EGFR Tyrosine Kinase Inhibitor Efficacy in Older Adult Patients with Advanced EGFR-Mutated Non-Small-Cell Lung Cancer: A Meta-Analysis and Systematic Review.

Background and Objectives: Lung cancer remains the most common malignancy worldwide. As the global population ages, the prevalence of epidermal growth factor receptor (EGFR)-mutation-positive non-small cell lung cancer (NSCLC) is increasing. Materials and Methods: We performed a meta-analysis and a systematic review of randomized, controlled trials to evaluate the efficacy of EGFR TKIs on progression-free survival (PFS) and overall survival (OS) in older adult patients with advanced EGFR-mutated NSCLC. A total of 1327 patients were included; among these, 662 patients were >65 years of age. Results: A pooled analysis indicated (1) an overall improvement in higher PFS for dacomitinib and osimetinib than that for other drugs (hazard ratio [HR] = 0.654, 95% CI: 0.474 to 0.903; p = 0.01) and (2) and no significant difference in the OS between the EGFR TKIs (HR = 0.989, 95% CI: 0.796 to 1.229; p = 921). Conclusion: Our study found that osimertinib achieved a higher PFS than all other EGFR TKIs did. Osimertinib is the preferred EGFR TKI for treatment of older adult patients with advanced EGFR-mutated NSCLC.

Carbon Arc Lamp Therapy Enhances the Repair Potential of Chronic Soft Tissue Injury in Rats Compared with the Ability of Photobiomodulation Therapy.

Objective: The effects of photobiomodulation therapy (PBMT) and carbon arc lamp therapy (CALT) on the repair of chronic soft tissue injury were compared. Background data: PBMT improves soft tissue repair of chronic injury. However, there has been no research on the effect of CALT. Methods: Human umbilical vein endothelial cells (HUVECs) were irradiated using PBMT and CALT at 2 J/cm2 to observe their effects on cell proliferation and migration. The effects of PBMT and CALT on soft tissue injury repair were assessed using a chronic gastrocnemius injury model of the posterior limb in rats. The malondialdehyde (MDA), superoxide dismutase (SOD), and prostaglandin E2 (PGE2) were examined by biochemical analyses. The degree of tissue damage repair was evaluated by the immunohistochemical method [CD45, CD34, vascular endothelial growth factor (VEGF), and actin] and the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) method. Results: Treatment by PBMT and CALT significantly accelerated the proliferation and migration of HUVECs. Moreover, significant decreases in the contents of MDA and PGE2 were observed in the PBMT and CALT groups, while SOD activity was increased. The histological assessment shows that the content of inflammatory cells and apoptotic cells significantly decreased in the CALT group. However, the microvascular density, VEGF content, and actin content were increased in the CALT group. Conclusions: The results demonstrate that CALT has a stronger effect on promoting chronic soft tissue injury repair in comparison with PBMT.

Bronchoscopy-guided bronchial epithelium sampling as a tool for selecting the optimal biologic treatment in a patient with severe asthma: a case report.

BACKGROUND: There are numerous biologics for treating patients with severe asthma. A cost-effective method for selecting the most appropriate biologic therapy for a patient is thus important. Bronchoscopy-guided bronchial epithelium sampling may provide information for determining the type of inflammation in the airways of severe asthma patients through immunochemical analysis and thus help clinicians select the correct biologics. CASE PRESENTATION: We report the case of a female with severe asthma and eosinophilia who initially responded to omalizumab treatment. She developed an allergic reaction after four injections of omalizumab. Omalizumab desensitization was successfully conducted. To select an appropriate biologic agent after this hypersensitivity episode, we performed bronchoscopy-guided bronchial epithelium sampling. Omalizumab treatment was resumed based on the findings of immunohistochemical staining after a successful desensitization procedure, leading to long-term control of her severe asthma. CONCLUSIONS: Selecting an adequate biologic agent for severe, uncontrolled asthma is a challenge in clinical medical practice. Although phenotypes, blood eosinophils, and serum IgE levels have been proposed for use as a reference, there is a dissociation between the blood immune-cell level and the airway epithelium immune reaction, as confirmed in previous studies. Airway epithelium immunohistochemistry staining for targeted immune cells has been used to determine various types of airway inflammation; however, this technique is rarely used in a clinical setting. Previous studies have revealed the relative safety of performing bronchoscopy biopsies for patients with severe asthma. Among the sampling techniques used for tissue diagnosis, including nasal biopsies, nasal or bronchial brushing, and bronchoalveolar lavage, bronchoscopy-guided bronchial epithelium sampling provides more accurate information about the epithelial and inflammatory cells in the tissue context. It is thus a powerful tool for selecting the most suitable biologics in difficult clinical conditions.

Effects of Carbon Arc Lamp Irradiation on Wound Healing in a Rat Cutaneous Full-Thickness Wound Model.

Objective: The objective of the present study was to investigate the application of a carbon arc lamp on wound healing in a rat cutaneous full-thickness wound model. Background data: In clinical practice, wound healing has been promoted by irradiation with a carbon arc lamp. However, the corresponding mechanism has not been clearly defined. Methods: A cutaneous full-thickness wound on the back of rats was irradiated using a carbon arc lamp at a wavelength peak range of 620-740 nm with 54 J/cm2. Injured sham-irradiated control rats were used as the control. The rats were euthanized after 7, 14, and 21 days, while wound reepithelialization and healing quality were examined by histological analyses with comparison between groups. Cell proliferation was observed by 5-bromo-2'-deoxyuridine (BrdU) immunohistochemical staining. Results: Irradiation by the carbon arc lamp significantly accelerated wound healing. The wound-healing rate in the treated group at day 21 was 98.42% ± 0.56%, compared with 93.58% ± 1.26% in the control group (p < 0.05). Significant increases in the length of epithelial edges, collagen content, and microvessel density were observed in the wound sites in the treated group at days 7, 14, and 21 (p < 0.05). Moreover, the number of BrdU-labeled cells increased in the wound edge at days 7 and 14 due to irradiation (p < 0.05). Conclusions: The results demonstrated that the carbon arc lamp can promote wound healing together with improvement in its quality by stimulating cell proliferation.

Effects of Carbon Arc Lamp Irradiation on Wound Healing in a Rat Cutaneous Full-Thickness Wound Model.

OBJECTIVE: The objective of the present study was to investigate the application of a carbon arc lamp on wound healing in a rat cutaneous full-thickness wound model. BACKGROUND DATA: In clinical practice, wound healing has been promoted by irradiation with a carbon arc lamp. However, the corresponding mechanism has not been clearly defined. METHODS: A cutaneous full-thickness wound on the back of rats was irradiated using a carbon arc lamp at a wavelength peak range of 620-740 nm with 54 J/cm2. Injured sham-irradiated control rats were used as the control. The rats were euthanized after 7, 14, and 21 days, while wound reepithelialization and healing quality were examined by histological analyses with comparison between groups. Cell proliferation was observed by 5-bromo-2'-deoxyuridine (BrdU) immunohistochemical staining. RESULTS: Irradiation by the carbon arc lamp significantly accelerated wound healing. The wound-healing rate in the treated group at day 21 was 98.42% ± 0.56%, compared with 93.58% ± 1.26% in the control group (p < 0.05). Significant increases in the length of epithelial edges, collagen content, and microvessel density were observed in the wound sites in the treated group at days 7, 14, and 21 (p < 0.05). Moreover, the number of BrdU-labeled cells increased in the wound edge at days 7 and 14 due to irradiation (p < 0.05). CONCLUSIONS: The results demonstrated that the carbon arc lamp can promote wound healing together with improvement in its quality by stimulating cell proliferation.

Lymphocytic interstitial pneumonia in a patient with mixed connective tissue disease - A case report.

Lymphocytic interstitial pneumonia (LIP) is an uncommon interstitial lung disease that is characterized by an interstitial infiltrate of lymphoplasmacytic cells. While idiopathic LIP appears to be extremely rare, most reported cases of LIP have been associated with coexisting immune derangements, particularly autoimmune diseases such as Sjögren's syndrome. In this report, we describe the presentation of LIP in a patient with underlying mixed connective tissue disease.

PotteryGo: A Virtual Pottery Making Training System.

This article presents a pottery-making training system with a focus on teaching fundamental knowledge and practical techniques in a virtual-reality environment. Gesture analysis makes it possible to correct the learners actions via visual feedback. Our results demonstrate the efficacy in assisting beginners with learning the gestures used in pottery-making.

Comparison of global initiative for chronic obstructive pulmonary disease 2013 classification and body mass index, airflow obstruction, dyspnea, and exacerbations index in predicting mortality and exacerbations in elderly adults with chronic obstructive pulmonary disease.

OBJECTIVES: To examine whether the Global Initiative for Chronic Obstructive Pulmonary Disease (GOLD) 2013 revision offers greater predictive ability than the body mass index, airflow obstruction, dyspnea, and exacerbations (BODEx) index in elderly adults with chronic obstructive pulmonary disease (COPD). DESIGN: Prospective cohort study. SETTING: University-affiliated medical center. PARTICIPANTS: Taiwanese outpatients with COPD (N = 354). MEASUREMENTS: Participants were classified as Group A (low risk with mild dyspnea), Group B (low risk with more-severe dyspnea), Group C (high risk with mild dyspnea), and Group D (high risk with more-severe dyspnea) for GOLD 2013 and from Quartile 1 (0-2 points) to 4 (7-9 points) for BODEx score. Ability to predict exacerbations and mortality was compared using logistic regression analysis with receiver operating characteristic (ROC) curve estimations and area under the ROC curve (AUC). RESULTS: Mortality was 14.1% for GOLD Group A, 14.5% for Group B, 6.5% for Group C, and 35.8% for Group D and 15.2% for BODEx Quartile 1, 22.5% for Quartile 2, 28.1% for Quartile 3, and 79.2% for Quartile 4. Risk of exacerbation relative to Group A was 1.7 (95% confidence interval (CI) = 0.6-4.3) for Group B, 14.1 (95% CI = 4.6-43.2) for Group C, and 17.9 (95% CI = 7.6-42.0) for Group D. The AUC for the GOLD classification and BODEx index were 0.65 and 0.67 for mortality (P = .60) and 0.79 and 0.73 for exacerbation (P = .03). CONCLUSION: The GOLD 2013 classification performed well in identifying individuals at risk of exacerbations, and its predictive ability for exacerbations was better than that of the BODEx index, although the predictive ability for mortality in elderly adults with COPD was poor for both indices.

Association of Egr-1 and autophagy-related gene polymorphism in men with chronic obstructive pulmonary disease.

BACKGROUND/PURPOSE: Autophagy is important in cellular homeostasis and control of inflammatory immune response. Increased autophagy has recently been associated with increased cell death and chronic obstructive pulmonary disease (COPD) pathogenesis. Two autophagy regulator genes have been identified: Egr-1 (early growth response), associated with different phenotype expressions in asthma; and, Atg16L1 (autophagy related 16-like 1), a candidate gene responsible for susceptibility to chronic inflammatory diseases. We will explore the role of the Egr-1 and Atg16L1 gene polymorphisms in COPD. METHODS: The genotypes of 151 male smoking patients with COPD and 100 male smoking controls were evaluated by polymerase chain reaction followed by restriction fragment length polymorphism analysis of the Egr-1 (-4071 A → G) rs7729723 and Atg16L-1 (T300A) rs2241880 variants. RESULTS: The G allele of the Egr-1 gene polymorphism was associated with an increased risk of developing COPD [odds ratio (OR), 2.05; 95% confidence interval (CI), 1.15-3.72], and participants with the G allele polymorphism (GG and GA genotypes) had a 2.56-fold higher risk (OR, 2.56; 95% CI, 1.31-5.16) of having COPD than those homozygous for the A allele [35.8% (54/151) vs. 24.0% (24/100); p = 0.007]. Participants with the A allele of the Atg16L1 gene polymorphism (AA and AG genotypes) had a 3.34-fold higher risk (OR, 3.34; 95% CI, 1.32-8.97) of having COPD than those homozygous for the G allele [93.4% (141/151) vs. 81.0% (81/100); p = 0.013]. CONCLUSION: The Egr-1 and Atg16L1 genes' polymorphisms were significant risk factors for susceptibility to COPD. These results demonstrate that autophagy regulator genetic mutations are associated with COPD in male smokers.

Estimation of loss of quality-adjusted life expectancy (QALE) for patients with operable versus inoperable lung cancer: adjusting quality-of-life and lead-time bias for utility of surgery.

OBJECTIVES: This study attempts to quantify the difference in loss of quality-adjusted life expectancy (QALE) for patients with operable and inoperable non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: A cohort consisting of 1652 pathologically verified NSCLC patients with performance status 0-1 was monitored for 7 years (2005-2011) to obtain the survival function. This was further extrapolated to lifetime, based on the survival ratios between patients and age- and sex-matched referents simulated from the life tables of the National Vital Statistics of Taiwan. Between 2011 and 2012, EuroQol 5-dimension questionnaires were used to prospectively measure the quality-of-life (QoL) of a 518 consecutive, cross-sectional subsample. We adjusted the lifetime survival function by the utility values of QoL for the cancer cohort to obtain the QALE, while that for the age and sex-matched referents were adjusted to the values collected from the 2009 National Health Interview Survey, and the difference between them was the loss-of-QALE. RESULTS: The QALE for patients with operable and inoperable NSCLC were 11.66±0.18 and 1.43±0.05 quality-adjusted life year (QALY), with the corresponding loss-of-QALE of 5.25±0.18 and 14.24±0.05 QALY, respectively. The lifetime utility difference for patients with operable and inoperable NSCLC was 9.00±0.18 QALY, after adjustment for QoL and lead-time bias. CONCLUSION: The utility gained from surgical operation for operable lung cancer is substantial, even after adjustment for lead-time bias. Future studies should compare screening programs with treatment strategies when carrying out cost-utility assessments to improve patients' values.

Reduced toll-like receptor 9 expression on peripheral CD14+ monocytes of chronic hepatitis B patients and its restoration by effective therapy.

BACKGROUND: Chronic hepatitis B (CHB) patients display Toll-like receptor 9 (TLR9)-dependent defective immune responses. We aimed to study TLR9 expression on CHB patients and its alteration during therapy. METHODS: We compared TLR9 expression on fresh peripheral CD14+ monocytes from a cohort of 97 CHB patients and 35 HBsAg-negative, anti-HCV-negative controls, during pegylated interferon or entecavir therapy. TLR9 expression on liver tissue was also investigated. RESULTS: Compared with controls, peripheral CD14+ monocytes of CHB patients displayed reduced expression of TLR9 mean fluorescence intensity (MFI; 9.90 ±3.64 versus 7.95 ±3.61; P=0.007) independent of age, gender and alanine aminotransferase (ALT; -2.09, 95% CI -3.568, -0.613; P=0.006). Furthermore, age, gender, ALT, HBeAg status, quantitative HBsAg (qHBsAg) or HBV DNA did not predict the TLR9 expression (P=0.863). Hepatic TLR9 messenger RNA (mRNA) was significantly reduced in 54 patients compared with 3 controls (0.45 ±0.32 versus 1-fold). Using response-guided therapy by qHBsAg levels and pretreatment TLR9 MFI as a reference, TLR9 MFI restored to a mean of 1.7- to 2.7-fold in pegylated interferon responders and reduced to a mean of 0.6- to 0.7-fold in non-responders starting from treatment week 12. Among 10 entecavir-treated patients, TLR9 MFI gradually restored to a mean of 1.2- to 2.1-fold starting from treatment week 48. CONCLUSIONS: CHB patients display reduced TLR9 expression on peripheral CD14+ monocytes, which is independent of host and viral markers, and on liver tissue. Responders to pegylated interferon and those under entecavir demonstrate restoration of TLR9 expression. On-treatment TLR9 expression on peripheral monocytes might predict response to pegylated interferon therapy.

Pulmonary function change in patients with Sauropus androgynus-related obstructive lung disease 15 years later.

BACKGROUND/PURPOSE: Little is understood about the clinical course and prognosis of patients with Sauropus androgynus-related obstructive lung disease. The aim of this study was to investigate their clinical manifestations and pulmonary function change 15 years after the acute episode. METHODS: A descriptive, observational study of patients with S androgynus-related obstructive lung disease, diagnosed 15 years ago, was conducted. We evaluated their pulmonary function and the Modified Medical Research Council (MMRC) dyspnea scale. Saint George's Respiratory Questionnaire (SGRQ) was also performed. Age- and forced expiratory volume in one second (FEV1)-matched chronic obstructive pulmonary disease (COPD) patients were used as a reference group for comparison of clinical manifestations. RESULTS: Twenty-nine of 49 patients, diagnosed at our hospital 15 years ago, could be contacted. Four patients died and one patient was ventilator-dependent. Sixteen patients were willing to come to our hospital to have pulmonary function and questionnaire evaluation. The FEV1 of these patients declined only 1.6 ± 21.6 mL/year over a 15-year period. Meanwhile, the severity of their dyspnea and their health-related quality of life were better than age- and FEV1-matched COPD patients as shown by the MMRC dyspnea scale (1.4 ± 0.8 vs. 2.0 ± 1.0; p = 0.037) and symptom domain of the SGRQ (32.6 ± 18.4 vs. 43.5 ± 20.3; p = 0.006). CONCLUSION: After an acute deterioration, patients with S androgynus-related obstructive lung disease had a stationary pulmonary function over a period of 15 years, and their clinical manifestations were less severe than age- and FEV1-matched COPD patients. A further study with a larger sample size may be needed to confirm these findings.

Increased risk of cirrhosis and its decompensation in chronic hepatitis B patients with newly diagnosed diabetes: a nationwide cohort study.

BACKGROUND: The impact of diabetes on cirrhosis, its decompensation, and their time relationship in patients with chronic hepatitis B (CHB) remain unclear. METHODS: We conducted a nationwide cohort study by using the Taiwanese National Health Insurance Research Database, which was comprised of data from >99% of the entire population. Among 1 million randomly sampled enrollees, 14 523 adult CHB patients were identified from 1997 to 2009. Diabetes was defined as newly diagnosed in CHB patients who were given the diagnosis in the years 1998-2001 but not in 1996-1997 and with physician visits of at least twice per year. The cohorts of CHB with newly diagnosed diabetes (n = 351) and without diabetes (n = 7886) were followed up from the diagnosis of diabetes and from 2000 in the patients without diabetes until development of cirrhosis or its decompensation, withdrawal from insurance, or December 2009. RESULTS: Kaplan-Meier survival analysis showed a significantly higher cumulative incidence of cirrhosis (relative risk [RR] = 3.43; 95% confidence interval [CI], 2.62-4.49; P < .001, log-rank test) and decompensated cirrhosis (RR = 4.11; 95% CI, 2.95-5.70; P < .001, log-rank test) among patients with newly developed diabetes compared with those without diabetes. After adjustment for age, sex, CHB treatment, hepatocellular carcinoma, and comorbidity index by Cox proportional hazards model, diabetes was still an independent predictor for cirrhosis (hazard ratio [HR] = 2.015; 95% CI, 1.393-2.915; P < .001) and its decompensation (HR = 1.792; 95% CI, 1.192-2.695; P = .005). CONCLUSIONS: Patients with CHB who develop diabetes are at an increased risk of liver cirrhosis and its decompensation over time.

Reduced Toll-like receptor 3 expression in chronic hepatitis B patients and its restoration by interferon therapy.

BACKGROUND: Toll-like receptor (TLR)3 gene variants may correlate with clinical significance of chronic viral infections including HBV. We aimed to investigate the expression of TLR3 in peripheral blood mononuclear cells (PBMCs) and liver cells of chronic hepatitis B (CHB) patients and its response to pegylated interferon or nucleoside analogue therapy. METHODS: We consecutively enrolled 127 CHB patients and 64 hepatitis B surface antigen-negative, anti-HCV-negative healthy individuals as controls. We compared the TLR3 expressions on fresh PBMCs and liver cells from patients and controls, before and during pegylated interferon or nucleoside analogue therapy. RESULTS: Compared to controls, patients had a lower TLR3 mean fluorescence intensity (MFI) on PBMCs (mean ± sd 14.61 ± 13.49 versus 9.70 ± 4.61; P < 0.001), independent of age, gender and alanine aminotransferase (ALT; -13.466, 95% CI -17.202, -9.730; P < 0.001). Patients had limited TLR3 stains on Kupffer cells, whereas controls had diffuse stains on Kupffer and hepatocytes. Hepatic TLR3 messenger RNA was lower in patients than controls (0.47 ± 0.30 versus 1-fold). Using pretreatment TLR3 MFI as a referent, among 5 of 12 pegylated-interferon-treated patients with sustained virological response (SVR), TLR3 MFI was restored to a mean of 1.5- to 1.7-folds immediately after treatment. Among seven non-responders or relapsers, TLR3 MFI reduced to a mean of 0.5- to 0.7-fold. Among 10 entecavir-treated patients with on-treatment virological response, TLR3 MFI gradually was restored to a mean of 1.2-folds during 48-week therapy. CONCLUSIONS: CHB patients have reduced TLR3 expression on PBMCs, independent of age, gender and ALT, and on liver cells. Patients with pegylated-interferon-induced SVR have a more significant restoration of TLR3 expression than those under entecavir.

Biphasic pattern of depression and its predictors during pegylated interferon-based therapy in chronic hepatitis B and C patients.

BACKGROUND: It remains unclear whether depression in chronic hepatitis B (CHB) and chronic hepatitis C (CHC) during pegylated interferon-based therapy is associated with the virus, drug or ethnic background. We aimed to perform a prospective study to evaluate the clinical course of depression and its predictors in consecutive non-cirrhotic CHB and CHC patients of the same ethnicity receiving pegylated interferon-based therapy. METHODS: The occurrence and severity of depression were actively assessed by the Hamilton Depression Rating Scale before therapy and at weeks 2, 4, 6, 8, 10, 12 and every 4 weeks during treatment until the end of therapy. Extensive numbers of variables (repeated measurements, time variables and interactions between all variables) were included in generalized estimating equations to analyse the predictors of depression. RESULTS: A total of 158 consecutive patients (73 CHB and 85 CHC patients) were enrolled. Depression (Hamilton Depression Rating Scale ≥ 11) occurred in a biphasic pattern at treatment weeks 2-10 and weeks 16-36. Treatment weeks < 10 predicts more depression, and treatment weeks >12 predicts less depression, suggesting the predictability of the time variable during treatment on depression. Furthermore, CHC or pre-existing depression is an independent predictor of depression in these patients (P < 0.001). CONCLUSIONS: Depression occurred in a biphasic pattern during pegylated interferon-based therapy and should be early and actively assessed, especially in patients with CHC or pre-existing depression.

The role of bactericidal/permeability-increasing protein in men with chronic obstructive pulmonary disease.

BACKGROUND AND OBJECTIVE: Bactericidal/permeability-increasing protein (BPI) is a member of the pattern recognition receptors of the innate immune system. Recently, an association between genetic polymorphism in the BPI gene and a risk of airflow decline after transplantation was demonstrated, but whether these findings are reproducible in nontransplantation populations, such as those with COPD, is still unknown. The aim of this study is to explore the role of BPI in COPD. METHODS: The genotypes of 107 patients with COPD and 110 control subjects were evaluated by polymerase chain reaction and polymorphism analysis of the BPI genes and ELISA analysis of the plasma BPI level. All subjects were men over 40 years old who smoked. RESULTS: BPI mutation PstI (T→C) polymorphism in intron 5 was associated with an increased risk of developing COPD (OR 3.73, 95%CI: 1.62-9.10), and the frequency was significantly increased in the COPD group compared with the control group (26/107 [24.3%] vs 12/110 [10.9%], p = 0.002). In addition, COPD patients exhibited a decreased plasma level of BPI compared with the control group (10.6 ± 2.2 vs 23.4 ± 2.1 ng/ml, p < 0.0001). CONCLUSIONS: BPI mutation (PstI in intron 5) and a decreased plasma BPI level were significant risk factors in susceptibility to COPD. These results demonstrate that BPI genetic mutation and impaired BPI production or release may result in airflow obstruction in smokers.

Using post-bronchodilator FEV1 is better than pre-bronchodilator FEV1 in evaluation of COPD severity.

BACKGROUND: The current standards for the diagnosis and treatment of patients with COPD clearly rely on the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria based on post-bronchodilator spirometric values. However, clinical evidence for using the post-bronchodilator FEV1 in the severity classification has not been fully investigated. METHODS: Patients with COPD were enrolled and followed up prospectively between October 2006 and January 2011. We compared the observed 3-year risk of all causes and respiratory mortality with the risk predicted by the pre- and post-bronchodilator percent predicted FEV1. Other important phenotypes including BMI, MMRC dyspnea scale, ECOG performance status and severe AECOPD (acute exacerbation) were also compared between the two groups. The different severity classifications of COPD, measured according the GOLD guidelines by post- and pre-bronchodilator percent predicted FEV1 were compared for prediction of mortality. RESULTS: There were 35 deaths among the 300 COPD patients (11.7%). Multivariate analysis showed that the post-bronchodilator percent predicted FEV1 was a significant independent predictor of mortality but pre-bronchodilator percent predicted FEV1 was not (p = 0.008 vs 0.126) and it was more strongly correlated with all studied predictors of outcome than the pre-bronchodilator percent predicted FEV1. Kaplan-Meier analysis showed that the discrimination ability to predict mortality from the GOLD criteria using post bronchodilator percent predicted FEV1 (p = 0.009) was better than using pre-bronchodilator percent predicted FEV1 (p = 0.131). CONCLUSIONS: The post-bronchodilator percent predicted FEV1 is better than the pre-bronchodilator percent predicted FEV1 in the evaluation of the severity of disease in COPD patients and is more accurate in predicting the risk of death by the GOLD classification.

Polymorphism of microsomal epoxide hydrolase is associated with chronic obstructive pulmonary disease and bronchodilator response.

BACKGROUND/PURPOSE: Microsomal epoxide hydrolase (EPHX) is an important enzyme that metabolizes harmful reactive epoxides from smoking. Genetic variations of this enzyme are thought to increase the risk of developing chronic obstructive pulmonary disease (COPD). The aim of this study was to confirm and advance our knowledge of the role of this genetic variation in COPD. In addition, the association between this gene and important COPD-related phenotype bronchodilator responses (BDRs) was studied. METHODS: This was a hospital-based case-control study. The EPHX1 genetic mutations of 105 smokers with COPD and 103 control smokers without COPD were evaluated by polymerase chain reaction, followed by restriction fragment length polymorphism analysis. The association of genetic mutations and COPD phenotypes was also studied. RESULTS: Subjects with EPHX1 113 (His(113)/His(113)) homozygote mutation had a strong correlation with COPD (odds ratio: 2.7, 95% confidence interval: 1.5-5.2). In addition, compared with other genotypes, the His(113) homozygote mutation patients had significantly lower BDRs, as shown by the absolute and percentage changes from baseline, in COPD patients (91.7 ± 12.5 mL vs. 141.6 ± 15.1 mL, p = 0.01 and 8.3 ± 1.2% vs. 13.4 ± 1.4%, p = 0.006). CONCLUSION: A strong correlation between the EPHX1 113 mutant homozygote and smoking-related COPD was noted. This genetic polymorphism was also associated with lower BDRs in COPD patients.

Involvement of purinergic neurotransmission in ketamine induced bladder dysfunction.

PURPOSE: Long-term ketamine abuse in humans causes significant lower urinary tract symptoms. However, the etiology of ketamine associated cystitis is still not clear. We created a mouse model of ketamine induced lower urinary tract dysfunction to explore the pathogenesis of this condition. MATERIALS AND METHODS: Female C57BL/6 mice randomly distributed into control and ketamine groups received daily intraperitoneal injection of saline and ketamine (100 mg/kg), respectively. Cystometry was done in each group at 4, 8 and 16 weeks. After sacrifice the bladders were harvested for isometric muscle tension recording and immunohistochemical examination. RESULTS: After 8 weeks of treatment body weight growth was significantly decreased in ketamine treated mice. Cystometry revealed a significantly decreased intercontraction interval (mean±SEM 237±9 vs 360±20 seconds, p<0.001) and decreased bladder capacity (0.1±0.004 vs 0.13±0.006 ml, p<0.001) in ketamine vs saline injected mice. Increased adenosine triphosphate evoked detrusor contraction developed in the ketamine group. Immunohistochemical examination revealed increased P2X1 receptor expression in ketamine treated mouse bladders while M2 and M3 receptor expression was unchanged. CONCLUSIONS: At 8 weeks mice treated with ketamine showed increased voiding frequency and decreased bladder capacity, the same symptoms that develop in human ketamine abusers. Enhanced noncholinergic contractions and P2X1 receptor expression in the ketamine bladder indicate that dysregulation of purinergic neurotransmission may underlie detrusor overactivity in cases of ketamine induced bladder dysfunction.