BACKGROUND/AIMS: Several studies have identified a role for nuclear factor erythroid 2-related factor 2 (Nrf2) in the development of chronic obstructive pulmonary disease (COPD). However, the relationship between the plasma Nrf2 level and the extent of systemic inflammation associated with COPD status remains unclear. METHODS: Patients diagnosed with COPD were recruited from St. Paul’s Hospital, The Catholic University of Korea, between July 2009 and May 2012. Patients were classified into two groups according to the severity of their symptoms on initial presentation, a COPD-stable group (n = 25) and a COPD-exacerbation group (n = 30). Seventeen patients were enrolled as a control group (n = 17). The plasma levels of Nrf2 and other systemic inf lammatory biomarkers, including interleukin 6 (IL-6), surfactant protein D (SP-D), and C-reactive protein (CRP), were measured. We collected clinical data including pulmonary function test results, and analyzed the relationships between the biomarker levels and the clinical parameters. RESULTS: Plasma Nrf2 and CRP levels significantly increased in a stepwise manner with an increase in inflammatory status (control vs. COPD-stable vs. COPD-exacerbation) (p = 0.002, p < 0.001). Other biomarkers of systemic inflammation (IL-6, SP-D) exhibited similar tendencies, but significant differences were not apparent. Furthermore, we observed negative correlations between the plasma level of Nrf2 and both the forced expiratory volume in 1 second (FEV1) (r = –0.339, p = 0.015) and the forced expiratory ratio (FEV1/forced vital capacity [FVC]) (r = –0.342, p = 0.014). However, CRP level was not correlated with any measured parameter. CONCLUSIONS: Plasma Nrf2 levels gradually increased in line with disease severity and the extent of systemic inflammation in patients with COPD.
Biomarkers ; C-Reactive Protein ; Forced Expiratory Volume ; Humans ; Inflammation ; Interleukin-6 ; Korea ; Lung Diseases ; NF-E2-Related Factor 2 ; Plasma ; Pulmonary Disease, Chronic Obstructive* ; Pulmonary Surfactant-Associated Protein D ; Respiratory Function Tests ; Vital Capacity

OBJECTIVETo investigate the relationship between polymorphisms of surfactant protein D (rs3088308 and rs721917) and the susceptibility to silicosis.

METHODSThis case-control study included 125 silicosis patients and 125 individuals exposed to industrial dust but without silicosis (control group), who were strictly matched with the case group for age, gender, work type and cumulative length of dust exposure. The rs3088308 and rs721917 polymorphisms of surfactant protein-D were detected in all the participants using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).

RESULTSThe frequencies of T/T, T/A and A/A genotypes of surfactant protein-D rs3088308 locus were 22.2%, 71.2% and 5.6% in the case group, significantly different from the frequencies of 17.6%, 58.4% and 24.0% in the control group, respectively (P<0.05). The frequencies of C/C, C/T and T/T genotypes of rs721917 locus were 17.6%, 56.8% and 25.6% in the case group, similar to the frequencies of 15.2%, 60.0% and 24.8% in the control group, respectively (P>0.05).

CONCLUSIONSurfactant protein-D rs3088308 polymorphism is significantly associated with silicosis, and the T allele may be a risk factor for silicosis in individuals exposed to industrial dust.

Alleles ; Case-Control Studies ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Humans ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Polymorphism, Restriction Fragment Length ; Pulmonary Surfactant-Associated Protein D ; genetics ; Risk Factors ; Silicosis ; genetics

OBJECTIVETo observe the levels of pulmonary surfactant proteins A and D (SP-A, SP-D) in bronchoalveolar lavage fluid (BALF) of children with pneumonia, and to explore their relationships with clinical characteristics.

METHODSThirty-five children with pneumonia were enrolled in this study. Differential cell counts were obtained by Countstar counting board. The levels of SP-A and SP-D in BALF were detected using ELISA.

RESULTSIn children with pneumonia, SP-D levels were significantly higher than SP-A levels (P<0.001). SP-D levels were negatively correlated with the neutrophil percentage in BALF (r(s)=-0.5255, P<0.01). SP-D levels in BALF in children with increased blood C-reactive protein levels (>8 mg/L) were significantly lower than in those with a normal level of C-reactive protein (P<0.05). Compared with those in children without wheezing, SP-D levels in children with wheezing were significantly lower (P<0.01). There was no correlation between SP-A levels and clinical characteristics.

CONCLUSIONSSP-D levels in BALF are significantly higher than SP-A levels, and have a certain correlation with clinical characteristics in children with pneumonia. As a protective factor, SP-D plays a more important role than SP-A in regulating the immune and inflammatory responses.

Bronchoalveolar Lavage Fluid ; chemistry ; C-Reactive Protein ; analysis ; Child ; Child, Preschool ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Infant ; Male ; Pneumonia ; metabolism ; Pulmonary Surfactant-Associated Protein A ; analysis ; Pulmonary Surfactant-Associated Protein D ; analysis

OBJECTIVETo investigate the dynamic changes in the expression of clara cell protein (CC16) and surfactant protein D (SP-D) in the lung tissues and bronchoalveolar lavage fluid (BALF) of silica-treated rats.

METHODSEighty-four Wistar rats were randomly divided into control group (n = 42) and silica group (n = 42). The silica group was subsequently divided into 3, 7, 14, 21, 28, and 60 d subgroups. The silicotic model was made by instilling silica suspension directly through the trachea into rat lungs. At 3, 7, 14, 21, 28, and 60 d after silica instillation, 8 rats in each group were sacrificed and their lung tissues and BALF were collected. The expression of SP-D and CC16 in lung tissues was detected by immunohistochemistry. Enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of SP-D and CCl6 in BALF.

RESULTSThe immunohistochemical assay indicated that CCl6 and SP-D were expressed in lung cells. The ELISA found that in 7, 14, 21, 28, and 60 d silica subgroups, the content of CCl6 in rat BALF was 8.14±0.70, 7.15±0.66, 7.00±0.69, 6.34 ± 0.59, and 5.27±0.49 ng/L, respectively; CCl6 expression decreased gradually with the silica exposure time prolonged, indicating a negative correlation (ra = -0.953, P < 0.01). Compared with the control group, all silica subgroups had significantly decreased CCl6 levels (P < 0.05). The content of SP-D in BALF was 12.20 ± 1.57, 14.41 ± 0.65, and 12.18 ± 0.74 ng/L, respectively, in the 7, 14, and 21 d silica subgroups, significantly higher than that in the control group (P < 0.05).

CONCLUSIONThe dynamic changes in SP-D and CCl6 protein levels in the lung tissues and BALF of rats could be induced by silica exposure and are related to silica exposure time. With the extension of silica exposure, CCl6 levels are gradually reduced, while the SP-D levels first increase and then fall.

Animals ; Bronchoalveolar Lavage Fluid ; chemistry ; Epithelial Cells ; metabolism ; Lung ; metabolism ; Pulmonary Surfactant-Associated Protein D ; metabolism ; Rats ; Rats, Wistar ; Silicon Dioxide ; toxicity ; Uteroglobin ; metabolism

OBJECTIVES: The present study was designed to determine whether there is a relationship between indium compound exposure and interstitial lung damage in workers employed at indium tin oxide manufacturing and reclaiming factories in Korea. METHODS: In 2012, we conducted a study for the prevention of indium induced lung damage in Korea and identified 78 workers who had serum indium or Krebs von den Lungen-6 (KL-6) levels that were higher than the reference values set in Japan (3 microg/L and 500 U/mL, respectively). Thirty-four of the 78 workers underwent chest high-resolution computed tomography (HRCT), and their data were used for statistical analysis. RESULTS: Geometric means (geometric standard deviations) for serum indium, KL-6, and surfactant protein D (SP-D) were 10.9 (6.65) microg/L, 859.0 (1.85) U/mL, and 179.27 (1.81) ng/mL, respectively. HRCT showed intralobular interstitial thickening in 9 workers. A dose-response trend was statistically significant for blood KL-6 levels. All workers who had indium levels > or =50 microg/L had KL-6 levels that exceeded the reference values. However, dose-response trends for blood SP-D levels, KL-6 levels, SP-D levels, and interstitial changes on the HRCT scans were not significantly different. CONCLUSIONS: Our findings suggest that interstitial lung changes could be present in workers with indium exposure. Further studies are required and health risk information regarding indium exposure should be communicated to workers and employers in industries where indium compounds are used to prevent indium induced lung damage in Korea.
Indium* ; Japan ; Korea ; Lung Diseases, Interstitial ; Lung* ; Occupational Exposure ; Pulmonary Surfactant-Associated Protein D ; Reference Values ; Thorax ; Tin

PURPOSE: Collectin family is an important component of innate immunity, of which surfactant protein (SP)-D and mannose-binding lectin (MBL) are the most characterized. We examined SP-D and MBL in young children with acute respiratory syncytial virus (RSV) bronchiolitis. METHODS: Sixty-three children (< or =24 months of age) admitted with the first RSV bronchiolitis during 2 epidemics and followed for 1 year after discharge were enrolled. The patients were defined as severe group when they had 2 of followings during admission: hypoxemia (<92% oxygen saturation), rapid breathing (and/or lower chest wall indrawing), and >7 days of hospital stay. All children were evaluated if they had recurrent wheezing during follow-up. SP-D and MBL were measured using enzyme-linked immunosorbent assay in serum collected on admission and compared with controls. Their levels were evaluated in relation to the symptom severity during admission and recurrence of wheezing after discharge. RESULTS: Serum SP-D increased significantly in the patients (P<0.01), but MBL showed no difference compared to the controls. SP-D levels were significantly higher in severe group compared with nonsevere group (P<0.05). SP-D levels in the patients with recurrent wheezing after discharge were significantly higher than in those without (P<0.05). MBL showed no difference in relation to the symptom severity or recurrence of wheezing. CONCLUSION: Our study showed that serum SP-D was associated with the severity of RSV bronchiolitis and suggests that it might be a biomarker of lung injury and recurrence of wheezing illnesses in the young children admitted with their first RSV bronchiolitis.
Anoxia ; Bronchiolitis ; Child ; Collectins ; Enzyme-Linked Immunosorbent Assay ; Follow-Up Studies ; Humans ; Immunity, Innate ; Infant ; Length of Stay ; Lung Injury ; Mannose-Binding Lectin ; Oxygen ; Pulmonary Surfactant-Associated Protein D ; Recurrence ; Respiration ; Respiratory Sounds ; Respiratory Syncytial Viruses ; Thoracic Wall

OBJECTIVETo study the alterations and relationship of surfactant protein (SP)-A, SP-D and KL-6 in serum and bronchoalveolar lavage fluids (BALF) in children with Mycoplasma pneumoniae pneumonia (MPP).

METHODSelf-control method was used for the study on SP-A, SP-D and KL-6 in serum, infected and non-infected BALFs in 32 MMP children with only one side of MPP.

RESULTThe contents of SP-A, SP-D and KL-6 in infected BALF were [mg/L;M (IQR) ]: 243 (90-468) , 187 (43-333) , 148 (47-426) ;104 (37-257) , 56 (25-131) , 35 (12-147) in non-infected BALF; 35 (25-69) , 33 (9-149) and 24 (15-62) in serum. The correlation coefficient of KL-6 between serum and infected BALF were -0.534 and -0.378 (P < 0.05).

CONCLUSIONThere were significant correlation between the alterations of SP-A, SP-D and KL-6 in serum and lung infection in children with CAP. KL-6 in serum may be more sensitive than SP-A and SP-D.

Adolescent ; Biomarkers ; blood ; metabolism ; Bronchoalveolar Lavage Fluid ; chemistry ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Lung ; metabolism ; pathology ; Male ; Mucin-1 ; blood ; metabolism ; Pneumonia, Mycoplasma ; blood ; metabolism ; Pulmonary Surfactant-Associated Protein A ; blood ; metabolism ; Pulmonary Surfactant-Associated Protein D ; blood ; metabolism ; Severity of Illness Index

OBJECTIVETo study the variation and clinical significance of serum levels of surfactant proteins A (SP-A) and D (SP-D) among children with different degrees of bronchiolitis.

METHODSSeventy children with bronchiolitis were divided into acute (n=42) and recovery phase groups (n=28). According to the severity of symptoms, the acute phase group was further divided into severe (n=12) and mild subgroups (n=30). Another 26 children who were hospitalized in the same period due to non-infectious diseases and had not undergone surgery were used as the control group. Competitive enzyme-linked immunosorbent assay was performed to measure serum levels of SP-A and SP-D in each group.

RESULTSThe acute phase group had significantly higher serum levels of SP-A and SP-D compared with the recovery phase (P<0.01) and control groups (P<0.01). Compared with the control group, the recovery phase group had elevated levels of SP-A and SP-D (P<0.01). Within the acute phase group, serum levels of SP-A and SP-D in the severe subgroup were significantly higher than in the mild subgroup (P<0.01).

CONCLUSIONSSerum levels of SP-A and SP-D are significantly elevated in children with acute bronchiolitis, and severe cases have higher serum levels of SP-A and SP-D than mild cases. Even after the relief of clinical symptoms, serum levels of SP-A and SP-D remain high. These findings suggest that serum levels of SP-A and SP-D might be useful biomarkers for evaluating the severity of bronchiolitis among children.

Acute Disease ; Biomarkers ; Bronchiolitis ; blood ; Female ; Humans ; Infant ; Male ; Pulmonary Surfactant-Associated Protein A ; blood ; Pulmonary Surfactant-Associated Protein D ; blood ; Severity of Illness Index

OBJECTIVE: To detect the expression and distribution of the lung surfactant protein D (surfactant protein D,SP-D ) and IL-16 in nasal mucosa of allergic rhinitis and nasal polyps, and then probe into their significance in the pathology of allergic rhinitis and nasal polyps. METHOD: Fifteen cases of allergic rhinitis, fifteen cases of nasal polyps and fifteen cases of inferior turbinate mucosa were studied to detect the expression of SP-D and IL-16 by immunohistochemistry method. RESULT: The expression of SP-D and IL-16 in allergic rhinitis and nasal polyps were dramatically higher in controls (P < 0.01). There was no remarkable difference in the expression of SP-D and IL-16 between allergic rhinitis and nasal polyps (P > 0.05). CONCLUSION Both normal tissue and diseased tissue express SP-D and IL-16. SP-D is likely to play key roles in the inflammatory reaction process of allergic rhinitis and nasal polyps. IL-16 is an important eosinophil chemokine in the process of allergic rhinitis and nasal polyps,and it can also enhance the local role of eosinophils,thus it can involve in the process of allergic rhinitis and nasal polyps disease.
Adolescent ; Adult ; Female ; Humans ; Interleukin-16 ; metabolism ; Male ; Middle Aged ; Nasal Polyps ; metabolism ; pathology ; Pulmonary Surfactant-Associated Protein D ; metabolism ; Rhinitis, Allergic ; Rhinitis, Allergic, Perennial ; metabolism ; pathology ; Young Adult

Surfactant proteins A (SP-A) and D (SP-D), both members of the collectin family, play a well established role in apoptotic cell recognition and clearance. Recent in vitro data show that SP-A and SP-D interact with apoptotic neutrophils in a distinct manner. SP-A and SP-D bind in a Ca(2+)-dependent manner to viable and early apoptotic neutrophils whereas the much greater interaction with late apoptotic neutrophils is Ca(2+)-independent. Cell surface molecules on the apoptotic target cells responsible for these interactions had not been identified and this study was done to find candidate target molecules. Myeloperoxidase (MPO), a specific intracellular defense molecule of neutrophils that becomes exposed on the outside of the cell upon apoptosis, was identified by affinity purification, mass-spectrometry and western blotting as a novel binding molecule for SP-A and SP-D. To confirm its role in recognition, it was shown that purified immobilised MPO binds SP-A and SP-D, and that MPO is surface-exposed on late apoptotic neutrophils. SP-A and SP-D inhibit binding of an anti-MPO monoclonal Ab to late apoptotic cells. Fluorescence microscopy confirmed that anti-MPO mAb and SP-A/SP-D colocalise on late apoptotic neutrophils. Desmoplakin was identified as a further potential ligand for SP-A, and neutrophil defensin as a target for both proteins.
Apoptosis ; Binding, Competitive ; Fluorescent Antibody Technique, Indirect ; Humans ; Neutrophils ; chemistry ; cytology ; metabolism ; Peroxidase ; isolation & purification ; metabolism ; Protein Binding ; Pulmonary Surfactant-Associated Protein A ; isolation & purification ; metabolism ; Pulmonary Surfactant-Associated Protein D ; isolation & purification ; metabolism