Epidemiology and outcomes of multidrug-resistant bacterial infection in non-cystic fibrosis bronchiectasis.

PURPOSE: Multidrug-resistant (MDR) bacteria impose a considerable health-care burden and are associated with bronchiectasis exacerbation. This study investigated the clinical outcomes of adult patients with bronchiectasis following MDR bacterial infection. METHODS: From the Chang Gung Research Database, we identified patients with bronchiectasis and MDR bacterial infection from 2008 to 2017. The control group comprised patients with bronchiectasis who did not have MDR bacterial infection and were propensity-score matched at a 1:2 ratio. The main outcomes were in-hospital and 3-year mortality. RESULTS: In total, 554 patients with both bronchiectasis and MDR bacterial infection were identified. The types of MDR bacteria that most commonly affected the patients were MDR- Acinetobacter baumannii (38.6%) and methicillin-resistant Staphylococcus aureus (18.4%), Extended-spectrum-beta-lactamases (ESBL)- Klebsiella pneumoniae (17.8%), MDR-Pseudomonas (14.8%), and ESBL-E. coli (7.5%). Compared with the control group, the MDR group exhibited lower body mass index scores, higher rate of chronic bacterial colonization, a higher rate of previous exacerbations, and an increased use of antibiotics. Furthermore, the MDR group exhibited a higher rate of respiratory failure during hospitalization (MDR vs. control, 41.3% vs. 12.4%; p < 0.001). The MDR and control groups exhibited in-hospital mortality rates of 26.7% and 7.6%, respectively (p < 0.001); 3-year respiratory failure rates of 33.5% and 13.5%, respectively (p < 0.001); and 3-year mortality rates of 73.3% and 41.5%, respectively (p < 0.001). After adjustments were made for confounding factors, the infection with MDR and MDR bacteria species were determined to be independent risk factors affecting in-hospital and 3-year mortality. CONCLUSIONS: MDR bacteria were discovered in patients with more severe bronchiectasis and were independently associated with an increased risk of in-hospital and 3-year mortality. Given our findings, we recommend that clinicians identify patients at risk of MDR bacterial infection and follow the principle of antimicrobial stewardship to prevent the emergence of resistant bacteria among patients with bronchiectasis.

Urinary cadmium concentration is associated with the severity and clinical outcomes of COVID-19: a bicenter observational cohort study.

BACKGROUND: Cadmium and nickel exposure can cause oxidative stress, induce inflammation, inhibit immune function, and therefore has significant impacts on the pathogenesis and severity of many diseases. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can also provoke oxidative stress and the dysregulation of inflammatory and immune responses. This study aimed to assess the potential associations of cadmium and nickel exposure with the severity and clinical outcomes of patients with coronavirus disease 2019 (COVID-19). METHODS: We performed a retrospective, observational, bicenter cohort analysis of patients with SARS-CoV-2 infection in Taiwan between June 2022 and July 2023. Cadmium and nickel concentrations in blood and urine were measured within 3 days of the diagnosis of acute SARS-CoV-2 infection, and the severity and clinical outcomes of patients with COVID-19 were analyzed. RESULTS: A total of 574 patients were analyzed and divided into a severe COVID-19 group (hospitalized patients) (n = 252; 43.9%), and non-severe COVID-19 group (n = 322; 56.1%). The overall in-hospital mortality rate was 11.8% (n = 68). The severe COVID-19 patients were older, had significantly more comorbidities, and significantly higher neutrophil/lymphocyte ratio, C-reactive protein, and interleukin-6 than the non-severe COVID-19 patients (all p < 0.05). Blood and urine cadmium and urine nickel concentrations were significantly higher in the severe COVID-19 patients than in the non-severe COVID-19 patients. Among the severe COVID-19 patients, those in higher urine cadmium/creatinine quartiles had a significantly higher risk of organ failure (i.e., higher APACHE II and SOFA scores), higher neutrophil/lymphocyte ratio, lower PaO2/FiO2 requiring higher invasive mechanical ventilation support, higher risk of acute respiratory distress syndrome, and higher 60-, 90-day, and all-cause hospital mortality (all p < 0.05). Multivariable logistic regression models revealed that urine cadmium/creatinine was independently associated with severe COVID-19 (adjusted OR 1.643 [95% CI 1.060-2.547], p = 0.026), and that a urine cadmium/creatinine value > 2.05 µg/g had the highest predictive value (adjusted OR 5.349, [95% CI 1.118-25.580], p = 0.036). CONCLUSIONS: Urine cadmium concentration in the early course of COVID-19 could predict the severity and clinical outcomes of patients and was independently associated with the risk of severe COVID-19.

Mucinous Adenocarcinoma of the Lung Diagnosed by Radial Endobronchial Ultrasound-guided Bronchoscopic Cryobiopsy and Presenting as Interstitial Lung Disease in a Patient with Systemic Sclerosis.

We report a patient with systemic sclerosis who was diagnosed with advanced-stage mucinous adenocarcinoma of the lungs. The clinical presentation, imaging findings, pathological results, and molecular diagnoses are presented. A 64-year-old woman with systemic sclerosis was administered prednisolone and hydroxychloroquine sulfate to control her disease. High-resolution computed tomography (HRCT) revealed an interstitial pattern in both lungs during annual imaging. Connective tissue disease-associated interstitial lung disease (CTD-ILD) was diagnosed using blood tests, pulmonary function tests, and imaging findings. One year later, the patient underwent follow-up chest HRCT, which showed progressive lung disease. The patient underwent endobronchial ultrasound (EBUS)-guided transbronchial lung cryobiopsy and computed tomography-guided biopsy for a pathological diagnosis. The pathology reports of bilateral lungs disclosed mucinous adenocarcinoma. After tumor staging and mutation testing, the patient received chemotherapy with pemetrexed and cisplatin. The bilateral lung lesions subsided after four cycles of first-line chemotherapy. Patients with CTD and lung involvement may be diagnosed with CTD-ILD. Although histopathological results are not mandatory for ILD diagnosis, EBUS-guided transbronchial lung biopsy or lung cryobiopsy should be considered when ILD has atypical or unexplained features.

Comparison of Clinical Characteristics and Outcomes of Hospitalized Patients Infected with the D614G Strain or Alpha Variant of COVID-19 in Taiwan: A Multi-Center Cohort Study.

Objective: Direct comparison of the clinical traits of coronavirus disease 2019 (COVID-19) in strain D614G, which originated from Wuhan, China, and the Alpha variant, which contains 17 mutations, infected patients could help physicians distinguish between strains and make clinical decisions accordingly. This study sought to compare the clinical characteristics and outcomes of the D614G strain and Alpha variant of SARS-COV-2 and identify the predictors for viral RNA clearance and in-hospital mortality in patients with COVID-19. Methods: This study recruited consecutive patients from four hospitals between March 1, 2020, and July 31, 2021. Demographic characteristics, laboratory results, and clinical outcomes were determined. Results: Among the 239 enrolled patients, 11.2% (27/239) were infected with strain D614G and 88.7% (212/239) were infected with the Alpha variant. There were no significant differences in disease progression, rate of respiratory failure, subsequent development of acute respiratory distress syndrome (ARDS), acute kidney injury, cardiac injury, duration of stay in the intensive care unit or hospital, discharge rate, mortality rate, or viral RNA clearance time between the two groups. Multivariate Cox regression revealed that antibiotic therapy reduced the risk of delayed viral RNA clearance (hazard ratio [HR], 0.26; 95% confidence interval [CI], 0.13-0.55), while autoimmune disease increased the risk of delayed viral RNA clearance (HR, 3.98; 95% CI, 1.21-13.04). Elderly patients (age > 65 years) and patients with a history of cerebrovascular accident (CVA) were at increased risk of in-hospital mortality (HR, 5.14; 95% CI, 1.06-24.72 and HR, 3.62; 95% CI, 1.25-10.42, respectively). Conclusions: There were no significant differences between the D614G strain and Alpha variant of COVID-19 in terms of clinical characteristics and outcomes. However, factors affecting viral RNA clearance and the risk of in-hospital mortality were identified. These results could help to inform the future prioritization of resource allocation and identify patients in need of intense monitoring.

Clinical outcomes and prognostic factors for prolonged mechanical ventilation in patients with acute stroke and brain trauma.

BACKGROUND/PURPOSE: Neurological dysfunction is a common condition necessitating prolonged mechanical ventilation (PMV). We investigated the clinical features and outcomes of patients with acute neurological diseases requiring PMV. METHODS: This retrospective observational study was conducted at the Respiratory Care Center (RCC) of Chang Gung Memorial Hospital, Taiwan, between January 2011 and January 2014. The main outcome was weaning success, defined as successful withdrawal from mechanical ventilator support for more than 5 days. RESULTS: The study included 103 patients with acute stroke and brain trauma receiving PMV. Weaning success was reported in 63 (61%) patients and weaning failure was reported in 40 (39%) patients. Patients in the weaning failure group were older and had a lower RCC Glasgow Coma Scale (GCS) score (6.0 vs 7.9, p = 0.005), lower albumin level (2.8 vs 3.1, p = 0.015), longer RCC stay (28.7 vs 21.3 days, p = 0.017), and higher in-hospital mortality rate (47% vs 9%, p < 0.01). Multivariate analysis revealed that reduced RCC GCS score is an independent prognostic factor for weaning failure (odds ratio [OR] = 1.22, 95% confidence interval [CI] = 1.05-1.46, p = 0.016) and that per unit increase of RCC GCS score is associated with a lower risk of in-hospital mortality (OR = 0.83, 95% CI = 0.70-0.96, p = 0.019). CONCLUSION: Reduced RCC GCS score is an independent prognostic factor for weaning failure, and is associated with increased in-hospital mortality rates in patients with acute stroke and brain trauma requiring PMV.

The Clinical Experience of Mycobacterial Culture Yield of Pleural Tissue by Pleuroscopic Pleural Biopsy among Tuberculous Pleurisy Patients.

Background and Objectives: Tuberculous pleurisy is a common extrapulmonary TB that poses a health threat. However, diagnosis of TB pleurisy is challenging because of the low positivity rate of pleural effusion mycobacterial culture and difficulty in retrieval of optimal pleural tissue. This study aimed to investigate the efficacy of mycobacterial culture from pleural tissue, obtained by forceps biopsy through medical pleuroscopy, in the diagnosis of TB pleurisy. Materials and Methods: This study retrospectively enrolled 68 TB pleurisy patients. Among them, 46 patients received semi-rigid pleuroscopy from April 2016 to March 2021 in a tertiary hospital. We analyzed the mycobacterial culture from pleural tissue obtained by forceps biopsy. Results: The average age of the study participants was 62.8 years, and 64.7% of them were men. In the pleuroscopic group, the sensitivity of positive Mycobacterium tuberculosis (M. TB) cultures for sputum, pleural effusion, and pleural tissue were 35.7% (15/42), 34.8% (16/46), and 78.3% (18/23), respectively. High sensitivities of M. TB culture from pleural tissue were up to 94.4% and 91.7% when pleural characteristic patterns showed adhesion lesions and both adhesion lesions and presence of micronodules, respectively. Conclusions: M. TB culture from pleural tissue should be considered a routine test when facing unknown pleural effusion during pleuroscopic examination.

Mechanical power during extracorporeal membrane oxygenation and hospital mortality in patients with acute respiratory distress syndrome.

BACKGROUND: Mechanical power (MP) refers to the energy delivered by a ventilator to the respiratory system per unit of time. MP referenced to predicted body weight (PBW) or respiratory system compliance have better predictive value for mortality than MP alone in acute respiratory distress syndrome (ARDS). Our objective was to assess the potential impact of consecutive changes of MP on hospital mortality among ARDS patients receiving extracorporeal membrane oxygenation (ECMO). METHODS: We performed a retrospective analysis of patients with severe ARDS receiving ECMO in a tertiary care referral center in Taiwan between May 2006 and October 2015. Serial changes of MP during ECMO were recorded. RESULTS: A total of 152 patients with severe ARDS rescued with ECMO were analyzed. Overall hospital mortality was 53.3%. There were no significant differences between survivors and nonsurvivors in terms of baseline values of MP or other ventilator settings. Cox regression models demonstrated that mean MP alone, MP referenced to PBW, and MP referenced to compliance during the first 3 days of ECMO were all independently associated with hospital mortality. Higher MP referenced to compliance (HR 2.289 [95% CI 1.214-4.314], p = 0.010) was associated with a higher risk of death than MP itself (HR 1.060 [95% CI 1.018-1.104], p = 0.005) or MP referenced to PBW (HR 1.004 [95% CI 1.002-1.007], p < 0.001). The 90-day hospital mortality of patients with high MP (> 14.4 J/min) during the first 3 days of ECMO was significantly higher than that of patients with low MP (≦ 14.4 J/min) (70.7% vs. 46.8%, p = 0.004), and the 90-day hospital mortality of patients with high MP referenced to compliance (> 0.53 J/min/ml/cm H2O) during the first 3 days of ECMO was significantly higher than that of patients with low MP referenced to compliance (≦ 0.53 J/min/ml/cm H2O) (63.6% vs. 29.7%, p < 0.001). CONCLUSIONS: MP during the first 3 days of ECMO was the only ventilatory variable independently associated with 90-day hospital mortality, and MP referenced to compliance during ECMO was more predictive for mortality than was MP alone.

Blood Cadmium Levels and Oxygen Desaturation during the 6-Minute Walk Test in Patients with Chronic Obstructive Pulmonary Disease.

Background and Objectives: chronic obstructive pulmonary disease (COPD) is characterized by persistent airflow limitation and a history of exposure to noxious stimuli. Cigarette smoking is the most important causal factor for developing COPD. Cadmium, a minor metallic element, is one of the main inorganic components in tobacco smoke. Inhaled cadmium was associated with a decline in lung function, gas exchange impairment, and the development of obstructive lung disease. Patients with COPD who had oxygen desaturation during the 6-min walk test (6MWT) had a significantly worse prognosis than non-desaturation in COPD patients. Nonetheless, few studies have addressed the influence of blood cadmium levels on exercise-induced oxygen desaturation in COPD patients. Our objective was to assess the potential impact of blood cadmium levels on oxygen desaturation during the 6MWT among COPD patients. Materials and Methods: we performed a retrospective analysis of patients with COPD who were examined for blood cadmium levels in a tertiary care referral center in Taiwan, between March 2020 and May 2021. The 6-min walk test was performed. Normal control subjects who had no evidence of COPD were also enrolled. Results: a total of 73 COPD patients were analyzed and stratified into the high-blood cadmium group (13 patients) and low-blood cadmium group (60 patients). A total of 50 normal control subjects without a diagnosis of COPD were enrolled. The high-blood cadmium group had a significantly higher extent of desaturation than the low-blood cadmium group. The frequency of desaturation during 6MWT revealed a stepwise-increasing trend with an increase in blood cadmium levels. A multivariable logistic regression model revealed that blood cadmium levels were independently associated with desaturation during the 6MWT (odds ratio 12.849 [95% CI 1.168-141.329]; p = 0.037). Conclusions: our findings indicate that blood cadmium levels, within the normal range, were significantly associated with desaturation during 6MWT in patients with COPD.

Outcomes of severe H1N1 pneumoniae: A retrospective study at intensive care units.

BACKGROUND: The incidence of acute respiratory distress syndrome (ARDS) and the mortality rate of H1N1 influenza pneumonia are unclear. The aim of this study is to investigate the clinical features and outcomes of adult patients admitted to intensive care units (ICUs) with H1N1 pneumonia related ARDS. METHODS: This retrospective study included patients with confirmed H1N1 influenza pneumonia admitted to the ICUs of a medical center between July 2009 and May 2014. We investigated the patients' characteristics, clinical presentations, illness severities, and outcomes. RESULTS: Sixty-six patients were confirmed to have H1N1 influenza pneumonia requiring mechanical ventilation. Fifty-four of those patients (82%) developed ARDS, while their hospital mortality rate was 33% (22/66). There were no significant differences in the ICU and hospital mortality rates of the ARDS and non-ARDS patients. Among the ARDS patients, there were higher rates of solid malignant disease (22.8% vs. 2.8%, p = 0.038) and sepsis (66.7% vs. 33.3%, p = 0.020) and a higher mean tidal volume (8.9 ± 1.8 vs. 7.8 ± 1.9 ml/kg, p = 0.032) in the non-survivors than the survivors. Logistic regression analysis revealed that a high tidal volume (odds ratio = 1.448, 95 % CI = 1.033-2.030; p = 0.032) and sequential organ failure assessment (SOFA) score (odds ratio = 1.233, 95% CI = 1.029-1.478; p = 0.023) were the risk factors of hospital mortality. CONCLUSION: For H1N1 influenza pneumonia patients admitted to ICUs with mechanical ventilation, there is a high probability of developing ARDS with a modest mortality rate. For patients with ARDS due to H1N1 influenza pneumonia, the tidal volume and SOFA score are the predictors of hospital mortality.

Low-Molecular-Weight Heparin Reduces Ventilation-Induced Lung Injury through Hypoxia Inducible Factor-1α in a Murine Endotoxemia Model.

Patients with sepsis frequently require mechanical ventilation (MV) to survive. However, MV has been shown to induce the production of proinflammatory cytokines, causing ventilator-induced lung injury (VILI). It has been demonstrated that hypoxia-inducible factor (HIF)-1α plays a crucial role in inducing both apoptotic and inflammatory processes. Low-molecular-weight heparin (LMWH) has been shown to have anti-inflammatory activities. However, the effects of HIF-1α and LMWH on sepsis-related acute lung injury (ALI) have not been fully delineated. We hypothesized that LMWH would reduce lung injury, production of free radicals and epithelial apoptosis through the HIF-1α pathway. Male C57BL/6 mice were exposed to 6-mL/kg or 30-mL/kg MV for 5 h. Enoxaparin, 4 mg/kg, was administered subcutaneously 30 min before MV. We observed that MV with endotoxemia induced microvascular permeability; interleukin-6, tumor necrosis factor-α, macrophage inflammatory protein-2 and vascular endothelial growth factor protein production; neutrophil infiltration; oxidative loads; HIF-1α mRNA activation; HIF-1α expression; bronchial epithelial apoptosis; and decreased respiratory function in mice (p < 0.05). Endotoxin-induced augmentation of VILI and epithelial apoptosis were reduced in the HIF-1α-deficient mice and in the wild-type mice following enoxaparin administration (p < 0.05). Our data suggest that enoxaparin reduces endotoxin-augmented MV-induced ALI, partially by inhibiting the HIF-1α pathway.

Factors affecting survival in patients with endobronchial malignant mass after flexible Bronchoscopic cryotherapy: a cohort study.

BACKGROUND: Malignant endobronchial mass (MEM) has poor prognosis, cryotherapy is reportedly to diagnose MEM, however, the therapeutic role of cryotherapy impacts on survival has not be well addressed. METHODS: Cohort data on post-cryotherapy MEM patients in a university-affiliated hospital between 2007 and 2012 were evaluated. Factors that impact survival of these subjects were analyzed using multivariate regression analysis. RESULTS: During study period, 67 patients (47 males), with median age was 63 years (range, 50-77 and median performance status of 2 (inter-quartile range [IQR], 2-3). Twenty-five had primary lung squamous cell carcinoma, 14 primary had lung adenocarcinoma, seven had metastatic colon adenocarcinoma, four had sarcoma, four had non-small cell lung cancer, four had small cell lung cancer, three had large cell carcinoma, two had lymphoma, one had muco-epidermoid carcinoma, two had esophageal squamous cell carcinoma, and one had metastatic renal cell carcinoma. MEM were observed as follows: 15 at the trachea, 14 at the left main bronchus, 12 at the right main bronchus, 12 at the right upper lobe bronchus, five at the right intermediate bronchus, three at the right lower lobe bronchus, three at the left upper lobe bronchus, two at the left lower lobe bronchus, and one at the right middle lobe bronchus Post-cryotherapy complications included minor bleeding (n = 14) and need for multiple procedures (n = 12); outcomes were relief of symptoms (n = 56), improved performance status (n = 49) and ability to receive chemotherapy (n = 43). After controlling for other variables, performance status improved after cryotherapy (odds ratio [OR] 3.7; p = 0.03; 95% confidence interval [CI] 1.2~10.7) and ability to receive chemotherapy (OR 4.3; p = 0.02; 95% CI 1.4~13.7) remained significant survival factor. Patients who received chemotherapy and cryotherapy had better survival than patients who received only cryotherapy (median, 472 vs. 169 days; log-rank test, p = 0.02; HR 0.37; 95% CI 0.16-0.89). CONCLUSION: Cryotherapy could be useful management of MEM by flexible bronchoscopy. The performance status after cryotherapy improved and caused further chemotherapy possible for the study patients and thereby, improved survival. However, the mechanism in detail of cryotherapy improve survival should be explored in the future.

Three-dimensional photography for the evaluation of facial profiles in obstructive sleep apnoea.

BACKGROUND AND OBJECTIVE: Craniofacial structure is an important determinant of obstructive sleep apnoea (OSA) syndrome risk. Three-dimensional stereo-photogrammetry (3dMD) is a novel technique which allows quantification of the craniofacial profile. This study compares the facial images of OSA patients captured by 3dMD to three-dimensional computed tomography (3-D CT) and two-dimensional (2-D) digital photogrammetry. Measurements were correlated with indices of OSA severity. METHODS: Thirty-eight patients diagnosed with OSA were included, and digital photogrammetry, 3dMD and 3-D CT were performed. Distances, areas, angles and volumes from the images captured by three methods were analysed. RESULTS: Almost all measurements captured by 3dMD showed strong agreement with 3-D CT measurements. Results from 2-D digital photogrammetry showed poor agreement with 3-D CT. Mandibular width, neck perimeter size and maxillary volume measurements correlated well with the severity of OSA using all three imaging methods. Mandibular length, facial width, binocular width, neck width, cranial base triangle area, cranial base area 1 and middle cranial fossa volume correlated well with OSA severity using 3dMD and 3-D CT, but not with 2-D digital photogrammetry. CONCLUSION: 3dMD provided accurate craniofacial measurements of OSA patients, which were highly concordant with those obtained by CT, while avoiding the radiation associated with CT.

Nintedanib reduces ventilation-augmented bleomycin-induced epithelial-mesenchymal transition and lung fibrosis through suppression of the Src pathway.

Mechanical ventilation (MV) used in patients with acute respiratory distress syndrome (ARDS) can increase lung inflammation and pulmonary fibrogenesis. Src is crucial in mediating the transforming growth factor (TGF)-ß1-induced epithelial-mesenchymal transition (EMT) during the fibroproliferative phase of ARDS. Nintedanib, a multitargeted tyrosine kinase inhibitor that directly blocks Src, has been approved for the treatment of idiopathic pulmonary fibrosis. The mechanisms regulating interactions among MV, EMT and Src remain unclear. In this study, we suggested hypothesized that nintedanib can suppress MV-augmented bleomycin-induced EMT and pulmonary fibrosis by inhibiting the Src pathway. Five days after administrating bleomycin to mimic acute lung injury (ALI), C57BL/6 mice, either wild-type or Src-deficient were exposed to low tidal volume (VT ) (6 ml/kg) or high VT (30 ml/kg) MV with room air for 5 hrs. Oral nintedanib was administered once daily in doses of 30, 60 and 100 mg/kg for 5 days before MV. Non-ventilated mice were used as control groups. Following bleomycin exposure in wild-type mice, high VT MV induced substantial increases in microvascular permeability, TGF-ß1, malondialdehyde, Masson's trichrome staining, collagen 1a1 gene expression, EMT (identified by colocalization of increased staining of α-smooth muscle actin and decreased staining of E-cadherin) and alveolar epithelial apoptosis (P < 0.05). Oral nintedanib, which simulated genetic downregulation of Src signalling using Src-deficient mice, dampened the MV-augmented profibrotic mediators, EMT profile, epithelial apoptotic cell death and pathologic fibrotic scores (P < 0.05). Our data indicate that nintedanib reduces high VT MV-augmented EMT and pulmonary fibrosis after bleomycin-induced ALI, partly by inhibiting the Src pathway.

Factors responsible for poor sleep quality in patients with chronic obstructive pulmonary disease.

BACKGROUND: Sleep disturbance is a common complaint in patients with chronic obstructive lung disease (COPD). However, the factors resulting in sleep disturbance remain unclear. This retrospective, observational, multicenter study aimed to identify the factors associated with sleep disturbance in patients with COPD. METHODS: The study was a retrospective, observational, and multicenter research. Data including age, sex, body mass index, smoking status, COPD inhaler prescribed, clinical symptoms, pulmonary function tests, medical history of comorbidities, and questionnaires were collected. Parameters including demographics, symptoms, medication, severity, functional classification, and comorbidities were correlated with sleep quality scores. RESULTS: Among 377 patients with COPD, 200 (53 %) patients experienced poor sleep quality (Pittsburg Sleep Quality Index scores > 5). A significant difference in sleep quality, as measured by PSQI scores, was noted between groups based on the 2011 Global Initiatives for Chronic Obstructive Lung Disease (GOLD) classification system. The most common sleep disturbances included "getting up to use the bathroom" (70.3 %), "wake up at night or early morning" (40.3 %), and "cough and snore loudly at night" (15.9 %). The use of inhaled corticosteroids, the presence of wheezing, COPD Assessment Test (CAT) scores, and Modified Medical Research Council (mMRC) dyspnea scale scores positively correlated with poor sleep quality (odds ratio: 1.51, 1.66, 1.09, and 1.30, respectively). Upon multivariate analysis, the CAT score was an independent factor for poor sleep quality in these patients. With the exception of sleep problem items, based on the CAT questionnaire, phlegm was significantly higher in COPD patients with poor sleep quality. CONCLUSIONS: Poor sleep quality is common among patients with COPD and symptoms including wheeze, phlegm, and inhaled corticosteroid use may contribute to poor sleep quality. The CAT score is a good indicator of poor sleep quality in patients with COPD.

Activation of Src-dependent Smad3 signaling mediates the neutrophilic inflammation and oxidative stress in hyperoxia-augmented ventilator-induced lung injury.

BACKGROUND: Mechanical ventilation and concomitant administration of hyperoxia in patients with acute respiratory distress syndrome can damage the alveolar epithelial and capillary endothelial barrier by producing inflammatory cytokines and reactive oxygen species. The Src tyrosine kinase and Smad3 are crucial inflammatory regulators used for ventilator-induced lung injury (VILI). The mechanisms regulating interactions between high-tidal-volume mechanical ventilation, hyperoxia, and acute lung injury (ALI) are unclear. We hypothesized that high-tidal-volume mechanical stretches and hyperoxia augment lung inflammation through upregulation of the Src and Smad3 pathways. METHODS: Wild-type or Src-deficient C57BL/6 mice, aged between 6 and 8 weeks, were exposed to high-tidal-volume (30 mL/kg) ventilation with room air or hyperoxia for 1-4 h after 2-mg/kg Smad3 inhibitor (SIS3) administration. Nonventilated mice were used as control subjects. RESULTS: We observed that the addition of hyperoxia to high-tidal-volume mechanical ventilation further induced microvascular permeability, neutrophil infiltration, macrophage inflammatory protein-2 and matrix metalloproteinase-9 (MMP-9) production, malondialdehyde, nicotinamide adenine dinucleotide phosphate oxidase activity, MMP-9 mRNA expression, hypoxemia, and Src and Smad3 activation (P < 0.05). Hyperoxia-induced augmentation of VILI was attenuated in Src-deficient mice and mice with pharmacological inhibition of Smad3 activity by SIS3 (P < 0.05). Mechanical ventilation of Src-deficient mice with hyperoxia further reduced the activation of Smad3. CONCLUSIONS: Our data suggest that hyperoxia-increased high-tidal-volume ventilation-induced ALI partially depends on the Src and Smad3 pathways.

Association between statin use and tuberculosis risk in patients with bronchiectasis: a retrospective population-based cohort study in Taiwan.

BACKGROUND: Chronic airway diseases have been associated with an increased risk of tuberculosis (TB); however, data in patients with bronchiectasis is limited. Statins have been shown to exhibit anti-inflammatory effects by modulating the inflammatory response. This study investigated whether statin treatment could reduce the risk of TB in patients with bronchiectasis. METHODS: We conducted a retrospective cohort study using a nationwide population database of patients with bronchiectasis who did or did not receive statin treatment. The defined daily dose (DDD) of statin, current or past statin user and statin exposure time were measured for the impact of statin use. The primary outcome was the incidence of new-onset TB. Considering of potential immortal time bias due to stain exposure time, Cox regression models with time-dependent covariates were employed to estimate HRs with 95% CIs for TB incidence among patients with bronchiectasis. RESULTS: Patients with bronchiectasis receiving statin treatment had a decreased risk of TB. After adjusting for age, sex, income, comorbidities and Charlson Comorbidity Index, statin users had a 0.59-fold lower risk of TB incidence compared with non-statin users (95% CI 0.40 to 0.88; p=0.0087). Additionally, compared with non-statin users, statin treatment was a protective factor against TB in users with a cumulative DDD greater than 180 per year, with an HR of 0.32 (95% CI 0.12 to 0.87; p=0.0255). CONCLUSIONS: Statin treatment demonstrated a dose-dependent protective effect and was associated with a reduced risk of TB in patients with bronchiectasis. These findings suggest that statins may play a role in lowering TB risk by modulating airway inflammation in this patient population.

Major adverse cardiovascular events in advanced-stage lung cancer: a multicenter cohort study.

Background: Lung cancers are common worldwide. First-line targeted therapy and chemotherapy are both standard treatments in the current guidelines. With the development of new anticancer therapy, the lifespan of patients with late-stage lung cancer has increased. Cardiovascular events can occur during cancer treatment. This observational study aimed to report the incidence of major adverse cardiovascular events (MACE) after cancer treatment using real-world data. Objectives: Patients diagnosed with advanced-stage lung cancer between January 2011 and December 2017 were enrolled. Data were collected from the Chang Gung Research Database (CGRD). Design: Retrospective cohort study. Methods: Baseline characteristics, clinical stages, pathologies, and outcomes were retrieved from the CGRD. Results: We identified 4406 patients with advanced lung cancer, of whom 2197 received first-line epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) therapy and 2209 received first-line platinum-based chemotherapy. Most patients in the first-line EGFR-TKI group were never-smokers (74.9%), whereas those in the first-line chemotherapy group were ever-smokers (66.0%). The incidence of MACE was not significantly different between the two groups (12.0% versus 11.9%, p = 0.910). However, the incidence of ischemic stroke was higher in the first-line EGFR-TKI group than in the first-line chemotherapy group (3.9% versus 1.9%, p < 0.001). Conclusion: MACEs are common in patients with advanced-stage lung cancer during treatment. The incidence of MACE was similar between the first-line EGFR-TKI therapy and first-line chemotherapy groups. Although more patients in the EGFR-TKI group were female and never-smokers, the risk of ischemic stroke was higher in patients who received first-line EGFR-TKI therapy than in those who received first-line chemotherapy.

Prior treated tuberculosis and mortality risk in lung cancer.

Background: Lung cancer is one of the leading causes of cancer death worldwide, and tuberculosis (TB) is a common pre-existing disease. However, there is scarce literature studying the mortality risk in patients with prior TB and subsequent lung cancer. Methods: We recruited lung cancer patients from the Taiwan Cancer Registry from 2011 to 2015 and classified them into two groups according to presence or absence of prior TB. We then matched them in a ratio of 1:4 using the exact matching approach. The mortality risk within 3 years after diagnosis of lung cancer was analyzed and compared between these two groups. Results: During the study period, 43,472 patients with lung cancer were recruited, and of these, 1,211 (2.79%) patients had prior TB. After matching, this cohort included 5,935 patients with lung cancer in two groups: patients with prior TB before lung cancer (n = 1,187) and those without (n = 4,748). After controlling for demographic factors and comorbidities, the patients with prior TB had increased adjusted hazard ratios of 1.13 (95% CI: 1.04-1.23) and 1.11 (1.02-1.21) for all-cause and cancer-specific 3-year mortality, respectively, compared to the lung cancer patients without prior TB. Duration between TB and lung cancer (<1 year vs. 1-3 years vs. >3 years) had no differences for mortality risk. Conclusion: In the present study, 2.79% patients with lung cancer had prior TB, which was associated with higher 3-year mortality after they developed lung cancer. The mortality risk with prior TB did not decrease even if >3 years passed before diagnosis of lung cancer.