Se Hwa Yoo

Proteomic analysis in lung tissue of smokers and COPD patients.

RATIONALE Although cigarette smoking is the most important risk factor for COPD, COPD develops in only a minority of smokers, suggesting a significant genetic role. To solve the underlying pathophysiologic mechanism, it is critical to understand genes and their final product, ie, proteins. We investigated the exclusive proteins from the lung tissues obtained from COPD patients using proteomics. METHODS Nontumorous lung tissue specimens were obtained from patients who underwent surgery for lung cancer. We included 22 subjects: nonsmokers (n = 8), smokers without COPD (healthy smokers, n = 7), and smokers with COPD (n = 7). Proteins were separated from their spots with two-dimensional polyacrylamide gel electrophoresis and examined by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). To validate the proteins from the above procedures, Western blotting and immunohistochemistry were conducted. RESULTS Twelve protein spots from COPD group significantly increased or decreased compared with the other two groups were chosen for MALDI-TOF-MS analysis. Eight proteins were up-regulated in the COPD group as compared with the nonsmokers. Meanwhile, five proteins from the COPD group were up-regulated and five were down-regulated when compared with healthy smokers. Of these, matrix metalloproteinase (MMP)-13 and thioredoxin-like 2 were significantly increased in the COPD patients by Western blot and immunohistochemistry. MMP-13 was mainly expressed in the alveolar macrophages and type II pneumocytes; however, thioredoxin-like 2 was primarily seen in the bronchial epithelium. CONCLUSIONS MMP-13 and thioredoxin-like 2 in lungs increased in patients with COPD. MMP-13 was mainly expressed in the alveolar macrophages and type II pneumocytes. In contrast, thioredoxin-like 2 was primarily seen in the bronchial epithelium.

Asthma-Like Symptoms are Increased in the Metabolic Syndrome

Background. The prevalence of obesity and asthma has been increasing during the last several decades. Obesity has been reported to be associated with asthma. Obesity, especially abdominal obesity, is the main component of the metabolic syndrome. Objectives. We thus hypothesized that metabolic syndrome is an important contributing factor for the development of asthma-like symptoms. Methods. The Korean Health and Genome Study started in 2001 as an ongoing population-based study of Korean adults 40 to 69 years of age. The prevalence of asthma-like symptoms in the previous 12 months was obtained by a questionnaire, and spirometric testing was conducted. Results. Among the 10,038 participants, the data from 9,942 individuals (4,716 men and 5,226 women) was available. Asthma-like symptoms (wheeze [p = 0.0006], resting dyspnea [p = 0.0062], and post-exercise dyspnea [p < 0.0001]) were increased in the subjects of the metabolic syndrome group. Subjects with asthma-like symptoms had a decreased lung function compared to subjects without asthma-like symptoms. Among the components of the metabolic syndrome, abdominal obesity and hypertension were the risk factors for asthma-like symptoms. Conclusions. Metabolic syndrome is associated with asthma-like symptoms. Among the components of metabolic syndrome, abdominal obesity and hypertension are the risk factors for asthma-like symptoms.

Inflammatory and transcriptional roles of poly (ADP-ribose) polymerase in ventilator-induced lung injury

IntroductionPoly (ADP-ribose) polymerase (PARP) participates in inflammation by cellular necrosis and the nuclear factor-kappa-B (NF-κB)-dependent transcription. The purpose of this study was to examine the roles of PARP in ventilator-induced lung injury (VILI) in normal mice lung.MethodsMale C57BL/6 mice were divided into four groups: sham tracheostomized (sham), lung-protective ventilation (LPV), VILI, and VILI with PARP inhibitor PJ34 pretreatment (PJ34+VILI) groups. Mechanical ventilation (MV) settings were peak inspiratory pressure (PIP) 15 cm H2O + positive end-expiratory pressure (PEEP) 3 cm H2O + 90 breaths per minute for the LPV group and PIP 40 cm H2O + PEEP 0 cm H2O + 90 breaths per minute for the VILI and PJ34+VILI groups. After 2 hours of MV, acute lung injury (ALI) score, wet-to-dry (W/D) weight ratio, PARP activity, and dynamic compliance (CD) were recorded. Tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), myeloperoxidase (MPO) activity, and nitrite/nitrate (NOX) in the bronchoalveolar lavage fluid and NF-κB DNA-binding activity in tissue homogenates were measured.ResultsThe VILI group showed higher ALI score, W/D weight ratio, MPO activity, NOX, and concentrations of TNF-α and IL-6 along with lower CD than the sham and LPV groups (P < 0.05). In the PJ34+VILI group, PJ34 pretreatment improved all histopathologic ALI, inflammatory profiles, and pulmonary dynamics (P < 0.05). NF-κB activity was increased in the VILI group as compared with the sham and LPV groups (P < 0.05) and was decreased in the PJ34+VILI group as compared with the VILI group (P = 0.009). Changes in all parameters were closely correlated with the PARP activity (P < 0.05).ConclusionOveractivation of PARP plays an important role in the inflammatory and transcriptional pathogenesis of VILI, and PARP inhibition has potentially beneficial effects on the prevention and treatment of VILI.

Substance P-Immunoreactive Nerves in Endobronchial Biopsies in Cough-Variant Asthma and Classic Asthma

Background: Unlike classic asthma, cough-variant asthma does not show any evidence of airway obstruction. The main symptom is a dry cough with little known pathophysiology. Hypersensitivity of the cough receptors in cough-variant asthma and an increase in the sensory nerve density of the airway epithelium in persistent dry cough patients have been reported. Therefore, it is possible that there is a higher sensory nerve density in cough-variant asthma patients than in classic asthma patients. Objectives: This study was undertaken to compare the substance P (SP)-immunoreactive nerve density in mucosal biopsies of cough-variant asthma patients, classic asthma patients, and in control subjects. Methods: Bronchoscopic biopsies were performed in 6 cough-variant asthma patients, 14 classic asthma patients, and 5 normal controls. The tissues obtained were stained immunohistochemically. The SP-immunoreactive nerve density was measured in the bronchial epithelium using a light microscope at 400× magnification. Results: SP- immunoreactive nerve density for the cough-variant asthma group was significantly higher than that of the classic asthma group (p = 0.001), and of the normal control group (p = 0.006). Conclusions: It is possible that a sensory nerve abnormality within the airway may be related to hypersensitivity of the cough receptor, and that this may be one of the pathophysiologies of cough-variant asthma.

Association between stress and asthma symptoms: a population-based study.

Objective:  Although it is believed that stress contributes to asthma, there are no data from studies in the general population to support this belief. To determine whether stress influences asthma in the general population, a database from a nationwide survey to evaluate the relationship between stress and asthma symptoms was used in the present study.

Mercury inhalation poisoning and acute lung injury

Acute mercury inhalation poisoning is a rare cause of acute lung injury. It is usually fatal because of progressive pulmonary failure. We experienced a patient with acute respiratory distress syndrome (ARDS) after illicit use of mercury vapor for hemorrhoid treatment; he developed acute chemical pneumonitis following exposure to mercury vapor. Prompt treatment with corticosteroids and penicillamine for acute chemical pneumonitis was instituted; radiologic pulmonary infiltrates disappeared within a week, but late phase neurologic sequelae and pulmonary interstitial fibrosis progressed.

Clinical effects of pranlukast, an oral leukotriene receptor antagonist, in mild‐to‐moderate asthma: A 4 week randomized multicentre controlled trial

Objective: Leukotriene antagonists are increasingly used in asthma management. Pranlukast is a new, orally active, selective inhibitor of CysLt1 leukotriene receptor. The present clinical trial was performed to study the effect and safety of pranlukast in mild‐to‐moderate asthma.

Relation of Epidermal Growth Factor Receptor Expression to Mucus Hypersecretion in Diffuse Panbronchiolitis

STUDY OBJECT Diffuse panbronchiolitis (DPB) is a hypersecretory airway disease, and the mechanism of mucus hypersecretion in DPB is poorly understood. Moreover, mucin synthesis in the airways has been reported to be regulated by neutrophilic inflammation-induced epidermal growth factor receptor (EGFR) expression, and the degranulation of goblet cells is known to be mediated by neutrophilic elastase. In this study, we examined the relationship between EGFR expression in the bronchiolar epithelium with neutrophilic inflammation and mucus hypersecretion in the tissues of DPB patients. DESIGN The tissue specimens of 13 DPB patients and 6 healthy control subjects were examined by alcian blue/periodic acid-Schiff (AB/PAS) staining for mucous glycoconjugates, and by immunohistochemical staining for MUC5AC, EGFR, tumor necrosis factor-alpha, and CD16 on neutrophils. RESULTS Neutrophilic inflammation was significantly higher in the tissue of DPB patients than in that of control subjects (p = 0.002). In the bronchiolar epithelium, goblet cell metaplasia, by AB/PAS staining and mucin MUC5AC expression, was significantly higher than that in control subjects (p = 0.001 and p = 0.002, respectively). In addition, the morphometric quantification of intraluminal mucus secretion showed that the areas of the bronchiolar lumen occupied by mucus secretion were significantly increased in the tissue of DPB patients (p = 0.001), suggesting goblet cell degranulation. EGFR expression was observed in the bronchiolar epithelium of DPB patients, but not in that of control subjects. CONCLUSIONS In DPB, we suggest that mucus hypersecretion due to goblet cell metaplasia is closely associated with neutrophilic inflammation and the expression of EGFR. The study also shows that intraluminal secretion due to the degranulation of goblet cells degranulation is related to neutrophilic inflammation.

Relationships of coagulation factor XIII activity with cell-type and stage of non-small cell lung cancer

Purpose Factor XIII (FXIII), a thrombin-activated plasma transglutaminase zymogen, is involved in cancer development and progression through a triggered coagulation pathway. The aim of this study was to examine whether FXIII activity levels differed in non-small cell lung cancer (NSCLC) patients according to histological types and TNM stage when compared with healthy subjects. Materials and Methods Twenty-eight NSCLC patients and 28 normal controls who had been individually age-, gender-, body mass index-, smoking status-, and smoking amount-matched were enrolled: 13 adenocarcinomas, 11 squamous cell carcinomas, and four undifferentiated NSCLCs; four stage I, two stage II, 12 stage III, and 10 stage IV NSCLCs. FXIII activity was measured using fluorescence-based protein arrays. Results The median FXIII activity level of the NSCLC group [24.2 Loewy U/mL, interquartile range (IQR) 14.9-40.4 Loewy U/mL] was significantly higher than that of the healthy group (17.5 Loewy U/mL, IQR 12.6-26.4 Loewy U/mL) (p=0.01). There were no differences in FXIII activity between adenocarcinoma (median 18.6 Loewy U/mL) and squamous cell carcinoma (median 28.7 Loewy U/mL). NSCLC stage significantly influenced FXIII activity (p=0.02). The FXIII activity of patients with stage III NSCLC (median 27.3 Loewy U/mL, IQR 19.3-40.5 Loewy U/mL) was significantly higher than those of patients with stage I or II (median 14.0 Loewy U/mL, IQR 13.1-23.1 Loewy U/mL, p=0.04). FXIII activity was negatively correlated with aPTT in NSCLC patients (r=-0.38, p=0.04). Conclusion Patients with advanced-stage NSCLC exhibited higher coagulation FXIII activity than healthy controls and early-stage NSCLC patients.

A Case of Extramedullary Plasmacytoma Arising from the Posterior Mediastinum

Plasmacytomas are a localized proliferation of plasma cells in the bone marrow, and are less frequently seen in extraosseous organs or tissues. Extramedullary plasmacytoma is a rare malignant neoplasm, and is especially uncommon when it arises from the mediastinum. Here, we report on a case of posterior mediastinal extramedullary plasmacytoma in a 64-year-old man. He was admitted with an asymptomatic right apical mediastinal mass, which was provisionally diagnosed as a neurogenic mass. However, a subsequent investigation revealed that this tumor was a rare case of IgG kappa type extramedullary plasmacytoma arising from the posterior mediastinum. The patient was treated with local radiation to the mediastinum and is doing well without further evidence of disease.