 0.04 (r = 0.29)).Conclusion Our study showed that serum SP-D was found to be a useful biomarker in predicting emergency admission and predictor of the health status of COPD patients but did not predict early mortality after the exacerbation.

INVESTIGATION OF SERUM SURFACTANT PROTEIN A AND D LEVELS IN CHILDREN EXPOSED TO CIGARETTE SMOKE

Background: Depending on the degree of exposure to cigarette smoke, various health problems can emerge in children. It is needed to have biochemical data of passive smoking to define the risks and to count the benefits of anti-smoking responses. Objective: The objective of the study was to evaluate the effect of smoke exposure on the surfactant protein (SP) A and D by measuring the cotinine level in the lungs of the children who are exposed to passive cigarette smoke. Methods: This case–control study was conducted between December 2012 and September 2013. İn this study, total 79 children were included who were admitted to the general pediatric outpatient clinic of a medical university. Out of them, 51 children were exposed to cigarette smoke and 28 children were not exposed to cigarette smoke. In a survey was applied to evaluate the smoke exposure, and urinary cotinine levels were measured. Cotinine level was measured by chemiluminescence method (children’s urines are used), and serum SP-D and SP-A levels were measured by ELISA method (peripheral venous blood is used). Results: The average urinary cotinine level of the children who were exposed to smoking was 622.27±600.66 ng/ml and 4.25±7.50 ng/ml of the children who were not exposed. The mean serum SP-A level was high (2.64±0.78 U/L) in children exposed to smoking than that in non-exposed children (2.2±0.76 U/L) and this difference was statistically significant (p&lt;0.001). The serum SP-D level was high in children who were exposed to smoking, but it was not statistically significant. It was verified that there was a correlation between the average urinary cotinine level and serum SP-A level (r=0.257, p=0.02) but it was not true for SP-D level. Conclusion: We found that the serum SP-A level, which has a big role on lungs’ natural immune system, is higher in the children who are exposed to smoking when compared to the non-exposed children. This indicates that cigarette’s inflammatory effect increases as a response to its anti-inflammatory effect in the serum level.Key words: Child, Cotinine, Exposure to smoke, Surfactant proteins D, Surfactant proteins A

Serum surfactant protein D and exhaled nitric oxide as biomarkers of early lung damage in systemic sclerosis.

Interstitial lung disease (ILD) complicates the course of systemic sclerosis (SSc), representing the main cause of death in these patients. The identification of parameters that can predict the early onset and progression of ILD in SSc represents an unmet need in clinical practice. The study was designed to explore whether the surfactant proteins (SP) A and D may be used as noninvasive tools for the early identification of ILD in SSc. Alveolar exhaled nitric oxide (NO) was investigated as a surrogate marker of distal inflammation. Unselected consecutive subjects newly diagnosed with scleroderma and subjects free of respiratory and systemic diseases were recruited. All patients underwent clinical, lung functional, radiological and biological assessments. 15 individuals affected by SSc (M/F: 3/12), and 10 healthy subjects (M/F: 3/7) participated to the study. The serum SP-D values were 115.3±81.36 ng/mL in SSc subjects and 32±11.9 ng/mL in healthy controls (P=0.004). The concentrations of serum SP-A were not statistically different between groups. Serum SP-D inversely correlated with FEV1% predicted (rs=-0.29; P=0.004), FVC% predicted (rs=-0.20; P=0.02) and DLCO% predicted (rs=-0.36; P=0.001). Alveolar NO concentrations were significantly different between SSc and control subjects (6.5±2.9 ppb vs. 2.2±1.3 ppb, respectively; P=0.001), and positively associated with the levels of serum SP-D (r=0.60, P=0.03). These findings suggest that, in patients with scleroderma, SP-D and exhaled alveolar NO could represent novel non-invasive markers of early detection and activity of lung involvement.

Endurance exercise training decreased serum levels of surfactant protein D and improved aerobic fitness of obese women with type-2 diabetes

BackgroundSurfactant protein D (SP-D) is a member of the collectin family and is an important component of the pulmonary innate host defense. To find the relationship between exercise training and SP-D in diabetes, we examined the possible effects of a 10-week endurance exercise-training program on serum levels of SP-D, leptin, lipid profile and insulin resistance in obese women with type-2 diabetes mellitus (T2DM).MethodsTwenty-two obese women with T2DM were randomly assigned to either exercise training (ET) or control (C) group. A subject dropped from ET group due to personal reasons and 1 subject dropped from C group due to commitment to experiments conditions. A total of twenty obese women with T2DM were randomly assigned into endurance exercise training (ET = 10) and control (C = 10) groups. The training group underwent a progressive endurance-training program for 10 weeks (running on a treadmill for 30–55 min/day at 50–75% heart rate reserve) and the control group did not participate in any exercise program. Venous blood samples were collected from both groups before and 72 h after the last session of exercise training for analysis of serum SP-D, leptin, lipid profile, glucose and insulin. Data were analyzed using 2 (group: control, endurance training) × 2 (time: pre, post) ANOVA with repeated measures on the second factor. Absolute changes from rest (∆ baseline) values were calculated according to the following formula: ((measure-baseline)·baseline-1)·100. Percent change between groups was analyzed using independent t-tests (p < 0.05). All analyses were completed using SPSS 19.ResultsThe serum SP-D levels were decreased after exercise training in ET (∆ = − 78.78 ± 17.14%, p = 0.001) when compare to C (∆ = 9.41 ± 4.75%). Obese diabetic women in the ET group showed significantly lower serum leptin levels (8053.27 ± 878.7 pg/ml, ∆ = − 26.97 ± 16.41%) when compared with women in the control group (9885.5 ± 696 pg/ml, ∆ = 7.02 ± 3.46%, p = 0.003). Fasting glucose was favorably and significantly affected by the intervention (ET ∆ = − 17.01 ± 12.74%, Control ∆ = 15.47 ± 7.32%, p = 0.011). VO2max as an index of aerobic fitness was significantly increased after 10-weeks of endurance exercise training (ET ∆ = 19.29 ± 6.18%).ConclusionsEndurance exercise training with improvement in aerobic fitness induced a significant reduction of serum SP-D levels in obese women with T2DM.

Serum surfactant protein D predicts the outcome of patients with idiopathic pulmonary fibrosis treated with pirfenidone.

Idiopathic pulmonary fibrosis (IPF) is a fatal pulmonary disease with poor prognosis. Pirfenidone, the first antifibrotic drug, suppresses the decline in forced vital capacity (FVC) and improves prognosis in some, but not all, patients with IPF; therefore, an indicator for identifying improved outcomes in pirfenidone therapy is desirable. This study aims to clarify whether baseline parameters can be predictors of disease progression and prognosis in patients with IPF treated with pirfenidone. We retrospectively investigated patients with IPF who started treatment with pirfenidone between December 2008 and November 2014at the Sapporo Medical University Hospital. Patients treated with pirfenidone for ≥6 months were enrolled in this study and were observed until November 2015. We investigated the association of clinical characteristics, pulmonary function test results, and blood examination results at the start of pirfenidone with the outcome of patients. Sixty patients were included in this study. In multivariate logistic regression analysis, % predicted FVC and serum surfactant protein (SP)-D levels were predictors of a ≥10% decline in FVC in the initial 12 months. In the Cox proportional hazards model, these two factors predicted progression-free survival. Pack-years, % predicted diffusing capacity for carbon monoxide, and SP-D levels predicted overall survival. The serum SP-D level was a predictor of disease progression and prognosis in patients with IPF treated with pirfenidone. In addition, this analysis describes the relative usefulness of other clinical parameters at baseline in estimating the prognosis of patients with IPF who are candidates for pirfenidone therapy.

Impact of serum SP-A and SP-D levels on comparison and prognosis of idiopathic pulmonary fibrosis: A systematic review and meta-analysis.

Idiopathic pulmonary fibrosis (IPF) has a poor prognosis in general; however, it is heterogeneous to detect relative biomarkers for predicting the disease progression. Serum biomarkers can be conveniently collected to detect and help to differentially diagnose IPF and predict IPF prognosis. This meta-analysis aimed to evaluate the use of serum surfactant proteins A and D (SP-A and SP-D) for differential diagnosis and prognosis of IPF. Relevant articles were searched in PubMed, Embase, and Chinese National Knowledge Infrastructure databases and reviewed by 2 independent readers. Standard mean difference (SMD) and 95% confidence interval (CI) were calculated to assess the difference in serum levels of SP-A/D among patients with IPF, when compared to patients with non-IPF interstitial lung disease (ILD), pulmonary infection, and healthy control. Hazard ratio (HR) and 95% CI were used to compare the relative risk of mortality. Twenty-one articles (totalling 1289 IPF patients) were included in final meta-analysis. Serum SP-A levels were significantly higher in patients with IPF than in patients with non-IPF ILD (SMD: 1.108 [0.584, 1.632], P < .001), or pulmonary infection (SMD: 1.320 [0.999, 1.640], P < .001) and healthy controls (SMD: 2.802 [1.901, 3.702], P < .001). There was no significant difference in serum SP-D levels between patients with IPF and those with non-IPF ILD patients (SMD: 0.459 [-0.000, 0.919], P = .050). Serum SP-D levels were significantly higher in patients with IPF than in patients with pulmonary infection (SMD: 1.308 [0.813, 1.803], P < .001) and healthy controls (SMD: 2.235 [1.739, 2.731], P < .001). Risk of death in patients with IPF and elevated serum SP-A was increased 39% compared to patients with low SP-A groups. Elevated SP-D increased risk by 111% when compared to low SP-D. In acute exacerbation of IPF, serum SP-A/D were higher than those in stable stage. The comparisons and prognosis might be different in Asian and Caucasian patients. Serum SP-A/D detection might be useful for differential diagnosis and prediction of survival in patients with IPF.

Surfactant Protein-D: A sensitive predictor for efficiency of preoperative pulmonary rehabilitation

BackgroundSurfactant Protein D (SP-D) as a lung-derived biomarker for inflammatory lung disease is being studied in depth. Meanwhile, the Pre-operative Rehabilitation Program (PRP) has been proposed as an effective treatment to reduce the incidence of Post-operative Pulmonary Complications (PPCs) and further improve quality of life. However, the relationship between serum SP-D levels and PRP remains unclear. This study aimed to explore the correlation between these two phenomena and validate the feasibility of using preoperative serum SP-D levels to predict or assess the effectiveness of PRP. MethodsA prospective study with a total of 80 lung cancer patients with risk factors for PPCs was conducted; subjects were randomly divided into an Intervention Group (IG, n = 36) and a Control Group (CG, n = 44). The IG was treated with one week of PRP, and the CG was treated for the same duration with routine preoperative preparation before the lobectomy. Peripheral venous blood samples were collected at five time points and serum SP-D levels were measured by enzyme-linked immunosorbent assay (ELISA). We analysed the serum level changes of SP-D as well as the PPCs occurred between the two groups. ResultsBoth groups were comparable at baseline. The average levels of SP-D in both groups showed a decline trend with time, and levels before the day of surgery revealed a significant decline range in the IG compared with the CG (6.56 ± 5.30 vs. 1.05 ± 2.79 ng/ml, P < 0.001). The incidence of PPCs in the IG was significantly lower than in the CG (2/36 vs. 10/44, p = 0.032), as were the PPC person-times occurring from postoperative days 1–4 (POD 1–4) (5/36 vs. 15/44, p = 0.038) and the total person-times (5/36 vs. 19/44, p = 0.004). The overall SP-D levels on the day before surgery in patients with PPCs were significantly higher than those without PPCs (34.07 ± 4.32 vs. 30.30 ± 6.52 ng/ml, p = 0.005); furthermore, the overall SP-D levels on admission day in CG patients with PPCs were also significantly higher than those without PPCs (34.93 ± 4.15 vs. 29.81 ± 7.47 ng/ml, p = 0.045). ConclusionsThe Preoperative Intensity Rehabilitation Program could positively decrease the serum SP-D levels in lung cancer patients with PPC risk factors, and higher preoperative serum SP-D levels may related to a higher incidence of PPCs. Serum SP-D may be a potential predictor for evaluating the efficiency of PRPs and the risk of PPC occurrence.

Surfactant protein D is a useful biomarker for monitoring acute lung injury in rats

ABSTRACTPurpose: The purpose of this study is to investigate the serial changes in the SP-D concentrations of serum and bronchoalveolar lavage fluid (BALF) in a bleomycin-induced lung injury rat model and compare them with the levels of conventional biochemical markers. Materials and Methods: Male Wister rats were anesthetized and intratracheally administered bleomycin (1.0 mg/kg). We evaluated the histological changes and SP-D expression of their lung tissues. We also measured the concentrations of SP-D, albumin, and lactate dehydrogenase (LDH) and the numbers of various types of cells in BALF, and the serum levels of SP-D and conventional markers, including LDH, high mobility group box 1, monocyte chemoattractant protein-1, and C-reactive protein. Results: The BALF SP-D level increased and peaked on day 3, and then gradually decreased. These variations were significantly correlated with the changes in the BALF albumin level and granulocyte cell count. The serum SP-D level increased from day 5, peaked on day 10, and then gradually decreased until day 28. The changes in the serum SP-D level accurately reflected the extent of the histological changes caused by the lung injury. On the other hand, the serum levels of conventional biomarkers were only elevated for a few days or did not change during the study period. Conclusions: The SP-D level is the most useful marker of the severity of lung injuries. These results suggest that the measurement of SP-D levels is an additional tool for monitoring acute lung injuries in rats.

Significance of surfactant proteins in the diagnosis of therapeutic diseases

The lung provides not only respiration, but also the functioning of innate immunity mechanisms. The hydrophilic proteins SP-A and SP-D are responsible for the regulation of the latter. In the literature, there is evidence for elevated serum SP-A and SP-D levels in respiratory diseases accompanied by enhanced mucosal inflammation of the lung or its parenchymal injury and their association with age and cardiovascular diseases has been recently found. Studies of the efficiency of using SP-A and SP-D as specific markers for inflammatory lung diseases are presently worthwhile.