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.

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.

Update on guidelines for the treatment of COPD in Taiwan using evidence and GRADE system-based recommendations.

Chronic obstructive pulmonary disease (COPD) has significant contributions to morbidity and mortality world-wide. Early symptoms of COPD are not readily distinguishable, resulting in a low rate of diagnosis and intervention. Different guidelines and recommendatations for the diagnosis and treatment of COPD exist globally. The first edition of clinical practice guidelines for COPD was published in 2016 by the Ministry of Health and Welfare in Taiwan in collaboration with the Taiwan evidence-based medicine association and Cochrane Taiwan, and was revised in 2019 in order to update recent diagnostic and therapeutic modalities for COPD and its acute exacerbation. This revised guideline covered a range of topics highlighted in the Global Initiative for Chronic Obstructive Lung Disease (GOLD) report, including strategies for the diagnosis, assessment, monitoring, and management of stable COPD and exacerbations, with particular focus on evidence from Taiwan. The recommendations included in the revised guideline were formed based on a comprehensive systematic review or meta-analysis of specific clinical issues identified by an expert panel that surveyed relevant scientific evidence in the literature and guidelines published by the clinical communities and organizations nationally and internationally. The guidelines and recommendations are applicable to the clinical settings in Taiwan. We expect this revised guideline to facilitate the diagnosis, treatment and management of patients with COPD by physicians and health care professionals in Taiwan. Adaptations of the materials included herein for educational and training purposes is encouraged.

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.

Etiology and characteristics of patients with bronchiectasis in Taiwan: a cohort study from 2002 to 2016.

BACKGROUND: Bronchiectasis is a chronic infectious respiratory disease with diverse causes and ethnic or geographic differences. However, few large-scale studies of its etiology have been conducted in Asia. This study aimed to determine the etiology and clinical features of bronchiectasis in Taiwan. METHODS: This longitudinal cohort study investigated the etiology and clinical features of newly diagnosed non-cystic fibrosis bronchiectasis patients from January 2002 to December 2016. The clinical, functional and microbiological data of patients were retrieved from the Chang Gung Research Database, which includes seven medical facilities throughout Taiwan. The index date was the date of the first bronchiectasis diagnosis. Known diseases that were diagnosed before the index date were regarded as etiologies of bronchiectasis. RESULTS: The cohort comprised 15,729 adult patients with bronchiectasis. Idiopathic (32%) was the most common cause, followed by post-pneumonia (24%). Other causes included post-tuberculosis (12%), chronic obstructive pulmonary disease (14%), asthma (10%), gastroesophageal reflux disease (2%) and rheumatic diseases (2%). At diagnosis, 8487 patients had sputum culture. Pseudomonas aeruginosa (5.3%) was the most common bacteria, followed by non-tuberculosis mycobacteria (3.6%), Haemophilus influenzae (3.4%) and Klebsiella pneumoniae (3.1%), but 6155 (72.1%) had negative sputum cultures. Patients with post-tuberculosis had a higher sputum isolation rate of non-tuberculosis mycobacteria than P. aeruginosa. Patients with post-tuberculosis and post-pneumonia bronchiectasis had a higher frequency of chronic lung infection than other groups (p < 0.05). Clinical characteristics, such as gender, lung function, comorbidities and microbiology, were significantly different between idiopathic and known etiologies. CONCLUSIONS: Idiopathic, post-infection and tuberculosis constitute major bronchiectasis etiologies in Taiwan. Clinical characteristics and sputum microbiology were distinct among separate etiology phenotypes.

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.

Prediction of 30-Day Readmission for COPD Patients Using Accelerometer-Based Activity Monitoring.

Chronic obstructive pulmonary disease (COPD) claimed 3.0 million lives in 2016 and ranked 3rd among the top 10 global causes of death. Moreover, once diagnosed and discharged from the hospital, the 30-day readmission risk in COPD patients is found to be the highest among all chronic diseases. The existing diagnosis methods, such as Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2019, Body-mass index, airflow Obstruction, Dyspnea, and Exercise (BODE) index, modified Medical Research Council (mMRC), COPD assessment test (CAT), 6-minute walking distance, which are adopted currently by physicians cannot predict the potential readmission of COPD patients, especially within the 30 days after discharge from the hospital. In this paper, a statistical model was proposed to predict the readmission risk of COPD patients within 30-days by monitoring their physical activity (PA) in daily living with accelerometer-based wrist-worn wearable devices. This proposed model was based on our previously reported PA models for activity index (AI) and regularity index (RI) and it introduced a new parameter, quality of activity (QoA), which incorporates previously proposed parameters, such as AI and RI, with other activity-based indices to predict the readmission risk. Data were collected from continuous PA monitoring of 16 COPD patients after hospital discharge as test subjects and readmission prediction criteria were proposed, with a 63% sensitivity and a 37.78% positive prediction rate. Compared to other clinical assessment, diagnosis, and prevention methods, the proposed model showed significant improvement in predicting the 30-day readmission risk.

Practice Patterns for Chronic Respiratory Diseases in the Asia-Pacific Region: A Cross-Sectional Observational Study.

BACKGROUND: Allergic rhinitis (AR), asthma, chronic obstructive pulmonary disease (COPD), and rhinosinusitis are common and little studied in the Asia-Pacific region. OBJECTIVES: We sought to investigate real-world practice patterns for these respiratory diseases in India, Korea, Malaysia, Singapore, Taiwan, and Thailand. METHODS: This cross-sectional observational study enrolled adults (age ≥18 years) presenting to general practitioners (GP) or specialists for physician-diagnosed AR, asthma, COPD, or rhinosinusitis. Physicians and patients completed study-specific surveys at one visit, recording patient characteristics, health-related quality of life (QoL), work impairment, and healthcare resource use. Findings by country and physician category (GP or specialist) were summarized. RESULTS: Of the 13,902 patients screened, 7,243 (52%) presented with AR (18%), asthma (18%), COPD (7%), or rhinosinusitis (9%); 5,250 of the 7,243 (72%) patients were eligible for this study. Most eligible patients (70-100%) in India, Korea, Malaysia, and Singapore attended GP, while most (83-85%) in Taiwan and Thailand attended specialists. From 42% (rhinosinusitis) to 67% (AR) of new diagnoses were made by GP. On average, patients with COPD reported the worst health-related QoL, particularly to GP. Median losses of work productivity for each condition and activity impairment, except for asthma, were numerically greater for patients presenting to GP vs. specialists. GP prescribed more antibiotics for AR and asthma, and fewer intranasal corticosteroids for AR, than specialists (p < 0.001 for all comparisons). CONCLUSIONS: Our findings, albeit mostly descriptive and influenced by between-country differences, suggest that practice patterns differ between physician types, and the disease burden may be substantial for patients presenting in general practice.

Obstructive sleep apnoea accelerates FEV1 decline in asthmatic patients.

BACKGROUND: Although the prevalence of both obstructive sleep apnoea (OSA) and asthma are both increasing, little is known about the impact of OSA on the natural history of lung function in asthmatic patients. METHODS: A total of 466 patients from our sleep laboratory were retrospectively enrolled. Of them, 77 patients (16.5%) had asthma with regular follow-up for more than 5 years. Their clinical characteristics, pulmonary function, emergency room visits, and results of polysomnography results were analysed. RESULTS: The patients were divided into three groups according to the severity of the apnoea-hypopnea index (AHI). The decline in FEV1 among asthma patients with severe OSA (AHI > 30/h) was 72.4 ± 61.7 ml/year (N = 34), as compared to 41.9 ± 45.3 ml/year (N = 33, P = 0.020) in those with mild to moderate OSA (5 < AHI ≤ 30) and 24.3 ± 27.5 ml/year (N = 10, P = 0.016) in those without OSA (AHI ≤ 5). For those patients with severe OSA, the decline of FEV1 significantly decreased after continuous positive airway pressure (CPAP) treatment. After multivariate stepwise linear regression analysis, only AHI was remained independent factor for the decline of FEV1 decline. CONCLUSIONS: Asthmatic patients with OSA had substantially greater declines in FEV1 than those without OSA. Moreover, CPAP treatment alleviated the decline of FEV1 in asthma patients with severe OSA.

Respiratory disease in the Asia-Pacific region: Cough as a key symptom.

BACKGROUND: Respiratory diseases represent a significant impact on health care. A cross-sectional, multicountry (India, Korea, Malaysia, Singapore, Taiwan, and Thailand) observational study was conducted to investigate the proportion of adult patients who received care for a primary diagnosis of asthma, allergic rhinitis (AR), chronic obstructive pulmonary disease (COPD), or rhinosinusitis. OBJECTIVE: To determine the proportion of patients who received care for asthma, AR, COPD, and rhinosinusitis, and the frequency and main symptoms reported. METHODS: Patients ages ≥18 years, who presented to a physician with symptoms that met the diagnostic criteria for a primary diagnosis of asthma, AR, COPD, or rhinosinusitis were enrolled. Patients and physicians completed a survey that contained questions related to demographics and respiratory symptoms. RESULTS: A total of 13,902 patients with a respiratory disorder were screened, of whom 7030 were eligible and 5250 enrolled. The highest percentage of patients who received care had a primary diagnosis of AR (14.0% [95% confidence interval {CI}, 13.4-14.6%]), followed by asthma (13.5% [95% CI, 12.9-14.1%]), rhinosinusitis (5.4% [95% CI, 4.6-5.3%]), and COPD (4.9% [95% CI, 5.0-5.7%]). Patients with a primary diagnosis of COPD (73%), followed by asthma (61%), rhinosinusitis (59%), and AR (47%) most frequently reported cough as a symptom. Cough was the main reason for seeking medical care among patients with a primary diagnosis of COPD (43%), asthma (33%), rhinosinusitis (13%), and AR (11%). CONCLUSION: Asthma, AR, COPD, and rhinosinusitis represent a significant proportion of respiratory disorders in patients who presented to health care professionals in the Asia-Pacific region, many with concomitant disease. Cough was a prominent symptom and the major reason for patients with respiratory diseases to seek medical care.

Mobile-phone-based home exercise training program decreases systemic inflammation in COPD: a pilot study.

BACKGROUND: Moderate-intensity exercise training improves skeletal muscle aerobic capacity and increased oxidative enzyme activity, as well as exercise tolerance in COPD patients. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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).

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.

Different Impacts of Traffic-Related Air Pollution on Early-Onset and Late-Onset Asthma.

Background: Early-onset asthma (EOA) and late-onset asthma (LOA) are two distinct phenotypes. Air pollution has been associated with an increase in poorer asthma outcomes. The objective of this study was to examine the effects of traffic-related air pollution (TRAP) on asthma outcomes in EOA and LOA patients. Methods: A cross-sectional study was conducted on 675 asthma patients (LOA: 415) recruited from a major medical center in Taiwan. The land-use regression (LUR) model was used to estimate the level of exposure to PM10, PM2.5, NO2, and O3 on an individual level. We investigated the association between TRAP and asthma outcomes in EOA and LOA patients, stratified by allergic sensitization status, using a regression approach. Results: An increase in PM10 was associated with younger age of onset, increased asthma duration, and decreased lung function in EOA patients (p<0.05). An increase in PM10 was associated with older age of onset, and decreased asthma duration, eosinophil count, and Asthma Control Test (ACT) score in LOA patients. An increase in PM2.5 was associated with younger age of onset, increased asthma duration, decreased eosinophil count, and lung function in EOA patients (p<0.05). An increase in PM2.5 was associated with decreased lung function and ACT score in LOA patients. An increase in NO2 was associated with increased eosinophil count and decreased lung function in EOA patients (p<0.05). An increase in O3 was associated with decreased lung function in LOA patients (p<0.05). In addition, associations of TRAP with age of onset and eosinophil counts were mainly observed in both EOA and LOA patients with allergic sensitization, and an association with ACT was mainly observed in LOA patients without allergic sensitization. Conclusion: The impact of TRAP on age of onset, eosinophil count, and lung function in EOA patients, and ACT in LOA patients, was affected by the status of allergic sensitization.

Correlating Reiff scores with clinical, functional, and prognostic factors: characterizing noncystic fibrosis bronchiectasis severity: validation from a nationwide multicenter study in Taiwan.

BACKGROUND: Our study aimed to confirm a simplified radiological scoring system, derived from a modified Reiff score, to evaluate its relationship with clinical symptoms and predictive outcomes in Taiwanese patients with noncystic fibrosis bronchiectasis (NCFB). METHODS: This extensive multicenter retrospective study, performed in Taiwan, concentrated on patients diagnosed with NCFB verified through high-resolution computed tomography (HRCT) scans. We not only compared the clinical features of various types of bronchiectasis (cylindrical, varicose, and cystic). Furthermore, we established relationships between the severity of clinical factors, including symptom scores, pulmonary function, pseudomonas aeruginosa colonization, exacerbation and admission rates, and HRCT parameters using modified Reiff scores. RESULTS: Data from 2,753 patients were classified based on HRCT patterns (cylindrical, varicose, and cystic) and severity, assessed by modified Reiff scores (mild, moderate, and severe). With increasing HRCT severity, a significant correlation was found with decreased forced expiratory volume in the first second (FEV1) (p < 0.001), heightened clinical symptoms (p < 0.001), elevated pathogen colonization (pseudomonas aeruginosa) (p < 0.001), and an increased annual hospitalization rate (p < 0.001). In the following multivariate analysis, elderly age, pseudomonas aeruginosa pneumonia, and hospitalizations per year emerged as the only independent predictors of mortality. CONCLUSION: Based on our large cohort study, the simplified CT scoring system (Reiff score) can serve as a useful adjunct to clinical factors in predicting disease severity and prognosis among Taiwanese patients with NCFB.

Exercise training with negative pressure ventilation improves exercise capacity in patients with severe restrictive lung disease: a prospective controlled study.

BACKGROUND: Exercise training is of benefit for patients with restrictive lung disease. However, it tends to be intolerable for those with severe disease. We examined whether providing ventilatory assistance by using negative pressure ventilators (NPV) during exercise training is feasible for such patients and the effects of training. METHODS: 36 patients with restrictive lung disease were prospectively enrolled for a 12-week multidisciplinary rehabilitation program. During this program, half of them (n:18; 60.3 ± 11.6 years; 6 men; FVC: 32.5 ± 11.7% predicted ) received regular sessions of exercise training under NPV, whilst the 18 others (59.6 ± 12.3 years; 8 men; FVC: 37.7 ± 10.2% predicted) did not. Exercise capacity, pulmonary function, dyspnea and quality of life were measured. The primary endpoint was the between-group difference in change of 6 minute-walk distance (6MWD) after 12 weeks of rehabilitation. RESULTS: All patients in the NPV-exercise group were able to tolerate and completed the program. The between-group differences were significantly better in the NPV-exercise group in changes of 6MWD (34.1 ± 12.7 m vs. -32.5 ± 17.5 m; P = 0.011) and St George Score (-14.5 ± 3.6 vs. 11.8 ± 6.0; P < 0.01). There was an improvement in dyspnea sensation (Borg's scale, from 1.4 ± 1.5 point to 0.8 ± 1.3 point, P = 0.049) and a small increase in FVC (from 0.85 ± 0.09 L to 0.91 ± 0.08 L, P = 0.029) in the NPV-exercise group compared to the control group. CONCLUSION: Exercise training with NPV support is feasible for patients with severe restrictive lung diseases, and improves exercise capacity and health-related quality of life.

Increased activation of fibrocytes in patients with chronic obstructive asthma through an epidermal growth factor receptor-dependent pathway.

BACKGROUND: Fibrocytes are circulating progenitor cells that are increased in asthmatic patients with chronic obstructive asthma (COA) and rapid decrease in lung function. Fibrocytes from patients with COA have a greater capacity for proliferation and differentiation. OBJECTIVE: We investigated whether epidermal growth factor receptor (EGFR) activation mediated the proliferation of fibrocytes in patients with COA and whether oxidative stress was involved in this activation. METHODS: Circulating fibrocytes from nonadherent non-T-cell mononuclear cell fractions from healthy subjects, asthmatic patients with normal pulmonary function, and patients with COA were determined by using flow cytometric coexpression of collagen I, CD45, and CD34 or EGFR or a disintegrin and metalloprotease domain 17 and placed in culture. RESULTS: Expression of EGFR was increased in fibrocytes from patients with COA compared with that seen in patients with NPF. AG1478 and gefitinib, inhibitors of EGFR tyrosine kinase, reduced fibrocyte proliferation and myofibroblast transformation. Increased expression of EGFR and fibrocyte proliferation and transformation were induced by hydrogen peroxide, and these effects were inhibited by N-acetylcysteine. CONCLUSIONS: Enhanced fibrocyte proliferation and transformation found in patients with COA might be mediated through an oxidant-sensitive EGFR-dependent pathway.

The Effectiveness of Home-Based Inspiratory Muscle Training on Small Airway Function and Disease-Associated Symptoms in Patients with Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) is characterized by persistent airflow limitations, occurring mainly in the small airways. Weakness in the respiratory muscles contributes to dyspnea and a decreased exercise capacity in COPD patients. This study aimed to investigate the effectiveness of home-based inspiratory muscle training (IMT) on small airway function and symptoms in COPD patients. This research adopted a non-randomized controlled-study quasi-experimental design. The IMT program consisted of two 15 min sessions·d-1, 5 d·wk-1, with 40% of the maximal inspiratory pressure (PImax) on each participant's assessment results and lasted for 12 weeks. Small airway function was assessed using plethysmography at baseline and after 12 weeks. The modified British Medical Research Council (mMRC), COPD assessment test (CAT), PImax, and 6 min walking distance (6MWD) were recorded at baseline as well as four, eight, and twelve weeks. Twenty-three participants with at least moderate COPD were enrolled in IMT (n = 16) or in the control group (n = 7) in this study. The study participants were mostly male (82.6%), and the average age was 68.29 ± 10.87 years, with a mean body mass index (BMI) of 23.54 ± 4.79. After 12 weeks, the ratios of the first second of forced expiration to the forced vital capacity (FEV1/FVC%) (B coefficient [95% Wald confidence interval] of 5.21 [0.46 to 9.96], p = 0.032), forced expiratory flow (FEF25-75%) (0.20 [0.04 to 0.35] L/s, p = 0.012), and FEF50% (0.26 [0.08 to 0.43] L/s, p = 0.004) in the IMT group were significantly better than in the control group. The IMT group showed significantly lower CAT scores at week 8 (-5.50 [-10.31 to -0.695] scores, p = 0.025) than the control group. The mMRC grade, CAT score, PImax, and 6MWD were significantly improved compared to their values at baseline in the IMT group. Home-based IMT effectively improved post-bronchodilator small airway function and disease-associated symptoms in COPD patients.

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.

Anti-Inflammatory Effect of Resveratrol Derivatives via the Downregulation of Oxidative-Stress-Dependent and c-Src Transactivation EGFR Pathways on Rat Mesangial Cells.

In Taiwan, the root extract of Vitis thunbergii Sieb. et Zucc. (Vitaceae, VT) is rich in stilbenes, with resveratrol (Res) and its derivatives being the most abundant. Previously, we showed that the effect of Res derivatives against tumor necrosis factor-α (TNF-α)-stimulated inflammatory responses occurs via cPLA2/COX-2/PGE2 inhibition. This study compared and explored the underlying anti-inflammatory pharmacological mechanisms. Before stimulation with TNF-α, RMCs were treated with/without pharmacological inhibitors of specific protein kinases. The expression of inflammatory mediators was determined by Western blotting, gelatin zymography, real-time PCR, and luciferase assay. Cellular and mitochondrial ROS were measured by H2DHFDA or DHE and MitoSOX™ Red staining, respectively. The RNS level was indirectly measured by Griess reagent assay. Kinase activation and association were assayed by immunoprecipitation followed by Western blotting. TNF-α binding to TNFR recruited Rac1 and p47phox, thus activating the NAPDH oxidase-dependent MAPK and NF-κB pathways. The TNF-α-induced NF-κB activation via c-Src-driven ROS was independent from the EGFR signaling pathway. The anti-inflammatory effects of Res derivatives occurred via the inhibition of ROS derived from mitochondria and NADPH oxidase; RNS derived from iNOS; and the activation of the ERK1/2, JNK1/2, and NF-κB pathways. Overall, this study provides an understanding of the various activities of Res derivatives and their pharmacological mechanisms. In the future, the application of the active molecules of VT to health foods and medicine in Taiwan may increase.