Jang Won Sohn

Reference values and determinants of exhaled nitric oxide in healthy Korean adults.

Background: Measuring fractional exhaled nitric oxide (FeNO) provides an indication of airway inflammation and is used as an inflammatory marker for asthma management. However, reference values and determinants of FeNO levels are not well defined in healthy Asian adults. This study aimed to establish FeNO reference values in nonsmoking, healthy Asian adults and to determine the factors related to FeNO levels. Methods. The authors measured FeNO in 166 nonsmoking, healthy Korean adults and collected data regarding factors possibly associated with FeNO, including age, height, weight, and respiratory symptoms. Lung function was measured using spirometry, and atopic status was determined based on the skin-prick test. Results. In a multivariate linear regression analysis, FeNO levels were positively associated with male gender (p = .008) and atopy (p = .044) after adjusting for age, height, weight, forced expiratory volume in one second (FEV1), and chronic rhinitis. Reference values were presented according to gender and atopic status, and the mean FeNO value was highest in male atopic subjects (37.3 ± 12.1 ppb), followed by nonatopic males (33.9 ± 14.3 ppb), atopic females (28.6 ± 17.7 ppb), and nonatopic females (24.1 ± 10.6 ppb). In healthy Korean adults, FeNO levels showed a significant and independent association with male gender and atopy. Conclusions. We believe that the presented FeNO reference values and the determining factors could be useful for research and clinical practice in the adult Asian population.

Comparison of two exhaled nitric oxide analyzers: The NIOX MINO hand‐held electrochemical analyzer and the NOA280i stationary chemiluminescence analyzer

Background and objective:  Measurement of the fraction of nitric oxide (FeNO) in exhaled air is useful in the management of asthma. A new hand‐held nitric oxide (NO) analyzer, the NIOX MINO, is simple and easy to use in clinical practice. In this study, FeNO values measured using the NIOX MINO were compared with those obtained using a stationary chemiluminescence analyzer, the Sievers NOA280i.

The Wnt/β-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/β-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/β-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 β-catenin was detected in the lung tissue of mice with chronic asthma compared to control mice. Blocking β-catenin expression with a specific siRNA attenuated airway inflammation and airway remodeling. Decreased subepithelial fibrosis and collagen accumulation in the β-catenin siRNA-treated mice was accompanied by reduced expression of transforming growth factor-β. We further showed that suppressing β-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/β-catenin signaling pathway is highly expressed and regulates the development of airway remodeling in chronic asthma.

Adiposity, adipokines, and exhaled nitric oxide in healthy adults without asthma.

Background. Epidemiological studies have shown that obesity/adiposity is closely associated with asthma in terms of development, severity, and control of asthma. However, effects of obesity/adiposity on airway inflammation are not well known in subjects without asthma. We assessed whether fractional exhaled nitric oxide (FeNO), a marker of eosinophilic airway inflammation, was associated with obesity/adiposity in nonasthmatic healthy adults. Methods. We measured FeNO and serum levels of adipose-derived hormones and adipokines in 117 adult subjects without a previous diagnosis of asthma or current asthmatic symptoms. Associations between FeNO and measures of obesity/adiposity [body mass index (BMI), body fat mass, and body fat percentages] were examined by correlation analyses and uni- and multivariate linear regression analyses. Results. FeNO was not significantly associated with BMI, body fat mass, or body fat percentage by a multivariate linear regression model, adjusting for age, gender, chronic rhinitis, atopy, and lung function. No significant association of FeNO with serum levels of leptin, adiponectin, tumor necrosis factor (TNF)-α, or interleukin (IL)-6 was observed. Conclusions. These findings suggest that in healthy subjects without asthma, obesity/adiposity has no significant effect on eosinophilic airway inflammation and that hormones and systemic inflammation derived from adipose tissue do not affect eosinophilic airway inflammation.

Benign Pulmonary Metastasizing Leiomyomatosis: Case Report and a Review of the Literature

The authors report here on a case of a nearly asymptomatic 51-year-old Korean woman who was found to have diffuse, multiple nodules of the lungs on a routine chest radiograph. She had undergone hysterectomy 16 years previously for uterine myoma. An open lung biopsy revealed tumor that was composed of interlacing bundles of spindle cells with cigar shaped nucleus and eosinophilic myofibrils in the cytoplasm; consistent with multiple leiomyomas. The stains for SMA, desmin, MSA and Ki-67 were positive and the stain for c-kit was negative. The other stains for estrogen and progesterone receptor were positive. During the open lung biopsy procedure, all the nodules were excised. We report here on an interesting case of benign metastasizing leiomyoma (BML) in 51-year-old patient. To the best of our knowledge, this case showed the longest period of clinical progression in Korea. This is also one of a few cases in which curative excision was successfully performed.

Acute Eosinophilic Pneumonia

Acute eosinophilic pneumonia is a severe and rapidly progressive lung disease that can cause fatal respiratory failure. Since this disease exhibits totally different clinical features to other eosinophilic lung diseases (ELD), it is not difficult to distinguish it among other ELDs. However, this can be similar to other diseases causing acute respiratory distress syndrome or severe community-acquired pneumonia, so the diagnosis can be delayed. The cause of this disease in the majority of patients is unknown, even though some cases may be caused by smoke, other patients inhaled dust or drugs. The diagnosis is established by bronchoalveolar lavage. Treatment with corticosteroids shows a rapid and dramatic positive response without recurrence.

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 ≥ 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.

Clinical Significance of Aberrant Wnt7a Promoter Methylation in Human Non-Small Cell Lung Cancer in Koreans

The Wnt signaling pathway has regulatory roles in cell proliferation, differentiation, and polarity. Aberrant Wnt pathway regulation can lead to abnormal cell proliferation and cancer, and loss of Wnt7a expression has been demonstrated in lung cancer cell lines. E-cadherin keeps intercellular integrity and prevents metastasis. Therefore, E-cadherin has been known as a prognostic factor in cancer. In the present study, we investigated the E-cadherin expression status by immunohistochemical stain and the Wnt7a promoter methylation status in human non-small cell lung carcinoma (NSCLC) by methylation-specific PCR. We also analyzed their correlations with clinicopathological factors. Methylation of the Wnt7a gene promoter was detected in the lung tissues of 32 of 121 (26.4%) patients with NSCLC. Wnt7a promoter methylation was correlated with advanced tumor stage (P = 0.036) and distant metastasis (P = 0.037). In addition, Wnt7a promoter methylation showed correlation with loss of E-cadherin expression (P < 0.001). However, Wnt7a promoter methylation was not closely related with gender, age, histological type, or smoking habit. Even though Wnt7a methylation could not show significant correlation with the long term survival of the patients with limited follow up data, these findings suggest that loss of the Wnt7a gene induced by promoter methylation might be another prognostic factor for NSCLC and that restoration of Wnt7a may be a promising treatment for NSCLC. Graphical Abstract

Primary pulmonary plasmacytoma presenting as multiple lung nodules.

To the Editor, Extramedullary plasmacytoma is a plasma cell tumor arising outside the bone marrow and usually occurs as a solitary tumor in the upper respiratory tract, such as the pharynx, paranasal sinuses, nasal cavity, or oral cavity [1]. Other cases develop in the lymph nodes, skin, gastrointestinal tract, genitourinary tract, and other regions. Primary pulmonary plasmacytomas are very rare and usually present as solitary lung nodules or masses [2]. Unusual cases manifest as diffuse pulmonary infiltration [3,4]. We describe here a unique case of primary pulmonary plasmacytoma, which presented as multiple lung nodules during regular screening in a patient with systemic lupus erythematosus. A 26-year-old woman was admitted and referred to the pulmonary service for an evaluation of multiple lung lesions on simple chest radiographs. The patient was diagnosed with systemic lupus erythematosus 11 years ago and had been treated with methotrexate, hydroxycholoroquine, and deflazacort. At the time of the systemic lupus erythematosus diagnosis, she was treated successfully for pulmonary tuberculosis with antituberculosis medication, and follow-up chest radiographs showed no active lung lesions. A chest radiograph, taken 3 months before admission as a screening for chest abnormalities, showed infiltrative lesions in both lower lung fields and focal consolidation in the right lower lobe but no specific change in her condition. Chest radiographs just before admission showed a slight aggravation of multiple patchy opacities. On admission, she presented slight sputum without other respiratory symptoms such as dyspnea or chest pain, and a review of systems was unremarkable. Vital signs were normal and there were no abnormal findings in the chest. A chest computed tomography (CT) scan revealed ill-defined nodular opacity and consolidation in both lungs (Fig. 1). Nodular lesions were scattered in both lung parenchymas and some were accompanied by ground glass opacities. A CT-guided needle aspiration biopsy specimen was non-diagnostic and, therefore, a subsequent surgical wedge resection via a thoracotomy was performed. The biopsy samples showed two relatively poorly demarcated round grayish white colored masses measuring 1.2 and 3 cm in diameter, respectively. A microscopic examination demonstrated diffuse infiltration of plasma cells (Fig. 2A), which were positive for lambda chain immunohistochemical staining (Fig. 2B). Serum protein and albumin levels were 8.2 g/dL and 3.4 g/dL, respectively. An electrophoretic analysis of serum proteins showed decreased albumin and an increased gamma globulin region without the M component. Serum immunoelectrophoresis detected no abnormal findings. Urine protein electrophoresis and immunoelectrophoresis were normal. An examination of serum immunoglobulins showed the following: IgG, 2,280 mg/dL; IgM, 1,540 mg/dL; IgA, 312 mg/dL; and IgD, 11 mg/dL. A peripheral blood white cell count was 3,800/mm3, and hemoglobin was 9.5 g/dL. A morphological analysis of the peripheral blood smear showed a slight microcytic and hypochromic pattern. A bone marrow examination revealed a normocellular pattern with about 50% cellularity and no increase in the plasma cell proportion. No hypercalcemia or increase in serum creatinine was noted. Chemotherapy with melphalan and prednisolone was initiated, because multiple plasmacytoma nodules were scattered in both lungs. Chest radiographs and CT scans taken after 4 months of pharmacological treatment showed near complete resolution of previously observed ill-defined nodular lesions and ground glass opacities. Figure 1 Chest computed tomography (CT) scan on admission showing ill defined nodular opacities and consolidations in both lungs. Figure 2 Histology of lung nodule showing diffuse infiltration of plasma cells (A, HE B, immunohistochemical stain for lambda chain, × 200). Primary plasmacotyma in the lung is a very rare form of extramedullary plasmacytoma. Clinical manifestations and courses are not well defined because of the small number of reported cases. A review article of 19 cases reported that about half of cases are asymptomatic, whereas the others developed cough, dyspnea, chest pain, and fever, mostly due to the mass effect [2]. The age of incidence was relatively old, and most cases developed in subjects > 40 years old. A slight male preference of incidence was noted with a ratio of 1.4:1. Contrary to previous cases, our patient was female and 24 years old at the time of diagnosis. The diagnosis of primary pulmonary plasmacotyma is based on the histological confirmation of plasma cell infiltration in lung lesions. Additionally, it requires normal bone marrow, normal skeletal survey, no related organ or tissue impairment, and no M protein in serum and/or urine. Thus, the current case fulfilled the diagnostic criteria. Typical lung lesions in previous primary pulmonary plasmacotyma cases were solitary lung nodules or masses, and they occurred in the hilar or parenchymal areas with slight preference to the lower lobes [2]. These tumors were round or ovoid shape, with sizes of 1.5-6 cm. They appeared as homogeneous nodules or masses with smooth and well delineated margins. The most common form of primary pulmonary plasmacotyma is a solitary tumor but different radiographic presentations have been reported. Horiuchi et al. [3] reported a case in a 45-year-old Japanese woman with bilateral reticulonodular infiltration in the lower lobes accompanied by fever, dyspnea, and hypoxemia. In a case report by Lazarevic et al. [4], bilateral reticulonodular opacities in both lungs were noted in an elderly male, who developed malaise, weight loss, and dry cough without fever or dyspnea. In addition to diffuse lung infiltrates in both cases, two separate plasmacytoma masses involving bilateral lungs were reported [5]. In the current case, primary pulmonary plasmacotyma presented as multiple lung nodular opacities in both lungs, which were detected by routine follow-up chest radiographs. These lesions increased in size over time without causing definite symptoms except for slight sputum. The present case is the first report of primary pulmonary plasmacotyma presenting as multiple lung nodules in both lungs. These findings suggest primary pulmonary plasmacotyma should be considered in the differential diagnosis of multiple lung nodules. While most cases of solitary pulmonary plasmacytoma are treated with surgical resection and/or irradiation [2], the previous two cases of diffuse pulmonary infiltration underwent combination chemotherapy including melphalan and prednisolone [3,4]. The clinical responses were relatively good, although the long-term response to chemotherapy remains to be evaluated. Similar to cases of diffuse lung infiltration, the patient in this study was also treated with melphalan and prednisolone, and near complete radiological resolution was observed after six cycles of treatment.

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 patients 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. Graphical Abstract