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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 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.

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 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.

Purpose Brain metastasis has a poor prognosis in patients with advanced non-small cell lung cancer (NSCLC). In this study, we evaluated the prognosis of NSCLC patients with brain metastases. Methods We analyzed a total of 313 NSCLC patients with brain metastasis. We compared the prognoses between a group of less than four (group A) and a group of more than four or equal to four (≥4) (group B) brain metastases. Results The median survival time was 334 days (group A, 164 patients, 52.4%) and 234 days (group B, 149 patients, 47.6%). Univariate analysis showed that the number of metastases, age at diagnosis of brain metastasis, smoking history, histologic type, and former stage of primary lung cancer before brain metastasis, had a significant influence. In addition, treatment for primary lung cancer lesions and brain metastasis also affected the overall survival (p < .0001). However, there was no difference in the overall survival between the two groups in the multivariate analysis. Conclusion Our results show that the number of brain metastases, classified by group A (

Background and objective: Vitamin D deficiency has been reported to be associated with the development of active tuberculosis (TB), but many discrepancies exist among studies. The aims of this study were to compare the frequency of vitamin D deficiency in a Korean population of TB patients and control subjects, and to monitor the changes in vitamin D levels during TB treatment. Methods: Patients with newly diagnosed TB were prospectively enrolled. In addition, healthy volunteers or patients with diseases other than TB were enrolled as controls. Baseline serum 25-hydroxyvitamin D (25-OHD) levels were measured in both groups and compared. In the TB patients, measurements of serum 25-OHD were repeated 1 month after the initiation of treatment and again after completion of treatment. Results: In total, 116 patients with TB and 86 control subjects were recruited. The median 25-OHD concentration was not different in TB patients at diagnosis (13.9 ng/mL; interquartile range (IQR) 8.80–21.8) compared with control subjects (13.2 ng/mL; IQR 9.6–19.3) (P = 0.97). The frequency of vitamin D deficiency (≤10 ng/mL) was also not different in TB patients (36.2%) compared with controls (27.3%) (P = 0.21). In TB patients, the median 25-OHD concentration decreased significantly during treatment, to 12.5 ng/mL at 1 month and 11.0 ng/mL on completion of treatment (P = 0.01). Conclusions: Vitamin D levels do not appear to be associated with the development of TB in the Korean population. The median 25-OHD concentration decreased after treatment for TB.

Background and objective: Antimicrobial resistance is a global problem and the prevalence is high in many Asian countries. Methods: A prospective observational study of the prevalence of bacterial pathogens and their antimicrobial susceptibilities in patients with acute exacerbations of chronic bronchitis (AECB) was conducted in Indonesia, Philippines, Korea, Thailand, Malaysia, Taiwan and Hong Kong from August 2006 to April 2008. The diagnosis of AECB was based on increased cough and worsening of two of following: dyspnoea, increased sputum volume or purulence. Patients who had taken antibiotics within 72 h of presentation were excluded. All bacterial strains were submitted to a central laboratory for re-identification and antimicrobial susceptibility testing to 16 antimicrobial agents according to Clinical and Laboratory Standards Institute. Results: Four hundred and seven isolates were identified among 447 patients of AECB. The most frequent organisms isolated were Klebsiella pneumoniae and associated species (n = 91 + 17), Haemophilus influenzae (n = 71), Pseudomonas aeruginosa (n = 63), Streptococcus pneumoniae (n = 32), Acinetobacter baumannii (n = 22) and Moraxella catarrhalis (n = 21). According to Clinical and Laboratory Standards Institute susceptibility breakpoints, 85.7% and >90% of these pathogens were susceptible to levofloxacin and cefepime respectively. Other options with overall lower susceptibilities include imipenem, ceftazidime, ceftriaxone and amoxicillin/clavulanate. Conclusions: Gram-negative bacteria including Klebsiella spp., P. aeruginosa and Acinetobacter spp. constitute a large proportion of pathogens identified in patients with AECB in some Asian countries. Surveillance on the local prevalence and antibiotic resistance of these organisms is important in guiding appropriate choice of antimicrobials in the management of AECB.

Background and objective: Accurate staging at the time of diagnosis is very important in deciding on the appropriate treatment for cancer patients. FDG PET indicates metabolic changes in cancer cells, enabling the early detection of lesions. This has the advantage of allowing more accurate staging than is possible with conventional staging tools, and has led to the incorporation of FDG PET in the initial work-up protocols for lung cancer patients. In this study, we evaluated the clinical impact of FDG PET as an initial staging tool, on the therapeutic management of patients with non-small cell lung cancer (NSCLC). Methods: Patients diagnosed with NSCLC by histopathology were retrospectively identified and both chest CT and FDG PET were performed for initial staging. Information was collected regarding the results of conventional versus FDG PET staging, and any resulting modifications of treatment were evaluated. Results: Among the 537 patients who were evaluated FDG PET resulted in upstaging of the tumour in 91 (17%) and downstaging of the tumour in 68 (13%). Consequently, therapeutic management was modified in 118 patients (22%). Furthermore, use of FDG PET resulted in the detection of a second primary cancer in six patients. Conclusions: This study confirms that FDG PET has a considerable impact on the initial staging and therapeutic management of patients with NSCLC.

Connective tissue diseases are the most common disorders causing diffuse alveolar haemorrhage (DAH) confirmed by open lung biopsy. However, it is not known whether these diseases are also the most common causes of DAH in patients presenting with the features of ARDS/acute lung injury (ALI). This study evaluated the frequency of concomitant disease in patients with ARDS/ALI and DAH.The sampling frame comprised all patients in a tertiary referral hospital diagnosed with ARDS/ALI and who underwent BAL between January 2000 and July 2006. The medical records of those patients who had BAL fluid findings compatible with DAH were reviewed.Of the 97 patients diagnosed with ARDS/ALI and who underwent BAL, 27 had BAL fluid findings compatible with DAH. Sixteen of the 27 patients did not have connective tissue diseases (59%); of these 12 patients had concomitant haematological malignancies or solid tumours. Of the seven patients who presented with DAH and no known underlying disease, only two were subsequently diagnosed with a connective tissue disorder. The in-hospital mortality rate was 55% and 63% for patients with DAH with and without connective tissue diseases, respectively (P = 0.710).The majority of patients with DAH presenting with the features of ARDS/ALI did not have underlying connective tissue diseases. Concomitant malignancies were found frequently in these patients. The outcome did not differ between patients with DAH with or without connective tissue diseases.

The effective control of tuberculosis (TB) requires that people at high risk for the reactivation of TB are identified. Haematological malignancy has been shown to be a risk factor for the development of TB, either through immune suppression by the tumour or through the effects of chemotherapy. This study assessed the hypothesis that solid-organ malignancy is a risk factor for the development of TB.A retrospective cohort study was performed to determine the incidence of TB in patients with solid-organ malignancy and in control subjects without malignancy. Risk factors for the development of TB among patients with cancer were also assessed.The study recruited 1809 cases with cancer and 1809 control subjects and followed them for 3 years. The incidence of active TB per 1000 person-years was 3.07 in patients with cancer and 0.77 in controls (P = 0.009). Compared with the control group, patients with cancer had an increased risk of developing TB (incidence rate ratio (IRR) 4.69, 95% CI: 1.52-14.46). Proportional hazards regression analysis showed that the risk factors for development of TB were chronic renal failure (IRR 9.91, 95% CI: 1.17-83.60), old healed TB on CXR (IRR 45.05, 95% CI: 5.74-353.88), and anticancer chemotherapy (IRR 4.32, 95% CI: 1.10-16.89). An interaction between old healed TB and anticancer chemotherapy was observed.These findings indicate that immune suppression by cancer or by anticancer chemotherapy increases vulnerability to reactivation of TB, especially in cancer patients with old healed TB.

OBJECTIVE Alpha1-antitrypsin (AAT) deficiency is a recognized susceptible factor for chronic obstructive pulmonary disease (COPD) in Western countries, but its importance in Korea is unclear. To date, no definitive case of alpha1-antitrypsin deficiency has been reported in Korea. This study aimed to clarify whether alpha1-antitrypsin deficiency exists and to determine the distribution of alpha1-antitrypsin alleles in the Korean population. METHODOLOGY The serum concentrations of alpha1-antitrypsin were determined and polymorphisms of the alpha1-antitrypsin gene in 114 COPD patients and in 196 healthy controls were examined. Phenotyping by isoelectric focusing and the genotyping of alpha1-antitrypsin gene by polymerase chain reaction and restriction fragment length polymorphism were performed. RESULTS No alpha1-antitrypsin level abnormality was found in the patients. M1(Val)/M1(Val) was found to be the most frequent genotype in both groups (69.2% and 66.8%, respectively), and M1(Val) the most frequent allele. The distributions of alpha1-antitrypsin alleles were similar in the patient and control groups, and no S or Z allele was found. CONCLUSION Alpha1-antitrypsin deficiency is unlikely to be an important cause of chronic obstructive pulmonary disease in the Korean population.

Cigarette smoke (CS) induces lung inflammation and simultaneously activates anti-oxidative pathway as a defense mechanism. Recently, we found that neutrophil elastase (NE) enhances cigarette smoke extract (CSE)-induced inflammation. Therefore, this study was undertaken to investigate the roles of NE on CSE-induced activation of anti-oxidative pathway and its regulatory mechanism in bronchial epithelial cells. CSE activated Nrf2, a transcription factor, which regulates the expression of several antioxidants. CSE increased anti-oxidants such as HO-1 and NQO1. Interestingly, NE suppressed CSE-induced expression of HO-1 mRNA and protein, but not NQO1. Therefore, we first determined the effects of NE on Nrf2. Although NE did not affect the basal and inducible level of Nrf2 mRNA, it significantly decreased the expression of Nrf2 protein. Nrf2 protein stability has been reported to be regulated by DJ-1 and Keap1. However, the expression level of DJ-1 and Keap1 did not change in NE-treated cells. Nrf2 down-regula...

A 61-year-old Korean housewife developed dyspnoea, cough and weight loss in the summer of 1994. The case was diagnosed as definite summer-type hypersensitivity pneumonitis (SHP) according to the criteria proposed for hypersensitivity pneumonitis and for SHP. Her serum antibodies to Trichosporon were positive. Her symptoms were exacerbated after she returned home and Trichosporon was isolated from the patient's home, indicating Trichosporon as the causative antigen. This is the first confirmed case of SHP outside Japan. On the basis of our research in SHP to date, we propose that SHP occurs in other Asian countries and that the assay of anti-Trichosporon antibodies is useful for the diagnosis of the disease.