The Wnt/beta-catenin signaling pathway regulates the development of airway remodeling in patients with asthma

Airway remodeling is a key characteristic of chronic asthma, particularly in patients with a fixed airflow limitation. The mechanisms underlying airway remodeling are poorly understood, and no therapeutic option is available. The Wnt/beta-catenin signaling pathway is involved in various physiological and pathological processes, including fibrosis and smooth muscle hypertrophy. In this study, we investigated the roles of Wnt/beta-catenin signaling in airway remodeling in patients with asthma. Wnt7a mRNA expression was prominent in induced sputum from patients with asthma compared with that from healthy controls. Next, we induced a chronic asthma mouse model with airway remodeling features, including subepithelial fibrosis and airway smooth muscle hyperplasia. Higher expression of Wnt family proteins and beta-catenin was detected in the lung tissue of mice with chronic asthma compared to control mice. Blocking beta-catenin expression with a specific siRNA attenuated airway inflammation and airway remodeling. Decreased subepithelial fibrosis and collagen accumulation in the beta-catenin siRNA-treated mice was accompanied by reduced expression of transforming growth factor-beta. We further showed that suppressing beta-catenin in the chronic asthma model inhibited smooth muscle hyperplasia by downregulating the tenascin C/platelet-derived growth factor receptor pathway. Taken together, these findings demonstrate that the Wnt/beta-catenin signaling pathway is highly expressed and regulates the development of airway remodeling in chronic asthma.

Pulmonary Foreign Body Granulomatosis in Dental Technician / 결핵및호흡기질환

Occupational lung diseases are caused by several toxic substances including heavy metals; however, the exact pathologic mechanisms remain unknown. In the workplace, dental technicians are often exposed to heavy metals such as cobalt, nickel, or beryllium and occasionally develop occupational lung diseases. We described a case of occupational lung disease in a patient who was employed as a dental technician for over a decade. A 31-year-old, non-smoking woman presented with productive cough and shortness of breath of several weeks duration. Chest computed tomography revealed a large number of scattered, bilateral small pulmonary nodules throughout the lung field, and multiple mediastinal lymph nodes enlargement. Percutaneous needle biopsy showed multifocal small granulomas with foreign body type giant cells suggestive of heavy metals inhalation. The patient's condition improved on simple avoidance strategy for several months. This case highlighted the importance of proper workplace safety.

A Case of Significant Endobronchial Injury due to Recurrent Iron Pill Aspiration / 결핵및호흡기질환

Gastric mucosal damage by iron pills is often reported. However, iron pill aspiration is uncommon. Oxidation of the impacted iron pill causes bronchial mucosal damage that progresses to chronic bronchial inflammation, necrosis, endobronchial stenosis and rarely, perforation. We reported a case of a 92-year-old woman with chronic productive cough and significant left-sided atelectasis. Bronchoscopy revealed substantial luminal narrowing with exudative inflammation of the left main bronchus. Bronchial washing cytology showed necroinflammatory exudate and a small amount of brown material. Mucosal biopsy showed diffuse brown pigments indicative of ferrous pigments, crystal deposition, and marked tissue degeneration. After vigorous coughing, she expectorated dark sediments and her symptoms and radiological abnormalities improved. There are a few such reports worldwide; however, this was the first case reported in Korea. Careful observation of aspiration-prone patients and early detection of iron pill aspiration may prevent iron pill-induced bronchial injury.

The Extended Rapid Response System: 1-Year Experience in a University Hospital

The rapid response system (RRS) is an innovative system designed for in-hospital, at-risk patients but underutilization of the RRS generally results in unexpected cardiopulmonary arrests. We implemented an extended RRS (E-RRS) that was triggered by actively screening at-risk patients prior to calls from primary medical attendants. These patients were identified from laboratory data, emergency consults, and step-down units. A four-member rapid response team was assembled that included an ICU staff, and the team visited the patients more than twice per day for evaluation, triage, and treatment of the patients with evidence of acute physiological decline. The goal was to provide this treatment before the team received a call from the patient's primary physician. We sought to describe the effectiveness of the E-RRS at preventing sudden and unexpected arrests and in-hospital mortality. Over the 1-yr intervention period, 2,722 patients were screened by the E-RRS program from 28,661 admissions. There were a total of 1,996 E-RRS activations of simple consultations for invasive procedures. After E-RRS implementation, the mean hospital code rate decreased by 31.1% and the mean in-hospital mortality rate was reduced by 15.3%. In conclusion, the implementation of E-RRS is associated with a reduction in the in-hospital code and mortality rates.

Fatal Clinical Course of Probable Invasive Pulmonary Aspergillosis with Influenza B Infection in an Immunocompetent Patient / 결핵및호흡기질환

Invasive pulmonary aspergillosis (IPA) is rarely reported in patients who have normal immune function. Recently, IPA risk was reported in nonimmunocompromised hosts, such as patients with chronic obstructive pulmonary disease and critically ill patients in intensive care units. Moreover, influenza infection is also believed to be associated with IPA among immunocompetent patients. However, most reports on IPA with influenza A infection, including pandemic influenza H1N1, and IPA associated with influenza B infection were scarcely reported. Here, we report probable IPA with a fatal clinical course in an immunocompetent patient with influenza B infection. We demonstrate IPA as a possible complication in immunocompetent patients with influenza B infection. Early clinical suspicion of IPA and timely antifungal therapy are required for better outcomes in such cases.

The effects of secondhand smoke on chronic obstructive pulmonary disease in nonsmoking Korean adults

BACKGROUND/AIMS: Smoking is widely acknowledged as the single most important risk factor for chronic obstructive pulmonary disease (COPD). However, the risk of COPD in nonsmokers exposed to secondhand smoke remains controversial. In this study, we investigated the association of secondhand smoke exposure with COPD prevalence in nonsmokers who reported never smoking. METHODS: This study was based on data obtained from the Korean National Health and Nutrition Examination Surveys (KNHANES) conducted from 2008 to 2010. Using nationwide stratified random sampling, 8,596 participants aged > or = 40 years of age with available spirometry results were recruited. After selecting participants who never smoked, the duration of exposure to secondhand smoke was assessed based on the KNHANES questionnaire. RESULTS: The prevalence of COPD was 6.67% in participants who never smoked. We divided the participants who had never smoked into those with or without exposure to secondhand smoke. The group exposed to secondhand smoke was younger with less history of asthma and tuberculosis, higher income, and higher educational status. Multivariate logistic regression analysis determined that secondhand smoke did not increase the prevalence of COPD. CONCLUSIONS: There was no significant difference in the prevalence of COPD between participants who had never smoked with or without exposure to secondhand smoke in our study. Thus, secondhand smoke may not be an important risk factor for the development of COPD in patients who have never smoked.

Incidence and Risk Factors of Contrast-Induced Nephropathy after Bronchial Arteriography or Bronchial Artery Embolization / 결핵및호흡기질환

BACKGROUND: In uncontrolled hemoptysis patient, bronchial arteriography and bronchial artery embolization (BAE) is a important procedure in diagnosis and treatment. The aim of this study is to assess the incidence of contrast-induced nephropathy and the risk factors of contrast-induced nephropathy (CIN) after bronchial arteriography and BAE. METHODS: We retrospectively reviewed the medical records of the patients who underwent bronchial arteriography and BAE in two university hospitals from January 2003 to December 2011. CIN was defined as rise of serum creatinine more than 25% of baseline value or 0.5 mg/dL at between 48 hours and 96 hours after bronchial arteriography and BAE. We excluded patients who already had severe renal insufficiency (serum creatinine> or =4.0) or had been receiving dialysis. RESULTS: Of the total 100 screened patients, 88 patients met the enrollment criteria. CIN developed in 7 patients (8.0%). The mean duration between the exposure and development of CIN was 2.35+/-0.81 days. By using multivariate analysis, serum albumin level was found to be significantly associated with the development of CIN (p=0.0219). CONCLUSION: These findings suggest that the incidence of CIN was higher than expected and patients with hypoalbuminemia should be monitored more carefully to prevent the development of CIN after bronchial arteriography and BAE.

A Case of Thyroid Papillary Carcinoma With Pulmonary Tumor Embolism

The tumor embolism is defined as tumor cells within the vascular system such as pulmonary artery that is not contiguous with the other metastatic foci. The incidence of tumor embolism varies widely ranging from 3% to 26% among several studies; whereas lung cancer, prostate cancer, colorectal cancer, breast cancer, pancreas cancer are associated with high risks for tumor embolism. However thyroid cancer is rarely associated with tumor embolism. Among the rare cases, tumor embolism was reported as being mostly of follicular carcinoma or undifferentiated carcinoma, but few of papillary carcinoma. We report an unusual presentation that pulmonary tumor embolism from thyroid papillary carcinoma was diagnosed with positron emission tomography/computed tomography (CT) and chest CT.

The Reliability and Validity of the Korean Version of Burden Assessment Scale (K-BAS) / 신경정신의학

OBJECTIVES: This study was conducted for evaluation of the reliability and validity of the Korean version of the Burden Assessment Scale (K-BAS). METHODS: A sample of 256 first-order relatives of schizophrenics completed the K-BAS and the data were analyzed for internal consistency and factor structure. In addition, a subset of participants (n=112) refilled the K-BAS after two weeks for test-retest reliability. To test for validity, the Family Burden Scale (FBS), Korean version of Drug Attitude Inventory-10 (KDAI-10), and Korean version of the Scale to Assess Unawareness of Mental Disorder (SUMD-K) were administered. RESULTS: The Cronbach's alpha coefficient of the K-BAS was high (0.91), which provided evidence for good internal consistency. The test-retest reliability of K-BAS was 0.86 (correlation coefficient, p<0.001). Convergent validity was examined through correlations between the K-BAS and the FBS (r=0.80, p<0.001). Divergent validity was examined through correlations between the K-BAS and KDAI-10 (r=-0.21, p=0.001), and between the K-BAS and SUMD-K (r=-0.02, p=0.796). Results of the factor analysis revealed a three-factor solution: activity limitation, social strain, and feelings of worry and guilt. CONCLUSION: These results suggest that the K-BAS had good psychometric properties and may be a useful instrument for evaluation of burden of families with schizophrenics.

Cerebral Air Embolism Following Pigtail Catheter Insertion for Pleural Fluid Drainage / 결핵및호흡기질환

Pigtail catheter drainage is a common procedure for the treatment of pleural effusion and pneumothorax. The most common complications of pigtail catheter insertion are pneumothorax, hemorrhage and chest pains. Cerebral air embolism is rare, but often fatal. In this paper, we report a case of cerebral air embolism in association with the insertion of a pigtail catheter for the drainage of a pleural effusion. A 67-year-old man is being presented with dyspnea, cough and right-side chest pains and was administered antibiotics for the treatment of pneumonia. The pneumonia failed to resolve and a loculated parapneumonic pleural effusion developed. A pigtail catheter was inserted in order to drain the pleural effusion, which resulted in cerebral air embolism. The patient was administered high-flow oxygen therapy and recovered without any neurologic complications.

Congenital Cystic Adenomatoid Malformation with Bronchial Atresia in Elderly Patients / 결핵및호흡기질환

Congenital cystic adenomatoid malformation (CCAM) is an uncommon, nonhereditary anomaly caused by arrest of lung. Patients with CCAM may present with respiratory distress as newborns, or may remain asymptomatic until later in life. CCAM type I is rarely found in association with bronchial atresia (BA) in adults; we present such a case. Case: A 54-year-old female presented with chronic cough and blood-tinged sputum. Physical examination and laboratory tests were unremarkable. Chest radiographs and a CT scan of the chest showed multiple large air-filled cysts consistent with a CCAM in the right lower lobe, and an oval-shaped opacity in the distal right middle lobal bronchus. Based on the radiologic findings, right middle lobectomy and a medial basal segmentectomy of the right lower lobe were performed via a thoracotomy. These lesions were consistent with Stocker's Type I CCAM and BA in the different lobes.

Amyotrophic Lateral Sclerosis Identified by Failure to Wean From Mechanical Ventilation

In most cases of amyotrophic lateral sclerosis (ALS), respiratory muscle involvement is a late complication. Only 2.7% of ALS patients presenting with their first clinical symptoms in the extremities also experience respiratory symptoms. We report a case of an 81-year-old man with ALS, diagnosed by an unexplained failure to wean from mechanical ventilation. The patient was presented with acute respiratory failure, tachypnea and respiratory acidosis. Computed tomography of the chest showed large amounts of sputum in the trachea. An endotracheal tube was inserted, and the patient was placed on volume-controlled ventilation. However, in the course of recovery, he could not be weaned from mechanical ventilation, despite the absence of cardiopulmonary impairment. Having considered other causes of respiratory failure, wediagnosed ALS after a physical and neurologic examination and electrodiagnostic testing.

Exhaled Nitric Oxide in Patients with Ventilator Associated Pneumonia / 대한구급학회지

BACKGROUND: Fraction of exhaled nitric oxide (FENO) is known as a marker of inflammation in asthma, cystic fibrosis and exacerbation of COPD. However, its importance has not been established in patients using mechanical ventilation. We assessed whether FENO is elevated in patients with ventilator associated pneumonia (VAP), and physiologic or pathologic factors affecting levels of FENO in patients with mechanical ventilation. METHODS: All patients (over 18-year-old) using mechanical ventilation were included, and among them, VAP patients were diagnosed on the basis of clinical pulmonary infection score (CPIS). We measured FENO in air collected during the end-expiratory pause via an off-line method. We compared the levels of FENO between patients with VAP and without, and assessed the relationship between FENO and other physiologic or pathologic characteristics; age, gender, PaO2, oxygenation index, CPIS. RESULTS: A total of 43 patients (23 male, mean age 67.7 +/- 10.7) in an ICU were enrolled; 19 of them were VAP-patients (10 male, mean age 64.8 +/- 12.9). The level of FENO in the VAP-patients was substantially higher than in the non-VAP group (55.8 +/- 25.3 ppb Vs. 31.8 +/- 13.5 ppb, p < 0.001). CPIS on day 1 and day 3, and duration of mechanical ventilation, were associated with the level of FENO, but oxygenation index, PaO2, PaO2/FiO2, and the mean PEEP were not. CONCLUSIONS: FENO may be useful for the diagnosis of VAP, and is related to CPIS, as well as the duration of mechanical ventilation.

Relationship between Exhaled Nitric Oxide and Levels of Asthma Control in Asthma Patients Treated with Inhaled Corticosteroid / 결핵및호흡기질환

BACKGROUND: While asthma control is defined as the extent to which the various manifestations of asthma are reduced by treatment, current guidelines of asthma recommend assessment of asthma control without consideration of airway inflammation. Our aim was to investigate the relationships between fractional exhaled nitric oxide (FeNO), a reliable marker of airway inflammation, and levels of asthma control in patients treated with inhaled corticosteroids (ICS). METHODS: We enrolled 71 adult patients with asthma who had been treated with ICS for more than four months. FeNO was measured and spirometry was performed at the time of enrollment. Asthma control was assessed (a) by the physician based on the Global Initiative for Asthma guidelines, (b) by the patients, and (c) by using the Asthma Control Test (ACT). Statistical analyses were done to analyze the relationships between (i) FeNO and (ii) measures of asthma control and clinical indices for asthma manifestations. RESULTS: There was no significant difference in FeNO levels between the three groups according to levels of asthma control (controlled, partly controlled and uncontrolled) as determined by the physician (p=0.81), or by the patients (p=0.81). In addition, FeNO values were not significantly correlated with the ACT scores (r=0.031, p=0.807), while FeNO showed a correlation with peripheral blood eosinophil counts (p<0.001). CONCLUSION: These findings demonstrate that FeNO levels are not associated with measures of asthma control in patients treated with ICS. Information on airway inflammation from FeNO concentrations seems to be unrelated to levels of asthma control.

Sarcoidosis Induced by Adalimumab in Rheumatoid Arthritis / 결핵및호흡기질환

Adalimumab is a full human monoclonal antibody that inhibits tumor necrosis factor-alpha (TNF-alpha). This has recently been shown to be effective in the treatment of rheumatoid arthritis (RA), ankylosing spondylitis, and other conditions. Sacoidosis is known to be the target for adalimumab but we describe a patient who has developed sarcoidosis with lung involvement during adalimumab therapy for RA. A 48-year-old woman, who was treated with adalimumab for 5 months, was admitted because of chronic cough and both hilar lymphadenopathy on chest radiography. Chest computed tomography revealed the enlargement of multiple lymph nodes in the right supraclavicular, subcarinal, both hilar and right axillary area. She was diagnosed with sarcoidosis based on the biopsy of supraclavicular lymph node, skin and lung through video-associated thoracoscopic surgery, which was non-caseating epitheloid cell granuloma and excluded from a similar disease. She was treated for sarcoidosis with prednisolone and methotrexate instead of adalimumab.

Asymptomatic Solitary Renal Metastasis Detected during Surveillance after Curative Surgery for Squamous Cell Carcinoma of Lung / 결핵및호흡기질환

Non small cell lung cancer (NSCLC) frequently metastasizes to brain, bone, liver, and adrenal glands. While an autopsy of NSCLC reveals some cases of metastasis to the kidney, clinical detection of renal metastases is extremely rare. Furthermore, metastases to the kidney usually present as multifocal or bilateral lesions and solitary renal metastases are usually suspected to be renal cell carcinoma. We now report a case of asymptomatic solitary renal metastasis from a primary squamous cell carcinoma, which was detected by routine surveillance with abdominal CT after curative surgery.

Prognostic Value of Preoperative Positron Emission Tomography-Computed Tomography in Surgically Resected Stage I and II Non-Small Cell Lung Cancer / 결핵및호흡기질환

BACKGROUND: High 2-[18F] fluoro-2-deoxy-D-glucose (FDG) uptake on positron emission tomography-computed tomography (PET-CT) is a prognostic factor for poor survival in non-small cell lung cancer (NSCLC), especially in Stage I. We determined whether the high FDG uptake value of a primary tumor was associated with recurrence and death in patients with resected Stage I and Stage II NSCLC. METHODS: We identified consecutive patients who underwent complete surgical resection for Stage I and II NSCLC between 2006 and 2009, who had preoperative PET-CT, and reviewed clinical records retrospectively. FDG uptake was measured as the maximal standardized uptake value (SUVmax) for body weight. Patients were divided into two groups based on SUVmax: (i) above or (ii) below the cut-off value (SUVmax=5.9) determined by a receiver operating characteristic (ROC) curve. RESULTS: Of 57 patients who were enrolled consecutively, 32 (56%) had Stage I NSCLC and 25 (44%) had Stage II. The 5-year recurrence-free survival (RFS) for patients with high (> or =5.9) and low (<5.9) SUVmax were 31% and 57%, respectively (p=0.014). The 5-year overall survival (OS) rates were 39% and 60%, respectively (p=0.029). In univariate analyses, SUVmax (p=0.014), T staging (p=0.025), and differentiation of tumor tissue (p=0.034) were significantly associated with RFS. But, multivariate analyses did not show that SUVmax was an independently significant factor for RFS (p=0.180). CONCLUSION: High FDG uptake on PET-CT is not an independent prognostic factor for poor outcomes (disease recurrence in patients with resected Stage I and II NSCLC).

Clinicopathologic Characteristics of Recurrence after Curative-intent Surgical Therapy of Non-small Cell Lung Cancer / 결핵및호흡기질환

BACKGROUND: The clinicopathologic characteristics of patients with non-small cell lung cancer (NSCLC) have been changing. Recently, Positron emission tomography-computed tomography (PET-CT) has usually been used for diagnosis, follow-up to treatment and surveillance of NSCLC. We studied the pattern of recurrence and prognosis in patients who underwent complete resection for NSCLC according to histologic subtype. METHODS: All patients who underwent complete resection for pathological stage I or II NSCLC between January 2005 and June 2009 were identified and clinical records were reviewed retrospectively, especially the histologic subtype. RESULTS: Recurrences were identified in 50 of 112 patients who had complete resection of an NSCLC. Sites of recurrence were locoregional in 15 (30%), locoregional and distant in 20 (40%), and distant in 15 (30%). Also, sites of recurrence were intra-thoracic in 29 (58%), extrathoracic and intra-thoracic recurrence in 15 (30%), and extrathoracic in 6 (12%). In locoregional recurrence, there was 37% recurrence for non-squamous cell carcinoma (non-SQC) and 25% for squamous cell carcinoma (SQC). In distant recurrence, there was 39% recurrence for non-SQC and 18% for SQC. Locoregional recurrence in the bronchial stump was more common in SQC than non-SQC (14% vs. 45%, p=0.025). Prognosis of recurrence was not influenced by histologic subtype and the recurrence-free survival curve showed that the non-SQC group did not differ from the SQC group according to stage. CONCLUSION: The prognosis for recurrence does not seem to be influenced by histologic types, but locoregional recurrence in the bronchial stump seems to be more common in SQC than non-SQC in completely resected stage I and II NSCLC.

A Case of a Solitary Fibrous Tumor of the Pleura Presenting as Pneumonia and Acute Respiratory Failure / 결핵및호흡기질환

Solitary fibrous tumors of the pleura (SFTPs) are relatively rare tumors that originate from the mesenchymal cells of the submesothelial tissue of the pleura. Patients with SFTPs are often asymptomatic, while some patients experience pleuritic chest pain, cough and/or dyspnea. We report here on a case of SFTP, and the patient presented with septic shock and respiratory failure that required mechanical ventilation. A 68-year-old woman was admitted for the evaluation of her dyspnea and generalized edema. Chest imaging studies showed an 18 cm-sized voluminous mass occupying the right thoracic cavity with anterior displacement of hilar structures and atelectasis of the right lung. Immediately after admission, she developed pneumonia and septic shock that required antibiotics and mechanical ventilation. She displayed a partial response to medical treatment, and then complete excision of the tumor was performed and the pathologic examination revealed benign SFTP. Afterward, she fully improved without evidence of recurrence until now.

A Case of Concomitant Scrub Typhus and Leptospirosis / 결핵및호흡기질환

Tsutsugamushi disease (Scrub typhus) is an acute, febrile illness caused by Orientia tsutsugamushi, which is transmitted to humans through chigger bites. Leptospirosis, a febrile disease caused by various pathogenic Leptospira, and is acquired by exposure to contaminated water and soil. Both diseases have been the most common acute febrile diseases in the autumn in Korea for many years. Concomitant leptospirosis and scrub typhus is quite rare. We report a case of a coinfection with leptospirosis and scrub typhus in a 51-year-old male who presented with fever, abdominal pain and acute dyspnea. The patient was diagnosed with as acalculous cholecystitis, acute respiratory distress syndrome, and septic shock caused by the infection. This is the first case report of a coinfection with leptospirosis and scrub typhus in Korea.