Chun-Nin Lee

Cigarette smoke is a risk factor for severity and treatment outcome in patients with culture-positive tuberculosis.

Objective Smoking has been associated with tuberculosis (TB); however, the effects of smoking on the effectiveness of TB treatment remain unclear. Materials and methods Data were retrieved from case notes and interviews of subjects registered in the TB-reporting system from 2010 to 2012. Study cases were defined as subjects with TB-positive sputum cultures, whereas the controls were defined as subjects with non-TB-related pulmonary diseases. Statistical analyses included logistic regression and multivariate Cox proportional hazard regression models. Results A total of 245 cases with cultures positive for TB and 114 controls with non-TB-related pulmonary diseases and negative sputum cultures were recruited. Current smokers had the highest failure rate (33%) for TB treatment, and they had the most severe pulmonary lesions based on chest X-ray grading. Current smokers had a 1.36-fold (95% confidence interval 1.03–2.36, P<0.05) higher odds ratio for cultures positive for TB compared with nonsmokers. In subjects with TB-positive cultures, current smoking was associated with an increase in treatment days required for cultures to convert from positive to negative (hazard ratio 1.12, 95% confidence interval 1.03–1.39; P<0.05). Conclusion Longer periods of treatment may be required for TB patients who are current smokers.

Protein oxidation and degradation caused by particulate matter

Particulate matter (PM) modulates the expression of autophagy; however, the role of selective autophagy by PM remains unclear. The objective of this study was to determine the underlying mechanisms in protein oxidation and degradation caused by PM. Human epithelial A549 cells were exposed to diesel exhaust particles (DEPs), urban dust (UD), and carbon black (CB; control particles). Cell survival and proliferation were significantly reduced by DEPs and UD in A549 cells. First, benzo(a)pyrene diolepoxide (BPDE) protein adduct was caused by DEPs at 150 μg/ml. Methionine oxidation (MetO) of human albumin proteins was induced by DEPs, UD, and CB; however, the protein repair mechanism that converts MetO back to methionine by methionine sulfoxide reductases A (MSRA) and B3 (MSRB3) was activated by DEPs and inhibited by UD, suggesting that oxidized protein was accumulating in cells. As to the degradation of oxidized proteins, proteasome and autophagy activation was induced by CB with ubiquitin accumulation, whereas proteasome and autophagy activation was induced by DEPs without ubiquitin accumulation. The results suggest that CB-induced protein degradation may be via an ubiquitin-dependent autophagy pathway, whereas DEP-induced protein degradation may be via an ubiquitin-independent autophagy pathway. A distinct proteotoxic effect may depend on the physicochemistry of PM.

Comparison of domiciliary oxygen using liquid oxygen and concentrator in northern Taiwan

BACKGROUND/PURPOSE Long-term oxygen therapy has become standard treatment for patients with chronic respiratory insufficiency. However, patterns of long-term home oxygen therapy have not been well studied in Taiwan. Oxygen concentrator systems are commonly used in Taiwan, but liquid oxygen delivery systems are portable and may provide advantages over the concentrator system. This study compared oxygen usage between patients from a liquid oxygen group (LOG) and an oxygen concentrator group (OCG). The authors also assessed the physiologic responses of patients with chronic obstructive pulmonary disease (COPD) to ambulatory oxygen use at home. METHODS The study used a retrospective, cross-sectional, observational survey design. The LOG comprised 42 patients, and the OCG comprised 102 patients. We recruited participants in northern Taiwan from July 2009 to April 2010. The questionnaire instruments that were used to collect data consisted of three parts: demographic characteristics, devices used in respiratory care, and activity status with portable oxygen. Two-minute walking tests were performed on COPD patients in their homes. RESULTS COPD was the most common diagnosis in our study, with more than 50% of patients who received oxygen long term in both groups having received this diagnosis. The LOG used oxygen for an average of 21.7 hours per day, whereas OCG averaged 15.2 hours per day (p<0.001). In the OCG, 92.2% of patients used a concentrator alone, whereas 23.8% of the LOG used liquid oxygen alone (p<0.001). The LOG patients were involved in significantly more outdoors activities (p=0.002) and reported traveling with oxygen more often (p<0.001) than the OCG patients. For patients with the same dyspnea level of COPD severity, those using liquid oxygen had a lower increase in pulse rate after the walking test, in comparison with the concentrator users. CONCLUSION Patients in the LOG used oxygen for longer hours, went on more outings, and were more likely to travel with oxygen than patients in the OCG. Being ambulatory with liquid oxygen might enable patients with COPD to walk more effectively.

Bevacizumab Reduces S100A9-Positive MDSCs Linked to Intracranial Control in Patients with EGFR-Mutant Lung Adenocarcinoma

Introduction: In vitro models have demonstrated immune‐modulating effects of bevacizumab (BEV). Combinations of an EGFR tyrosine kinase inhibitor (TKI) with BEV improve progression‐free survival (PFS) in patients with EGFR‐mutated lung adenocarcinoma. How BEV confers this clinical effect and the underlying mechanisms of its effect are not clear. Methods: A total of 55 patients with stage 4 EGFR‐mutated lung adenocarcinoma were enrolled. Myeloid‐derived suppressor cells (MDSCs), type 1 and type 2 helper T cells, and cytotoxic T lymphocytes were analyzed by flow cytometry. Clinical data were collected for analysis. Result: In all, 25 patients received EGFR TKI and BEV combination therapy (the BEV/TKI group) and 30 patients received EGFR TKI monotherapy (the TKI‐only group). The BEV/TKI group had longer PFS (23.0 versus 8.6 months [p = 0.001]) and, in particular, better intracranial control rates (80.0% versus 43.0% [p = 0.03]), a longer time to intracranial progression (49.1 versus 12.9 months [p = 0.002]), and fewer new brain metastases (38.0% versus 71.0% [p = 0.03]) than the TKI‐only group did. The BEV/TKI group had a lower percentage of circulating MDSCs (20.4% ± 6.5% before treatment versus 12.8% ± 6.6% after treatment, respectively [p = 0.02]), and higher percentages of type 1 helper T cells (22.9% ± 15.3% versus 33.2% ± 15.6% [p < 0.01]) and cytotoxic T lymphocytes (15.5% ± 7.2% versus 21.2% ± 5.6% [p < 0.01]) after treatment, changes that were not seen in the TKI‐only group. Pretreatment percentage of MDSCs was correlated with PFS, with this correlation attenuated after BEV/TKI treatment. Percentage of MDSCs was also associated with shorter time to intracranial progression. Conclusion: Combining a EGFR TKI with BEV extended PFS and protected against brain metastasis. Those effects were probably due to the reduction of circulating S100A9‐positive MDSCs by BEV, which leads to restoration of effective antitumor immunity. Our data also support the rationale for a BEV–immune checkpoint inhibitor combination.

Flexible Bronchoscopy-Guided, Self-expandable, Metallic Stents Improve Survival in Patients with Esophageal Cancer Complicated with Esophago-Respiratory Fistula

Background: Esophago-respiratory fistula, which develops in some esophageal cancer patients, is a devastating and life-threatening complication. When patients are in serious condition, general anesthesia, rigid bronchoscopy and subsequent silicone stent implantation are not feasible. Airway stent implantation can seal the fistula and avoid further complications, such as repeated aspiration. The aim of our study was to evaluate the outcome of airway stent implantation in esophageal cancer patients with esophago-respiratory fistula. Patients and Methods: From April 2002 to October 2009, 16 consecutive patients with esophago-respiratory fistula-associated esophageal cancer were reviewed. Nine patients received airway stent implantation and 7 did not. The outcomes evaluated included emergency department visit episodes, pneumonia episodes, total hospitalized days due to pneumonia, and days of survival after fistula diagnosis. Results: The days of survival after fistula diagnosis were significantly different between the airway stent implantation group and the group without an airway stent implantation (80.22±55.14 versus 32.71±70.86, p＜0.05). The other outcomes were not statistically different between the 2 groups. Conclusions: Airway stent implantation improves the number of days of survival in patients with esophageal cancer complicated with esophago-respiratory fistula.

Favorable Response to Pemetrexed as a Salvage Agent for Patients with Advanced Lung Cancer Who Have Failed Conventional Platinum-Based Chemotherapy and EGFR Tyrosine Kinase Inhibitors

Background: For locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC), pemetrexed is currently recommended as first-line treatment in combination with platinum agents or second-line chemotherapy after the disease has become refractory to platinum-based doublet regimens, but few reports have addressed its role as salvage chemotherapy after failure of multiple therapies and the relationship between response rate and EGFR and K-ras mutations. Methods: We retrospectively evaluated the efficacy of pemetrexed in 11 patients with advanced NSCLC, who had failed at least platinum-based doublet combinations and erlotinib or gefitinib. The gender, performance status, number of cycles given, EGFR and K-ras mutation status, best response, adverse reactions, time to progression (TTP) and overall survival (OS) were used to assess the effects. Results: A median of 6.17 cycles of infusion was given. Six out of 11 patients experienced partial response, three stable disease and two disease progression. The TTP and OS of salvage pemetrexed therapy were 108 and 346 days, respectively. The EGFR mutation status did not affect its efficacy. It was well-tolerated and required no dose modification. Conclusions: Pemetrexed is a good option for patients with good performance status who have failed platinum-and taxane-containing regimens and EGFR tyrosine kinase inhibitors.