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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.

An imbalance between oxidative stress and antioxidant activity plays an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Cigarette smoke, a major risk factor of COPD, induces cellular oxidative stress, but levels of antioxidants such as heme oxygenase-1 (HO-1) are reduced in individuals with severe COPD. In this study, we evaluated the molecular mechanism of reduced HO-1 expression in human bronchial epithelial cells. We found that cigarette smoke extract (CSE) increases HO-1 levels via activation of NFE2-related factor 2 (Nrf2). However, pretreating cells with the protease neutrophil elastase (NE) suppressed the CSE-induced expression of HO-1 mRNA and protein. NE also decreased the sirtuin 1 (SIRT1) level, but did not inhibit CSE-induced nuclear translocation and DNA-binding activity of Nrf2. Transfection of cells with a Myc/His-tagged SIRT1 expression vector completely blocked the NE-mediated suppression of HO-1 expression. We further noted that the NE-induced down-regulation of SIRT1 was not due to decreased transcription or proteasomal/lysosomal degradation or loss of solubility. Immunofluorescence staining revealed that NE enters the cell cytoplasm, and we observed that NE directly cleaved SIRT1 in vitro, indicating that SIRT1 levels are decreased via direct degradation by internalized NE. Of note, we observed decreased SIRT1 levels in NE-treated primary human bronchial epithelial cells and in lung homogenates from both smokers and patients with COPD. In conclusion, NE suppresses CSE-induced HO-1 expression by cleaving SIRT1. This finding indicates the importance of cross-talk between oxidative stress and protease responses in the pathogenesis of COPD.

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 effct 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 du- ration 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.

Background All-cause mortality risk and causes of death in bronchiectasis patients have not been fully investigated. The aim of this study was to compare the mortality risk and causes of death between individuals with bronchiectasis and those without bronchiectasis. Methods Patients with or without bronchiectasis determined based on chest computed tomography (CT) at one centre between 2005 and 2016 were enrolled. Among the patients without bronchiectasis, a control group was selected after applying additional exclusion criteria. We compared the mortality risk and causes of death between the bronchiectasis and control groups without lung disease. Subgroup analyses were also performed according to identification of Pseudomonas or non-tuberculous mycobacteria, airflow limitation, and smoking status. Results Of the total 217,702 patients who underwent chest CT, 18,134 bronchiectasis patients and 90,313 non-bronchiectasis patients were included. The all-cause mortality rate in the bronchiectasis group was 1608.8 per 100,000 person-years (95% confidence interval (CI), 1531.5–1690.0), which was higher than that in the control group (133.5 per 100,000 person-years; 95% CI, 124.1–143.8; P P for multiplicative interaction, 0.030, RERI, 0.432; 95% CI, 0.097–0.769) and lung cancer-related mortality (RERI, 8.68; 95% CI, 1.631–15.736). Conclusion Individuals with bronchiectasis had a higher risk of all-cause, respiratory, and lung cancer-related mortality compared to control group. The risk of all-cause mortality was more prominent in those with airflow limitation and in ever smokers.

Background A predictive scoring system for acute respiratory distress syndrome (ARDS) patients, which incorporates age, PaO2/FlO2, and plateau pressure, APPS, was developed recently. It was validated externally in a Caucasian population but has not been studied in Asian populations. The aim of this study was to validate APPS in Korean ARDS patients. Methods We retrospectively reviewed the medical records of patients who were diagnosed with ARDS using the Berlin criteria and admitted to the medical ICU at Seoul National University Hospital from January 2015 to December 2016. The validation of the APPS was performed by evaluating its calibration and predictive accuracy. Its calibration was plotted and quantified using the Hosmer–Lemeshow test. Its predictive accuracy was assessed by calculating the area under the receiver operating characteristics (AUC–ROC) curve. Results A total of 116 patients were analyzed, 32 of whom survived. Of the 116 patients, 11 (9.5%) were classified as APPS grade 1 (score 3–4), 88 (75.9%) as grade 2 (score 5–7) and 17 (14.6%) as grade 3 (score 8–9). In-hospital mortality was 27.3% for grade 1, 73.9% for grade 2 and 94.1% for grade 3 (P for trend

Background and objective Alveolar macrophages of patients with COPD display impaired cytokine release and diminished phagocytosis. COPD exacerbations exhibit immune dysfunction towards the respiratory pathogens. CS and CSE were reported to aggravate bacterial infections in COPD patients. Methods MARCO is highly expressed in lungs and is involved in pathogen clearance. We investigated the effect of CSE on MARCO expression and its regulatory mechanisms. After relevant siRNA transfection and treatment with CSE and/or LPS, we measured the levels of MARCO by q-RT PCR, immunoblotting and flow cytometry. Immunofluorescence staining and immunoprecipitation were used to evaluate the mechanism. Results CSE decreased LPS-induced expression of MARCO mRNA and protein. Upregulation of MARCO by LPS was Nrf2-dependent. Nrf2 knockdown significantly suppressed LPS-induced increase in MARCO transcripts. CSE did not block nuclear translocation of Nrf2 in LPS-treated cells, but rather CSE itself strongly accumulated Nrf2 in the nucleus through the degradation of its cytoplasmic inhibitor, KEAP1. However, CSE markedly suppressed LPS-induced Nrf2 acetylation. Histone acetyltransferase p300/CBP directly acetylates Nrf2, which augments promoter-specific DNA binding of Nrf2. Our results reveal CSE-induced polyubiquitinylation and subsequent degradation of p300 via the proteasome. Pretreatment with proteasome inhibitors completely blocked CSE-induced degradation of p300 and suppression of MARCO expression. Conclusion These findings suggest that CSE decreases MARCO expression via the proteasomal degradation of p300 in macrophages, which may be in part responsible for impaired bacterial phagocytosis.

Background: It has been suggested that a high-flow nasal cannula (HFNC) could help to remove carbon dioxide (CO2) from anatomical dead spaces, but evidence to support that is lacking. The objective of this study was to elucidate whether use of an HFNC could reduce the arterial partial pressure of CO2 (PaCO2) in patients with acute hypercapnic respiratory failure who are receiving conventional oxygen (O2) therapy. Methods: A propensity score-matched observational study was conducted to evaluate patients treated with an HFNC for acute hypercapnic respiratory failure from 2015 to 2016. The hypercapnia group was defined as patients with a PaCO2 >50 mm Hg and arterial pH

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.

Background: The number of elderly patients admitted to the intensive care unit is constantly growing. However, a decision regarding intensive care in these populations remains a challenge. Aim: To identify factors that influences the decision of elderly patients and their families about whether to initiate intensive care in case of an acute event. Design/participants: Medical records of patients (>80 years), who were admitted to general wards and referred for intensive care, were retrospectively reviewed. Patients who received intensive care were compared with those not agreeing to the initiation of intensive care. Results: Among the 125 patients, 45 agreed to receiving intensive care. Baseline characteristics at the time of intensive care unit referral were similar between the intensive care and non-intensive care groups. Only one patient had advance directives before the intensive care unit referral. Lower economic status (odds ratio = 0.27, 95% confidence interval = 0.08–0.94) and cognitive impairment (odds ratio = 0.20, 95% confidence interval = 0.07–0.56) were found associated with a lower likelihood of agreeing to intensive care, while a large number of participants involved in the decision-making process were associated with a higher likelihood of intensive care unit use (odds ratio = 1.82, 95% confidence interval = 1.08–3.09). Mean duration of hospital stay was longer for the intensive care group as compared with the non-intensive care group (28.8 days and 19.8 days, respectively, p = 0.03). However, there was no significant difference in the survival rate. Conclusion: The initiation of intensive care in elderly patients was influenced not only by medical conditions but also by the patient’s economic status and the number of family members involved in the decision-making process.

Erdosteine is widely used as a mucolytic agent and also has free radical scavenging and antioxidant activities. However, little is known about the mechanisms of the anti-inflammatory effect of erdosteine. We investigated the effect of erdosteine on the activation of the nuclear factor (NF)-kB/inhibitor of NFkB (IkB), and the mitogen-activated protein kinase (MAPK) and Akt pathways in the mouse macrophage cell line RAW 264.7. Cultured RAW 264.7 cells were pretreated with erdosteine and stimulated with lipopolysaccharide (LPS). In Western blotting, pretreatment with erdosteine inhibited the IkBα degradation induced in RAW 264.7 cells by LPS. LPS-induced IkB kinase (IKK) activity and NF-kB transcription were inhibited by pretreatment with erdosteine. Production of IL-6 and IL-1β was also inhibited by erdosteine pretreatment. However, erdosteine did not inhibit LPS-induced phosphorylation of Akt and MAPKs. These results suggest that the anti-inflammatory effect of erdosteine in mouse macrophages is mediated through inhibition of LPS-induced NF-kB activation.

Background and objective There are limited data regarding serum activin-A as a biomarker for sepsis. We examined whether serum activin-A concentration could predict sepsis severity and prognosis in the management of critically ill patients with sepsis. Methods The subjects were adult patients suspected of having sepsis and admitted to intensive care unit (ICU) from January 2013 to March 2014. Serum activin-A concentration was measured in blood sampled within 48 h after ICU admission. The primary and secondary outcomes were the diagnostic value of serum activin-A concentration as a biomarker of sepsis and the prognostic value for predicting the clinical outcomes of sepsis, respectively. Results One hundred and thirty patients who had clinically suspected sepsis were included. Most (66.2%) were male; their median age was 65 years, and their Acute Physiology and Chronic Health Evaluation II score was 22.3. Serum activin-A concentration tended to increase with sepsis severity and differed significantly between those with non-sepsis and severe sepsis and between those with severe sepsis and septic shock. The risks of sepsis, severe sepsis and septic shock were significantly higher in patients with a serum activin-A concentration of 251, 319 and 432 pg/mL or greater, respectively. Serum activin-A concentration was significantly associated with the Acute Physiology and Chronic Health Evaluation II score, Sequential Organ Failure Assessment score, Charlson comorbidity index and ICU mortality. Conclusion Serum activin-A was a predictor of sepsis severity and a prognostic marker in critically ill patients with sepsis. Serum activin-A concentration in the early phase of sepsis was associated with prognostic indexes on ICU admission and with ICU mortality.

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.

SETTING A referral centre in South Korea. OBJECTIVE To investigate trends in drug resistance, treatment modalities and outcomes, and adverse events of multidrug-resistant tuberculosis (MDR-TB) over two decades. DESIGN MDR-TB patients treated at Seoul National Hospital University between 1996 and 2015 were divided into four 5-year cohorts according to the date of initial diagnosis. Changes in demographic characteristics, drug resistance, drugs used, treatment outcomes and adverse events over time were elucidated. RESULTS Between 1996 and 2015, 418 patients were treated for MDR-TB: 86 patients between 1996 and 2000, 125 between 2001 and 2005, 123 between 2006 and 2010, and 84 between 2011 and 2015. The proportion of patients with positive acid-fast bacilli sputum (60.5-29.7%, P < 0.001) or cavities on chest radiographs (86.0-40.5%, P < 0.001) decreased over time. Resistance to pyrazinamide, fluoroquinolones, cycloserine and p-aminosalicylic acid decreased. Later-generation fluoroquinolones (77.9-90.5%) and linezolid (0-26.2%) became more frequently prescribed. The treatment success rate increased (45.3-88.1%, P < 0.001); neurological adverse events, including peripheral neuropathy also increased (4.7-13.1%, P = 0.027). CONCLUSION MDR-TB patients presented with less severe disease and better resistance profiles over time in South Korea, with treatment outcomes improving continuously.

Additional file 2. Adjusted HR and 95% CI of each risk factor from multivariate Cox regression analysis

Table S1. Association between other variables with serum activin-A. Table S2. Prognostic value of serum activin level. Table S3. aDifference in survival during hospitalization among Quartiles of serum activin level. Table S4. Comparison of patients with low and high serum activin-A with cut-off value 708pg/mL. Figure S1. Flow diagram of the study population. Figure S2. Serum activin-A concentration according to ARDS severity and PaO2/FiO2. Figure S3. Serum activin-A concentration between indirect and direct ARDS patients. Figure S4. Comparisons of serum activin-A concentrations among healthy control, patients with sepsis (without ARDS), and patients with direct lung injury. (DOCX 186 kb)

IκB, a cytoplasmic inhibitor of nuclear factor-κB (NF-κB), is reportedly degraded via the proteasome. However, we recently found that long-term incubation with proteasome inhibitors (PIs) such as PS-341 or MG132 induces IκBα degradation via an alternative pathway, lysosome, which results in NF-κB activation and confers resistance to PI-induced lung cancer cell death. To enhance the anti-cancer efficacy of PIs, elucidation of the regulatory mechanism of PI-induced IκBα degradation is necessary. Here, we demonstrated that PI upregulates nuclear factor (erythroid-derived 2)-like 2 (Nrf2) via both de novo protein synthesis and Kelch-like ECH-associated protein 1 (KEAP1) degradation, which is responsible for IκBα degradation via macroautophagy activation. PIs increased the protein level of light chain 3B (LC3B, macroautophagy marker), but not lysosome-associated membrane protein 2a (Lamp2a, the receptor for chaperone-mediated autophagy) in NCI-H157 and A549 lung cancer cells. Pretreatment with macroautophagy inhibitor or knock-down of LC3B blocked PI-induced IκBα degradation. PIs up-regulated Nrf2 by increasing its transcription and mediating degradation of KEAP1 (cytoplasmic inhibitor of Nrf2). Overexpression of dominant-negative Nrf2, which lacks an N-terminal transactivating domain, or knock-down of Nrf2 suppressed PI-induced LC3B protein expression and subsequent IκBα degradation. Thus, blocking of the Nrf2 pathway enhanced PI-induced cell death. These findings suggest that Nrf2-driven induction of LC3B plays an essential role in PI-induced activation of the IκB/NF-κB pathway, which attenuates the anti-tumor efficacy of PIs.

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 ≥ 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 ≥ 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 ≥ 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 ≥ 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.

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.

Inflammation by IL-8-induced neutrophil recruitment and apoptosis of epithelial cells by decreased expression of VEGF have been suggested as one of the complicated pathogenic mechanisms of chronic obstructive pulmonary disease (COPD). The role of neutrophil elastase (NE) in the development of COPD is also well known. However, little is known about how they interact. The objective of this study was to elucidate the effect of NE on cigarette smoke extract (CSE)-induced IL-8 and VEGF production and its molecular mechanism in bronchial epithelial cells. CSE increased both IL-8 and VEGF production in human bronchial epithelial cells (BEAS-2B). Although NE significantly enhanced CSE-induced IL-8 production, it suppressed VEGF production. This differential regulation was not CSE-specific. The effect of NE on IL-8 production, but not VEGF, was ERK-dependent. Interestingly, in contrast to decreased VEGF protein expression, NE accelerated VEGF transcription by CSE, suggesting post-translational modification. When cells were incubated with purified NE, it was detected in the cytoplasm, suggesting the intracellular translocation of NE. Furthermore, NE fragmented recombinant human VEGF in vitro but not recombinant human IL-8. These results indicate that VEGF down-regulation is due to direct degradation by NE, which is translocated into cells. Similar to in vitro cell experiments, elastase treatment increased CSE-induced IL-8; however, it suppressed VEGF production in bronchoalveolar lavage fluid of CSE-treated mice. Moreover, elastase treatment enhanced CSE-induced emphysema in mice. Considering the actions of IL-8 and VEGF, our results suggest that NE contributes to the pathogenesis of COPD by enhancing inflammation and apoptosis.

SETTING After several changes in treatment modalities, it is time to re-evaluate treatment outcomes of multidrug-resistant tuberculosis (MDR-TB). OBJECTIVE To evaluate treatment outcomes, elucidate changes in outcomes over time and identify predictors of treatment success for MDR-TB. DESIGN Patients diagnosed with MDR-TB at a tertiary referral centre in South Korea between January 2006 and December 2010 were included. Treatment modalities and outcomes were assessed. Predictors of treatment success were analysed using multiple logistic regression. The treatment modalities and outcomes of these patients were compared with those of MDR-TB patients between January 1996 and December 2005. RESULTS Of the 123 MDR-TB patients diagnosed during the later study period, treatment was successful in 103 (83.7%). Extensive drug resistance (OR 0.31, P = 0.044) and additional resistance to fluoroquinolones (OR 0.23, P = 0.039) were inversely associated with treatment success. The treatment success rate improved from 53.5% in 1996-2000 to 68.8% in 2001-2005 and 83.7% in 2006-2010 (P < 0.001). Improved outcomes were accompanied with more frequent use of later-generation fluoroquinolones and linezolid and less frequent surgical resection. CONCLUSION Treatment outcomes for MDR-TB improved at a tertiary referral centre in South Korea. The improvement was associated with more frequent use of later-generation fluoroquinolones and linezolid.

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.

Yong Suk Jo,1 Ho Il Yoon,2 Deog Kyeom Kim,3 Chul-Gyu Yoo,1 Chang-Hoon Lee1 1Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Hospital, Seoul, 2Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Gyeonggi, 3Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul, Republic of Korea Background and objective: Guidelines recommend the use of simple but comprehensive tools such as COPD Assessment Test (CAT) and Clinical COPD Questionnaire (CCQ) to assess health status in COPD patients. We aimed to compare the ability of CAT and CCQ to predict exacerbation in COPD patients. Methods: We organized a multicenter prospective cohort study that included COPD patients. The relationships between CAT, CCQ, and other clinical measurements were analyzed by correlation analysis, and the impact of CAT and CCQ scores on exacerbation was analyzed by logistic regression analyses and receiver operating characteristic curve. Results: Among 121 COPD patients, CAT and CCQ score correlated with other symptom measures, lung function and exercise capacity as well. Compared with patients who did not experience exacerbation, those who experienced exacerbation (n=45; 38.2%) exhibited more severe airflow limitation, were more likely to have a history of exacerbation in the year prior to enrollment, and demonstrated higher CAT scores. CCQ scores were not significantly associated with exacerbations. A CAT score of ≥15 was an independent risk factor for exacerbation (adjusted odds ratio [aOR], 2.40; 95% CI, 1.03–6.50; P=0.04). Furthermore, CAT scores of ≥15 demonstrated an increased predictive ability for exacerbation compared with currently accepted guidelines for the use of CAT (≥10) and CCQ (≥1) in the assessment of COPD patients (area under the curve for CAT ≥15, CAT ≥10, and CCQ ≥1 was 0.61±0.04, 0.53±0.03, and 0.50±0.03, respectively; P=0.03). Conclusion: A CAT score of ≥15 indicates increased risk of exacerbation in COPD patients, whereas there is no evidence for increased risk based on CCQ score. Keywords: COPD, exacerbation, questionnaire

Adiponectin, a hormone produced by adipose tissue, is very abundant in plasma, and its anti- and pro-inflammatory effects are reported. However, the mechanisms of these pro- and anti-inflammatory effects are not fully defined. Herein, we evaluated the dual inflammatory response mechanism of adiponectin in macrophages. Short-term globular adiponectin (gAd) treatment induced IκBα degradation, NF-κB nuclear translocation, and TNF-α production in RAW 264.7 cells. Polymyxin B pretreatment did not block gAd-induced IκBα degradation, and heated gAd was unable to degrade IκBα, suggesting that the effects of gAd were not due to endotoxin contamination. gAd activated IKK and Akt, and inhibition of either IKK or Akt by dominant-negative IKKβ (DN-IKKβ) or DN-Akt overexpression blocked gAd-induced IκBα degradation, suggesting that short-term incubation with gAd mediates inflammatory responses by activating the IκB/NF-κB and PI3K/Akt pathways. Contrastingly, long-term stimulation with gAd induced, upon subsequent stimulation, tolerance to gAd, lipopolysaccharide, and CpG-oligodeoxynucleotide, which is associated with gAd-induced downregulation of IL-receptor-associated kinase-1 (IRAK-1) due to IRAK-1 transcriptional repression. Conclusively, our findings demonstrate that the pro- and anti-inflammatory responses to gAd in innate immune cells are time-dependent, and mediated by the activation of the IκB/NF-κB pathway, and IRAK-1 downregulation, respectively.

Background: All-cause mortality risk and causes of death in bronchiectasis patients have not been fully investigated yet. The aim of this study was to compare the mortality risk and causes of death between individuals with bronchiectasis and those without bronchiectasis. Methods: Patients with or without bronchiectasis determined based on chest computed tomography (CT) at one centre between 2005 and 2016 were enrolled. We compared the mortality risk and causes of death between the bronchiectasis and non-bronchiectasis groups. Subgroup analyses were also performed according to identification of Pseudomonas or non-tuberculous mycobacteria, airflow limitation, and smoking status. Findings: Of the total 217,702 patients who underwent chest CT, 18,134 bronchiectasis patients and 90,313 non-bronchiectasis patients were eventually included. The all-cause mortality rate in the bronchiectasis group was 1608·8 per 100,000 person-years (95% CI 1531·5-1690·0), which was higher than that in the non-bronchiectasis group (133·5 per 100,000 person-years; 95% CI 124·1-143·8; P

No study has determined whether the risk of mortality predicted by the GAP (gender, age, and physiologic variables) model matches the observed mortality from idiopathic pulmonary fibrosis (IPF) in non-Western populations. We evaluated the clinical course of IPF and validated the GAP model in Korean patients with IPF.We included 268 patients who received a diagnosis of IPF at Seoul National University Hospital between 2005 and 2009. For each patient, demographics and clinical data, such as lung physiologic parameters at IPF diagnosis, were evaluated. We validated the GAP model using discrimination and calibration to predict the risk of death in Korean patients with IPF.The study population comprised 181 men and 87 women (mean age, 65.9 years). The mean baseline % predicted FVC was 77, and % predicted diffusing capacity of lung for carbon monoxide was 65.9. A total of 157 deaths (58.6%) occurred during follow-up, and the median time to death was 4.64 years. The observed cumulative mortality at 1, 2, and 3 years was 10.4%, 20.9%, and 31.0%, respectively. The GAP model produced estimates of 1-year mortality risk consistent with the observed data (C statistic: GAP calculator, 0.74; GAP index and staging system, 0.72; P.29). However, calibration of the GAP model at 3 years was not satisfactory.The GAP model showed similar discrimination power compared with the original cohort but did not predict the 3-year risk of death accurately. Further multinational validation studies are needed.

SummaryBackgroundMultiple comorbidities related to chronic obstructive pulmonary disease (COPD) make it a difficult disease to treat. The relationship between these comorbidities and COPD has not been fully investigated. We aimed to determine whether COPD was independently associated with various comorbidities.MethodsThis was a cross-sectional study, which used data from the Korean National Health and Nutrition Examination Survey (KNHANES) V conducted between 2010 and 2012. Survey design analysis was employed to determine the association between COPD and 15 comorbidities. A COPD patient was defined as a smoker with forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC)

Inflammation and oxidative stress have been suggested as an important pathogenesis of chronic obstructive pulmonary disease (COPD). We investigated the effect of YPL-001, the drug substance of Pseudolysimachion rotundum var. subintegrum , on cigarette smoke extract (CSE)-induced inflammation and anti-oxidative pathway in human bronchial epithelial cells. CSE induced interleukin-8 (IL-8) which was significantly suppressed by YPL-001. YPL-001 also suppressed IL-17A-induced IL-8 release, which suggests that the inhibitory effect of YPL-001 on IL-8 production is not CSE stimulation-specific. NF-κB is a major transcription factor that regulates the expression of several genes including inflammatory cytokines. Although YPL-001 did not block nuclear translocation of NF-κB subunit p65, it suppressed transcriptional activity of NF-κB by blocking acetylation of p65 (Lys310) and suppressed CSE or IL-17A-induced transcription of IL-8 gene. Histone deacetylases (HDACs) prevent gene transcription by condensing DNA structure and affecting NF-κB nuclear binding. YPL-001 alone increased HDAC activity and enhanced CSE-induced activation of HDAC. YPL-001-induced suppression of NF-κB transcriptional activity might be caused by increase in HDAC activity. Moreover, we found that YPL-001 increased Nrf2 expression via both degradation of its inhibitory protein, Keap1 and de novo protein synthesis, resulting in nuclear translocation of Nrf2. YPL-001 increased DNA binding activity of Nrf2. Consequently, YPL-001 up-regulated the expression of Nrf2-targeted anti-oxidant genes such as NQO1 and HO-1. Altogether, these results suggest that YPL-001 could be a good therapeutic candidate for treatment of COPD.

Background: The clinical outcome of eosinophilic airway inflammation in patients with chronic airway diseases is still unclear. Objectives: This study aimed to evaluate the incidence and predictors of exacerbations in patients with nonasthmatic eosinophilic bronchitis (NAEB), and to investigate predictors of improvement in eosinophilic inflammation in chronic airway diseases. Methods: We retrospectively enrolled patients with confirmed sputum eosinophilia (≥ 3%) who had visited our tertiary hospital between 2012 and 2015. About half of the patients were followed up with induced sputum tests for at least 1 year. Results: In total, 398 patients with sputum eosinophilia were enrolled. Of these, 152 (38.2%) had NAEB. The incidence rate of exacerbations requiring treatment with antibiotics, systemic corticosteroids, or hospital admission was 0.13 per patient-year (95% CI, 0.06–0.19) in patients with NAEB. Inhaled corticosteroid (ICS) therapy did not affect the risk of exacerbations, even in an analysis of propensity score. One hundred seventy-six patients had chronic airway diseases; in 37 of these (21.0%), sputum eosinophilia had improved at the 1-year follow-up. Patients who had persistent airflow limitation were less likely to show an improvement in eosinophilic inflammation (aOR, 0.26; 95% CI, 0.09–0.77) when they were treated with ICSs for less than 75% of the follow-up days. Conclusions: Exacerbations requiring systemic corticosteroids, antibiotics, or hospitalization did occur in NAEB patients. Among patients with chronic airway diseases, those with persistent airflow limitation were less likely to show an improvement in eosinophilic airway inflammation.

Cheong-Ju Kim,1 Hyoung-Kyu Yoon,2 Myung-Jae Park,3 Kwang-Ha Yoo,4 Ki-Suck Jung,5 Jeong-Woong Park,6 Seong Yong Lim,7 Jae Jeong Shim,8 Yong Chul Lee,9 Young-Sam Kim,10 Yeon-Mok Oh,11 Song Kim,12 Chul-Gyu Yoo13 1Department of Internal Medicine, National Health Insurance System Ilsan Hospital, Koyang, 2Division of Pulmonology, Department of Internal Medicine, St Mary’s Hospital, College of Medicine, The Catholic University of Korea, 3Division of Respiratory and Critical Care Medicine, Kyung Hee University Hospital, Kyung Hee University, Seoul, 4Department of Internal Medicine, Konkuk University School of Medicine, Gwangjin-gu, 5Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, Hallym University Sacred Heart Hospital, Hallym University Medical School, Anyang-si, 6Division of Pulmonary and Allergy Medicine, Gachon University Gil Medical Center, Incheon, 7Division of Pulmonary and Critical Care Medicine, Department of Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 8Department of Internal Medicine, Korea University College of Medicine, Seoul, 9Department of Internal Medicine and Research Center for Pulmonary Disorders, Chonbuk National University Medical School, Jeonbuk, 10Department of Internal Medicine, Yonsei University College of Medicine, 11Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, 12Clinical Development and Medical Affairs, Novartis Korea Ltd., Seoul, 13Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea Background and objective: Pulmonary tuberculosis (TB) is a risk factor for chronic obstructive pulmonary disease (COPD); however, few clinical studies have investigated treatment effectiveness in COPD patients with destroyed lung by TB. The Indacaterol effectiveness in COPD patients with Tuberculosis history (INFINITY) study assessed the efficacy and safety of once-daily inhaled indacaterol 150 µg for the treatment of Korean COPD patients with destroyed lung by TB and moderate-to-severe airflow limitation. Methods: This was a multicenter, double-blind, parallel-group study, in which eligible patients were randomized (1:1) to receive either once-daily indacaterol 150 µg or placebo for 8 weeks. The primary efficacy endpoint was change from baseline in trough forced expiratory volume in 1 s at Week 8; the secondary endpoints included changes in transition dyspnea index score and St George’s Respiratory Questionnaire for COPD score at Week 8. Safety was evaluated over 8 weeks. Results: Of the 136 patients randomized, 119 (87.5%) completed the study treatment. At Week 8, indacaterol significantly improved trough forced expiratory volume in 1 s versus placebo (treatment difference [TD] 140 mL, P

Purpose:Uric acid acts as both a pathogenic inflammatory mediator and an antioxidative agent. Several studies have shown that uric acid level correlates with the incidence, severity, and prognosis of pulmonary diseases. However, the association between uric acid level and acute respiratory distress syndrome (ARDS) has not been studied. This study was conducted to elucidate how serum uric acid level is related with clinical prognosis of ARDS.Methods:A retrospective cohort study with propensity score matching was conducted at a medical intensive care unit of a tertiary teaching hospital. The medical records of patients diagnosed with ARDS admitted from 2005 through 2011 were reviewed.Results:Two hundred thirty-seven patients with ARDS met the inclusion criteria. Patients with a serum uric acid level Conclusion:In patients with ARDS, a low serum uric acid level may be a prognostic marker of a low risk of in-hospital mortality.

Background Inhaled corticosteroid (ICS) is recommended in the management of patients with asthma–chronic obstructive pulmonary disease overlap syndrome (ACOS), but its effectiveness has not been clearly proved. Objective To evaluate whether ICS has effects on outcomes of ACOS. Methods In this observational 12-year retrospective cohort study involving 125 patients with ACOS from Seoul National University Hospital, the annual rate of decrease in forced expiration volume in 1 second, the incidence rate of severe exacerbation, and overall mortality in an ICS-treated group were compared with those in a non-ICS–treated group. Results Of 125 patients with ACOS, 90 and 35 were categorized to the ICS and non-ICS treatment groups, respectively. There were no significant differences between the 2 groups in the annual rate of decrease in forced expiration volume in 1 second (9.61 mL/year in ICS treatment group vs 15.68 mL/year in non-ICS treatment group, P = .598). Compared with the non-ICS treatment group, the ICS treatment group did not show a decrease in the risk of severe exacerbation (adjusted incidence rate ratio 1.24, 95% confidence interval 0.44–3.46). Time to death also did not differ between the 2 groups. Even when analyses with propensity score matching were performed, the results were similar. Conclusion In the management of ACOS, the use of ICS was not significantly associated with improvements in the annual rate of decrease in forced expiration volume in 1 second, the incidence of severe exacerbations, and overall mortality compared with the non-ICS treatment group.

Patients admitted to medical intensive care unit (MICU) are at increased risk for venous thromboembolism (VTE); and prophylaxis is recommended. However, the actual range and frequency of VTE prophylaxis administered to MICU patients are not well defined. Patients over 40 yr of age and expected MICU stay of more than 48 hr were eligible for this observational cohort study of 23 MICUs in Korea. Patients already on anticoagulation therapy or those requiring anticoagulation for reasons other than VTE were excluded. Among 830 patients, VTE prophylaxis was given to 560 (67.5%) patients. Among 560 patients, 323 (38.9%) received pharmacoprophylaxis, 318 (38.4%) received mechanical prophylaxis and 81 (9.8%) received both forms of prophylaxis. About 74% of patients in the pharmacoprophylaxis group received low molecular weight heparin and 53% of the patients in the mechanical prophylaxis group used intermittent pneumatic compression. Most of the patients (90%) had more than one risk factor for VTE and the most common risk factor was old age, followed by heart and respiratory failure. In this observational cohort study of 23 MICUs in Korea, 67.5% of patients received thromboprophylaxis. Further studies are needed to clarify the role and efficacy of VTE prophylaxis in Korean critically ill patients.

Background/Aims This study was conducted to assess the disease burden of pneumonia according to age and presence of underlying diseases in patients admitted with community-acquired pneumonia (CAP). Methods We performed a retrospective, observational study and collected data targeting patients with CAP (≥ 50 years) from 11 hospitals. Disease burden was defined as total per-capita medical fee, severity (CURB-65), hospital length of stay (LOS), and mortality. Results Of the 693 enrolled subjects, elderly subjects (age, ≥ 65 years) had a higher mean CURB-65 score (1.56 vs. 0.25; p < 0.01) and higher mortality than nonelderly subjects (4.4% [n = 21] vs. 0.5% [n = 1]; p = 0.00). In addition, the total cost of pneumonia treatment was higher in elderly patients compared to in nonelderly patients (KRW 2,088,190 vs. US $1,701,386; p < 0.01). Those with an underlying disease had a higher CURB-65 score (1.26 vs. 0.68; p < 0.01), were much older (mean age, 71.24 years vs. 64.24 years; p < 0.01), and had a higher mortality rate than those without an underlying disease (3.5% [n = 20] vs. 1.7% [n = 2]; p = 0.56). Total per-capita medical fees were higher (KRW 2,074,520 vs. US $1,440,471; p < 0.01) and hospital LOS was longer (mean, 8.38 days vs. 6.42 days; p < 0.01) in patients with underlying diseases compared to those without. Conclusions Due to the relatively high disease burden in Korea, particularly in the elderly and in those with an underlying disease, closer and more careful observation is needed to improve the outcomes of patients with CAP.

Background and Aims The solitary pulmonary nodule (SPN) is a common clinical problem usually detected incidentally during screening tests for lung cancer. Video-assisted thoracoscopic surgery (VATS) is performed for diagnosing SPNs when there are technical difficulties with transthoracic needle aspiration biopsy or bronchoscopic biopsy, inconclusive biopsy results, or when there is a high suspicion of malignancy. This study aimed to identify factors that can reduce unnecessary VATS for the diagnosis of SPNs. Methods We retrospectively analysed patients with SPNs (n = 107) who had undergone diagnostic VATS at Seoul National University Hospital from January 2007 to December 2008. Clinical and radiological parameters were evaluated to compare benign and malignant SPNs. Results Benign SPNs were diagnosed in 31 patients (29.0%). The most common reason for patients to undergo a diagnostic VATS was a history of malignancy. The most common histological findings in patients with benign SPNs were non-specific inflammatory lesions (29.0%) and tuberculosis (16.1%). The presence of respiratory symptoms was significantly associated with benign diseases [P = 0.004, odds ratio (OR) 0.189, 95% confidence interval (CI) 0.060–0.590], and part-solid nodules were significantly related to malignancy (P = 0.026, OR 6.34, 95% CI 1.248–32.169). Conclusion Approximately 30% of SPNs resected by VATS were benign. Although we did not identify a definite factor for predicting benign disease or malignancy, the presence of respiratory symptoms was related to benign disease, and part-solid nodules were associated with malignancy.

Summary Objectives The incidence of Pneumocystis jirovecii pneumonia (PCP) in patients without HIV infection (non-HIV PCP) has been increasing along with the increased use of chemotherapeutic agents and immunosuppressants, but the prognostic factors of non-HIV PCP remain unclear. This study aimed to identify the prognostic factors of non-HIV PCP. Methods Immunocompromised patients without HIV infection who were diagnosed and treated for PCP were included. The PCP diagnosis was based on positive direct fluorescent antibody (DFA) or polymerase chain reaction (PCR) results and compatible clinical symptoms and radiological findings. Results In total, 372 non-HIV patients with positive PCP DFA or PCR findings were screened and 173 were included. Univariate analysis indicated that age, smoking, chronic lung disease or hematologic malignancy, chemotherapeutic agents, high alveolar–arterial oxygen gradient (D[A–a]O 2 ), C-reactive protein, albumin, blood urea nitrogen (BUN), CMV antigenemia, combined bacteremia, high percentage of neutrophils and rate of co-infection in BAL fluid, and mechanical ventilator care were related to the prognosis of non-HIV PCP. Multivariate analysis revealed that high D(A–a)O 2, combined bacteremia, increased BUN and preexisting lung disease were indicators of a poor prognosis. Conclusions High D(A–a)O 2, combined bacteremia, increased BUN and preexisting lung disease were independent factors of poor prognosis in non-HIV PCP patients.

Introduction: The impact of chronic obstructive pulmonary disease (COPD) on the mortality of patients with lung cancer has not been studied extensively. The objective of this study is to compare the mortality and clinical characteristics of patients with non–small-cell lung cancer (NSCLC) according to the presence of COPD. Methods: The medical records of 221 smokers diagnosed with NSCLC were reviewed. Eligible patients were dichotomized into the COPD group ( n = 111) and the non-COPD group ( n = 110). The overall survival and clinical characteristics were compared, and predictors of worse survival were analyzed using Cox proportional hazards regression. Results: COPD was present in 50.2% of all patients with NSCLC, and most of the patients (92.8%) with COPD were unaware of the disease before the diagnosis of lung cancer. Patients in the COPD group were older and had a lower body mass index, higher pack-years smoking history, higher frequency of dyspnea, and higher incidence of previous malignancy. The overall survival of enrolled patients and propensity score-matched subjects was comparable between the two groups (log-rank test, p = 0.2 and 0.396, respectively). Old age, low body mass index, advanced disease stage (stages III and IV), non-squamous histology, Eastern Cooperative Oncology Group performance status of greater than or equal to 2, weight loss, and coexistence of interstitial lung disease were independent risk factors for shorter survival. Conclusion: COPD frequently and subliminally coexists with NSCLC. Although differences in clinical characteristic did exist, there was no impact of COPD on the mortality of patients with NSCLC with a positive smoking history in this study.

Background The aspirates from endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) were examined using the tissue core and cytology. We assessed that the tissue core was a more reliable specimen and attempted to analyze how many discrepancies were found between the two specimens. We investigated diagnostic concordance rate between histology and cytology. Methods From January 2011 to December 2011, a total of 267 consecutive patients with lung cancer, who underwent EBUS-TBNA, were included in this retrospective study. Results Of the 267 lung cancer patients, 207 (77.5%) were men. The median age was 65 years old. The most common pathologic type was adenocarcinoma (120, 44.9%), followed by squamous cell carcinoma (79, 29.6%). Among the 267 patients, 579 mediastinal and hilar lymph nodes were punctured. The right lower paratracheal (204, 35.2%) and subcarinal (172, 29.7%) lymph nodes were the most common nodal stations. Among the 579 lymph nodes, malignant cells were observed in 267 (46.1%) nodes, in either the histologic, cytologic or both slides: 209 in both histology and cytology, 37 in histology only, and 21 in cytology only slides. The diagnostic concordance rate between the tissue core and cytology was 90.0% (95% confidence interval CI, 87.1–92.2) (κ = 0.79). Conclusions The diagnostic concordance rate between the histology and cytology of EBUS-TBNA in lung cancer was 90.0% (95% CI, 87.1–92.2) (κ = 0.79).

Background The association of inhaler use with haemoptysis has rarely been reported in patients with non-cystic fibrosis (CF) bronchiectasis. Objective To elucidate the effect of inhaler use on the development of haemoptysis in patients with non-CF bronchiectasis. Methods In a case-crossover study of 192 non-CF bronchiectasis patients with a history of haemoptysis and inhaler use, the risk of haemoptysis associated with the use of inhalers was elucidated. Two inhaled corticosteroids/long-acting β₂-agonists (ICS/LABA), one long-acting muscarinic antagonist and one short-acting β₂-agonist (SABA) were evaluated. The case and control periods were defined respectively as 030 and 180210 days before haemoptysis. Results The risk of haemoptysis during the case period was 3.51 times higher than during the control period with any use of inhalers (95%CI 1.966.28). The results of clinically significant haemoptysis showed good agreement with those of total events. These associations were consistent with the sensitivity analyses. In the sub-analysis according to inhaler type, ICS/LABA and SABA were significantly associated with an increased risk of haemoptysis (aOR 2.62, 95%CI 1.255.45; aOR 2.51, 95%CI 2.235.15). Conclusions In patients with non-CF bronchiectasis, the use of inhalers, especially including 2-agonist, was associated with an increased risk of haemoptysis.

This study identified the key chemical components based on an analysis of the seasonal variations of ground level PM2.5 concentrations and its major chemical constituents (sulfate, nitrate, ammonium, organic carbon, and elemental carbon) in the Seoul Metropolitan Area (SMA), over a period of five years, ranging from 2012 to 2016. It was found that the mean PM2.5 concentration in the SMA was 33.7 &mu, g/m3, while inorganic ions accounted for 53% of the total mass concentration. The component ratio of inorganic ions increased by up to 61%&ndash, 63% as the daily mean PM2.5 concentration increased. In spring, nitrate was the dominant component of PM2.5, accounting for 17%&ndash, 32% of the monthly mean PM2.5 concentrations. In order to quantify the impact of long-range transport on the SMA PM2.5, a set of sensitivity simulations with the community multiscale air-quality model was performed. Results show that the annual averaged impact of Chinese emissions on SMA PM2.5 concentrations ranged from 41% to 44% during the five years. Chinese emissions&rsquo, impact on SMA nitrate ranged from 50% (winter) to 67% (spring). This result exhibits that reductions in SO2 and NOX emissions are crucial to alleviate the PM2.5 concentration. It is expected that NOX emission reduction efforts in China will help decrease PM2.5 concentrations in the SMA.

Blood lactate levels and central venous oxygen saturation (ScvO(2)) are known to be useful indicators of global tissue hypoxia. However, it is unclear whether ScvO(2) correlates with lactate levels when measured simultaneously and whether changes in ScvO(2) or lactate levels in serial measurements have prognostic value. We investigated the correlation between ScvO(2) and lactate levels measured simultaneously and their association with clinical outcomes.We performed a prospective observational study of patients with severe systemic inflammatory response syndrome (SIRS) and severe sepsis who were admitted to the medical intensive care unit. ScvO(2) and lactate levels were measured simultaneously at the time of study enrollment, every 6 h for 24 h, and then every 24 h until the goal was reached.Twenty-five patients were enrolled in the study; 13 have died and 12 have survived. There was no correlation between lactate levels and ScvO(2). Neither lactate levels nor ScvO(2) at the time of admission differed between nonsurvivors and survivors. Normalization of lactate levels within 48 h was significantly associated with survival.In patients with severe SIRS and severe sepsis, simultaneously measured ScvO(2) and lactate levels showed no correlation, and normalization of lactate levels within 48 h was a predictive factor for survival.

Background: Patients with interstitial lung disease (ILD) have a high incidence of postoperative pulmonary complications (PPCs) after lung resection, but there is little data about these complications in ILD after other types of surgery. Objectives: The aim of this study was to examine the characteristics and predictors of PPCs after major surgery in patients with ILD. Methods: We included 336 patients with ILD who underwent major surgery between January 2005 and December 2010 at two tertiary hospitals in Korea. All types of surgery that had been performed under general anesthesia were included. Demographic characteristics, preoperative lung function, and operative conditions including anesthesia time and estimated blood loss were compared between patients with and without PPCs. Results: PPCs occurred in 37 patients (11%). Thirteen patients developed pneumonia, the most common PPC, and 11 had acute exacerbation of ILD. In multivariable analysis, BMI Conclusions: The incidence of PPCs detected over all surgeries was not as high as that reported for lung surgery alone in ILD patients. Lower BMI, emergency surgery, lung surgery, and longer anesthesia time were risk factors. Operative conditions as well as lung function should be considered in preoperative planning and management for ILD patients undergoing major surgery.

Background Cigarette smoking is one of the major causes of lung cancer. However, the correlation between smoking status and the survival of patients with lung cancer is uncertain. The present study aimed to evaluate the impact of smoking status on the mortality of patients with non-small cell lung cancer (NSCLC). Methods The medical records of 313 patients newly diagnosed with NSCLC between January 2005 and January 2006 were reviewed. Eligible patients were divided into ever-smokers (221 patients) and never-smokers (92 patients), and the overall survival and clinical characteristics of the two groups were compared. Predictors of survival were analyzed using Cox's proportional hazards regression. Results In ever-smokers, the mean age was higher, and male gender and squamous histology were predominant compared to never-smokers. The median survival time was longer in never-smokers (21.1 vs. 41.9 months, ever-smokers vs. never-smokers, respectively; P = 0.027). Overall survival estimates at 12, 24, and 60 months were 62.9 versus 82.6%, 43.4 versus 65.2%, and 31.2 versus 42.4%, in each group. Advanced age, advanced disease stage (stages III and IV), and coexistence of interstitial lung disease were analyzed as independent risk factors for shorter survival. Although ever-smoking was not an independent risk factor, current smoking was a risk factor for higher mortality. Conclusions The overall mortality of ever-smokers was higher than that of never-smokers in patients with newly diagnosed NSCLC, and current smoking was an independent risk factor for a poorer prognosis.