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The aim of this study was to evaluate the prevalence, risk factors, and survival of lung cancer in patients with idiopathic pulmonary fibrosis (IPF).IPF with lung cancer from tertiary hospitals consisted of 1685 patients who had been diagnosed between 2003 and 2007. We reviewed their medical records retrospectively to evaluate the prevalence, risk factors and prognosis of lung cancer in IPF patients.Among all patients with IPF, 114 cases (6.8%) had lung cancer with IPF. The incidence of lung cancer in patients with IPF was 1.03 persons per 100 person-year (25 patients/2408 years). Most cases of lung cancer (73/114, 68.9%) were located in IPF-associated areas; the lung cancer typically developed in peripheral and lower lobe areas. The study revealed that forced vital capacity (% predicted) at the initial diagnosis and development of lung cancer were independent prognostic factors in patients with IPF.Lung cancer in patients with IPF was significantly related with the IPF prognosis. An active evaluation should be performed in patients with IPF to detect lung cancer early.

BACKGROUND: Combined pulmonary fibrosis and emphysema (CPFE) have different pulmonary function tests (PFTs) and outcomes than idiopathic pulmonary fibrosis (IPF). The intention of this study was to identify unknown differences between CPFE and IPF by a retrospective comparison of clinical data including baseline and annual changes in pulmonary function, comorbidities, laboratory findings, clinical characteristics and cause of hospitalization. METHODS: This study retrospectively enrolled patients with CPFE and IPF who had undergone PFTs once or several times per year during a follow-up period of three years. Baseline clinical characteristics and the annual changes in the pulmonary function during the follow-up period were compared between 26 with CPFE and 42 patients with IPF. RESULTS: The baseline ratio of forced expiratory volume in one second to forced vital capacity (FEV1/FVC%) in patients with CPFE was lower than that in patients with IPF (78.6±1.7 vs. 82.9±1.1, p=0.041). The annual decrease in FEV1/FVC in the CPFE was significantly higher than in the IPF. The annual decreases in diffusion capacity of carbon monoxide and FVC showed no significant differences between the two groups. The symptom durations of cough and sputum were in the CPFE significantly lower than in the IPF. The serum erythrocyte sedimentation rate level at the acute stage was significantly higher than in the IPF. There were no significant differences in the hospitalization rate and pneumonia was the most common cause of hospitalization in both study groups. CONCLUSION: The annual decrease of FEV1/FVC was in patients with CPFE significantly higher than in the patients with IPF.

Severe adenovirus pneumonia that causes acute respiratory failure can occur in infants, children, and immunocompromised patients. However, severe adenovirus pneumonia is rare in adults with a normal immune system. Adenovirus pneumonia may progress to acute respiratory failure in a few hours or a few days, and its clinical course cannot be predicted. In addition, the mortality rate is very high (range, 50% to 66%). However, the optimal treatment of adenovirus pneumonia has not been established. Herein, we report the successful treatment of acute respiratory failure due to adenovirus pneumonia with extracorporeal membrane oxygenation.

Purpose Genexol-PM is a Cremorphor EL (CrEL)-free polymeric micelle formulation of paclitaxel that allows higher-dose administration with less hypersensitivity. This study was designed to evaluate the efficacy and safety of Genexol-PM and gemcitabine combination in advanced non-small cell lung cancer patients as a first-line treatment. Patients and methods This is a prospective, single-arm, single-center phase II study. Patients with advanced NSCLC received Genexol-PM at 230 mg/m2 on day 1 and gemcitabine 1,000 mg/m2 on day 1 and day 8 of a 3-week cycle. Six cycles of chemotherapy were planned unless there was disease progression. The primary endpoint was overall response rate. Results Forty-three patients received the study drugs with a median of 4 cycles per patient (range 1–6). The overall response rate was 46.5 %. The median progression-free survival was 4.0 months (95 % CI 2.0–6.0 months), and median overall survival was 14.8 months (95 % CI 9.1–20.5 months). The most common toxicities were anemia (n = 29, 67 %), asthenia (n = 17, 40 %), myalgia (n = 16, 37 %), peripheral neuropathy (n = 15, 35 %), and diarrhea (n = 12, 30 %). The most common grade 3/4 adverse events were neutropenia (n = 7, 16 %) and pneumonia (n = 5, 12 %). Two patients died of pneumonia and dyspnea. Conclusions CrEL-free paclitaxel in combination with gemcitabine demonstrated favorable antitumor activity with little emetogenicities in non-small cell lung cancer patients. However, frequent grade 3/4 toxicities were observed, and safety should be evaluated thoroughly in future studies.

Diagnostic tests for respiratory viral infections use traditionally either nasopharyngeal washes or swabs. Sputum is representative of the lower respiratory tract but is used rarely for viral testing. The aim of this study was to compare the detection rates of respiratory viruses from nasopharyngeal swabs and sputum using a multiplex real-time reverse transcription-polymerase chain reaction (RT-PCR). Adults who were admitted or presented to the clinics of Gil Medical Center with acute respiratory symptoms were recruited from 1 November 2012 to 31 March 2013. Paired specimens of nasopharyngeal swabs and sputum were obtained from 154 subjects, and RNA was extracted and tested for 16 different respiratory viruses using the Anyplex II RV16 Detection kit (Seegene, Seoul, Korea). The positive rate was 53% (81/154) for nasopharyngeal swabs and 68% (105/154) for sputum (P

Background: Idiopathic interstitial pneumonia is characterized by fibroblast proliferation and extracellular matrix (ECM) accumulation. Matrix metalloproteases (MMPs) and tissue inhibitors of metalloproteases (TIMPs) have been shown to regulate remodeling of the ECM, which indicates that they are important factors in the process of lung fibrosis. Therefore, we evaluated the expression of MMPs and TIMPs in tissues obtained from patients with idiopathic interstitial pneumonia and control tissues. Methods: Thirty-seven patients who were diagnosed with IIP (22: IPF, 13: NSIP, 2: COP) and 5 controls were enrolled in this study. The MMP-2 and -9 activity in lung tissue obtained from these patients was analyzed using gelatin zymography and the levels of TIMP-1 and -2 were measured by western blotting. We also evaluated the expression of MMP-2 and -9, as well as that of TIMP-1 and -2 in lung tissue using immunohistochemistry. Results: The levels of MMP-2 and MMP-9 were significantly increased in patients with IPF compared to those with NSIP and COP. The activities of TIMP-1 and -2 were also higher in patients with IPF than NSIP/COP patients and control subjects. There were no significant differences observed in the activities of MMPs and TIMPs obtained from patients with NSIP/COP and control subjects. The immunohistochemical analysis showed that TIMP-2 and MMP-2 were strongly stained at the fibroblasts of the fibroblastic foci in patients with IPF. Conclusions: These results suggest that over-expression of gelatinases and TIMPs in patients with IPF are important factors in the irreversible fibrosis that is associated with lung parenchyma.

Exacerbation of COPD is a major risk factor for bad prognosis of COPD. A few plasma proteins have been discovered to associate with hospital admission due to exacerbation up to date. We tried to find new plasma biomarkers to predict the exacerbation of COPD.We examined the plasma of normal control (n = 8) and COPD stable (n = 8) and exacerbation (n = 8) using 2-Dimentional Electrophoresis. The differentially expressed protein spots were identified by MALDI-TOF. ELISA were performed for quantitative measurement of RARα in plasma from normal control (n = 37) and COPD (n = 35).17 proteins were differentially expressed in plasma between stable and exacerbation state in the subjects with COPD. Identification using MALDI-TOF showed that retinoic acid receptor alpha, ninein, isoform CRA_a, alpha-1 antitrypsin, fibrinogen gamma, tyrosyl-DNA phosphodiesterase 2, and T cell receptor delta chain were increased in exacerbation of COPD, while fibrin beta, Crystal Structure Of An Autoimmune Complex Between A Human Igm RF* And Igg1 Fc, transferrin, serpin peptidase inhibitor member 6, complement factor B preproprotein, Chain B, Crig Bound To C3c, and WD repeat-containing protein 1 isoform 1 were decreased. Quantitative measurement showed that RARα plasma levels significantly increased in exacerbation state compared to stable state of COPD (n = 14). In the plasma of stable state, the COPD subjects (n = 14) having more than 0.4 time/yr of admission had very high levels of RAR alpha protein and those (n = 11) having less than 0.4 times/yr of admission had the intermediate levels compared to those having no exacerbation (n = 10). ROC analysis of RAR alpha levels to frequency of admission showed an area under the curve of 0.844. A cut-off of 0.154 ng/ml of RAR alpha predicted hospital admission with a sensitivity of 71.4% and a specificity of 92.8%.The proteomic analysis of plasma indicates that alteration of several proteins may be associated with admission of COPD. Among them, plasma RAR alpha level may predict hospital admission with a sensitivity of 71.4% and a specificity of 92.8%.

This study suggests a method of detecting the still object, which becomes a cause of danger within the crossroad. The Inverse Perspective Transform was performed in order to make the object size consistent by being inputted the real-time image from CCTV that is installed within the crossroad. It established the detection area in the image with the perspective transform and generated the adaptative background image with the use of the moving information on object. The detection of the stop object was detected the candidate region of the stop object by using the background-image differential method. To grasp the appearance of truth on the detected candidate region, a method is proposed that uses the gradient information on image and EHD(Edge Histogram Descriptor). To examine performance of the suggested algorithm, it experimented by storing the images in the commuting time and the daytime through DVR, which is installed on the cross street. As a result of experiment, it could efficiently detect the stop vehicle within the detection region inside the crossroad. The processing speed is shown in 13~18 frame per second according to the area of the detection region, thereby being judged to likely have no problem about the real-time processing.

Cigarette smoke, a major causative agent of chronic obstructive pulmonary disease (COPD), induces lung cell death by incompletely understood mechanisms. The induction of apoptosis in lung structural cells by cigarette smoke may contribute to the pathogenesis of emphysema. Phosphodiesterase-4 (PDE4) inhibitors are anti-inflammatory agents used in COPD therapy that can prevent cigarette smoke-induced emphysema in mice. We investigated the effect of rolipram, a first generation PDE4 inhibitor, on the regulation of cigarette smoke-induced apoptosis. Human lung fibroblast (MRC-5) cells were exposed to cigarette smoke extract (CSE). Cell viability and apoptosis were determined by MTT assay and Annexin-V staining, respectively. Caspase activation was determined by Western immunoblot analysis. Rolipram protected against cell death and increased viability in MRC-5 fibroblasts after CSE exposure. Furthermore, rolipram protected against apoptosis, decreased caspase-3 and -8 cleavage in MRC-5 cells exposed to CSE. Pre-treatment with rolipram enhanced Akt phosphorylation and associated cytoprotection in CSE-treated cells, which could be reversed by the PI3K inhibitor LY294002 partly. In conclusion, rolipram protects against apoptosis of MRC-5 cells through inhibition of caspase-3 and caspase-8. Rolipram may represent an effective therapeutic agent to reduce cigarette smoke-induced apoptosis of lung fibroblasts.

Pneumonia is a important cause of hospitalized excerbation COPD patients. Also, virus or influenza are frequently complicated by bacterial pneumonia. We examined the risk factors and clinical characteristics contributing to bacterial co-infection with virus or influenza among the hospitalized pneumonia with COPD patients. Pneumonia in COPD patients were admitted to gachon university Gil Medical Center from 1 January 2013 to 30 August 2014. They were divided into 2 groups based upon the presence of virus or influenza. One hudred fifty four patients identified virus or influenza(Virus group). Three hundred six patients not identified virus or influenza(control group). Retrospectively, we analysed the clinical characteristics, the results of blood examination and lung function tests from medical records of both groups. Mean age of each group was 74.4±9.7 years in virus group and 72.0 ± 9.7 years in control group. Age and female ratio was significantly higher in virus group. Pack year, smoking history and tuberculosis history were significantly lower in virus group. Virus group have significantly higher level of Blood pressure, serum albumin, P, hemoglobin, stable FVC(%) and FEV 1 (%). Virus group have significantly lower level of FVC(L), FEV 1 (L), FEV 1 (%) and lymphocyte when they hospitalized. The two groups have no significant difference in other clinical features: hypertenstion, diabetes mellitus, ischemic heart disease, survival, hosptital day, body mass index, weight. Age, female, smoking and tuberculosis history may be associated with virus or influenza infection among the hospitalized pneumonia with COPD patients.

Background: Asian dust storms can be transported across eastern Asia. In vitro, Asian dust particle-induced inflammation and enhancement of the allergic reaction have been observed. However, the fibrotic effects of Asian dust particles are not clear. Production of transforming growth factor β1 (TGF-β1) and fibronectin were investigated in the bronchial epithelial cells after exposure to Asian dust particulate matter (AD-PM10). Methods: During Asian dust storm periods, air samples were collected. The bronchial epithelial cells were exposed to AD-PM10 with and without the antioxidant, N-acetyl-L-cysteine (NAC). Then TGF-β1 and fibronectin were detected by Western blotting. The reactive oxygen species (ROS) was detected by the measurement of dicholorodihydrofluorescin (DCF), using a FACScan, and visualized by a confocal microscopy. Results: The expression of TGF-β1, fibronectin and ROS was high after being exposed to AD-PM10, compared to the control. NAC attenuated both TGF-β1 and fibronectin expression in the AD-PM10-exposed the bronchial epithelial cells. Conclusion: AD-PM10 may have fibrotic potential in the bronchial epithelial cells and the possible mechanism is AD-PM10-induced intracellular ROS.

Background: The aim of this study was to evaluate the prevalence, risk factors, and survival of lung cancer in patients with idiopathic pulmonary fibrosis (IPF). Methods: IPF with lung cancer from tertiary hospitals consisted of 1685 patients who had been diagnosed between 2003 and 2007. We reviewed their medical records retrospectively to evaluate the prevalence, risk factors and prognosis of lung cancer in IPF patients. Results: Among all patients with IPF, 114 cases (6.8%) had lung cancer with IPF. The incidence of lung cancer in patients with IPF was 1.03 persons per 100 person-year (25 patients/2408 years). Most cases of lung cancer (73/114, 68.9%) were located in IPF-associated areas; the lung cancer typically developed in peripheral and lower lobe areas. The study revealed that forced vital capacity (% predicted) at the initial diagnosis and development of lung cancer were independent prognostic factors in patients with IPF. Conclusions: Lung cancer in patients with IPF was significantly related with the IPF prognosis. An active evaluation should be performed in patients with IPF to detect lung cancer early.

In this paper, we suggest a system of detecting a vehicle with lane violation, which can detect the vehicle with lane violation, by using the feature point tracking. The whole algorism in the suggested system of detecting a vehicle with lane violation is composed of three stages such as feature extraction, register and tracking in feature for the tracking-targeted vehicle, and detecting a vehicle with lane violation. The feature is extracted from the morphological gradient image, which results in constructing robust detection system against shadows, weather conditions, head lights and illumination conditions without distinction day and night. The system shows excellent performance for the data captured at day time, night time, and rainy night time as much as 99.49% for positive recognition ratio and 0.51% for error ratio. Also the system is so fast as much as 91.34 frames per second in average that it may be possible for real-time processing.

There are sporadic reports in the literature in which radiologic liver and lung lesions found incidentally during follow-up metastatic surveillance were shown to be caused by toxocariasis.The objective of the work discussed in this report was to identify common clinical and histopathological features of toxocariasis resembling metastatic nodules in five patients with gastrointestinal cancer.We retrospectively analyzed clinical features of five gastrointestinal cancer patients with liver or lung nodules mimicking metastasis. Serologic tests for parasitic infestations and pathologic examinations were performed.All five patients were males and three patients had gastric cancer and two had colorectal cancer. All the cases of toxocariasis were confirmed serologically. On follow-up imaging, the lesions improved or resolved, suggestive of the phenomenon of visceral larva migrans. In two patients, liver biopsy was performed and showed eosinophilic abscess.Serologic tests and liver or lung biopsy should be performed aggressively to exclude toxocariasis when patients with underlying gastrointestinal cancer present with hepatic or pulmonary nodules associated with eosinophilia, particularly if the patients have a clinical history of raw animal liver ingestion. Curative surgical intervention should not be excluded just because of multiple nodules in the liver or the lungs.

The purpose of this study is to produce a better way to detect crossroad accidents, which involves an efficient method to produce background images in consideration of object movement and preserve/demonstrate the candidate accident region. One of the prior studies proposed an employment of traffic signal interval within crossroad to detect accidents on crossroad, but it may cause a failure to detect unwanted accidents if any object is covered on an accident site. This study adopted inverse perspective mapping to control the scale of object, and proposed different ways such as producing robust background images enough to resist surrounding noise, generating candidate accident regions through information on object movement, and by using edge information to preserve and delete the candidate accident region. In order to measure the performance of proposed algorithm, a variety of traffic images were saved and used for experiment (e.g. recorded images on rush hours via DVR installed on crossroad, different accident images recorded in day and night rainy days, and recorded images including surrounding noise of lighting and shades). As a result, it was found that there were all 20 experiment cases of accident detected and actual effective rate of accident detection amounted to 76.9% on average. In addition, the image processing rate ranged from 10~14 frame/sec depending on the area of detection region. Thus, it is concluded that there will be no problem in real-time image processing.

To determine the efficacy and safety of belotecan in combination with cisplatin as first-line chemotherapy for extensive disease of small cell lung cancer (ED SCLC).Patients with chemotherapy-naïve ED SCLC were eligible if the following criteria were met: age ≥18 years; a measurable lesion; Eastern Cooperative Oncology Group Performance Status (PS) 0-2; and adequate organ function. Each cycle consisted of belotecan (0.5 mg/m(2)/day) on days 1-4 and cisplatin (60 mg/m(2)) intravenously on day 1. The cycle was repeated every 3 weeks until the completion of the 6th cycle, disease progression, or intolerable toxicity.Thirty-five patients (median age, 68 years) were enrolled: 32 males (91.4%); and PS = 0 (n = 3), PS = 1 (n = 18), and PS = 2 (n = 14). The median number of cycles delivered was 5 (range, 1-6). The relative dose intensity was 70.1% for belotecan and 83.0% for cisplatin. Of 30 evaluable patients, objective response rate was 71.4% (95% confidence interval [CI], 55.7-87.2) by the intent-to-treat principle. The median duration of follow-up was 14.3 months. The median progression-free survival was 5.7 months (95% CI, 3.9-7.5) and the median overall survival was 10.2 months (95% CI, 9.3-11.1). The frequently reported grade 3 or 4 toxicities included neutropenia in 24 patients (68.6%), thrombocytopenia in 10 (28.6%), and anemia in 7 (20.0%). There was no grade 3 or 4 non-hematologic toxicity except three patients (8.6%) with fatigue.Belotecan and cisplatin combination therapy showed significant efficacy in ED SCLC with improved non-hematologic toxicities.

Paragonimiasis is an infectious disease caused by trematodes of the genus Paragonimus. This trematode can be treated successfully with praziquantel in more than 90% of the cases. Although praziquantel is generally well tolerated, anaphylactic reactions to this drug have been reported in a few cases. We report here a 46-year-old Korean female with paragonimiasis, presumed to be due to Paragonimus westermani, who displayed an allergic reaction to praziquantel and resistance to triclabendazole treatment. The patient was successfully treated with praziquantel following a rapid desensitization procedure. Desensitization to praziquantel could be considered when no alternative drugs are available.

Inhaled particulate matter (PM) might influence many adverse health effects in human body, including increased exacerbations of pulmonary and cardiovascular diseases. In this study, we examined the associations between PM and pulmonary adverse effects. Two types of particles, Asian dust (AD) and titanium dioxide (TiO(2)), were administered intratracheally to C57BL/6 mice. The mice were exposed to saline and saline suspensions of 20 mg/kg of AD, TiO(2) particles twice a week for 12 weeks. Following exposure with these particles, the lungs were analyzed histopathologically by hematoxylin and eosin (H&E) and Masson's trichrome (MT) staining. Oxidative injuries were determined by immunohistochemistry (IHC) for 8-oxoguanine in the lungs and Comet assays in peripheral blood mononuclear cells (PBMCs) of C57BL/6 mice. Mice exposed to AD and TiO(2) showed significant inflammatory changes and oxidative damages in the lungs as compared with the control group. DNA damage in PBMCs was also increased significantly in AD and TiO(2)-exposed mice. However, lung fibrosis was minimal and there was no significant difference between PM exposed and control mice. Exposure to AD and TiO(2) particles-induced similar inflammatory damages in the lungs and elicited oxidative DNA damage in the PBMCs.

This paper suggests the background image and the algorism of detecting an accident at crossroads by using the sequence of traffic light at crossroads, which is installed within the crossroads, in order to detect an accident within crossroads. A method of using the existing image contains a problem that the accident-detection ratio gets lower in a situation that noise occurs loudly given using new accident model, the confused situation, or sound source. This study used the accident detection by developing a filter of using the property of histogram in the sequence of traffic light at crossroads and the background image, in order to reduce misjudgment of an accident caused by external shadow, vehicle stoppage, vehicle headlight, and externally environmental influence. As a result of experimenting by acquiring 15 actual accident images in order to examine the performance of the suggested algorism, the accident was detected in all the 15 videos. Even as for a new accident model, the accident within crossroads could be detected.

Docetaxel and gemcitabine combination chemotherapy has been reported to be active against non-small cell lung cancer (NSCLC) and myelosuppression is the most common dose-limiting toxicity. This prospective phase II study was designed to test the hypothesis that better tolerance and increased dose intensity might be achieved if patients are treated with weekly administration schedule. Thirty-five patients with stage IIIB/IV NSCLC and a performance status 0-2 received first-line chemotherapy with docetaxel 35mg/m2 and gemcitabine 600mg/m2 on days 1, 8 and 15. Treatment was repeated every 4 weeks, for up to 4 cycles. In total, 85 chemotherapy cycles were given (median, 2; range, 1-4). Other than the completion of all 4 planned cycles (n=6), the main reasons for treatment discontinuation were toxicity (n=15) and progressive disease (n=14). The most frequently encountered toxic effects were anemia (52% of patients), nausea and vomiting (60%), fatigue (71%) and anorexia (57%). One patient died of bilateral pneumonitis, which developed shortly after the administration of second cycle. Disease control (objective response and stable disease) in the intent-to-treat (ITT) population was achieved in 60% of patients and the overall response rate was 29% (95% CI, 14-44%). With a median follow-up duration of 13 months, the median progression-free survival and overall survival were 2.8 (95% CI, 0.7-4.8) months and 10.6 (95% CI, 7.0-14.3) months, respectively. In conclusion, weekly schedule of docetaxel and gemcitabine has modest activity with acceptable toxicity profile in advanced NSCLC, but as high frequency of early discontinuation occurred does not merit further study with the present regimen.

Background/Aims : Legal pulmonary disability in Korea is decided for chronic respiratory patients who have been diagnosed for a year or more, and the patients haven't gotten better after more than 2 months of sufficient treatment and they have shown no change in their pulmonary function within the two years after their original diagnosis. The purpose of this study was to investigate the clinical features and progress of those patients who have been diagnosed as having pulmonary disability. Methods : We reviewed retrospectively the medical records of the patients who had been decided as having pulmonary disability at a tertiary university hospital from 2003 to 2004, and these patients could be followed up for more than 6 months. Results : The number of enrolled patients was 118 (male : female = 95 : 23) and their mean age was 60±10 years. Their major underlying diseases were chronic obstructive pulmonary disease (n=45, 38%), tuberculous destroyed lung (n=29, 25%), and bronchial asthma (n=27, 23%). Of them, the num ber of patients with a class 1 pulmonary disability were 24 (20%), there were 28 class 2 patients (24%) and 66 class 3 patients (56%). The FEV 1 could be followed up for 42 of these patients, of whom 20 patients showed no change or a decrease in their FEV1 but 22 showed an increased FEV 1. Especially, some of them showed the increase of their FEV1 of 10% or more, and the 50% of them were patients with bronchial asthma. During the follow-up perio d, 6 patients died; 3 were class 1, 1 was class 2 and 2 were class 3. Five of these patients died of their underlying pulmonary diseases or combined pneumonia. Conclusions : It is necessary to decide the pulmonary disability after sufficient treatment and to perform periodic follow-up testing even after the disability decision for confirming that the disability is stable and also to adjust the class of the disability. Further studies are needed to observe the clinical progress and prognosis of patients with pulmonary disability by performing long-term follow-up for a large number of patients.

Although the efficacy of topotecan as a second-line chemotherapy for small-cell lung cancer (SCLC) has been consistently demonstrated in phase II/III clinical trials, the choice of irinotecan as the first-line therapy prevented the use of evidence-based option. This pilot study was conducted to determine the activity and safety of topotecan in SCLC patients refractory to first-line therapy with irinotecan and platinum.Patients with primary refractory (no response, or progression during oror =90 days after last chemotherapy) SCLC after treatment with a combination of irinotecan and platinum, received topotecan 1.5 mg/m(2) per day as a 30-min infusion daily for 5 days, every 3 weeks.Of 17 eligible patients, ten patients were previously treated with irinotecan plus cisplatin and 7 were treated with irinotecan plus carboplatin. The median age was 68 years (range 44-75) and the median interval from the last chemotherapy was 50 days (range 21-89). A total of 33 chemotherapy cycles were delivered (median 2; range 1-5). All 17 patients discontinued therapy due to disease progression and 5 patients had progressive disease before second cycle. Toxic effects were mainly hematologic (gradeor =3 neutropenia in 65% of patients) and fatigue (grade 3 in 47%). In an intent-to-treat analysis, two (12%) patients had a confirmed partial response and two patients achieved stable disease. Median progression-free and overall survivals were 1.7 months (95% CI, 1.5-1.9) and 3.4 months (95% CI, 1.7-5.0), respectively.Topotecan monotherapy for patients with irinotecan-refractory SCLC does not appear highly active but the observation of some responses merits further study in patients with chemosensitive disease.

Objective: Nail toxicity is one of the most frequent non-hematologic toxicities of docetaxel and often deteriorates patients’ quality of life, leading to treatment discontinuation. To define the incidence of nail change as well as its association with specific risk factors, we prospectively investigated data of 84 consecutive patients with advanced non-small cell lung cancer who received first-line docetaxel/cisplatin combination chemotherapy. Methods: Chemotherapy-nao¨ve patients were treated with docetaxel, either 3-weekly or weekly, in combination with cisplatin. All patients received adequate premedications including corticosteroids, antiemetics and intravenous hydration. Toxicity was evaluated using National Cancer Institute (NCI) CTCAE version 3. Results: Twenty-two patients (26%) developed nail changes, including nine (11%) with grade 3. Nine patients who developed grade 3 nail changes (seven of whom received weekly docetaxel) were not able to complete planned chemotherapy despite topical and/or oral antibiotic treatment. Most occurrences of nail changes were diagnosed in patients who were treated with weekly schedule (P ¼ 0.02). The number of chemotherapy cycles and cumulative docetaxel doses were strongly associated with the development of nail changes. The cumulative hazard of developing nail changes increased above 10% after 2.8 months up to 40% at 6 months. A multivariate analysis of factors associated with the development of nail changes identified the following to have independent adverse significance: weekly docetaxel administration (odds ratio, 0.084; 95% CI, 0.014 –0.510; P ¼ 0.01) and the number of chemotherapy cycles given (odds ratio, 0.232; 95% CI, 0.067–0.805; P ¼ 0.02). Conclusion: Nail changes occur with more frequent and prolonged use of docetaxel.

Summary The purpose of this study was to assess the role of bronchoalveolar lavage (BAL) in differentiating usual interstitial peumonia (UIP) from non-specific interstitial pneumonia (NSIP) and in predicting the prognosis in fibrotic idiopathic interstitial pneumonia (IIP). A retrospective review of 122 patients (age 58±8 years, 70 male) with UIP ( n = 87 ) and NSIP ( n = 35 ) was carried out. Prior to surgical lung biopsy, all of them underwent BAL and high-resolution-computed tomography (HRCT) of the chest. Neutrophil count in BAL fluid was higher in UIP (7.0%) than NSIP (3.0%) ( P = 0.027 ). In contrast, BAL lymphocyte count was significantly higher in NSIP (29.0%) than UIP (5.5%) ( P 0.0001 ). In 62 patients whose HRCT findings were atypical for UIP, BAL lymphocytosis was more frequently observed in NSIP (20/33) than UIP (4/29) ( P 0.001 ) and the absence of BAL lymphocytosis suggested a diagnosis of UIP rather than NSIP (odds ratio 12.7, P 0.001 ). Pathologic diagnosis of NSIP was the only independent factor predicting a longer survival of our patients (median follow-up 21 months) (hazard ratio (HR) 0.035, P = 0.005 ). When NSIP was not included in the survival analysis, higher BAL lymphocyte count was the only independent predictor of a longer survival (HR 0.909, P = 0.029 ). BAL is an useful non-invasive tool in fibrotic IIP, not only for excluding a variety of specific non-IIP diseases but also for narrowing the differential diagnosis and predicting the prognosis in the absence of the histopathologic diagnosis.

Background Recent studies show that mitophagy, the autophagy-dependent turnover of mitochondria, mediates pulmonary epithelial cell death in response to cigarette smoke extract (CSE) exposure and contributes to the development of emphysema in vivo during chronic cigarette smoke (CS) exposure, although the underlying mechanisms remain unclear. Methods In this study, we investigated the role of mitophagy in the regulation of CSE-exposed lung bronchial epithelial cell (Beas-2B) death. We also investigated the role of a phosphodiesterase 4 inhibitor, roflumilast, in CSE-induced mitophagy-dependent cell death. Results Our results demonstrated that CSE induces mitophagy in Beas-2B cells through mitochondrial dysfunction and increased the expression levels of the mitophagy regulator protein, PTEN-induced putative kinase-1 (PINK1), and the mitochondrial fission protein, dynamin-1-like protein (DRP1). CSE-induced epithelial cell death was significantly increased in Beas-2B cells exposed to CSE but was decreased by small interfering RNA-dependent knockdown of DRP1. Treatment with roflumilast in Beas-2B cells inhibited CSE-induced mitochondrial dysfunction and mitophagy by inhibiting the expression of phospho-DRP1 and -PINK1. Roflumilast protected against cell death and increased cell viability, as determined by the lactate dehydrogenase release test and the MTT assay, respectively, in Beas-2B cells exposed to CSE. Conclusion These findings suggest that roflumilast plays a protective role in CS-induced mitophagy-dependent cell death.

Introduction Automatic fire suppression systems use hydrofluorocarbons (HF) to extinguish fires chemically. At high temperatures, HF can release hydrofluoric acid (HFA), a toxic, potentially lethal gas. Case report A 52-year-old male visited our Pulmonary Division with dyspnea of 8-months duration. He had been working at a facility that manufactured fire extinguishers. Bronchoscopy was performed and a transbronchial lung biopsy was taken from the right lower lobe. After the patient was diagnosed with pulmonary alveolar proteinosis (PAP), whole-lung lavage was performed. In this case, fire extinguisher gas induced pulmonary alveolar proteinosis. This material should be used with care and investigated further. Discussion HFA is corrosive and penetrates organic materials, including body tissues. Depending on the mode of exposure, skin ulceration, pulmonary injury, or even systemic shock can result. This report describes PAP that developed after chronic, repeated exposure to fire extinguisher spray. Hydrofluoric acid can induce pulmonary disorders such as PAP.

Purpose This study aimed to evaluate the efficacy and safety of pemetrexed versus gefitinib in patients with advanced non-small cell lung cancer (NSCLC) previously treated with chemotherapy. Materials and methods Patients with advanced (stage IIIB or IV) or recurrent NSCLC were randomly assigned to receive either 500 mg/m² of pemetrexed intravenously every 3 weeks or gefitinib 250 mg/day orally. The primary end point was progression-free survival (PFS) at 6 months. Results A total of 95 patients were enrolled (47 for pemetrexed and 48 for gefitinib). Most patients were male (72%) and current/ex-smokers (69%), and 80% had non-squamous cell carcinoma. The epidermal growth factor receptor (EGFR) mutation status was determined in 38 patients (40%); one patient per each arm was positive for EGFR mutation. The 6-month PFS rates were 22% and 15% for pemetrexed and gefitinib, respectively (p=0.35). Both arms showed an identical median PFS of 2.0 months and a median overall survival (OS) of 8.5 months. In EGFR wild-type patients, higher response rate (RR) and longer PFS as well as OS were achieved via pemetrexed compared with gefitinib, although there were no significant differences (RR: 39% vs. 9%, p=0.07; median PFS: 6.6 months vs. 3.1 months, p=0.45; median OS: 29.6 months vs. 12.9 months, p=0.62). Toxicities were mild in both treatment arms. Frequently reported toxicities were anemia and fatigue for pemetrexed, and skin rash and anorexia for gefitinib. Conclusion Both pemetrexed and gefitinib had similar efficacy with good tolerability as second-line treatment in unselected patients with advanced NSCLC. However, pemetrexed is considered more effective than gefitinib for EGFR wild-type patients.

Previous studies have investigated the relationship between occupational and environmental agents and idiopathic pulmonary fibrosis (IPF). However, there have been few studies regarding the prognosis of patients with IPF according to patient occupation.We investigated whether occupational dust exposure was associated with clinically decreased lung function and poor prognosis. The Korean Interstitial Lung Disease Research Group conducted a national survey to evaluate the clinical, physiologic, radiologic, and survival characteristics of patients with IPF. A total of 1,311 patients with IPF were stratified into five groups according to their occupation: (1) unemployed or homemakers (n = 628); (2) farmers, fishers, or ranchers (n = 230); (3) sales or service personnel (n = 131); (4) clerical or professional personnel (n = 151); and (5) specific dust-exposed workers (n = 171).The mean age of subjects at diagnosis, was 67.5 ± 9.7 years. Current smokers were 336 patients, 435 were exsmokers, and 456 were never smokers. Dust-exposed workers showed early onset of IPF (61.3 ± 8.6 years; P.001) and a longer duration of symptoms at diagnosis (17.0 ± 28.2 months; P = .004). Aging (P = .001; hazard ratio [HR], 1.034; 95% CI, 1.014-1.054), FVC % predicted at diagnosis (P = .004; HR, 0.984; 95% CI, 0.974-0.995), and dust-exposure occupation (P = .033; HR, 1.813; 95% CI, 1.049-3.133) were associated with mortality.These findings indicate that occupational dust may be an aggravating factor associated with a poor prognosis in IPF.

Advanced glycation end products (AGEs) are associated with the pathogenesis of various diseases. AGEs induce excess accumulation of extracellular matrix and expression of profibrotic cytokines. In addition, studies on receptor for advanced glycation end products (RAGE) have shown that the ligand-RAGE interaction activates several intracellular signaling cascades associated with several fibrotic diseases. We investigated the expression of AGEs and RAGE in samples from patients with idiopathic pulmonary fibrosis (IPF) and non-specific interstitial pneumonia (NSIP). Lung tissues and plasma samples from patients with IPF (n=10), NSIP (n=10), and control subjects (n=10) were obtained. Expression of AGEs and RAGE was determined by immunofluorescence assay of lung tissue. Circulating AGEs were measured by Western blot and enzyme-linked immunosorbent assay. Lungs with IPF showed strong expression for both AGEs and RAGE compared to that in NSIP and controls. However, no difference in AGE or RAGE expression was observed in lungs with NSIP compared to that in the controls. Levels of circulating AGEs also increased significantly in lungs of patients with IPF compared to those with NSIP and normal control. Increased AGE-RAGE interaction may play an important role in the pathogenesis of IPF.

Several recent clinical trials reported that intralymphatic immunotherapy (ILIT) for some allergens, such as cat dander and pollen, induce tolerance more rapidly than conventional subcutaneous or sublingual immunotherapy, have a comparable duration of effect after only 3 injections, and do not provoke serious local or systemic reactions. However, the efficacy and safety of ILIT are using Dermatophagoides farinae (Df), Dermatophagoides pteronyssinus (Dp), and dog, which are indoor allergens that are commonly found globally, need to be evaluated. Furthermore, use of multiple allergens in ILIT should be investigated. We assessed the clinical efficacy and adverse effects of ILIT using aqueous Df, Dp, dog, and cat allergens or mixtures thereof in patients with allergic rhinitis. A total of 11 subjects with AR sensitized to Df, Dp, cat, and/or dog allergens received 3 intralymphatic inguinal injections of sensitized allergen extract (HollisterStier, New Orleans, LA, USA). Clinical parameters were assessed before ILIT, and 4 months and 1 year after the first injection. Rhinitis symptoms were alleviated and quality of life was improved 4 months after ILIT (P=0.012 and P=0.007, respectively), and these improvements lasted for 1 year after ILIT (P=0.047 and P=0.009, respectively). However, we observed 2 cases of anaphylaxis, one case of a moderate-to-severe systemic hypersensitivity reaction and the other case of a severe local reaction at the injection site after ILIT. In conclusion, ILIT can rapidly improve allergy symptoms and quality of life, and this effect lasts for 1 year. In hypersensitized patients, however, ILIT can provoke severe systemic and/or local hypersensitivity reactions when performed using aqueous allergen extracts.

Background Neutrophilic airway inflammation is frequently observed in severe uncontrolled asthma (UA) and controlled asthma (CA). However, there is no sputum biomarker to differentiate the 2 conditions. Objective To identify biomarkers of severe uncontrolled asthma with neutrophilic airway inflammation. Methods Sputum with a neutrophil content larger than 70% was pooled from 5 patients with severe UA and from 10 patients with CA. Two-dimensional electrophoresis was adopted for differential display proteomics, and candidate proteins were identified using matrix-assisted laser adsorption/ionization–time of flight mass spectrometric analysis. S100 calcium binding protein A9 (S100A9) was identified by western blot and its level was measured in sputum from asthmatics with varying disease severity, patients with chronic obstructive lung disease, and normal controls using enzyme-linked immunosorbent assay. Results Fourteen protein spots exhibited differences in relative intensity between patients with severe UA and those with CA. Matrix-assisted laser adsorption/ionization–time of flight/time of flight of these spots showed an increase in human neutrophil peptide-2, S100A9, β-amylase, neutrophil gelatinase-associated lipocalin, 4-aminobutyrate transaminase, and cystatin SA in patients with UA compared with patients with CA. There was a decrease in the plunc precursor, complement C3 component, immunoglobulin heavy-chain variable region, glial fibrillary acidic protein isoform-1, IgM κIIIb SON, MLL-AF4 der(11) fusion protein, cytokeratin-8, and recombinant IgG4 heavy chain. S100A9 was detected at a higher level in western blots of neutrophilic sputum from patients with severe UA vs CA. S100A9 levels were significantly increased, as measured by enzyme-linked immunosorbent assay, in neutrophilic UA compared with CA, eosinophilic UA and CA, and chronic obstructive lung disease. Conclusion S100A9 in sputum may be a biomarker of neutrophilic inflammation in severe UA.

Background Interleukin-8 (IL-8) is a potent chemo-attractant cytokine responsible for neutrophil infiltration in lungs with idiopathic pulmonary fibrosis (IPF). The IL-8 protein and mRNA expression are increased in the lung with IPF. We evaluated the effect of single nucleotide polymorphisms (SNPs) of the IL-8 gene on the risk of IPF. Methods One promoter (rs4073T>A) and two intronic SNPs (rs2227307T>G and rs2227306C>T) of the IL-8 genes were genotyped in 237 subjects with IPF and 456 normal controls. Logistic regression analysis was applied to evaluate the association of these SNPs with IPF. IL-8 in BAL fluids was measured using a quantitative sandwich enzyme immunoassay, and promoter activity was assessed using the luciferase reporter assay. Results The minor allele frequencies of rs4073T>A and rs2227307T>G were significantly lower in the 162 subjects with surgical biopsy-proven IPF and 75 subjects with clinical IPF compared with normal controls in the recessive model (OR = 0.46 and 0.48, p = 0.006 and 0.007, respectively). The IL-8 protein concentration in BAL fluids significantly increased in 24 subjects with IPF compared with 14 controls (p = 0.009). Nine IPF subjects homozygous for the rs4073 T>A common allele exhibited higher levels of the IL-8 protein compared with six subjects homozygous for the minor allele (p = 0.024). The luciferase activity of the rs4073T>A common allele was significantly higher than that of the rs4073T>A minor allele (p = 0.002). Conclusion The common allele of a promoter SNP, rs4073T>A, may increase susceptibility to the development of IPF via up-regulation of IL-8.

In 2007, the Korean Interstitial Lung Disease Society had collected clinical data of patients who have diagnosed as Lymphangioleiomyomatosis (LAM) since 1990 through nationwide survey, which showed that LAM patients had increased sharply after 2004. The present study was performed to show the clinical features of Korean patients with LAM, and to establish the reason for the recent increase in the diagnosis. All 63 patients were women and the mean age at diagnosis was 36 yr. The most common presenting symptom was dyspnea and 8 patients had tuberous sclerosis complex. The survival rate at 5 yr after diagnosis was 84%. Compared with patients diagnosed after 2004 (n= 34 ), the patients diagnosed before 2004 (n= 29 ) complained with dyspnea more (P = 0.016) and had lower FEV 1 % predicted (P= 0 . 003 ), and DLco% predicted (P= 0 . 042 ). The higher proportion of patients diagnosed after 2004 showed the normal chest radiography, and they were detected by routine chest CT screening (P= 0 . 016 ). This study showed that clinical features of Korean patients with LAM were not different from those reported elsewhere. It is concluded that the reason for the increase of newly diagnosed patients is the result of increase in detection of the early stage LAM by the widespread use of chest CT screening.

Purpose: Veterinary researchers are exposed to variable animal allergens. However, sensitization to them and allergic symptoms during exposure to them in this group are not sufficiently evaluated worldwide, especially in Korea. The objective of this study is to evaluate sensitization to animal allergens and allergic symptoms during exposure to them in Korean veterinary researchers. Methods: Thirty-two veterinary researchers who participated in the 2016 annual symposium of the Korean Society of Veterinary Sci ence were asked to answer questionnaires regarding allergic symptoms during animal exposure and underwent skin prick tests for animal allergens. Animal allergens consisted of chicken feather and 10 mammals, epithelia as well as cow`s milk, hen`s egg, and 7 an imal types of meat. Results: There were 13 subjects who complained of allergic symptoms during exposure to certain animal epithelia and 19 who did not. Between the 2 groups, there were no differences in age, sex, underlying allergic disease, family history of allergy, current occu pation and its duration, numbers and specie of contact animals, or daily contact time. Meanwhile, the sensitization rates to mouse, horse, rabbit, and guinea pig were significantly higher in the symptomatic group. Rhinoconjunctivitis symptoms were the most common allergic symptoms related to animal exposure were most common followed by dermatologic symptom, and symptom of lower respiratory tract. Conclusion: We found that sensitizations to some animal epithelia were more frequent in Korean veterinary researchers with aller gic symptoms during exposure to animal compared to those without it, and their most common symptoms were rhinoconjunctivi tis symptoms. (Allergy Asthma Respir Dis 2016:4:406-414)

A 31-year-old man presented with a dry cough and exertional dyspnea. The chest X-ray showed multiple nodular opacities throughout the entire lung field. Chest computed tomography (CT) revealed variable-sized nodules with a peribronchiolar or centrilobular distribution, some of which revealed thick-walled cavitary change. Based on the chest CT findings, it was initially assumed that metastatic lung nodules with hematogenous spread were present; therefore, we performed an open lung biopsy. On microscopic examination, several compact cellular interstitial infiltrates composed of Langerhans' cells, eosinophils, and lymphocytes were observed. Immunochemically, the Langerhans' cells showed strong cytoplasmic staining for S-100 protein. Based on these findings, the patient was diagnosed with Langerhans' cell histiocytosis of the lung. High-resolution CT of the chest is a useful, sensitive tool in the diagnosis of pulmonary Langerhans' cell histiocytosis (PLCH). A typical radiologic finding of PLCH is irregularly shaped cysts. The radiological finding in this case of nodular opacities throughout the lung fields only without cysts is rare in PLCH. We report a case of PLCH with atypical multiple nodules mimicking hematogenous metastatic lung nodules.

BACKGROUND. There is increasing interest in the use of a weekly administration of docetaxel as a way of reducing its hematologic toxicity. The purpose of the current randomized study was to evaluate the toxicity and efficacy of docetaxel plus cisplatin combination on 2 schedules in patients with previously untreated, advanced nonsmall-cell lung cancer (NSCLC). METHODS. Consenting patients with advanced NSCLC were randomized to receive first-line chemotherapy with cisplatin 75 mg/m2 on Day 1, plus 3-weekly (75 mg/m2 on Day 1) or weekly (35 mg/m2 on Days 1, 8, and 15 of a 4-week cycle) docetaxel, for up to 6 cycles. RESULTS. Of 86 patients accrued, 41 patients were treated with 3-weekly and 43 with weekly docetaxel plus cisplatin. The most frequent grade 3/4 toxicity in the 3-weekly arm was neutropenia (56% of patients). In those receiving the weekly regimen, the frequent grade 3/4 toxicities were fatigue (44%) and nausea/vomiting (35%). The overall response rate was 40% with the 3-weekly and 39% with the weekly arm (P = .74). The median progression-free survival was 4.3 months in the 3-weekly arm and 3.9 months in the weekly arm (P = .08) and the median survival was 10.3 and 10.0 months, respectively (P = .76). Quality of life data showed no relevant difference between the arms. CONCLUSIONS. The weekly schedule of docetaxel plus cisplatin combination as first-line chemotherapy for advanced NSCLC, while feasible, has no clear advantage over the standard 3-weekly regimen. Cancer 2007. © 2007 American Cancer Society.

In this paper, a new rehabilitation training system was developed to improve equilibrium sense control by combining virtual reality technology with a fixed exercise bicycle. In order to evaluate the effectiveness of the training system, twenty normal healthy adults participated as test subjects in the investigation of the influence of different the parameters on equilibrium sensory control. Several factors including path deviation, cycling time, cycling velocity, center of pressure were evaluated and analyzed quantitatively. Also, we investigated the usefulness of virtual feedback information for weight shift on the improvement of the effect of equilibrium training. After conducting repeated tests, we found improvements not only in of the ability to controlling balance and weight shift but also in the overall cycling capabilities such as cycling speed. Therefore, the new training system utilizing an excise bike and a virtual reality system is found to be effective on the improvement of equilibrium sense, and the technology we have developed seems to have a good prospect in the rehabilitation field.

Methotrexate (MTX) has been established as a standard disease-modifying anti-rheumatic drug. If adequate disease control is achieved for a reasonable period of time, tapering the MTX dosage is recommended because the chronic use of MTX can result in opportunistic infection. We present here a case of a woman with rheumatoid arthritis taking MTX, and the woman developed actively caseating endobronchial Mycobacterium intracellulare disease with pulmonary infiltrations. After discontinuing the MTX, the patient was able to tolerate 18 months of antimycobacterial treatment without flare ups of rheumatoid arthritis, and she completely recovered from nontuberculous mycobacterial respiratory disease.

Recently, a novel influenza A (H1N1) has been recognized as the cause of a worldwide respiratory infection outbreak. Although the symptoms of a novel influenza A (H1N1) are usually mild, the disease can cause severe illness and death. A complication of novel influenza A (H1N1) is pneumomediastinum, a rarely reported condition. We report a case of influenza A (H1N1) complicating pneumomediastinum with subcutaneous emphysema, which had initially presented with blood tinged sputum and chest pain. In addition, we demonstrate bronchoalveolar lavage in influenza A (H1N1).