Machine Learning-Based Proteomics Reveals Ferroptosis in COPD PatientDerived Airway Epithelial Cells Upon Smoking Exposure

Background@#Proteomics and genomics studies have contributed to understanding the pathogenesis of chronic obstructive pulmonary disease (COPD), but previous studies have limitations. Here, using a machine learning (ML) algorithm, we attempted to identify pathways in cultured bronchial epithelial cells of COPD patients that were significantly affected when the cells were exposed to a cigarette smoke extract (CSE). @*Methods@#Small airway epithelial cells were collected from patients with COPD and those without COPD who underwent bronchoscopy. After expansion through primary cell culture, the cells were treated with or without CSEs, and the proteomics of the cells were analyzed by mass spectrometry. ML-based feature selection was used to determine the most distinctive patterns in the proteomes of COPD and non-COPD cells after exposure to smoke extract.Publicly available single-cell RNA sequencing data from patients with COPD (GSE136831) were used to analyze and validate our findings. @*Results@#Five patients with COPD and five without COPD were enrolled, and 7,953 proteins were detected. Ferroptosis was enriched in both COPD and non-COPD epithelial cells after their exposure to smoke extract. However, the ML-based analysis identified ferroptosis as the most dramatically different response between COPD and non-COPD epithelial cells, adjusted P value = 4.172 × 10−6 , showing that epithelial cells from COPD patients are particularly vulnerable to the effects of smoke. Single-cell RNA sequencing data showed that in cells from COPD patients, ferroptosis is enriched in basal, goblet, and club cells in COPD but not in other cell types. @*Conclusion@#Our ML-based feature selection from proteomic data reveals ferroptosis to be the most distinctive feature of cultured COPD epithelial cells compared to non-COPD epithelial cells upon exposure to smoke extract.

Prevalence and impact of airway diseases on clinical outcomes in idiopathic pulmonary fibrosis

Background/Aims@#The prevalence and effects of airway diseases, including asthma, eosinophilic bronchitis (EB), chronic obstructive pulmonary disease (COPD), and asthma-COPD overlap (ACO) have not been thoroughly studied in patients with idiopathic pulmonary fibrosis (IPF). This study aimed to evaluate the prevalence of airway diseases in patients with IPF and to identify the differences in symptoms based on the presence of airway diseases. @*Methods@#This single-institution prospective cohort study was conducted from June 2017 to September 2018, at the Seoul National University Hospital. Spirometry with bronchodilator, methacholine bronchial provocation test, induced sputum with eosinophil stain, and exhaled nitric oxide were performed to confirm the presence of airway disease. The modified Medical Research Council (mMRC) dyspnea scale, COPD assessment test (CAT), St. George’s Respiratory Questionnaire (SGRQ), EuroQol-5 dimension (EQ-5D) index, and cough-specific quality of life questionnaire (CQLQ) data were collected to assess symptom severity. @*Results@#Total 147 patients with IPF were screened, and 70 patients were analyzed. The prevalence of airway diseases in the participants was as follows: 5.0% had COPD, 1.7% had asthma, 3.3% had ACO, and 1.7% had EB. The mMRC, CAT, SGRQ, EQ-5D, and CQLQ scores did not differ regardless of combined airway disease. After 3 months, the SGRQ (p = 0.028) and CQLQ (p = 0.030) scores were significantly higher in patients with airway disease than in those without. @*Conclusions@#The prevalence of airway diseases in patients with IPF is low, but when airway diseases are accompanied by IPF, symptom severity and quality of life may worsen rapidly.

Histopathologic heterogeneity of acute respiratory distress syndrome revealed by surgical lung biopsy and its clinical implications

BACKGROUND/AIMS: Diffuse alveolar damage (DAD) is the histopathologic hallmark of acute respiratory distress syndrome (ARDS). However, there are several non-DAD conditions mimicking ARDS. The purpose of this study was to investigate the histopathologic heterogeneity of ARDS revealed by surgical lung biopsy and its clinical relevance. METHODS: We retrospectively analyzed 84 patients with ARDS who met the criteria of the Berlin definition and underwent surgical lung biopsy between January 2004 and December 2013 in three academic hospitals in Korea. We evaluated their histopathologic findings and compared the clinical outcomes. Additionally, the impact of surgical lung biopsy on therapeutic alterations was examined. RESULTS: The histopathologic findings were highly heterogeneous. Of 84 patients undergoing surgical lung biopsy, DAD was observed in 31 patients (36.9%), while 53 patients (63.1%) did not have DAD. Among the non-DAD patients, diffuse interstitial lung diseases and infections were the most frequent histopathologic findings in 19 and 17 patients, respectively. Although the mortality rate was slightly higher in DAD (71.0%) than in non-DAD (62.3%), the difference was not significant. Overall, the biopsy results led to treatment alterations in 40 patients (47.6%). Patients with non-DAD were more likely to change the treatment than those with DAD (58.5% vs. 29.0%), but there were no significant improvements regarding the mortality rate. CONCLUSIONS: The histopathologic findings of ARDS were highly heterogeneous and classic DAD was observed in one third of the patients who underwent surgical lung biopsy. Although therapeutic alterations were more common in patients with non-DAD-ARDS, there were no significant improvements in the mortality rate.

Utility of the National Lung Screening Trial Criteria for Estimation of Lung Cancer in the Korean Population / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Screening forlung cancerin high-risk patients using the National Lung Screening Trial (NLST) criteria resulted in a decreased lung cancer-related mortality rate. However, whether these criteria are applicable to the Korean has not been investigated thus far. Therefore, we estimated the utility of the NLST criteria as a screening tool for lung cancer in the Korean population. MATERIALS AND METHODS: The total number of newly diagnosed lung cancer cases in 2013 was obtained from the Korea National Statistical Office. The proportion of newly diagnosed lung cancer cases that met the NLST criteria was calculated via a retrospective cohort of a tertiary referral hospital. We estimated the nationwide proportion of patients who met the NLST criteria using the 5th Korea National Health and Nutrition Examination Survey conducted during 2010-2012 (KNHANES V). RESULTS: Using KNHANES V data, we found that approximately 6.92% of the general population of Korea would meet the NLST criteria. In the tertiary referral hospital, 29.6% of the 2,689 newly diagnosed lung cancer patients met the NLST criteria. In 2013, the total number of newly diagnosed lung cancer cases in Korea was 23,177. The estimated nationwide proportions of lung cancer patients who met and did not meet the NLST criteria were 0.37% and 0.06%, respectively, yielding a ratio of 5.78. CONCLUSION: The NLST criteria demonstrated sound clinical utility for lung cancer screening of high-risk patients in Korea.

Effect of Renin-Angiotensin System Blockage in Patients with Acute Respiratory Distress Syndrome: A Retrospective Case Control Study / 대한구급학회지

BACKGROUND: Acute respiratory distress syndrome (ARDS) remains a life-threatening disease. Many patients with ARDS do not recover fully, and progress to terminal lung fibrosis. Angiotensin-converting enzyme (ACE) inhibitor is known to modulate the neurohormonal system to reduce inflammation and to prevent tissue fibrosis. However, the role of ACE inhibitor in the lungs is not well understood. We therefore conducted this study to elucidate the effect of renin-angiotensin system (RAS) blockage on the prognosis of patients with ARDS. METHODS: We analyzed medical records of patients who were admitted to the medical intensive care unit (ICU) at a tertiary care hospital from January 2005 to December 2010. ARDS was determined using the Berlin definition. The primary outcome was the mortality rate of ICU. Survival analysis was performed after adjustment using propensity score matching. RESULTS: A total of 182 patients were included in the study. Thirty-seven patients (20.3%) took ACE inhibitor or angiotensin receptor blocker (ARB) during ICU admission, and 145 (79.7%) did not; both groups showed similar severity scores. In the ICU, mortality was 45.9% in the RAS inhibitor group and 58.6% in the non-RAS inhibitor group (P = 0.166). The RAS inhibitor group required a longer duration of mechanical ventilation (29.5 vs. 19.5, P = 0.013) and longer ICU stay (32.1 vs. 20.2 days, P < 0.001). In survival analysis, the RAS inhibitor group showed better survival rates than the non-RAS group (P < 0.001). CONCLUSIONS: ACE inhibitor or ARB may have beneficial effect on ARDS patients.

Analysis of Fifty Hotspot Mutations of Lung Squamous Cell Carcinoma in Never-smokers

Smoking is the major risk factor for lung squamous cell carcinoma (SCC), although a small number of lung SCCs occurs in never-smokers. The purpose of this study was to compare 50 hotspot mutations of lung SCCs between never-smokers and smokers. We retrospectively reviewed the medical records of patients newly diagnosed with lung SCC between January 1, 2011 and December 31, 2013 in the Seoul National University Hospital. Formalin-fixed, paraffin-embedded tumor samples were used for analysis of hotspot mutations. Fifty cancer-related genes in never-smokers were compared to those in ever-smokers. Of 379 lung SCC patients, 19 (5.0%) were never-smokers. The median age of these 19 patients was 67 years (interquartile range 57–73 years), and 10 of these patients were women (52.5%). The incidence rates of stage I, II, III, and IV disease in this group were 26.4%, 5.3%, 31.6%, and 36.8%, respectively, and sequencing was performed successfully in 14 cases. In the 26 lung SCC tumor samples (12 from never-smokers and 14 from ever-smokers) sequenced using personal genome machine, the most common mutations were in TP53 (75.0%), RAS (66.7%), and STK11 (33.3%), but mutations were also found in EGFR, KIT, and PTEN. The distribution of hotspot mutations in never-smokers was similar to that in ever-smokers. There was no significant difference in overall survival between the 2 groups. The 50 hotspot mutations of lung SCC in never-smokers were similar to those of ever-smokers.

Medical Thoracoscopy in Pleural Disease: Experience from a One-Center Study / 결핵및호흡기질환

BACKGROUND: Medical thoracoscopy (MT) is a minimally invasive, endoscopic procedure for exploration of the pleural cavity under conscious sedation and local anesthesia. MT has been performed at the Seoul National University Hospital since February 2014. This paper summarizes the findings and outcomes of MT cases at this hospital. METHODS: Patients who had undergone MT were enrolled in the study. MT was performed by pulmonologists, using both rigid and semi-rigid thoracoscopes. During the procedure, patients were under conscious sedation with fentanyl and midazolam. Medical records were reviewed for clinical data. RESULTS: From February 2014 to January 2016, 50 procedures (47 cases) were performed (diagnostic MT, 26 cases; therapeutic MT, 24 cases). The median age of patients was 66 years (59–73 years), and 38 patients (80.9%) were male. The median procedure duration from initial incision to insertion of the chest tube was 37 minutes. The median doses of fentanyl and midazolam were 50 µg and 5 mg, respectively. All procedures were performed without unexpected events. Of the 26 cases of pleural disease with an unknown cause, 19 were successfully diagnosed using MT. Additionally, diagnostic MT provided clinically useful information in the other six patients. Therapeutic MT was very effective for treatment of malignant pleural effusion or empyema. The median number of days with chest tube drainage was 6 (3 days for diagnostic MT and 8 days for therapeutic MT). CONCLUSION: MT is a useful and necessary procedure for both diagnosis and treatment of pleural diseases.

Incidence of Fever Following Endobronchial Ultrasound–Guided Transbronchial Needle Aspiration / 결핵및호흡기질환

BACKGROUND: Endobronchial ultrasound–guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive diagnostic method for mediastinal and hilar lymphadenopathy. This study aimed to investigate the incidence of fever following EBUS-TBNA. METHODS: A total of 684 patients who underwent EBUS-TBNA from May 2010 to July 2012 at Seoul National University Hospital were retrospectively reviewed. The patients were evaluated for fever by a physician every 6–8 hours during the first 24 hours following EBUS-TBNA. Fever was defined as an increase in axillary body temperature over 37.8℃. RESULTS: Fever after EBUS-TBNA developed in 110 of 552 patients (20%). The median onset time and duration of fever was 7 hours (range, 0.5–32 hours) after EBUS-TBNA and 7 hours (range, 1–52 hours), respectively, and the median peak body temperature was 38.3℃ (range, 37.8–39.9℃). In most patients, fever subsided within 24 hours; however, six cases (1.1%) developed fever lasting longer than 24 hours. Infectious complications developed in three cases (0.54%) (pneumonia, 2; mediastinal abscess, 1), and all three patients had diabetes mellitus. The number or location of sampled lymph nodes and necrosis of lymph node were not associated with fever after EBUS-TBNA. Multiple logistic regression analysis did not reveal any risk factors for developing fever after EBUS-TBNA. CONCLUSION: Fever is relatively common after EBUS-TBNA, but is transient in most patients. However, clinicians should be aware of the possibility of infectious complications among patients with diabetes mellitus.

The Impact of Autophagy on the Cigarette Smoke Extract-Induced Apoptosis of Bronchial Epithelial Cells / 결핵및호흡기질환

BACKGROUND: Previous studies report that apoptosis and autophagy are involved in the pathogenesis of emphysema, and macroautophagy is one of the processes regulating the apoptosis pathway. However, few studies have evaluated whether chaperone-mediated autophagy (CMA) contributes to the regulation of apoptosis. In this study, we investigated the impact of autophagy, including both macroautophagy and CMA, on the apoptosis in bronchial epithelial cells. METHODS: Cigarette smoke extract (CSE) was injected intratracheally into C57BL/6 mice, and emphysema and apoptosis were evaluated in the lungs. After treatment with CSE, apoptosis, macroautophagy, and CMA were measured in BEAS2-B cells, and the impact of autophagy on the apoptosis was evaluated following knockdown of autophagy-related genes by short interfering RNAs (siRNAs). RESULTS: Intratracheal CSE injection resulted in the development of emphysema and an increase in apoptosis in mice. CSE increased the apoptosis in BEAS2-B cells, and also elevated the expression of proteins related to both macroautophagy and CMA in BEAS2-B cells. The knockdown experiment with siRNAs showed that macroautophagy increases apoptosis in BEAS2-B cells, while CMA suppresses apoptosis. CONCLUSION: The intratracheal injection of CSE induces pulmonary emphysema and an increase in apoptosis in mice. CSE also induces apoptosis, macroautophagy, and CMA of bronchial epithelial cells. Macroautophagy and CMA regulate apoptosis in opposite directions.

Effect of Renin-Angiotensin System Blockage in Patients with Acute Respiratory Distress Syndrome: A Retrospective Case Control Study / 대한중환자의학회지

BACKGROUND: Acute respiratory distress syndrome (ARDS) remains a life-threatening disease. Many patients with ARDS do not recover fully, and progress to terminal lung fibrosis. Angiotensin-converting enzyme (ACE) inhibitor is known to modulate the neurohormonal system to reduce inflammation and to prevent tissue fibrosis. However, the role of ACE inhibitor in the lungs is not well understood. We therefore conducted this study to elucidate the effect of renin-angiotensin system (RAS) blockage on the prognosis of patients with ARDS. METHODS: We analyzed medical records of patients who were admitted to the medical intensive care unit (ICU) at a tertiary care hospital from January 2005 to December 2010. ARDS was determined using the Berlin definition. The primary outcome was the mortality rate of ICU. Survival analysis was performed after adjustment using propensity score matching. RESULTS: A total of 182 patients were included in the study. Thirty-seven patients (20.3%) took ACE inhibitor or angiotensin receptor blocker (ARB) during ICU admission, and 145 (79.7%) did not; both groups showed similar severity scores. In the ICU, mortality was 45.9% in the RAS inhibitor group and 58.6% in the non-RAS inhibitor group (P = 0.166). The RAS inhibitor group required a longer duration of mechanical ventilation (29.5 vs. 19.5, P = 0.013) and longer ICU stay (32.1 vs. 20.2 days, P < 0.001). In survival analysis, the RAS inhibitor group showed better survival rates than the non-RAS group (P < 0.001). CONCLUSIONS: ACE inhibitor or ARB may have beneficial effect on ARDS patients.

Effect of Preadmission Metformin Use on Clinical Outcome of Acute Respiratory Distress Syndrome among Critically Ill Patients with Diabetes / 결핵및호흡기질환

BACKGROUND: Acute respiratory distress syndrome (ARDS) is related to high mortality and morbidity. There are no proven therapeutic measures however, to improve the clinical course of ARDS, except using low tidal volume ventilation. Metformin is known to have pleiotropic effects including anti-inflammatory activity. We hypothesized that pre-admission metformin might alter the progress of ARDS among intensive care unit (ICU) patients with diabetes mellitus (DM). METHODS: We performed a retrospective cohort study from January 1, 2005, to April 30, 2005 of patients who were admitted to the medical ICU at Seoul National University Hospital because of ARDS, and reviewed ARDS patients with DM. Metformin use was defined as prescribed within 3-month pre-admission. RESULTS: Of 558 patients diagnosed with ARDS, 128 (23.3%) patients had diabetes and 33 patients were treated with metformin monotherapy or in combination with other antidiabetic medications. Demographic characteristics, cause of ARDS, and comorbid conditions (except chronic kidney disease) were not different between metformin users and nonusers. Several severity indexes of ARDS were similar in both groups. The 30-day mortality was 42.42% in metformin users and 55.32% in metformin nonusers. On multivariable regression analysis, use of metformin was not significantly related to a reduced 30-day mortality (adjusted β-coefficient, −0.19; 95% confidence interval, −1.76 to 1.39; p=0.816). Propensity score-matched analyses showed similar results. CONCLUSION: Pre-admission metformin use was not associated with reduced 30-day mortality among ARDS patients with DM in our medical ICU.

Trends in the Use of Intensive Care by Very Elderly Patients and Their Clinical Course in a Single Tertiary Hospital in Korea / 대한구급학회지

BACKGROUND: The number of elderly patients admitted to intensive care units (ICUs) is growing with the increasing proportion of elderly persons in the Korean general population. It is often difficult to make decisions about ICU care for elderly patients, especially when they are in their 90s. Data regarding the proportion of elderly patients in their 90s along with their clinical characteristics in ICU are scarce. METHODS: The records of Korean patients > or = 90 years old who were admitted to the medical ICU in a tertiary referral hospital between January 2005 and December 2014 were retrospectively reviewed. We compared the trend in ICU use and characteristics of these elderly patients between 2005-2009 and 2010-2014. RESULTS: Among 6,186 referred patients, 55 aged > or = 90 years were admitted to the medical ICU from 2005 to 2014. About 58.2% of these patients were male, and their mean age was 92.7 years. Their median Charlson comorbidity index score was 2 (IQR 1-3) and their mean APACHE II score was 25.0 (IQR 19.0-34.0). The most common reason for ICU care was acute respiratory failure. There were no differences in the survival rates between the earlier and more recent cohorts. However, after excluding patients who had specified "do not resuscitate" (DNR), the more recent group showed a significantly higher survival rate (53.8% mortality for the earlier group and 0% mortality for the recent group). Among the survivors, over half were discharged to their homes. More patients in the recent cohort (n=26 [78.8%]) specified DNR than in the earlier cohort (n=7 [35.0%], p=0.004). The number and proportion of patients > or = 90 years old among patients using ICU during the 2005-2014 study period did not differ. CONCLUSIONS: The use of ICU care by elderly patients > or = 90 years old was consistent from 2005-2014. The overall mortality rate tended to decrease, but this was not statistically significant. However, the proportion of patients specifying DNR was higher among more recent patients, and the recent group showed an even better survivorship after sensitivity analysis excluded patients specifying DNR.

Trends in the Use of Intensive Care by Very Elderly Patients and Their Clinical Course in a Single Tertiary Hospital in Korea / 대한중환자의학회지

BACKGROUND: The number of elderly patients admitted to intensive care units (ICUs) is growing with the increasing proportion of elderly persons in the Korean general population. It is often difficult to make decisions about ICU care for elderly patients, especially when they are in their 90s. Data regarding the proportion of elderly patients in their 90s along with their clinical characteristics in ICU are scarce. METHODS: The records of Korean patients > or = 90 years old who were admitted to the medical ICU in a tertiary referral hospital between January 2005 and December 2014 were retrospectively reviewed. We compared the trend in ICU use and characteristics of these elderly patients between 2005-2009 and 2010-2014. RESULTS: Among 6,186 referred patients, 55 aged > or = 90 years were admitted to the medical ICU from 2005 to 2014. About 58.2% of these patients were male, and their mean age was 92.7 years. Their median Charlson comorbidity index score was 2 (IQR 1-3) and their mean APACHE II score was 25.0 (IQR 19.0-34.0). The most common reason for ICU care was acute respiratory failure. There were no differences in the survival rates between the earlier and more recent cohorts. However, after excluding patients who had specified "do not resuscitate" (DNR), the more recent group showed a significantly higher survival rate (53.8% mortality for the earlier group and 0% mortality for the recent group). Among the survivors, over half were discharged to their homes. More patients in the recent cohort (n=26 [78.8%]) specified DNR than in the earlier cohort (n=7 [35.0%], p=0.004). The number and proportion of patients > or = 90 years old among patients using ICU during the 2005-2014 study period did not differ. CONCLUSIONS: The use of ICU care by elderly patients > or = 90 years old was consistent from 2005-2014. The overall mortality rate tended to decrease, but this was not statistically significant. However, the proportion of patients specifying DNR was higher among more recent patients, and the recent group showed an even better survivorship after sensitivity analysis excluded patients specifying DNR.

Bleeding complications in critically ill patients with liver cirrhosis

BACKGROUND/AIMS: Patients with liver cirrhosis (LC) are at risk for critical events leading to Intensive Care Unit (ICU) admission. Coagulopathy in cirrhotic patients is complex and can lead to bleeding as well as thrombosis. The aim of this study was to investigate bleeding complications in critically ill patients with LC admitted to a medical ICU (MICU). METHODS: All adult patients admitted to our MICU with a diagnosis of LC from January 2006 to December 2012 were retrospectively assessed. Patients with major bleeding at the time of MICU admission were excluded from the analysis. RESULTS: A total of 205 patients were included in the analysis. The median patient age was 62 years, and 69.3% of the patients were male. The most common reason for MICU admission was acute respiratory failure (45.4%), followed by sepsis (27.3%). Major bleeding occurred in 25 patients (12.2%). The gastrointestinal tract was the most common site of bleeding (64%), followed by the respiratory tract (20%). In a multivariate analysis, a low platelet count at MICU admission (odds ratio [OR], 0.98; 95% confidence interval [CI], 0.97 to 0.99) and sepsis (OR, 8.35; 95% CI, 1.04 to 67.05) were independent risk factors for major bleeding. The ICU fatality rate was significantly greater among patients with major bleeding (84.0% vs. 58.9%, respectively; p = 0.015). CONCLUSIONS: Major bleeding occurred in 12.2% of critically ill cirrhotic patients admitted to the MICU. A low platelet count at MICU admission and sepsis were associated with an increased risk of major bleeding during the MICU stay. Further study is needed to better understand hemostasis in critically ill patients with LC.

The Anti-Inflammatory Effect of Arginine-Vasopressin on Lipopolysaccharide-Induced IkappaBalpha/Nuclear Factor-kappaB Cascade / 대한구급학회지

BACKGROUND: Arginine vasopressin (AVP) is widely used as a vasopressor agent. Some recent studies have suggested that AVP may exert an immunomodulatory effect. However, the mechanism about the anti-inflammatory effect of AVP is not well known. We investigated the effect of AVP on the ihibitor of kappa B (IkappaBalpha)/nuclear factor-kappa B (NF-kappaB) pathway in RAW 264.7 cells. METHODS: Cultured RAW 264.7 cells were pretreated with AVP and stimulated with lipopolysaccharide (LPS). To evaluate the effect of AVP on inflammatory cytokines, the concentration of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) were assessed by an enzyme-linked immunosorbent assay technique. The expression of IkappaBalpha and nuclear translocation of NF-kappaB p65 were measured by Western blotting, and IkappaB kinase (IKK) activity was analyzed by an in vitro immune complex kinase assay. To confirm the AVP effect on IkappaBalpha/NF-kappaB cascade and via V2 receptor, we added tolvaptan (V2 receptor antagonist) after AVP pretreatment. RESULTS: The increase of IL-6 and TNF-alpha in LPS-stimulated RAW 264.7 cells was suppressed by a treatment with AVP. Pretreatment of AVP inhibited increasing of IKK activity and IkappaBalpha degradation induced by LPS in RAW 264.7 cells. Furthermore, LPS induced and NF-kappaB transcription was inhibited by AVP pretreatment. The observed changes in IKK activity, IkappaBalpha degradation and NF-kappaB transcription by AVP was abolished by tolvaptan treatment. CONCLUSIONS: Our results suggest that AVP showed anti-inflammatory effect on LPS-induced IkappaBalpha/NF-kappaB cascade in mouse macrophages via V2 receptors.

Massive Mediastinal Lymph Node Involvement of Cryptococcosis in Immunocompetent Host

Cryptococcosis is a systemic opportunistic infection mostly occurred in immunosuppressed patients. Pulmonary cryptococcosis in immunocompetent host is usually localized and self-limiting disease. Pulmonary nodule or mass is the most common radiologic finding, however involvement of mediastinal lymph nodes is rare. Here we report a case of pulmonary cryptococcosis with massive mediastinal lymph nodes involvement in immunocompetent host.

The Anti-Inflammatory Effect of Arginine-Vasopressin on Lipopolysaccharide-Induced IkappaBalpha/Nuclear Factor-kappaB Cascade / 대한중환자의학회지

BACKGROUND: Arginine vasopressin (AVP) is widely used as a vasopressor agent. Some recent studies have suggested that AVP may exert an immunomodulatory effect. However, the mechanism about the anti-inflammatory effect of AVP is not well known. We investigated the effect of AVP on the ihibitor of kappa B (IkappaBalpha)/nuclear factor-kappa B (NF-kappaB) pathway in RAW 264.7 cells. METHODS: Cultured RAW 264.7 cells were pretreated with AVP and stimulated with lipopolysaccharide (LPS). To evaluate the effect of AVP on inflammatory cytokines, the concentration of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) were assessed by an enzyme-linked immunosorbent assay technique. The expression of IkappaBalpha and nuclear translocation of NF-kappaB p65 were measured by Western blotting, and IkappaB kinase (IKK) activity was analyzed by an in vitro immune complex kinase assay. To confirm the AVP effect on IkappaBalpha/NF-kappaB cascade and via V2 receptor, we added tolvaptan (V2 receptor antagonist) after AVP pretreatment. RESULTS: The increase of IL-6 and TNF-alpha in LPS-stimulated RAW 264.7 cells was suppressed by a treatment with AVP. Pretreatment of AVP inhibited increasing of IKK activity and IkappaBalpha degradation induced by LPS in RAW 264.7 cells. Furthermore, LPS induced and NF-kappaB transcription was inhibited by AVP pretreatment. The observed changes in IKK activity, IkappaBalpha degradation and NF-kappaB transcription by AVP was abolished by tolvaptan treatment. CONCLUSIONS: Our results suggest that AVP showed anti-inflammatory effect on LPS-induced IkappaBalpha/NF-kappaB cascade in mouse macrophages via V2 receptors.

Erratum: Disease burden of pneumonia in Korean adults aged over 50 years stratified by age and underlying diseases

Results part of abstract has some error.

Changes in Diagnostic Methods for Pulmonary Tuberculosis between 2005 and 2013 / 결핵및호흡기질환

BACKGROUND: Diagnostic methods for pulmonary tuberculosis (TB) have recently advanced. The aim of this study was to evaluate the changes in TB diagnostic tests that prompted the initiation of anti-TB treatment over time in South Korea, an industrialized country with an intermediate TB burden. METHODS: Patients diagnosed with pulmonary TB in the first halves of 2005 and 2013 at a tertiary referral hospital were included. Diagnostic methods that prompted the initiation of anti-TB treatment were compared between the 2 groups of patients. RESULTS: A greater proportion of patients were diagnosed with pulmonary TB using bronchoscopy in 2013 than in 2005 (26.7% vs. 6.6%, respectively; p<0.001), while the proportion of patients clinically diagnosed with pulmonary TB was lower in 2013 than in 2005 (24.7% vs. 49.0%, respectively; p<0.001). Additionally, more patients started anti-TB treatment based on positive polymerase chain reaction (PCR) results for Mycobacterium tuberculosis DNA in 2013 than in 2005 (47.3% vs. 7.9%, respectively; p<0.001). CONCLUSION: The initiation of treatment for pulmonary TB in South Korea has become more frequently based on PCR and the use of bronchoscopic specimens.

Effect of Airflow Limitation on Acute Exacerbations in Patients with Destroyed Lungs by Tuberculosis

History of treatment for tuberculosis (TB) is a risk factor for obstructive lung disease. However, it has been unclear whether the clinical characteristics of patients with destroyed lung by TB differ according to the presence or absence of airflow limitation. The objective of the study was to evaluate differences in acute exacerbations and forced expiratory volume in 1 second (FEV1) decline in patients with destroyed lung by TB according to the presence or absence of airflow limitation. We performed a retrospective cohort study and enrolled patients with destroyed lung by TB. The presence of airflow limitation was defined as FEV1/forced vital capacity (FVC) < 0.7. One hundred and fifty-nine patients were enrolled, and 128 (80.5%) had airflow limitation. The proportion of patients who experienced acute exacerbation was higher in patients with airflow limitation compared to those without (89.1 vs. 67.7%, respectively; P = 0.009). The rate of acute exacerbation was higher in patients with airflow limitation (IRR, 1.19; 95% CI, 1.11-1.27). Low body mass index (X vs. X + 1; HR, 0.944; 95% CI, 0.895-0.996) in addition to airflow limitation (HR, 1.634; 95% CI, 1.012-2.638), was an independent risk factor for acute exacerbation. The annual decline of FEV1 was 2 mL in patients with airflow limitation and 36 mL in those without (P < 0.001). In conclusion, the presence of airflow limitation is an independent risk factor for acute exacerbation in patients with the destroyed lung by TB.