Plasma CRABP2 as a Novel Biomarker in Patients with Non-Small Cell Lung Cancer

BACKGROUND: Lung cancer is the most common cause of cancer-related mortality worldwide. We previously reported the identification of a new genetic marker, cellular retinoic acid binding protein 2 (CRABP2), in lung cancer tissues. The aim of this study was to assess plasma levels of CRABP2 from patients with non-small cell lung cancer (NSCLC). METHODS: Blood samples that were collected from 122 patients with NSCLC between September 2009 and September 2013 were selected for the analysis, along with samples from age- (± 5 years), sex-, and cigarette smoking history (± 10 pack-years [PY])-matched controls from the Korea Biobank Network. The control specimens were from patients who were without malignancies or pulmonary diseases. We measured plasma levels of CRABP2 using commercially available enzyme-linked immunosorbent assay kits. RESULTS: The mean age of the NSCLC patients was 71.8 ± 8.9 years, and the median cigarette smoking history was 32 PY (range, 0–150 PY). Plasma CRABP2 levels were significantly higher in patients with NSCLC than in the matched controls (37.63 ± 28.71 ng/mL vs. 24.09 ± 21.09 ng/mL, P < 0.001). Higher plasma CRABP2 levels were also correlated with lower survival rates in NSCLC patients (P = 0.014). CONCLUSION: Plasma CRABP2 levels might be a novel diagnostic and prognostic marker in NSCLC.

Cadmium-induced ER stress and inflammation are mediated through C/EBP–DDIT3 signaling in human bronchial epithelial cells

Cadmium (Cd), a major component of cigarette smoke, disrupts the normal functions of airway cells and can lead to the development of various pulmonary diseases such as chronic obstructive pulmonary disease (COPD). However, the molecular mechanisms involved in Cd-induced pulmonary diseases are poorly understood. Here, we identified a cluster of genes that are altered in response to Cd exposure in human bronchial epithelial cells (BEAS-2B) and demonstrated that Cd-induced ER stress and inflammation are mediated via CCAAT-enhancer-binding proteins (C/EBP)-DNA-damaged-inducible transcript 3 (DDIT3) signaling in BEAS-2B cells. Cd treatment led to marked upregulation and downregulation of genes associated with the cell cycle, apoptosis, oxidative stress and inflammation as well as various signal transduction pathways. Gene set enrichment analysis revealed that Cd treatment stimulated the C/EBP signaling pathway and induced transcriptional activation of its downstream target genes, including DDIT3. Suppression of DDIT3 expression using specific small interfering RNA effectively alleviated Cd-induced ER stress and inflammatory responses in both BEAS-2B and normal primary normal human bronchial epithelial cells. Taken together, these data suggest that C/EBP signaling may have a pivotal role in the early induction of ER stress and inflammatory responses by Cd exposure and could be a molecular target for Cd-induced pulmonary disease.

ACN9 Regulates the Inflammatory Responses in Human Bronchial Epithelial Cells / 결핵및호흡기질환

BACKGROUND: Airway epithelial cells are the first line of defense, against pathogens and environmental pollutants, in the lungs. Cellular stress by cadmium (Cd), resulting in airway inflammation, is assumed to be directly involved in tissue injury, linked to the development of lung cancer, and chronic obstructive pulmonary disease (COPD). We had earlier shown that ACN9 (chromosome 7q21), is a potential candidate gene for COPD, and identified significant interaction with smoking, based on genetic studies. However, the role of ACN9 in the inflammatory response, in the airway cells, has not yet been reported. METHODS: We first checked the anatomical distribution of ACN9 in lung tissues, using mRNA in situ hybridization, and immunohistochemistry. Gene expression profiling in bronchial epithelial cells (BEAS-2B), was performed, after silencing ACN9. We further tested the roles of ACN9, in the intracellular mechanism, leading to Cd-induced production, of proinflammatory cytokines in BEAS-2B. RESULTS: ACN9 was localized in lymphoid, and epithelial cells, of human lung tissues. ACN9 silencing, led to differential expression of 216 genes. Pathways of sensory perception to chemical stimuli, and cell surface receptor-linked signal transduction, were significantly enriched. ACN9 silencing, further increased the expression of proinflammatory cytokines, in BEAS-2B after Cd exposure. CONCLUSION: Our findings suggest, that ACN9 may have a role, in the inflammatory response in the airway.

Respiratory Failure Induced by Severe Hypothyroidism in a Korean Woman

A 76-year-old Korean woman visited to emergency room because of respiratory arrest and admitted to intensive care unit of the hospital. Severe hypothyroidism was diagnosed after repeated failure of weaning mechanical ventilator. Respiratory arrest and weaning failures were considered to be associated with hypoventilation due to hypothyroidism. She was recovered and weaned from mechanical ventilation after replacement of thyroid hormone. Severe hypothyroidism may be a cause of respiratory failure or weaning failure.

Chemical Pneumonitis due to Exposure to Waterproofing Spray Containing Perfluoroalkyl Acrylate Copolymer

Waterproofing spray is used to ensure that clothing, including mountain wear, leather, and other surfaces are waterproof. Respiratory illnesses related to the use of waterproofing spray have been reported globally. The composition of waterproofing spray varies depending on the manufacturer. We treated a patient with chemical pneumonitis and alveolar hemorrhage due to exposure to waterproofing spray containing perfluoroalkyl acrylate copolymer. We diagnosed the patient with chemical pneumonitis and alveolar hemorrhage based on computed tomography (CT) and bronchoalveolar lavage (BAL) test performed within 24 h after symptom occurrence. We believe that further study regarding the exact mechanism of pulmonary toxicity for waterproofing agents is required.

Plasma Osteopontin Is a Useful Diagnostic Biomarker for Advanced Non-Small Cell Lung Cancer / 결핵및호흡기질환

BACKGROUND: Osteopontin (OPN) and carbonic anhydrase IX (CAIX), which are expressed on the surface of tumor cells, are associated with hypoxia during tumor development and progression. However, the roles of these proteins in the plasma of patients with non-small cell lung cancer (NSCLC) are poorly understood. Herein, we hypothesized that plasma OPN and CAIX levels could be used as diagnostic and prognostic tumor markers in patients with NSCLC. METHODS: Fifty-three patients with NSCLC and 50 healthy control subjects were enrolled. We selected controls without malignancy and matched them with NSCLC patient cases according to age and gender. Blood samples were collected at the time of diagnosis; the plasma levels of OPN and CAIX were measured by enzyme-linked immunosorbent assays. RESULTS: The plasma levels of OPN in the patients with NSCLC were significantly elevated as compared to those in the controls (p=0.016). However, there was no difference in the plasma level of CAIX between the NSCLC patients and controls. NSCLC patients with a distant metastasis had a remarkable increase in plasma OPN compared with patients without metastasis (p=0.026), but no such correlation was found for CAIX. There was no difference in overall survival rates according to the plasma level of OPN between the two groups (by Kaplan-Meier survival analysis). CONCLUSION: Plasma OPN levels were elevated in patients with NSCLC as compared with the controls, with greater elevation of OPN levels in the advanced stages of disease. Therefore, plasma OPN may have utility as a diagnostic, but not prognostic, biomarker of advanced NSCLC.

Very Early Onset of Amiodarone-Induced Pulmonary Toxicity

Amiodarone is a widely used antiarrhythmic agent. Among its various adverse effects, amiodarone-induced pulmonary toxicity (APT) is the most life threatening complication, which has been described mostly in patients who have been in treatment with high accumulative doses for a long duration of time. However, amiodarone therapy in short-term duration induced APT was rarely reported. We describe a case of a 54-year-old man who is presented with symptoms of APT after a few days of therapy for post-myocardial infarction ventricular tachycardia. For early diagnosis and successful treatment, awareness and high suspicion of this rare type of early onset APT is crucial in patients with amiodarone therapy.

Interstitial Pneumonitis after Treatment with Pemetrexed for Non-small Cell Lung Cancer / Journal of the Korean Cancer Association, 대한암학회지

Pemetrexed is approved as a first-line treatment for advanced non-squamous non-small cell lung cancer (NSCLC) with cisplatin and as a single agent for second-line treatment or for patients who show no disease progression after four cycles of platinum-based doublet induction chemotherapy as maintenance therapy. Pemetrexed has a modest toxicity profile and has not traditionally been regarded as a cause of interstitial pneumonitis. Here, we report on a rare case of pemetrexed-induced pneumonitis in a patient with NSCLC.

Fluid-filled Giant Bulla Treated with Percutaneous Drainage and Talc Sclerotherapy: A Modified Brompton Technique

A 75-year-old man who was diagnosed as having a fluid-filled giant bulla was treated with a modified Brompton technique due to his poor performance status. Percutaneous drainage, suction, and talc sclerotherapy through a Foley catheter can be good treatment options for patients with conditions that are too poor to allow surgical intervention, especially if there is adhesion between a giant bulla and parietal pleura. Talc can also be used safely when mixed with normal saline as a sclerosant.

A Case of Multi-Organ Macronodular Tuberculosis / 결핵및호흡기질환

A 37 year old female presented with epigastric pain and weight loss over a period of 3 months. Her abdominal CT finding showed a 4.5 cm size hepatic mass and 4.3 cm size pancreatic head mass with multiple macronodules in the liver. At the same time, her chest CT revealed a 5 cm size necrotic mass in the left lower lobe of the lung with multiple bilateral pulmonary nodules. We diagnosed these lesions as tuberculosis through multiple biopsies. She was treated with anti-tuberculous medication. After taking the medications, her symptoms were improved. Twelve months later, imaging studies indicated an improvement in the patient's health. Here we report a case report of multi-organ macronodular tuberculosis in lung, liver and pancreas.

A Case of Massive Empyema Caused by Streptococcus constellatus and Anaerobic Bacteria for Mental Retardation / 결핵및호흡기질환

The Streptococcus milleri group, which also includes S. anginosus, S. intermedius and S. constellatus, is found in the oropharynx, upper respiratory tract, gastrointestinal tract, and urogenital tract mucosa. Bacteria in the Streptococcus milleri group are associated with bacteremia and abscess formation. Most of the reports of of Streptococcus milleri group (SMG) infection occur in patients with underlying medical conditions. Predisposing factors that have been associated with S. milleri group empyema include mucosal disturbances (sinusitis, periodontal disease, enteric disease), preceding to pneumonia, thoracic surgery, malignancy, neurological disease, alcohol abuse, and also diabetes mellitus. We report on a 42-year-old man with mental retardation. He who suffered from dyspnea and a fever that he had developed for over 14 days. S. constellatus and anaerobic bacterias (Prevotella buccae and Micromonas micros) were cultured. The patient was treated with the drainage of pleural effusion and clindamycin and levofloxacin.

A Case of a Patient with Dermatomyositis Who Developed a Diffuse Alveolar Hemorrhage

Dermatomyositis is a inflammatory myopathy associated with interstitial lung disease in 5~10% of cases. The occurrence of diffuse alveolar hemorrhage (DAH) is considered exceptional in the course of dermatomyositis. We experienced a case of DAH in a 58-year-old female with dermatomyositis. DAH was diagnosed by anemia, infiltration on chest X-ray and computed tomography, and a bloody aspirate on bronchoscopy. Combined Pneumocystis jiroveci (PJP) pneumonia was suspected, as the polymerase chain reaction for PJP was positive. After intravenous the administration of immunoglobulin and treatment for the PJP, she markedly improved but subsequently developed nosocomial pneumonia and died.

Diagnostic Role of C-reactive Protein, Procalcitonin and Lipopolysaccharide-Binding Protein in Discriminating Bacterial-Community Acquired Pneumonia from 2009 H1N1 Influenza A Infection / 결핵및호흡기질환

BACKGROUND: It is difficult but important to differentiate between bacterial and viral infections, especially for respiratory infections. Hence, there is an ongoing need for sensitive and specific markers of bacterial infections. We investigated novel biomarkers for discriminating community acquired bacterial pneumonia from 2009 H1N1 influenza A infections. METHODS: This was a prospective, observational study of patients with community acquired bacterial pneumonia, 2009 H1N1 Influenza A infection, and healthy controls. Serum samples were obtained on the initial visit to the hospital and stored at -80degrees C. We evaluated CRP (C-reactive protein), PCT (procalcitonin), LBP (lipopolysaccharide-binding protein) and copeptin. These analytes were all evaluated retrospectively except CRP. Receiver operating characteristic curve (ROC) analyses were performed on the resulting data. RESULTS: Enrolled patients included 27 with community acquired bacterial pneumonia, 20 with 2009 H1N1 Influenza A infection, and 26 who were healthy controls. In an ROC analysis for discriminating community acquired bacterial pneumonia from 2009 H1N1 influenza A infection, areas under the curve (AUCs) were 0.799 for CRP (95% Confidence interval [CI], 0.664~0.934), 0.753 for PCT (95% CI, 0.613~0.892) and 0.684 for LBP (95% CI, 0.531~0.837). Copeptin was not different among the three groups. CONCLUSION: These findings suggest that serum CRP, PCT and LBP can assist physicians in discriminating community acquired bacterial pneumonia from 2009 H1N1 influenza A infection.

Clinical Characteristics and Risk Factors for Nosocomial Candidemia in Medical Intensive Care Units: Experience in a Single Hospital in Korea for 6.6 Years

The aim of this study was to determine candidemia incidence among patients in a medical intensive-care unit (MICU) and the associated mortality rate and to identify risk factors associated with candidemia. We retrospectively performed a 1:3 matched case-control study of MICU patients with candidemia. Controls were matched for sex, age, and Acute Physiology and Chronic Health Evaluation (APACHE) II score. Candidemia incidence was 9.1 per 1,000 admissions. The most common pathogen was Candida albicans. Crude mortality was 96% among candidemia patients and 52% among controls (P<0.001). Mortality differed significantly between the groups according to Kaplan-Meier survival analysis (P=0.024). Multivariate analysis identified the following independent risk factors for candidemia: central venous catheterization (odds ratio [OR] = 3.2, 95% confidence interval [CI]=1.2-9.0), previous steroid therapy (OR=4.7, 95% CI=1.8-12.1), blood transfusion during the same admission period (OR=6.3, 95% CI=2.4-16.7), and hepatic failure upon MICU admission (OR=6.9, 95% CI=1.7-28.4). In conclusion, we identify an additional independent risk factor for candidemia, the presence of hepatic failure on MICU admission. Therefore, increased awareness of risk factors, including hepatic failure, is necessary for the management of candidemia.

A Case of Lipid Pneumonia by Green Perilla Oil / 결핵및호흡기질환

Exogenous lipid pneumonia is a rare disease resulting from the aspiration or inhalation of vegetable, animal, or mineral oils. In Korea, the most frequently implicated agent is squalen, which can be obtained from shark liver oil. Lipid pneumonia by aspiration of the vegetable oil is very rare. We experienced a 77-year-old man with a history of ingestion of green perilla oil. His clinical course was favorable; after exposure to the oil was stopped, the patient's symptoms improved.

Sequential Bilateral Lung Resection in a Patient with Mycobacterium Abscessus Lung Disease Refractory to Medical Treatment

Mycobacterium abscessus (M. abscessus) is the second most common nontuberculous mycobacteria (NTM) in South Korea. Nevertheless, the diagnosis and treatment of M. abscessus lung disease can be problematic. Surgical resection has been tried for patients with localized M. abscessus lung disease refractory to medical treatment. Here, we report on a 25-year-old woman with M. abscessus lung disease who had been diagnosed and treated three times for pulmonary tuberculosis. She was initially diagnosed as having M. intracellulare lung disease; however, M. abscessus was isolated after several months of medication. She had multiple bronchiectatic and cavitary lesions bilaterally, and M. abscessus was repeatedly isolated from her sputa despite prolonged treatment with clarithromycin, ethambutol, moxifloxacin, and amikacin. She improved only after sequential bilateral lung resection. Based on the experience with this patient, we suggest that, if medical treatment fails, surgical resection of a diseased lung should be considered even in patients with bilateral lesions.

Massive Paradoxical Air Embolism in Brain Occurring after Central Venous Catheterization: A Case Report

Cerebral air embolism is a rare but fatal complication of central venous catheterization. Here, we report a case of paradoxical cerebral air embolism associated with central venous catheterization. An 85-yr-old man underwent right internal jugular vein catheterization, and became obtunded. Brain MR imaging and CT revealed acute infarction with multiple air bubbles on the side of catheter insertion. The possibility of cerebral air embolism should be considered in patients developing neurological impairment after central venous catheterization, and efforts should be made to limit cerebral damage.

Subjective and Objective Results of Radiofrequency Ablation in Drug-Resistant Allergic Rhinitis Based on a 12-Month Follow-up Study

BACKGROUND AND OBJECTIVES: Allergic rhinitis is a common condition that has been treated using various methods. Nevertheless, it remains an intractable condition in some cases. We evaluated the long-term efficacy of radiofrequency ablation (RFA) therapy for drug-resistant allergic rhinitis. MATERIALS AND METHODS: Eighteen patients with allergic rhinitis were enrolled in this prospective interventional study. Their subjective symptoms and objective findings were assessed using a visual analogue scale and acoustic rhinometry before and after RFA therapy. Postoperative follow-up was carried out at 1, 3, 6, and 12 months. RESULTS: Nasal obstruction and rhinorrhea were improved significantly (p<0.001 and p=0.015, respectively), and these effects continued for 12 months after RFA therapy. However, the effects on nasal itching and sneezing did not last throughout the year of the study. Patients' overall satisfaction scores declined at 12 months. On acoustic rhinometry, the minimal cross-sectional area and the total nasal volume did not show improvement, and there were no correlations with the subjective symptoms. Most of the complications associated with the RFA procedure were minimal and resolved within 4 weeks. CONCLUSION: RFA is a safe, simple, and effective procedure for relieving nasal obstruction and rhinorrhea for at least 12 months in drug-resistant allergic rhinitis.

Effects of the polymorphic MDR1 genotype on the single-dose simvastatin pharmacokinetics in healthy subjects / 대한내과학회지

BACKGROUND/AIMS: Simvastatin has dramatically reduced cardiovascular disease due to elevated cholesterol. The human multidrug resistance 1 gene (MDR1) encodes a 170-kDa transmembrane glycoprotein (P-glycoprotein), which plays an important role in regulating the absorption, distribution, and excretion of simvastatin. To clarify the effects of the MDR1 gene polymorphism on simvastatin pharmacokinetics, we investigated whether there is an association between genotype and the pharmacokinetic parameters for simvastatin. METHODS: Thirty-one healthy unrelated Korean volunteers were genotyped for MDR1. Genomic DNA from blood was analyzed using the polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). Following an overnight fast, all of the subjects took a single 60-mg oral dose of simvastatin. Venous blood samples were taken for 12 hours after the oral drug intake. A statistical analysis of the MDR1 genotype and pharmacokinetic parameters of simvastatin was performed. RESULTS: The mean Tmax of the 1236TT genotype was significantly higher than that of CT and CC (p=0.02). The mean AUC0-12h of 3435TT was also significantly higher, compared with CT and CC (p=0.01). No significant difference was observed between the MDR1 single nucleotide polymorphism (SNP) for G2677A/T and the pharmacokinetic parameters. CONCLUSIONS: These findings suggest that polymorphic MDR1 genes are important in the inter-individual variation of the disposition of simvastatin in humans. s

Gene Expression Profile of Lung Cancer Cells Following Photodynamic Therapy / 결핵및호흡기질환

BACKGROUND: Photodynamic therapy is a viable option for lung cancer treatment, and many studies have shown that it is capable of inducing cell death in lung cancer cells. However, the precise mechanism of this cell death has not been fully elucidated. To investigate the early changes in cancer cell transcription, we treated A549 cells with the photosensitizer DH-I-180-3 and then we illuminated the cells. METHODS: We investigated the gene expression profiles of the the A549 lung cancer cell line, using a DEG kit, following photodynamic therapy and we evaluated the cell viability by performing flow cytometry. We identified the genes that were significantly changed following photodynamic therapy by performing DNA sequencing. RESULTS: The FACS data showed that the cell death of the lung cancer cells was mainly caused by necrosis. We found nine genes that were significantly changed and we identified eight of these genes. We evaluated the expression of two genes, 3-phosphoglycerate dehydrogenase and ribosomal protein S29. The expressed level of carbonic anhydrase XII, clusterin, MRP3s1 protein, complement 3, membrane cofactor protein and integrin beta 1 were decreased. CONCLUSION: Many of the gene products are membrane-associated proteins. The main mechanism of photodynamic therapy with using the photosensitizing agent DH-I-180-3 appears to be necrosis and this may be associated with the altered production of membrane proteins.