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.

Clinical manifestations and outcomes of fungus-associated asthma: A multi-institution database study in Taiwan.

BACKGROUND: Differences in the clinical phenotypes and outcomes of fungus-associated asthma remain unclear. We aimed to investigate the presentation of asthmatics with fungal sensitization and/or positive fungal isolates. METHODS: Clinical characteristics, pulmonary function, microbiological data, allergy test reports, emergency department (ED) visits and hospitalizations were retrieved from the Chang Gung Research Database between 2010 and 2018; the largest electronic medical record-based database in Taiwan. Follow-up care was provided to each patient for 3 years. RESULTS: A total of 30,754 asthmatics were enrolled, and 7976 were eligible for analysis after applying the exclusion criteria. Of these patients, 694 had sputum examinations for fungi. The patients were divided into four groups: group 1, neither fungal sensitization nor fungal isolates in the sputum (n = 386); group 2, positive fungal sensitization (n = 58); group 3, positive fungal isolates (n = 217); and group 4, concomitant positive fungal sensitization and positive fungal isolates (n = 33). Asthmatic patients with fungal sensitization (groups 2 and 4) demonstrated significantly higher IgE levels compared with those without (groups 1 and 3). Group 4 patients had a higher frequency of hospitalization. Amongst patients under Global Initiative for Asthma (GINA) step 4-5 therapies, group 4 asthmatics possessed significantly higher incidence of respiratory failure. CONCLUSIONS: The prevalence of fungal sensitization and fungal isolates from sputum were even across asthmatic severities, but the clinical impact of fungi may be more significant among patients with more severe disease.

The Impact of Higher Protein Intake in Patients with Prolonged Mechanical Ventilation.

Prolonged mechanical ventilation (PMV) is associated with poor outcomes and a high economic cost. The association between protein intake and PMV has rarely been investigated in previous studies. This study aimed to investigate the impact of protein intake on weaning from mechanical ventilation. Patients with the PMV (mechanical ventilation ≥6 h/day for ≥21 days) at our hospital between December 2020 and April 2022 were included in this study. Demographic data, nutrition records, laboratory data, weaning conditions, and survival data were retrieved from the patient's electronic medical records. A total of 172 patients were eligible for analysis. The patients were divided into two groups: weaning success (n = 109) and weaning failure (n = 63). Patients with daily protein intake greater than 1.2 g/kg/day had significant shorter median days of ventilator use than those with less daily protein intake (36.5 vs. 114 days, respectively, p < 0.0001). Daily protein intake ≥1.065 g/kg/day (odds ratio: 4.97, p = 0.033), daily protein intake ≥1.2 g/kg/day (odds ratio: 89.07, p = 0.001), improvement of serum albumin (odds ratio: 3.68, p = 0.027), and BMI (odds ratio: 1.235, p = 0.014) were independent predictor for successful weaning. The serum creatinine level in the 4th week remained similar in patients with daily protein intake either >1.065 g/kg/day or >1.2 g/kg/day (p = 0.5219 and p = 0.7796, respectively). Higher protein intake may have benefits in weaning in patients with PMV and had no negative impact on renal function.

Clinical outcomes and prognostic factors of bronchiectasis rheumatoid overlap syndrome: A multi-institution cohort study.

The information regarding bronchiectasis with RA (BROS) is limited in Asia. The objective of this study was to investigate the clinical characteristics and outcomes of BROS in Taiwan. This multi-institute cohort study included patients with BROS from January 2006 to December 2017. The clinical, functional and microbiological data of these patients were retrieved from the Chang Gung Research Database. Respiratory failure and mortality were the primary outcomes. Severe exacerbation was defined as bronchiectasis- related hospitalizations or emergency department visits. A total of 343 patients with BROS were identified. One hundred and eight patients had severe exacerbation and exhibited significantly more previous exacerbations, a lower FEV1 and higher BACI score (11.1 vs. 7.5) than patients without severe exacerbation. The most prevalent species in sputum were Non-tuberculous mycobacteria (NTM) (14.8 %), Pseudomonas aeruginosa (14.2 %), and fungus (5.9%). 68.8% of BROS patients used disease modifying antirheumatic drugs (DMARD), 7.9% used biological DMARD. NTM and tuberculosis infection rates were higher in bDMARD group compared with nbDMARD group and others. Overall, the 3-year respiratory failure rate and mortality rate were 14.6 and 25.7% respectively. Patients with RA diagnosed before bronchiectasis had a significantly higher cumulative incidence of mortality in a 3-year follow-up than those with RA diagnosed after bronchiectasis. In Cox regression, age, higher RF value and systemic steroid use were independent risk factors for mortality in BROS. BROS patients with severe exacerbation had a high mortality rate in Taiwan. bDMARD is associated with a trend of increased risk of NTM and TB infections.

Impacts of Nontuberculous Mycobacteria Isolates in Non-cystic Fibrosis Bronchiectasis: A 16-Year Cohort Study in Taiwan.

Background: The prevalence of nontuberculous mycobacteria (NTM) in patients with chronic respiratory disease has increased. The implication of NTM in non-CF bronchiectasis remained controversial. This study investigated the impact of NTM in non-CF bronchiectasis in Taiwan. Methods: Clinical manifestation, imaging, and microbiological data were retrieved from the Chang Gung Research Database, the largest electronic medical record-based database in Taiwan. Patients with bronchiectasis during 2001-2016 were included. Cox proportional hazard model was employed to compare outcomes between patients with negative and positive NTM isolates after 1:1 propensity score matching. Results: A total of 19,647 non-CF bronchiectasis patients were enrolled and 11,492 patients were eligible for analysis after exclusion screening. Finally, patients with negative and positive NTM isolates-650 each-were analyzed after propensity score matching. The patients with negative NTM isolates were divided into three groups: Pseudomonas aeruginosa isolates (n = 53); fungus isolates (n = 26); and concomitant P. aeruginosa and fungus isolates (n = 8). The patients with positive NTM isolates were divided into five groups: single NTM isolate (n = 458); multiple NTM isolates (n = 60); concomitant NTM and P. aeruginosa isolates (n = 89); concomitant NTM and fungus isolates (n = 33); and concomitant NTM, P. aeruginosa, and fungus isolates (n = 10). Patients with P. aeruginosa isolates; concomitant NTM and P. aeruginosa isolates; concomitant NTM, P. aeruginosa, and fungus isolates had independently associated with respiratory failure and death. Patients with single or multiple NTM isolates were not related to ventilator use, but both were independent risk factor for mortality. Conclusion: NTM, either combined with P. aeruginosa or fungus, exhibited more frequent exacerbations in non-CF bronchiectasis patients. Moreover, NTM predicted mortality in non-CF bronchiectasis patients and were also correlated to respiratory failure while concomitantly isolated with P. aeruginosa and fungus.

Predicting mortality in non-cystic fibrosis bronchiectasis patients using distance-saturation product.

BACKGROUND: The bronchiectasis severity index (BSI) and FACED score are currently used in predicting outcomes of non-cystic fibrosis bronchiectasis (NCFB). Distance-saturation product (DSP), the product of distance walked, and lowest oxygen saturation during the 6-min walk test showed strong predictive power of mortality in non-CF bronchiectasis patients. This study aimed to compare the efficacy of these scores and DSP in predicting mortality. METHODS AND PATIENTS: Our retrospective study included NCFB patients from January 2004 to December 2017. We recorded the basic data, pulmonary function, radiologic studies, sputum culture results, acute exacerbations (AE), emergency department (ED) visits, hospitalization, and mortality. RESULTS: A total 130 NCFB patients were analysed. The mean BSI score, FACED score, and DSP were 8.8 ± 4.9, 3.4 ± 1.7, and 413.1 ± 101.5 m%, respectively. BSI and FACED scores had comparable predictive power for AE (p=.011; p=.010, respectively). The BSI score demonstrated a significant correlation with ED visits (p=.0003). There were 12 deaths. Patients were stratified using a DSP cut-off value of 345 m% according to the best area under receiver operator characteristic curve (AUC) value in mortality. DSP was not correlated with AE and ED visits. BSI, FACED scores, and DSP demonstrated statistically significant correlations with hospitalization (p<.0001; p<.0001; p=.0007, respectively). The AUC for overall mortality was similar for BSI, FACED score, and DSP (0.80 versus 0.85, p=.491; 0.85 versus 0.83, p=.831). CONCLUSION: DSP had comparable predictive power for mortality as the well-validated BSI and FACED scores and is relatively easy to use in clinical practice.KEY MESSAGEDistance-saturation product (DSP) comprised with the product of distance walked, and lowest oxygen saturation during the 6-min walk test, which is common used in clinical practice.DSP demonstrated strong and comparable predictive power of mortality as the well-validated BSI and FACED scores in non-CF bronchiectasis patients.

Prognostic Factors in Lung Adenocarcinoma with Bone Metastasis Treated with EGFR-TKIs.

Background and Objectives: Patients who have advanced lung cancer and bone metastasis (BM) often suffer from skeletal-related events (SREs) that lead to poor quality of life and poor prognosis. Our study aimed to investigate the prognostic factors in patients with BM from epidermal growth factor receptor (EGFR) mutation-positive lung adenocarcinoma. Materials and Methods: This retrospective study included 77 lung adenocarcinoma patients with synchronous BM. These patients had first-line EGFR tyrosine kinase inhibitors (EGFR-TKIs) between January 2017 and December 2019. Among them, 42 patients were treated with 120 mg of subcutaneous denosumab monthly. We investigated their baseline characteristics, cancer management, SREs, progression-free survival (PFS), and overall survival (OS). Results: The PFS in the patients treated with or without denosumab were 10.1 vs. 12.5 months (p = 0.971). The median OS was 26.9 vs. 29.5 months (p = 0.967) in no denosumab and denosumab groups, respectively. Univariate analyses showed benefit of afatinib in PFS and good performance status in OS. Conclusion: Those patients that took afatinib as first-line EGFR-TKIs had significantly longer PFS than those treated with other TKIs. Denosumab had no prognostic effect on PFS or OS.

Chronic Obstructive Pulmonary Disease as a Phenotype of Bronchiectasis for Long-Term Clinical Presentation and Treatment.

Background and Objectives: Bronchiectasis and chronic obstructive pulmonary disease (COPD) often coexist, although the causality is not currently clear. Currently, the clinical influence of COPD on patients with major bronchiectasis over time has not yet been investigated. Material and Methods: This retrospective study recruited consecutive patients with bronchiectasis from outpatient clinic between January 2006 and December 2007. Under the setting of quantification with HRCT, patients who should undergo multiple pulmonary function and exercise tests with regularclinic follow-up were included. The final analysis consisted of 66 eligible patients who were evaluated for clinical status, treatment, and sputum culture from up to 10-year electronic medical records. Results: Of these 66 patients, 45 (68%) had bronchiectasis without COPD and 21 (32%) had COPD. Patients with COPD group had a higher bronchiectasis extent score (32.21 ± 13.09 points vs. 21.89 ± 10.08 points, p = 0.001). Sputum production was reported more frequently by patients with COPD; however, no significant difference was observed after 3 years of follow-up (82.4% vs. 81.6%, p = 0.945). Bronchiectasis extent score correlated with positive sputum culture with Pseudomonas without a synergistic effect from COPD (odds ratio: 1.06, confidence interval: 1.00-1.12, p = 0.031). Regardless of COPD, after 10 years, the proportion of patients using inhaled corticosteroids and/or long-acting ß2-agonist between the two groups was not significantly different. Conclusion: COPD aggravated bronchiectasis extension, which was correlated with chronic Pseudomonas aeruginosa colonisation. Moreover, COPD would affect the medium-term (in 3-5 years) bronchiectasis treatment. Therefore, the COPD phenotype of bronchiectasis could be a clinical predictor of the course of treatment.

Cardiorespiratory coupling is associated with exercise capacity in patients with chronic obstructive pulmonary disease.

BACKGROUND: The interaction between the pulmonary function and cardiovascular mechanics is a crucial issue, particularly when treating patients with chronic obstructive pulmonary disease (COPD). Synchrogram index is a new parameter that can quantify this interaction and has the potential to apply in COPD patients. Our objective in this study was to characterize cardiorespiratory interactions in terms of cardiorespiratory coupling (CRC) using the synchrogram index of the heart rate and respiratory flow signals in patients with chronic obstructive pulmonary disease. METHODS: This is a cross-sectional and preliminary data from a prospective study, which examines 55 COPD patients. K-means clustering analysis was applied to cluster COPD patients based on the synchrogram index. Linear regression and multivariable regression analysis were used to determine the correlation between the synchrogram index and the exercise capacity assessed by a six-minute walking test (6MWT). RESULTS: The 55 COPD patients were separated into a synchronized group (median 0.89 (0.64-0.97), n = 43) and a desynchronized group (median 0.23 (0.02-0.51), n = 12) based on K-means clustering analysis. Synchrogram index was correlated significantly with six minutes walking distance (r = 0.42, p = 0.001) and distance saturation product (r = 0.41, p = 0.001) assessed by 6MWT, and still was an independent variable by multivariable regression analysis. CONCLUSION: This is the first result studying the heart-lung interaction in terms of cardiorespiratory coupling in COPD patients by the synchrogram index, and COPD patients are clustered into synchronized and desynchronized groups. Cardiorespiratory coupling is associated with exercise capacity in patients with COPD.

Impaired interferon-α expression in plasmacytoid dendritic cells in asthma.

BACKGROUND: Toll-like receptor (TLR)-7-associated rhinovirus (RV) activation is involved in the pathogenesis of asthma. Plasmacytoid dendritic cells (pDCs) are the main interferon-α-producing cells against viruses. OBJECTIVE: To determine whether asthmatic patients and control subjects differ in terms of interferon-α expression in pDCs under TLR-7 or RV stimulation. METHODS: pDCs were identified in BDCA-2+ and HLA-DR+ peripheral blood mononuclear cells. Interferon-α expression of pDCs was analyzed after TLR-7 stimulation with or without interleukin 4 (IL-4)/IL-13 pretreatment. Interferon-α expression was also analyzed after RV stimulation over periods of 24, 48, or 96 h with or without IL-4 pretreatment. RV detection and molecular typing were assayed from throat swabs. RESULTS: Following TLR-7 stimulation, the expression of intracellular interferon-α was higher in the pDCs of normal subjects than those of asthmatic patients; however, pretreatment with IL-4 was shown to reduce this effect. After 48- and 96-h RV stimulation, we observed a notable increase in the production of interferon-α of pDCs in normal subjects but not in asthmatic patients. Baseline interferon-α expression in pDCs and the incidence of asthma exacerbation to emergency was higher among the 13% of patients identified as rhinovirus+ than among their RV counterparts. CONCLUSION: Our study discovered the response to TLR-7 stimulation in pDCs was compromised and the sustainability of interferon-α expression to RV stimulation was reduced in pDCs of asthmatic patients, which provide further evidence of defective innate response and subspeciality to RV infection in asthma. The high exacerbation history founded in RV+ patients agrees with these findings. Further research is required for the modulatory effect of IL-4 on TLR-7 stimulated pDCs.

Metabolic tumor volume predicts overall survival in patients with primary pulmonary lymphoepithelioma-like carcinoma.

Pretreatment tumor metabolic burden, measured using fluorine-18 fluorodeoxyglucose positron emission tomography/computerized tomography (18F-FDG PET/CT), has been demonstrated to predict outcomes in various types of malignancies. Additionally, Epstein-Barr virus (EBV) serum titer is associated with stages of pulmonary lymphoepithelioma-like carcinoma (LELC). The present study aimed to investigate the prognostic value of the functional parameters of 18F-FDG PET/CT in pulmonary LELC and their association with serum EBV DNA. The present retrospective study analyzed data from 71 patients with pulmonary LELC; among these, 32 patients with pulmonary LELC underwent pretreatment 18F-FDG PET/CT staging between January 2008 and December 2016. EBV viral load and functional parameters of 18F-FDG PET/CT were used for survival analysis. Multivariate analysis identified tumor stage IV as a significant predictor of poor progression-free survival [hazard ratio (HR), 4.85; P=0.049], whereas elevated total metabolic tumor volume (MTV ≥72.6 ml) independently predicted worse overall survival (OS; HR, 12.59; P=0.024). Pretreatment serum EBV DNA titer was significantly positively associated with total MTV (P=0.0337) and total lesion glycolysis (TLG; P=0.0093), but could not predict outcomes. Total MTV was an independent predictor of OS, and may guide clinical management for pulmonary LELC.

Impact of concomitant nontuberculous mycobacteria and Pseudomonas aeruginosa isolates in non-cystic fibrosis bronchiectasis.

PURPOSE: Pseudomonas aeruginosa is associated with pulmonary function decline and high disease severity in non-cystic fibrosis (CF) bronchiectasis. The prevalence of nontuberculous mycobacteria (NTM) in non-CF bronchiectasis patients has increased recently. This study investigated the impact of NTM with or without P. aeruginosa isolates in non-CF bronchiectasis patients. PATIENTS AND METHODS: Our retrospective study included 96 non-CF bronchiectasis patients from January 2005 to December 2014. We recorded the presentation, exacerbations, emergency department (ED) visits, hospitalization, serial pulmonary function, radiologic studies, and sputum culture results. All patients were followed up for at least 2 years. RESULTS: The 96 patients were divided into four groups: patients with concomitant negative NTM and P. aeruginosa isolates (n=41; group 1), patients with positive NTM isolates (n=20; group 2), patients with positive P. aeruginosa isolates (n=20; group 3), and patients with concomitant positive NTM and P. aeruginosa isolates (n=15; group 4). Compared with group 1 patients, patients in groups 2 and 3 showed a significant decline in forced expiratory volume in 1 second (FEV1). They also had more frequent annual acute exacerbations (AE), ED visits, and hospitalization. Group 4 patients had the greatest FEV1 and forced vital capacity (FVC) decline and the most frequent AE, ED visits, and hospitalization. CONCLUSION: Concomitant NTM and P. aeruginosa isolates in non-CF bronchiectasis are associated with the greatest pulmonary function decline and the worst disease severity. This result suggested that early recognition and prompt treatment of concomitant NTM and P. aeruginosa isolates may improve the outcome in non-CF bronchiectasis patients.

Distance-saturation product of the 6-minute walk test predicts mortality of patients with non-cystic fibrosis bronchiectasis.

BACKGROUND: Previous surveillance methods to monitor the prognoses of patients with bronchiectasis are too complex for use in daily practice. The 6-minute walk test (6MWT) is a simple exercise test to predict the prognosis of chronic obstructive airway disease and numerous chronic lung diseases, including idiopathic pulmonary fibrosis. No studies have investigated exercise-induced oxygen desaturation (EID) and distance-saturation product (DSP) of 6MWT to predict the prognoses of patients with bronchiectasis. METHODS: This was a prospective study to identify correlations between variables of 6MWT and mortality in patients with bronchiectasis over a 6-year period. The study cohort included 69 patients with stable non-cystic fibrosis (non-CF) bronchiectasis who were regularly evaluated for functional status via 6-minute walk distance (6MWD), spirometry, BODE index, EID, and DSP. RESULTS: Of the 69 patients, 9 (13%) died and 60 (87%) survived during the 6-year follow-up period. The percentage of EID was higher [7 of 9 patients (78%) vs. 22 of 60 patients (27%), P=0.003] in the non-survivors group. The 6MWD (467.9±77.1 vs. 363.7±126.7 m, P=0.001) was higher in the survivors group. DSP was significantly lower in the non-survivors group (411.0±78.4 vs. 283.9±90.0 m%, P<0.001). Multivariate analysis showed that DSP (OR =0.983; 95% CI: 0.974-0.993, P=0.001) was the best parameter of 6MWT to predict mortality. Patients with a lower DSP of <280 m% were at a 66.5-fold greater risk (OR =66.5; 95% CI: 9.4-469.2) of 6-year mortality compared with those with DSP >280 m% (P<0.001). CONCLUSIONS: DSP is a simple parameter to predict 6-year mortality in patients with non-CF bronchiectasis.

Prognostic implication of EGFR gene mutations and histological classification in patients with resected stage I lung adenocarcinoma.

INTRODUCTION: The prognostic value of epidermal growth factor receptor (EGFR) mutations and the correlation between EGFR mutations and the new International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) histological classification remain controversial. The current study aimed to investigate the pure prognostic role of EGFR mutations in treatment-naïve patients with resected stage I lung adenocarcinoma. METHODS: We retrospectively reviewed 373 patients with stage I pulmonary non-small-cell lung cancer who underwent complete surgical resection between January 2010 and May 2014. The tumors were classified according to IASLC/ATS/ERS criteria. EGFR mutation status was determined by established methods. RESULTS: A total of 120 patients were included for analysis; 87 had tumors with EGFR mutations and 33 had wild-type tumors. More low- and intermediate-grade tumors had EGFR mutations, and nearly half of the high-grade tumors were wild-type (75.7% versus 46.2%, p = 0.041). Patients with low-grade tumors had significantly greater median disease-free survival (DFS) (76.8 versus 13 months, p < 0.0001) and better overall survival (OS) (median OS not reached, p = 0.0003) than those with intermediate- and high-grade tumors. Tumor recurrence was 41.4% and 30.3% in mutant and wild-type patients. The 5-years survival rate was 54% and 71.2%. Multivariate analysis revealed that the new histological classification and the pathologic stage were independent predictors of both DFS and OS. EGFR mutation status had no prognostic implications. CONCLUSION: Low grade tumors according to IASLC/ATS/ERS histological classification and the pathologic stage IA tumors of resected stage I lung adenocarcinomas independently predict better DFS and OS. EGFR mutations were frequently seen in histologically low- and intermediate-grade tumors but not a prognostic factor.

Alveolar recruitment maneuver attenuates extravascular lung water in acute respiratory distress syndrome.

BACKGROUND: The alveolar recruitment maneuver (RM) has been reported to improve oxygenation in acute respiratory distress syndrome (ARDS) and may be related to reduced extravascular lung water (EVLW) in animals. This study was designed to investigate the effects of RM on EVLW in patients with ARDS. METHODS: An open label, prospective, randomized controlled trial including patients with ARDS was conducted in hospitals in North Taiwan between 2010 and 2016. The patients were divided into 2 groups (with and without RM). The primary endpoint was the comparison of the EVLW index between the 2 groups. RESULTS: Twenty-four patients with ARDS on mechanical ventilator support were randomized to receive ventilator treatment with RM (RM group, n = 12) or without RM (non-RM group, n = 12). Baseline demographic characteristics were similar between the 2 groups. After recruitment, the day 3 extravascular lung water index (EVLWI) (25.3 ±â€Š9.3 vs 15.5 ±â€Š7.3 mL/kg, P = .008) and the arterial oxygen tension/fractional inspired oxygen ratio (PaO2/FiO2) (132.3 ±â€Š43.5 vs 185.6 ±â€Š38.8 mL/kg, P = .003) both improved over that of day 1. However, both EVLWI and PaO2/FiO2 did not significantly change from day 1 to 3 in the non-RM group. CONCLUSION: RM is a feasible method for improving oxygenation and the EVLW index in patients with ARDS, as well as for decreasing ventilator days and intensive care unit stay duration.

Advanced primary pulmonary lymphoepithelioma-like carcinoma: clinical manifestations, treatment, and outcome.

BACKGROUND: Primary pulmonary lymphoepithelioma-like carcinoma (LELC) is rare, with better clinical outcomes than other lung cancers. However, reports on advanced LELC characteristics and prognosis are lacking. METHODS: This retrospective study included adults diagnosed with advanced LELC (at least stage IIIA) between January 2003 and December 2015. Clinical characteristics, treatment modalities, and outcomes were recorded. RESULTS: Study population comprised 23 patients with a mean age of 63.7±10.6 years. The Eastern Cooperative Oncology Group status on diagnosis was 0 in five patients and 1 in the others. Most patients received multimodality treatment and all received cisplatin-based chemotherapy. Median follow-up duration was 28.8 months. The median progression free survival (PFS) was 14.6 months in patients received palliative chemotherapy. There were nine (39.1%) deaths. The median overall survival (OS) was not achieved. Until July 31, 2016, median OS was 54.1 months for stage IIIB and 27.6 months for stage IV. There was no significant difference in OS among all stages. No prognostic factors were found. CONCLUSIONS: Advanced LELC responded well to cisplatin-based chemotherapy and/or radiotherapy. Main tumor resection is probably beneficial for advanced LELC. Long-term survival is possible for advanced LELC after multimodality treatment.

Afatinib in Treatment-Naive Patients With EGFR-Mutated Lung Adenocarcinoma With Brain Metastasis: A Case Series.

Tyrosine kinase inhibitors (TKIs) of epidermal growth factor receptor (EGFR) were previously the standard first-line treatments for lung cancers with activating EGFR mutations. The first-generation reversible EGFR TKIs, gefitinib and erlotinib, demonstrated substantial efficacy in the treatment of brain metastases from EGFR-mutated lung adenocarcinoma. However, the efficacy of afatinib, the second-generation irreversible EGFR TKI, as the first-line treatment in lung adenocarcinoma patients with brain metastasis has yet to be evaluated.Here, we report cases of 3 patients who received afatinib alone as the first-line treatment in combination with whole-brain radiotherapy or following surgical resection of brain metastases. All 3 patients had EGFR L858R mutation. The first patient had lung adenocarcinoma with brain metastasis and no neurologic symptoms. After consultation, she received afatinib as a first-line treatment. Chest computed tomography and brain magnetic resonance imaging (MRI) showed partial response. The second patient had lung adenocarcinoma accompanied with a metastatic brain lesion associated with seizures. This patient received whole-brain radiotherapy and afatinib treatment following brain MRI and subsequently showed significant regression of the brain metastasis. The third patient had strabismus of the right eye, and brain MRI showed a single tumor at the cerebellar pontine angle. This patient underwent surgical resection of the tumor followed by afatinib treatment. He refused adjuvant radiotherapy after surgery for brain metastasis. The brain MRI showed no recurrent brain metastasis, and the patient had relatively less neurologic deficiency.This series of 3 cases indicate that afatinib may be an appropriate first-line treatment alternative in patients having lung adenocarcinoma with EGFR mutations. Further retrospective analyses and prospective clinical trials are required to substantiate the efficacy of afatinib in the treatment of brain metastases of lung adenocarcinoma.

Flexible bronchoscopy with multiple modalities for foreign body removal in adults.

OBJECTIVES: Aspiration of the lower airways due to foreign body is rare in adults. This study aimed to determine the outcome of patients who received flexible bronchoscopy with different modalities for foreign body removal in the lower airways. PATIENTS AND METHODS: Between January 2003 and January 2014, 94 patients diagnosed with foreign body in the lower airways underwent flexible bronchoscopy with different modalities, which included forceps, loop, basket, knife, electromagnet, and cryotherapy. The clinical presentation, foreign body location and characteristics, and applications of flexible bronchoscopy were analyzed. RESULTS: Forty (43%) patients had acute aspiration, which developed within one week of foreign body entry and 54 (57%) had chronic aspiration. The most common foreign bodies were teeth or bone. More patients with chronic aspiration than those with acute aspiration were referred from the out-patient clinic (48% vs. 28%), but more patients with acute aspiration were referred from the emergency room (35% vs. 6%) and intensive care unit (18% vs. 2%). Flexible bronchoscopy with different modalities was used to remove the foreign bodies (85/94, 90%). Electromagnet or cryotherapy was used in nine patients to eliminate the surrounding granulation tissue before foreign body removal. In the nine patients with failed flexible bronchoscopy, eight underwent rigid bronchoscopy instead and one had right lower lung lobectomy for lung abscess. CONCLUSIONS: Flexible bronchoscopy with multiple modalities is effective for diagnosing and removing foreign bodies in the lower respiratory airways in adults, with a high success rate (90%) and no difference between acute and chronic aspirations.

Removal of endobronchial malignant mass by cryotherapy improved performance status to receive chemotherapy.

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.

Matrix metalloproteinase-1 polymorphism (-1607G) and disease severity in non-cystic fibrosis bronchiectasis in Taiwan.

OBJECTIVES: Bronchiectasis is characterized by an irreversible dilatation of bronchi and is associated with lung fibrosis. MMP-1 polymorphism may alter its transcriptional activity, and differentially modulate bronchial destruction and lung fibrosis. DESIGN: To investigate the association of MMP-1 polymorphisms with disease severity in non-cystic fibrosis (CF) bronchiectasis patients, 51 normal subjects and 113 patients with bronchiectasis were studied. The associations between MMP-1 polymorphisms, lung function, and disease severity evaluated by high resolution computed tomography (HRCT) were analyzed. RESULTS: The frequency of MMP-1(-1607G) allele was significantly higher in patients with bronchiectasis than normal subjects (70.8% vs 45.1%, p<0.01). Forced expiratory volume in 1 second (FEV1) was decreased in bronchiectasis patients with 1G/1G (1.2±0.1 L, n = 14) and 1G/2G (1.3±0.1 L, n = 66) genotypes compared to the 2G/2G genotype (1.7±0.1 L, n = 33, p<0.01). Six minute walking distance was decreased in bronchiectasis patients with 1G/1G and 1G/2G compared to that of 2G/2G genotype. Disease severity evaluated by HRCT score significantly increased in bronchiectasis patients with 1G/1G and 1G/2G genotypes compared to that of 2G/2G genotype. Bronchiectasis patients with at least one MMP-1 (-1607G) allele showed increased tendency for hospitalization. Serum levels of pro-MMP-1, active MMP-1 and TGF-ß1 were significantly increased in patients with bronchiectasis with 1G/1G and 1G/2G genotype compared with 2G/2G genotype or normal subjects. Under IL-1ß stimulation, peripheral blood monocytes from subjects with 1G/2G or 1G/1G genotype secreted higher levels of TGF-ß1compared to subjects with 2G/2G genotype. CONCLUSION: This is the first report to address the influence of MMP-1 polymorphisms on lung function and airway destruction in non-CF bronchiectasis patients. Bronchiectasis patients with MMP-1(-1607G) polymorphism may be more vulnerable to permanent lung fibrosis or airway destruction due to the enhanced MMP-1 and TGF-ß1 activity. Upregulated MMP-1 activity results in proteolytic destruction of matrix, and leads to subsequent fibrosis.