Middle East Respiratory Syndrome Coronavirus Superspreading Event Involving 81 Persons, Korea 2015

Since the first imported case of Middle East respiratory syndrome coronavirus (MERS-CoV) infection was reported on May 20, 2015 in Korea, there have been 186 laboratory-confirmed cases of MERS-CoV infection with 36 fatalities. Ninety-seven percent (181/186) of the cases had exposure to the health care facilities. We are reporting a superspreading event that transmitted MERS-CoV to 81 persons at a hospital emergency room (ER) during the Korean outbreak in 2015. The index case was a 35-yr-old man who had vigorous coughing while staying at the ER for 58 hr. As in severe acute respiratory syndrome outbreaks, superspreading events can cause a large outbreak of MERS in healthcare facilities with severe consequences. All healthcare facilities should establish and implement infection prevention and control measure as well as triage policies and procedures for early detection and isolation of suspected MERS-CoV cases.

Idiopathic Pleuroparenchymal Fibroelastosis Presenting in Recurrent Pneumothorax: A Case Report / 결핵및호흡기질환

Idiopathic pleuroparenchymal fibroelastosis (PPFE) is a rare, recently classified entity that consists of pleural and subjacent parenchymal fibrosis predominantly in the upper lungs. In an official American Thoracic Society/European Respiratory Society statement in 2013, this disease is introduced as a group of rare idiopathic interstitial pneumonias. We describe a case of a 76-year-old woman with cough and recurrent pneumothorax. She was admitted to our hospital with severe cough at first. High resolution computed tomography (HRCT) disclosed multifocal subpleural consolidations with reticular opacities in both lungs, primarily in the upper lobes, suggesting interstitial pneumonia. Rheumatoid lung was diagnosed initially through an elevated rheumatoid factor, HRCT and surgical biopsy at the right lower lobe. However, one month later, pneumothorax recurred. Surgical biopsy was performed at the right upper lobe at this time. The specimens revealed typical subpleural fibroelastosis. We report this as a first case of idiopathic PPFE in Korea after reviewing the symptoms, imaging and pathologic findings.

A Case of Chronic Arthritis Due to Mycobacterium intracellulare after Trauma / 결핵및호흡기질환

While nontuberculous mycobacterium (NTM) infections are recently on the rise, arthritis caused by NTM is hardly reported in Korea. NTM arthritis has no distinctive clinical characteristics from chronic arthritis. Tuberculosis of the joint specifically produces similar clinical and pathologic presentations to NTM arthritis, so it is not easy to distinguish between them. We report a case of Mycobacterium intracellulare in an arthritis patient after trauma and surgical repair of the injury. At the beginning, the patient was diagnosed as tuberculous tenosynovitis through pathology without microbiologic evidence. The final diagnosis was made after subsequent recurrences for several years. The misdiagnosis and delayed diagnosis led to irreversible joint destruction and functional impairment. NTM infection must be included in the differential diagnosis of chronic arthritis at the outset.

A Case of Disseminated Coccidioidomycosis Involving the Lymph Nodes, the Skin, and the Brain / 대한내과학회지

Coccidioidomycosis, a fungal infection caused by the fungus known as Coccidioides immitis, can affect many species of mammals and some reptiles. The fungus is endemic in the soil of the southwestern United States, Mexico, and parts of Central and South America. Most infections in humans are relatively mild or asymptomatic, but severe or fatal illness can also occur, especially in the elderly or immunocompromised. We report on a patient with disseminated coccidioidomycosis whose lymph nodes, skin, and especially brain were infected at diagnosis; however, the lung parenchyme was not infected. Because the brain infection could have been a fatal complication in this peculiar case, we recommended life-long fluconazole treatment for the patient. After 2 months of high doses of fluconazole, the patient's clinical signs were greatly improved with respect to fever, headache, skin lesions, and mediastinal widening on the chest X-ray.

Clinical Utility of Two Interferon-gamma Release Assays on Pleural Fluid for the Diagnosis of Tuberculous Pleurisy / 결핵및호흡기질환

BACKGROUND: The release of interferon-gamma (IFN-gamma) by T lymphocytes increases after rechallenge with Mycobacterium tuberculosis antigen, especially, at a localized site of tuberculosis (TB) infection. We aimed to compare the clincial efficacy of two commercial IFN-gamma release assays from pleural fluid for the diagnosis in tuberculous pleurisy. METHODS: We performed T-SPOT.TB and QuantiFERON-TB Gold tests simultaneously on pleural fluid and peripheral blood samples from patients with pleural effusion, in South Korea, an area with intermediate TB burden. RESULTS: Thirty-six patients were enrolled prospectively, and tuberculous pleurisy was found in 21 patients. Both the numbers of IFN-gamma secreting T cells and the concentration of IFN-gamma were greater in the pleural tuberculous group, comparing with the non-tuberculous group. Moreover, in the tuberculous group, there was a significant difference in IFN-gamma producing spot-forming cells using the T-SPOT.TB method between pleural fluid and peripheral blood. The receiver operating characteristic (ROC) curve, was the greatest for pleural fluid T-SPOT.TB test, followed by peripheral blood T-SPOT.TB test, peripheral blood QuantiFERON-TB Gold test, and pleural fluid QuantiFERON-TB Gold test (area under the ROC curve of 0.956, 0.890, 0.743, and 0.721, respectively). The T-SPOT.TB assay produced less indeterminate results than did QuantiFERON-TB Gold assay in both pleural fluid and peripheral blood. CONCLUSION: These findings suggest that the pleural fluid T-SPOT.TB test could be the most useful test among the IFN-gamma release assays for diagnosing tuberculous pleurisy in an area with an intermediate prevalence of TB infection.

A Case of Disseminated Coccidioidomycosis Involving the Lymph Nodes, the Skin, and the Brain / 대한내과학회지

Coccidioidomycosis, a fungal infection caused by the fungus known as Coccidioides immitis, can affect many species of mammals and some reptiles. The fungus is endemic in the soil of the southwestern United States, Mexico, and parts of Central and South America. Most infections in humans are relatively mild or asymptomatic, but severe or fatal illness can also occur, especially in the elderly or immunocompromised. We report on a patient with disseminated coccidioidomycosis whose lymph nodes, skin, and especially brain were infected at diagnosis; however, the lung parenchyme was not infected. Because the brain infection could have been a fatal complication in this peculiar case, we recommended life-long fluconazole treatment for the patient. After 2 months of high doses of fluconazole, the patient's clinical signs were greatly improved with respect to fever, headache, skin lesions, and mediastinal widening on the chest X-ray.

A Case of Bronchiolitis Obliterans Organizing Pneumonia after Radiation Therapy in Breast Cancer / 대한내과학회지

Pulmonary toxicity can develop following radiation therapy during breast cancer treatment. Of the pulmonary toxicities that can develop, radiation-induced bronchiolitis obliterans organizing pneumonia (BOOP) is relatively rare. A 43-year-old woman who had previously undergone radiation therapy for right breast cancer presented with fever and cough for 4 days. Chest radiology findings demonstrated consolidations in the right middle and lower lobe. Initially, we assumed that her findings were consistent with pneumonia and started empirical antibiotics. However, even after 10 days of antibiotic treatment, the fever persisted, and the consolidations showed progression. A transbronchial lung biopsy of the right middle lobe via bronchoscopy revealed organizing pneumonia. We strongly suspected radiation-induced BOOP and began steroid treatment. The symptoms and consolidations rapidly disappeared. We tapered the steroids, and no relapse has occurred since then. Considering the clinical, radiological, and pathological findings, we diagnosed the patient with radiation-induced BOOP. To our knowledge, this is the first case of radiation-induced BOOP in Korea.

Inhibition of Plasminogen Activator Inhibitor-1 Expression in Smoke-Exposed Alveolar Type II Epithelial Cells Attenuates Epithelial-Mesenchymal Transition / 결핵및호흡기질환

BACKGROUND: Smoking is a risk factor for idiopathic pulmonary fibrosis (IPF), but the mechanism of the association remains obscure. There is evidence demonstrating that plasminogen activator inhibitor-1 (PAI-1) is involved in the progression of pulmonary fibrosis. This study was to determine whether the administration of small interfering RNA (siRNA) targeting PAI-1 or PAI-1 inhibitor to the cigarette smoking extract (CSE)-exposed rat alveolar type II epithelial cells (ATII cells) limits the epithelial-mesenchymal transition (EMT). METHODS: ATII cells were isolated from lung of SD-rat using percoll gradient method and cultured with 5% CSE. The EMT was determined from the ATII cells by measuring the real-time RT PCR and western blotting after the PAI-1 siRNA transfection to the cells and after administration of tiplaxtinin, an inhibitor of PAI-1. The effect of PAI-1 inhibitor was also evaluated in the bleomycin-induced rats. RESULTS: PAI-1 was overexpressed in the smoking exposed ATII cells and was directly associated with EMT. The EMT from the ATII cells was suppressed by PAI-1 siRNA transfection or administration of tiplaxtinin. Signaling pathways for EMT by smoking extract were through the phosphorylation of SMAD2 and ERK1/2, and finally Snail expression. Tiplaxtinin also suppressed the pulmonary fibrosis and PAI-1 expression in the bleomycin-induced rats. CONCLUSION: Our data shows that CSE induces rat ATII cells to undergo EMT by PAI-1 via SMAD2-ERK1/2-Snail activation. This suppression of EMT by PAI-1 siRNA transfection or PAI-1 inhibitor in primary type II alveolar epithelial cells might be involved in the attenuation of bleomycin-induced pulmonary fibrosis in rats.

A Case of Pulmonary Thromboembolism in a Patient with Idiopathic Thrombocytopenic Purpura / 대한내과학회지

Idiopathic thrombocytopenic purpura (ITP) is an autoimmune blood disorder characterized by thrombocytopenia. Common clinical manifestations include bleeding events. Rarely, thrombotic complications may develop in ITP. A 43-year-old man was admitted with dyspnea. His platelet count at admission was 48,000/mm3. The patient had a history of ITP diagnosed 12 years earlier and had been treated with low-dose steroids. Two months before admission, he had been diagnosed with deep vein thrombosis and treated only with clopidogrel due to severe thrombocytopenia. Chest computed tomography showed filling defects in both pulmonary arteries. In the workup for precipitating factors, only lupus anticoagulant was positive. The concomitant administration of warfarin and methylprednisolone was used to treat the pulmonary thromboembolism and ITP, respectively. Six months later, the lupus anticoagulant test remained positive. The patient was confirmed to have a pulmonary thromboembolism due to antiphospholipid syndrome, which might be related to the underlying ITP. After 10 months, his symptoms and radiological findings had improved.

Inhibitory effect of receptor for advanced glycation end products (RAGE) on the TGF-beta-induced alveolar epithelial to mesenchymal transition

Idiopathic pulmonary fibrosis (IPF) is a lethal parenchymal lung disease characterized by myofibroblast proliferation. Alveolar epithelial cells (AECs) are thought to produce myofibroblasts through the epithelial to mesenchymal transition (EMT). Receptor for advanced glycation end products (RAGE) is a member of the immunoglobulin superfamily of cell surface receptors whose activation is associated with renal fibrosis during diabetes and liver fibrosis. RAGE is expressed at low basal levels in most adult tissues except the lung. In this study, we evaluated the interaction of ligand advanced glycation end products (AGE) with RAGE during the epithelial to myofibroblast transition in rat AECs. Our results indicate that AGE inhibited the TGF-beta-dependent alveolar EMT by increasing Smad7 expression, and that the effect was abolished by RAGE siRNA treatment. Thus, the induction of Smad7 by the AGE-RAGE interaction limits the development of pulmonary fibrosis by inhibiting TGF-beta-dependent signaling in AECs.

Inhibitory effect of CXC chemokine receptor 4 antagonist AMD3100 on bleomycin induced murine pulmonary fibrosis

CXC chemokine receptor 4 (CXCR4), which binds the stromal cell-derived factor-1 (SDF-1), has been shown to play a critical role in mobilizing the bone marrow (BM)-derived stem cells and inflammatory cells. We studied the effects of AMD3100, CXCR4 antagonist, on a murine bleomycin-induced pulmonary fibrosis model. Treatment of mice with AMD3100 in bleomycin-treated mice resulted in the decrease of SDF-1 in bronchoalveolar lavage (BAL) fluids at an early stage and was followed by the decrease of fibrocytes in the lung. AMD3100 treatment decreased the SDF-1 mRNA expression, fibrocyte numbers in the lung at an early stage (day 3) and CXCR4 expression at the later stage (day 7 and 21) after bleomycin injury. The collagen content and pulmonary fibrosis were significantly attenuated by AMD3100 treatment in later stage of bleomycin injury. AMD3100 treatment also decreased the murine mesenchymal and hematopoietic stem cell chemotaxis when either in the stimulation with bleomycin treated lung lysates or SDF-1 in vitro. In BM stem cell experiments, the phosphorylation of p38 MAPK which was induced by SDF-1 was significantly blocked by addition of AMD3100. Our data suggest that AMD3100 might be effective in preventing the pulmonary fibrosis by inhibiting the fibrocyte mobilization to the injured lung via blocking the SDF-1/CXCR4 axis.

A Case of Idiopathic Bronchiolocentric Interstitial Pneumonia / 결핵및호흡기질환

Idiopathic bronchiolocentric interstitial pneumonia is one of idiopathic interstitial pneumonia, which has a relatively aggressive course and poor prognosis. It is characterized by diffuse centrilobular nodules radiologically with mainly bronchiolocentric inflammation and fibrosis associated with patchy alveolitis lacking interstitial granuloma histologically. This disorder is a recently classified disease category, and to our knowledge, there is no case report in Korea. We present a case of idiopathic bronchiolocentric interstitial pneumonia. A 62-year-old man presented with exertional dyspnea with a 1 month duration. The radiological findings showed extensive centrilobular lesions at both lungs. The surgical lung biopsy specimen demonstrated a centrilobular inflammatory process with small airway fibrosis and inflammation partially radiating into the interstitium. Therefore, the patient was diagnosed with idiopathic bronchiolocentric interstitial pneumonia. He was treated with immunosuppressants including steroids and azathioprine. However, his symptoms did not improve and he expired 7 months later due to an acute exacerbation of the interstitial pneumonia and probable infectious pneumonia.

A Case of Pulmonary Thromboembolism in Crohn's Disease / 결핵및호흡기질환

Crohn's disease, a major form of inflammatory bowel disease (IBD), is a chronic inflammatory condition that is characterized by microvascular and macrovascular involvement. Some extraintestinal complications can occur due to chronic systemic inflammation in IBD. Among them, a pulmonary thromboembolism is a rare manifestation of IBD but is associated with a high morbidity and mortality. To our best of knowledge, there is only one case report of a pulmonary thromboembolism as a complication of Crohn's disease in Korea. We present another rare case of pulmonary thromboembolism as complication in a 25-year-old man with underlying Crohn's disease.

Relationship between Arousal Indices and Clinical Manifestations in Patients Who Performed Polysomnography / 결핵및호흡기질환

BACKGROUND: Repeated arousals during sleep have been known to be associated with excessive daytime sleepiness and cardiovascular complications. We investigated the relationship between arousal indices and clinical parameters. METHODS: We retrospectively reviewed medical records of 41 patients who performed polysomnography for a diagnosis of obstructive sleep apnea syndrome. We defined total arousal index (TAI) as the number of arousals per hour and respiratory arousal index (RAI) as the number of arousals associated with apnea or hypopnea per hour. RESULTS: There were significant positive correlations between arousal indices and apnea-hypopnea index (AHI) (RAI vs. AHI, r=0.958, p<0.001; TAI vs. AHI, r=0.840, p<0.001). RAI and mean oxygen saturation showed a significant negative correlation with each other (r=-0.460, p=0.002). TAI revealed a significant positive correlation with mean systolic blood pressure (MSBP) and mean diastolic blood pressure (MDBP) (TAI vs. MSBP, r=0.389, p=0.014; TAI vs. MDBP, r=0.373, p=0.019). There was no significant correlation between arousal indices and parameters of sleepiness. RAI had a significant positive correlation with body mass index (BMI) and neck circumference (NC) (RAI vs. BMI, r=0.371, p=0.017; RAI vs. NC, r=0.444, p=0.004). When partial correlation analysis was performed to adjust for other variables, there was significant correlation between RAI and AHI (r=0.935, p<0.001). CONCLUSION: This study shows that respiratory arousal index could be a useful index reflecting of severity of obstructive sleep apnea syndrome. Arousal during sleep would be concerned in the development of cardiovascular complication of obstructive sleep apnea. And some anthropometric factors would contribute to the development of arousals during sleep. Further studies are needed to clarify any cause-effect relationship.

The Soluble Tumor Necrosis Factor-Alpha Receptor Suppresses Airway Inflammation in a Murine Model of Acute Asthma

PURPOSE: Tumor necrosis factor-alpha (TNF-alpha) is a proinflammatory cytokine that has been implicated in many aspects of the airway pathology in asthma. TNF-alpha blocking strategies are now being tried in asthma patients. This study investigated whether TNF-alpha blocking therapy inhibits airway inflammation and airway hyperresponsiveness (AHR) in a mouse model of asthma. We also evaluated the effect of TNF-alpha blocking therapy on cytokine production and adhesion molecule expression. MATERIALS AND METHODS: Ovalbumin (OVA) sensitized BALB/c female mice were exposed to intranasal OVA administration on days 31, 33, 35, and 37. Mice were treated intraperitoneally with soluble TNF-alpha receptor (sTNFR) during the OVA challenge. RESULTS: There were statistically significant decreases in the numbers of total cell and eosinophil in bronchoalveolar lavage fluid (BALF) in the sTNFR treated group compared with the OVA group. However, sTNFR-treatment did not significantly decrease AHR. Anti-inflammatory effect of sTNFR was accompanied with reduction of T helper 2 cytokine levels including interleukin (IL)-4, IL-5 and IL-13 in BALF and vascular cell adhesion molecule 1 expression in lung tissue. CONCLUSION: These results suggest that sTNFR treatment can suppress the airway inflammation via regulation of Th2 cytokine production and adhesion molecule expression in bronchial asthma.

A Case of Chronic Expanding Hematoma with Initial Presentation as Massive Hemotpysis through Bronchopleural Fistula in the Thorax / 결핵및호흡기질환

Chronic expanding hematoma of the thorax is a specific subtype of the chronic empyema. It presents as a slowly expanding intrathoracic mass which result in dyspnea or recurrent hemoptysis. The symptoms develop months or years after tuberculous pleurisy, trauma or surgery. Usually, it shows three common findings: a giant mass lesion in the thorax, some surrounding calcifications, the absence of signs or symptoms of infection. We report a case of chronic expanding hematoma of the thorax, initially presenting as massive hemoptysis through bronchopleural fistula which resulted in radiologic findings of new air-fluid level within the previous pleural lesion filled with unknown materials.

Prognostic Value of Vascular Endothelial Growth Factor (VEGF) and Basic Fibroblast Growth Factor (bFGF) Expression in Resected Non-small Cell Lung Cancer / 결핵및호흡기질환

BACKGROUND: Tumor angiogenesis plays an important role in tumor growth, maintenance and metastatic potential. Tumor tissue produces many types of angiogenic growth factors. Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) have both been implicated to have roles in tumor angiogenesis. In this study, the expression of tissue VEGF and bFGF from non-small cell lung cancer (NSCLC) patients were analyzed. METHODS: We retrospectively investigated 35 patients with a histologically confirmed adenocarcinoma or squamous cell carcinoma of the lung, where the primary curative approach was surgery. An ELISA was employed to determine the expression of VEGF and bFGF in extracts prepared from 35 frozen tissue samples taken from the cancer patients. RESULTS: VEGF and bFGF concentrations were significantly increased in lung cancer tissue as compared with control (non-cancerous) tissue. The VEGF concentration was significantly increased in T2 and T3 cancers as compared with T1 cancer. Expression of VEGF was increased in node-positive lung cancer tissue as compared with node-negative lung cancer tissue (p=0.06). VEGF and bFGF expression were not directly related to the stage of lung cancer and patient survival. CONCLUSION: Expression of VEGF and bFGF were increased in lung cancer tissue, and the expression of VEGF concentration in lung cancer tissue was more likely related with tumor size and the presence of a lymph node metastasis than the expression of bFGF. However, in this study, expression of both VEGF and bFGF in tissue were not associated with patient prognosis.

A Case of Erdheim-Chester Disease Who Has Policythemia Vera / 결핵및호흡기질환

Erdheim-Chester disease (ECD) is a rare disease that is characterized by multi-organ involvement of foamy histiocytes. It causes systemic inflammation, and also demonstrates various clinical manifestations and has a poor prognosis. We encountered a case of ECD in a patient that had been treated for underlying polycythemia vera. As far as we know, this is the first reported case worldwide where ECD developed in association with polycythemia vera. A 59-year-old man visited our hospital due to pleuric pain at the right side of the chest. Pleural tissue that was obtained following a thoracoscopic biopsy showed non-Langerhan's cell histiocytosis, suggesting the presence of ECD. The histiocytes stained positively for CD68, but were negative for S-100 and CD1a. The patient also complained of pain at both hips and the right shoulder area. An X-ray and magnetic resonance image demonstrated that the lesion showed sclerosis and osteolysis in both the proximal femur and right humerus. Treatment was started with predinisolone, and subsequently cyclophosphamide was added. ECD is a very rare multi-systemic disease, and its cause and therapeutic options have not yet been defined. ECD has a poor prognosis. Therefore, we believe that additional case studies are needed prior to the determination of a novel therapy for ECD.

A Case of Tuberculosis-associated Hemophagocytic Syndrome during Antituberculosis Medication for Tuberculous Pericarditis / 결핵및호흡기질환

A 63-year old woman was admitted to our hospital for an evaluation of thrombocytopenia. She had been diagnosed with tuberculous pericarditis three months earlier in a local clinic and treated with anti-tuberculosis medication. Two months later, thrombocytopenia developed. The medication was subsequently stopped because it was suspected that the anti-tuberculosis medication, particularly rifampin, might have caused the severe platelet reduction. However, the thrombocytopenia was more aggravated. A bone marrow biopsy was performed, which showed moderate amounts of histiocytes with active hemophagocytosis. This finding strongly suggested that the critical thrombocytopenia had been caused by hemophagocytic syndrome, not by the side effects of the anti-tuberculosis medication. Furthermore, the development of hemophagocytosis might have been due to an uncontrolled tuberculosis infection and its associated aberrant immunity. Therefore, she was started with both standard anti-tuberculosis medication and chemotherapy using etoposide plus steroid. One month after the initiation of treatment, the thrombocytopenia had gradually improved and she was discharged in a tolerable condition. At the third month of the follow-up, her platelet level and ferritin, the activity marker of hemophagocytic syndrome, was within the normal range.

IP-10 Decreases TNF-alpha Induced MUC5AC Expression in Human Airway Epithelial Cells: a Possible Relation with Little Sputum Production in Idiopathic Pulmonary Fibrosis / 결핵및호흡기질환

BACKGROUND: IPF is characterized by chronic, fibrosing inflammatory lung disease of unknown etiology. Typical symptoms of IPF are exertional dyspnea with nonproductive cough. Why patients with typical IPF have dry cough rather than productive cough, is unknown. IP-10 plays an important regulatory role in leukocyte trafficking into the lung. The present study investigated the effect of IP-10 in the pathogenesis of dry cough rather than productive cough in IPF patients. METHODS: IP-10 concentration was measured by ELISA from BALF of IPF patients. To evaluate the role of IP-10 in mucin expression, the expression of the MUC5AC mucin gene was measured in NCI-H292 cells, a human pulmonary mucoepidermoid carcinoma cell line, after stimulation by TNF-alpha with or without IP-10 pretreatment. EGFR-MAPK expression was also examined as a possible mechanism. RESULTS: IP-10 levels were significantly higher in the BALF of IPF patients compared to healthy controls. IP-10 pretreatment reduced TNF-alpha induced MUC5AC mucin expression by inhibiting the EGFR-MAPK signal transduction pathway in NCI-H292 cells. CONCLUSION: These findings suggest that little mucus production in IPF patients might be attributable to IP-10 overproduction, which inhibits the EGFR-MAPK signal transduction pathway required for MUC5AC mucin gene expression.