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1.  Removal of Endobronchial Malignant Mass by Cryotherapy Improved Performance Status to Receive Chemotherapy 
The Scientific World Journal  2014;2014:369739.
Although malignant endobronchial mass (MEM) has poor prognosis, cryotherapy is reportedly a palliative treatment. Clinical data on postcryotherapy MEM patients in a university-affiliated hospital between 2007 and 2011 were evaluated. Survival curve with or without postcryotherapy chemotherapy and performance status (PS) improvement of these subjects were analyzed using the Kaplan-Meier method. There were 59 patients (42 males), with median age of 64 years (range, 51–76, and median performance status of 2 (interquartile range [IQR], 2-3). Postcryotherapy complications included minor bleeding (n = 12) and need for multiple procedures (n = 10), while outcomes were relief of symptoms (n = 51), improved PS (n = 45), and ability to receive chemotherapy (n = 40). The survival of patients with chemotherapy postcryotherapy was longer than that of patients without such chemotherapy (median, 534 versus 106 days; log-rank test, P = 0.007; hazard ratio, 0.25; 95% confidence interval, 0.10–0.69). The survival of patients with PS improvement postcryotherapy was longer than that of patients without PS improvement (median, 406 versus 106 days; log-rank test, P = 0.02; hazard ratio, 0.28; 95% confidence interval, 0.10–0.81). Cryotherapy is a feasible treatment for MEM. With better PS after cryotherapy, further chemotherapy becomes possible for patients to improve survival when MEM caused dyspnea and poor PS.
PMCID: PMC4212536  PMID: 25383370
2.  Associated bone mineral density and obstructive sleep apnea in chronic obstructive pulmonary disease 
Osteoporosis is an important issue for patients with chronic obstructive pulmonary disease (COPD). Worse systemic inflammation and reduced exercise capacity have been reported in COPD patients with obstructive sleep apnea (OSA), implying that OSA may be an independent factor for osteoporosis in COPD patients.
A total of 66 patients with bone mineral density (BMD) and polysomnography results from a previous COPD cohort (January 2008 to January 2013) were retrospectively enrolled. Clinical characteristics such as medication, pulmonary function, BMD, and results of polysomnography were analyzed.
The BMD in those with OSA was significantly lower than in those without OSA (−1.99±1.63 versus −1.27±1.14, P=0.045). In univariate analysis, body mass index, forced expiratory volume in 1 second, percentage of predicted value, incremental shuttle walk test, apnea–hypopnea index, and oxygen desaturation index (ODI) were significantly associated with BMD. After multivariate linear regression analysis, the ODI was still an independent factor for BMD. In addition, smaller total lung capacity is significantly associated with higher ODI and lower BMD, which implies that lower BMD might cause severer OSA via decreased total lung capacity.
OSA may be an independent factor for BMD in patients with COPD, which implies a possible vicious cycle takes place in these patients.
PMCID: PMC4321657
chronic obstructive pulmonary disease; osteoporosis; total lung capacity
3.  Feasibility of Bispectral Index-Guided Propofol Infusion for Flexible Bronchoscopy Sedation: A Randomized Controlled Trial 
PLoS ONE  2011;6(11):e27769.
There are safety issues associated with propofol use for flexible bronchoscopy (FB). The bispectral index (BIS) correlates well with the level of consciousness. The aim of this study was to show that BIS-guided propofol infusion is safe and may provide better sedation, benefiting the patients and bronchoscopists.
After administering alfentanil bolus, 500 patients were randomized to either propofol infusion titrated to a BIS level of 65-75 (study group) or incremental midazolam bolus based on clinical judgment to achieve moderate sedation. The primary endpoint was safety, while the secondary endpoints were recovery time, patient tolerance, and cooperation.
The proportion of patients with hypoxemia or hypotensive events were not different in the 2 groups (study vs. control groups: 39.9% vs. 35.7%, p = 0.340; 7.4% vs. 4.4%, p = 0.159, respectively). The mean lowest blood pressure was lower in the study group. Logistic regression revealed male gender, higher American Society of Anesthesiologists physical status, and electrocautery were associated with hypoxemia, whereas lower propofol dose for induction was associated with hypotension in the study group. The study group had better global tolerance (p<0.001), less procedural interference by movement or cough (13.6% vs. 36.1%, p<0.001; 30.0% vs. 44.2%, p = 0.001, respectively), and shorter time to orientation and ambulation (11.7±10.2 min vs. 29.7±26.8 min, p<0.001; 30.0±18.2 min vs. 55.7±40.6 min, p<0.001, respectively) compared to the control group.
BIS-guided propofol infusion combined with alfentanil for FB sedation provides excellent patient tolerance, with fast recovery and less procedure interference.
Trial Registration
ClinicalTrials. gov NCT00789815
PMCID: PMC3223212  PMID: 22132138
4.  Mobile-phone-based home exercise training program decreases systemic inflammation in COPD: a pilot study 
BMC Pulmonary Medicine  2014;14:142.
Moderate-intensity exercise training improves skeletal muscle aerobic capacity and increased oxidative enzyme activity, as well as exercise tolerance in COPD patients.
To investigate whether the home-based exercise training program can reduce inflammatory biomarkers in patients with COPD, twelve patients using mobile phone assistance and 14 with free walk were assessed by incremental shuttle walk test (ISWT), spirometry, strength of limb muscles, and serum C-reactive protein (CRP) and inflammatory cytokines.
Patients in the mobile phone group improved their ISWT walking distance, with decrease in serum CRP after 2 months, and sustained at 6 months. Patients in the control group had no improvement. Serum IL-8 in the mobile phone group was significantly reduced at 2, 3 and 6 months after doing home exercise training compared to baseline. IL-6 and TNF-α were significantly elevated at 3 and 6 months in control group, while there were no changes in mobile phone group. The strength of limb muscles was significantly greater compared to baseline at 3 and 6 months in the mobile phone group.
A mobile-phone-based system can provide an efficient home endurance exercise training program with improved exercise capacity, strength of limb muscles and a decrease in serum CRP and IL-8 in COPD patients. Decreased systemic inflammation may contribute to these clinical benefits. (Clinical trial registration No.: NCT01631019)
PMCID: PMC4236722  PMID: 25175787
Chronic obstructive pulmonary disease; Pulmonary rehabilitation; Mobile phone; Biomarker; Interleukin-8
5.  Clinical Characteristics and Treatment Outcomes of Patients with Low- and High-Concentration Isoniazid-Monoresistant Tuberculosis 
PLoS ONE  2014;9(1):e86316.
Isoniazid (INH) resistance is now the most common type of tuberculosis (TB) infection resistance worldwide. The aim of this study was to evaluate the clinical characteristics and treatment outcomes of patients with low- and high-concentration INH-monoresistant TB.
One hundred and thirty-four patients with culture-confirmed INH-monoresistant TB during 2006 January to 2007 December were retrospectively enrolled. INH resistance was classified as either low-concentration or high-concentration resistance according to the critical concentrations of 0.2 µg/mL or 1 µg/mL of INH, respectively. The patients’ clinical outcomes, treatment regimens, and treatment duration were analyzed.
The treatment success rates between low- and high-concentration INH-resistant TB were similar (81.8% vs. 86.7%). The treatment regimens and treatment duration were similar between both groups. Only a minor percentage of the patients in both groups received 6-month treatment regimens (low vs. high concentration resistance, 9.1% vs. 13.3%; respectively, p = 0.447) The most common reason for treatment duration longer than 6 months was pyrazinamide given for less than 6 months, followed by a delay in clinical response to treatment. Multivariable analysis showed that prior tuberculosis treatment (Odds ratio, 2.82, 95% C.I., 1.02–7.77, p = 0.045) was the only independent risk factor for unsuccessful treatment outcome.
Different levels of INH resistance did not affect the treatment outcomes of patients with INH-monoresistant tuberculosis. Prolonged Rifampin-containing regimens may achieve those good outcomes in patients with low- and high-concentration INH-monoresistant TB.
PMCID: PMC3899226  PMID: 24466020
6.  The Role of the High-Sensitivity C-Reactive Protein in Patients with Stable Non-Cystic Fibrosis Bronchiectasis 
Pulmonary Medicine  2013;2013:795140.
Study Objectives. The aim of this study is to investigate the correlation between serum high-sensitivity C-reactive protein (hs-CRP) and other clinical tools including high-resolution computed tomography (HRCT) in patients with stable non-CF bronchiectasis. Design. A within-subject correlational study of a group of patients with stable non-CF bronchiectasis, who were recruited from our outpatient clinic, was done over a two-year period. Measurements. Sixty-nine stable non-CF bronchiectasis patients were evaluated in terms of hs-CRP, 6-minute walk test, pulmonary function tests, and HRCT. Results. Circulating hs-CRP levels were significantly correlated with HRCT scores (n = 69, r = 0.473, P < 0.001) and resting oxygenation saturation (r = −0.269, P = 0.025). HRCT severity scores significantly increased in patients with hs-CRP level of 4.26 mg/L or higher (mean ± SD 28.1 ± 13.1) compared to those with hs-CRP level less than 4.26 mg/L (31.7 ± 9.8, P = 0.004). Oxygenation saturation at rest was lower in those with hs-CRP level of 4.26 mg/L or higher (93.5 ± 4.4%) compared to those with hs-CRP level less than 4.26 mg/L (96.4 ± 1.6%, P = 0.001). Conclusion. There was a good correlation between serum hs-CRP and HRCT scores in the patients with stable non-CF bronchiectasis.
PMCID: PMC3870862  PMID: 24381758
7.  CD14+S100A9+ Monocytic Myeloid-derived Suppressor Cells and Their Clinical Relevance in Non–Small Cell Lung Cancer 
Rationale: Myeloid-derived suppressor cells (MDSCs) are a heterogeneous family of myeloid cells that suppress T-cell immunity in tumor-bearing hosts. Their clinical relevance remains unclear.
Objectives: To identify subtypes of myeloid-derived suppressor cells in patients with non–small cell lung cancer (NSCLC) and their clinical relevance.
Methods: CD11b+CD14− and CD11b+CD14+ cells, determined and phenotyped by fluorescence-activated cell sorter analysis, in the peripheral blood mononuclear cells (PBMCs) of treatment-naive patients with advanced NSCLC were correlated with clinical data. T-cell activation in response to CD3/CD28 costimulation was determined by carboxy-fluorescein diacetate succinimidyl ester (CFSE) staining and ELISA analysis of IFN-γ. The percentage of CD11b+CD14+S100A9+ cells in PBMCs was correlated with and tested as a predictor for treatment response in a cohort of patients prospectively receiving first-line cisplatin-based chemotherapy.
Measurements and Main Results: Patients with NSCLC had a significantly higher ratio of CD11b+CD14+ cells than healthy subjects, which was correlated with poor performance status and poor response to chemotherapy. The depletion of these cells in the PBMC reversed the suppression of CD8+ and CD4+ T cells. Isolated CD11b+CD14+ cells suppressed CD8+ T-cell proliferation and IFN-γ production, and the former effect was attenuated by the inducible nitric oxide synthase (iNOS) inhibitor aminoguanidine hydrochloride, arginase inhibitor N-hydroxy-nor-l-arginine (nor-NOHA), and blocking antibodies for IL-4Rα+ and IL-10. CD11b+CD14+ cells were monocyte-like, expressing CD33+, CD15−/low, IL-4Rα+, and S100A9+ and producing iNOS, arginase, and several cytokines. The ratio of S100A9+ cells positively correlated with the suppressive ability of the CD11b+CD14+ cells, was associated with poor response to chemotherapy, and predicted shorter progression-free survival.
Conclusions: CD14+S100A9+ inflammatory monocytes in patients with NSCLC are a distinct subset of MDSCs, which suppress T cells by arginase, iNOS, and the IL-13/IL-4Rα axis. The amount of these inflammatory monocytes is associated with poor response to chemotherapy.
Clinical trial registered with (NCT 01204307).
PMCID: PMC4132576  PMID: 22955317
non–small cell lung cancer; myeloid-derived suppressor cell; S100A9; cancer immunity
8.  Chronic cough and obstructive sleep apnoea in a sleep laboratory-based pulmonary practice 
Obstructive sleep apnoea (OSA) has recently been identified as a possible aetiology for chronic cough. The aim of this study was to compare the incidence of chronic cough between patients with and without OSA and the impact of continuous positive airway pressure (CPAP) treatment in resolving chronic cough.
Patients referred to the sleep laboratory from January 2012 to June 2012 were retrospectively enrolled. Clinical data, treatment course and resolution of chronic cough were analysed. Specifically, gastro-oesophageal reflux (GERD), upper airway cough syndrome, asthma, apnoea-hypopnoea index and the impact of CPAP treatment on chronic cough were assessed.
A total of 131 patients were reviewed. The incidence of chronic cough in the OSA group was significantly higher than the non-OSA group (39/99 (39.4%) vs. 4/32 (12.5%), p = 0.005). Both GERD and apnoea-hypopnoea index were significantly associated with chronic cough in univariate analysis. After multivariate logistic regression, GERD was the only independent factor for chronic cough. Moreover, the resolution of chronic cough was more significant in the OSA patients with CPAP treatment compared with those not receiving CPAP treatment (12/18 (66.7%) vs. 2/21 (9.5%), p = 0.010).
The incidence of chronic cough was significantly higher in the OSA patients. In addition, CPAP treatment significantly improved chronic cough. Therefore, OSA may be a contributory factor to chronic cough.
PMCID: PMC4176501  PMID: 24188336
Chronic cough; Obstructive sleep apnoea; Continuous positive airway pressure
9.  Amplified Mycobacterium Tuberculosis Direct Test for Diagnosing Tuberculous Pleurisy—A Diagnostic Accuracy Study 
PLoS ONE  2012;7(9):e44842.
The study was designed to investigate the clinical usefulness of Amplified Mycobacterium Tuberculosis Direct (AMTD) tests for diagnosing TB pleurisy.
One hundred and fifty-two patients for whom the exclusion of tuberculous pleural effusion was necessary were retrospectively analyzed.
The sensitivity of AMTD in diagnosing pleural TB was 36.4% (20 of 55). Combining sputum and pleural effusion AFB smear, pleural biopsy, and AMTD test of pleural effusion increased sensitivity to 82.5% (33/40). There were significantly higher percentages of neutrophils in the pleural effusion in the positive than in the negative AMTD group (38.0±6.7% vs. 11.1±3.7%, p<0.001). Patients with symptom duration <18 days prior to pleural effusion studies had more positive AMTD tests than those with symptom >18 days (70% vs. 31.4%; OR 5.09; 95% CI 1.54–16.79; p = 0.011).
Combining AMTD tests with conventional diagnostic methods offer good sensitivity for pleural TB diagnosis. Patients in the early course of the disease are better candidates for AMTD tests.
PMCID: PMC3438172  PMID: 22970318
10.  Concomitant Active Tuberculosis Prolongs Survival in Non-Small Cell Lung Cancer: A Study in a Tuberculosis-Endemic Country 
PLoS ONE  2012;7(3):e33226.
Adjuvant tumor cell vaccine with chemotherapy against non-small cell lung cancer (NSCLC) shows limited clinical response. Whether it provokes effective cellular immunity in tumor microenvironment is questionable. Concomitant active tuberculosis in NSCLC (TBLC) resembles locoregional immunotherapy of tumor cell vaccine; thus, maximally enriches effective anti-tumor immunity. This study compares the survival and immunological cell profile in TBLC over NSCLC alone.
Retrospective review of NSCLC patients within 1-year-period of 2007 and follow-up till 2010.
A total 276 NSCLC patients were included. The median survival of TBLC is longer than those of NSCLC alone (11.6 vs. 8.8 month, p<0.01). Active tuberculosis is an independent predictor of better survival with HR of 0.68 (95% CI, 0.48∼0.97). Squamous cell carcinoma (SCC) (55.8 vs. 31.7%, p<0.01) is a significant risk factor for NSCLC with active TB. The median survival of SCC with active tuberculosis is significantly longer than adenocarcinoma or undetermined NSCLC with TB (14.2 vs. 6.6 and 2.8 months, p<0.05). Active tuberculosis in SCC increases the expression of CD3 (46.4±24.8 vs. 24.0±16.0, p<0.05), CXCR3 (35.1±16.4 vs. 19.2±13.3, p<0.01) and IP-10 (63.5±21.9 vs. 35.5±21.0, p<0.01), while expression of FOXP3 is decreased (3.5±0.5 vs. 13.3±3.7 p<0.05, p<0.05). Survival of SCC with high expression of CD3 (12.1 vs. 3.6 month, p<0.05) and CXCR3 (12.1 vs. 4.4 month, p<0.05) is longer than that with low expression.
Active tuberculosis in NSCLC shows better survival outcome. The effective T lymphocyte infiltration in tumor possibly underlies the mechanism. Locoregional immunotherapy of tumor cell vaccine may deserve further researches.
PMCID: PMC3306389  PMID: 22438899
11.  An outcome analysis of self-expandable metallic stents in central airway obstruction: a cohort study 
Self-expandable metallic stents (SEMSs) have provided satisfactory management of central airway obstruction. However, the long-term benefits and complications of this management modality in patients with benign and malignant obstructing lesions after SEMS placement are unclear. We performed this cohort study to analyze the outcomes of Ultraflex SEMSs in patients with tracheobronchial diseases.
Of 149 patients, 72 with benign and 77 with malignant tracheobronchial disease received 211 SEMSs (benign, 116; malignant, 95) and were retrospectively reviewed in a tertiary hospital.
The baseline characteristics of patients who received SEMS implantation for benign conditions and those who underwent implantation for malignant conditions were significantly different. These characteristics included age (mean, 63.9 vs. 58; p < 0.01), gender (male, 62% vs. 90%; p < 0.0001), smoking (47% vs. 85%; p < 0.0001), forced expiratory volume in 1 second (mean, 0.9 vs. 1.47 L/s; p < 0.0001), follow-up days after SEMS implantation (median; 429 vs. 57; p < 0.0001), and use of covered SEMS (36.2% vs. 94.7%; p < 0.0001). Symptoms improved more after SEMS implantation in patients with benign conditions than in those with malignant conditions (76.7% vs. 51.6%; p < 0.0001). The overall complication rate after SEMS implantation in patients with benign conditions was higher than that in patients with malignancy (42.2% vs. 21.1%; p = 0.001). Successful management of SEMS migration, granulation tissue formation, and SEMS fracture occurred in 100%, 81.25%, and 85% of patients, respectively.
Patients who received SEMS implantation owing to benign conditions had worse lung function and were older than those who received SEMS for malignancies. There was higher complication rate in patients with benign conditions after a longer follow-up period owing to the nature of the underlying diseases.
PMCID: PMC3090328  PMID: 21477303
12.  Diagnostic Value of EBUS-TBNA for Lung Cancer with Non-Enlarged Lymph Nodes: A Study in a Tuberculosis-Endemic Country 
PLoS ONE  2011;6(2):e16877.
In tuberculosis (TB)-endemic areas, contrast-enhanced computed tomography (CT) and positron emission tomography (PET) findings of lung cancer patients with non-enlarged lymph nodes are frequently discrepant. Endobronchial ultrasound-guided transbronchial aspiration (EBUS-TBNA) enables real-time nodal sampling, and thereby improves nodal diagnosis accuracy. This study aimed to compare the accuracy of nodal diagnosis by using EBUS-TBNA, and PET.
We studied 43 lung cancer patients with CT-defined non-enlarged mediastinal and hilar lymph nodes and examined 78 lymph nodes using EBUS-TBNA.
The sensitivity, specificity, positive predictive value, and negative predictive value of EBUS-TBNA were 80.6%, 100%, 100%, and 85.7%, respectively. PET had low specificity (18.9%) and a low positive predictive value (44.4%). The diagnostic accuracy of EBUS-TBNA was higher than that of PET (91% vs. 47.4%; p<0.001). Compared to CT-based nodal assessment, PET yielded a positive diagnostic impact in 36.9% nodes, a negative diagnostic impact in 46.2% nodes, and no diagnostic impact in 16.9% nodes. Patients with lymph nodes showing negative PET diagnostic impact had a high incidence of previous pulmonary TB. Multivariate analysis indicated that detection of hilar nodes on PET was an independent predictor of negative diagnostic impact of PET.
In a TB-endemic area with a condition of CT-defined non-enlarged lymph node, the negative diagnostic impact of PET limits its clinical usefulness for nodal staging; therefore, EBUS-TBNA, which facilitates direct diagnosis, is preferred.
PMCID: PMC3045379  PMID: 21364919
13.  Extravascular Lung Water Correlates Multiorgan Dysfunction Syndrome and Mortality in Sepsis 
PLoS ONE  2010;5(12):e15265.
This study was designated to investigate whether increased extravascular lung water index (EVLWI) may correlate multiple organ dysfunction syndrome (MODS) and mortality in sepsis.
We designed a prospective cohort study in an intensive care unit of a tertiary care hospital. Sixty-seven patients with severe sepsis were included. Data were used to determine an association between EVLWI and the development of MODS and mortality. These connections were determined by the multiple logistic regression, plotting the receiver operating characteristic (ROC) curve and by Spearman test.
EVLWI levels were higher in MODS patients on day 1 (median (IQR), 18(12.8–23.9) ml/kg, n = 38, p<0.0001) than in those without (median (IQR), 12.4 (7.9–16.3) ml/kg, n = 29) and day 3 (median (IQR), 17.8 (11.2–22.8) ml/kg, n = 29, p = 0.004) than in those without (median (IQR), 12.4 (8.0–16.3) ml/kg, n = 29). EVLWI was used as an independent predictor of the development of MODS (odds ratio, 1.6; p = 0.005; 95% confidence interval, 1.2∼2.2) during ICU stay. The area under the ROC curve showed that EVLWI levels could predict MODS (0.866) and mortality (0.881) during ICU stay. Meanwhile, the higher of SOFA score, the more EVLWI was found on day 1 (r = 0.7041, p<0.0001) and day 3 (r = 0.7732, p<0.0001).
Increased EVLWI levels correlates development of MODS and mortality during the patients' ICU stay. Further more, the potential of novel treatment in severe sepsis with lung injury may develop.
PMCID: PMC3002976  PMID: 21187890

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