Subtypes of Patients with Mild to Moderate Airflow Limitation as Predictors of Chronic Obstructive Pulmonary Disease Exacerbation.

COPD is a heterogeneous disease, and its acute exacerbation is a major prognostic factor. We used cluster analysis to predict COPD exacerbation due to subtypes of mild-moderate airflow limitation. In all, 924 patients from the Korea COPD Subgroup Study cohort, with a forced expiratory volume (FEV1) ≥ 50% and documented age, body mass index (BMI), smoking status, smoking pack-years, COPD assessment test (CAT) score, predicted post-bronchodilator FEV1, were enrolled. Four groups, putative chronic bronchitis (n = 224), emphysema (n = 235), young smokers (n = 248), and near normal (n = 217), were identified. The chronic bronchitis group had the highest BMI, and the one with emphysema had the oldest age, lowest BMI, and highest smoking pack-years. The young smokers group had the youngest age and the highest proportion of current smokers. The near-normal group had the highest proportion of never-smokers and near-normal lung function. When compared with the near-normal group, the emphysema group had a higher risk of acute exacerbation (OR: 1.93, 95% CI: 1.29-2.88). However, multiple logistic regression showed that chronic bronchitis (OR: 2.887, 95% CI: 1.065-8.192), predicted functional residual capacity (OR: 1.023, 95% CI: 1.007-1.040), fibrinogen (OR: 1.004, 95% CI: 1.001-1.008), and gastroesophageal reflux disease were independent predictors of exacerbation (OR: 2.646, 95% CI: 1.142-6.181). The exacerbation-susceptible subtypes require more aggressive prevention strategies.

Association of type 2 diabetes mellitus with lung cancer in patients with chronic obstructive pulmonary disease.

Background: Patients with chronic obstructive pulmonary disease (COPD) have an increased risk of developing lung cancer. Some studies have also suggested that diabetes mellitus (DM) may increase the risk of developing lung cancer. This study aimed to investigate whether type 2 DM (T2DM) is associated with an increased risk of lung cancer in patients with COPD. Materials and methods: We conducted a retrospective analysis on two cohorts: the National Health Insurance Service-National Sample Cohort (NHIS-NSC) of Korea and the Common Data Model (CDM) database of a university hospital. Among patients newly diagnosed with COPD in each cohort, those with a lung cancer diagnosis were included, and a control group was selected through propensity score matching. We used the Kaplan-Meier analysis and Cox proportional hazard models to compare lung cancer incidence between patients with COPD and T2DM and those without T2DM. Results: In the NHIS-NSC and CDM cohorts, we enrolled 3,474 and 858 patients with COPD, respectively. In both cohorts, T2DM was associated with an increased risk of lung cancer [NHIS-NSC: adjusted hazard ratio (aHR), 1.20; 95% confidence interval (CI), 1.02-1.41; and CDM: aHR, 1.45; 95% CI, 1.02-2.07). Furthermore, in the NHIS-NSC, among patients with COPD and T2DM, the risk of lung cancer was higher in current smokers than in never-smokers (aHR, 1.45; 95% CI, 1.09-1.91); in smokers with ≥30 pack-years than in never-smokers (aHR, 1.82; 95% CI, 1.49-2.25); and in rural residents than in metropolitan residents (aHR, 1.33; 95% CI, 1.06-1.68). Conclusion: Our findings suggest that patients with COPD and T2DM may have an increased risk of developing lung cancer compared to those without T2DM.

A modified method of measuring plasma volume with indocyanine green: reducing the frequency of blood sampling while maintaining accuracy.

Among various methods for measuring the plasma volume (PV), the indocyanine green (ICG) dilution technique is a relatively less invasive method. However, the ICG method is rather cumbersome because 10 blood samples need to be obtained within a short time after ICG administration. Thus, reducing the frequency of blood sampling while maintaining the accuracy would facilitate plasma volume measurement in clinical situations. We here developed a modified method to measure plasma volume using 2260 ICG plasma concentration data from 115 surgical patients. The mean relative error (MRE) and the percentage of cases with relative error (RE) greater than 5% in total (PRE) were used to quantify the difference between plasma volumes obtained by the original and modified methods. RE was determined as follows. RE(%) = (PV obtained by original method (PVoriginal)-PV obtained by modified method (PVmodified))/PVoriginal × 100. PVmodified was assumed to be equal to PVoriginal when the RE was < 5%. When the number of samples selected for the plasma volume estimation was 4 or less, the PRE was mostly 10% or more. Five out of the 10 blood samples (order: 1st, 2nd, 3rd, 9th, and 10th) showed similar accuracies with the plasma volume obtained by the original method (original: 2.72 ± 0.64 l, modified: 2.72 ± 0.65 l). This modified method may be able to aptly replace the original method and lead to a wider clinical application of the ICG dilution technique. Further validation is needed to determine if the results of this study may be applied in other populations.

The flavonoid ellagic acid from a medicinal herb inhibits host immune tolerance induced by the hepatitis B virus-e antigen.

The aim of this study is to characterize the role of ellagic acid, a flavonoid from a medicinal herb which blocks HBeAg secretion in a HBV infected cell line and in HBeAg transgenic mice, in immune tolerance in chronic HBV infection. Using the mouse strain C57ML/6, HBeAg-producing transgenic mice (HBeAg-Tg), under the control of metal ion-inducible promoter were generated. The effect on immune tolerance of HBeAg-Tg and the release of immune tolerance by the inhibitor of HBeAg secretion, ellagic acid, was tested using T/B cell proliferation, HBeAg/HBeAb production, cytotoxic T-lymphocyte (CTL) and cytokine assays. C57ML/6 based HBeAg-producing HBeAg-Tg mice were tolerant to HBeAg at the T and B-cell level, did not produce antibodies to HBeAg in vivo and in vitro, produced minimal levels of cytokines (IL-4 and IFN-gamma) and decreased CTL responses, while feeding mice with ellagic acid (5mg/kg body weight) blocked the immune tolerance caused by HBeAg. Our results suggest that host immune tolerance induced by HBeAg during HBV infection, a viral strategy to guarantee HBV infection, can be overcome by ellagic acid, thus it can be used as a therapeutic for HBV-carriers.

A flavonoid from medicinal plants blocks hepatitis B virus-e antigen secretion in HBV-infected hepatocytes.

A flavonoid molecule that showed a unique anti-HBV function was isolated from Phyllanthus urinaria. The molecular formula was determined as C14H6O8 based on FAM-MS analysis and the structure was determined by NMR. The identified flavonoid molecule, ellagic acid, showed unique anti-HBV functions. Ellagic acid did not inhibit either HBV polymerase activity, HBV replication or block HBsAg secretion. Rather, ellagic acid blocks effectively HBeAg secretion in HepG2 2.2.15 cells (IC50=0.07 microg/ml). Since HBeAg is involved in immune tolerance during HBV infection, ellagic acid, a newly identified functional anti-HBV compound, may be a new candidate therapeutic against immune tolerance in HBV-infected individuals.