Recent work has suggested a microbial dysbiosis association between the lung and gut in respiratory diseases. Here, we demonstrated that gut microbiome modulation attenuated emphysema development. To ...modulate the gut microbiome, fecal microbiota transplantation (FMT) and diet modification were adopted in mice exposed to smoking and poly I:C for the emphysema model. We analyzed the severity of emphysema by the mean linear intercept (MLI) and apoptosis by the fluorescent TUNEL assay. Microbiome analysis was also performed in feces and fecal extracellular vesicles (EVs). The MLI was significantly increased with smoking exposure. FMT or a high-fiber diet (HFD) attenuated the increase. Weight loss, combined with smoking exposure, was not noted in mice with FMT. HFD significantly decreased macrophages and lymphocytes in bronchoalveolar lavage fluid. Furthermore, IL-6 and IFN-γ were decreased in the bronchoalveolar lavage fluid and serum. The TUNEL score was significantly lower in mice with FMT or HFD, suggesting decreased cell apoptosis. In the microbiome analysis, Bacteroidaceae and Lachnospiraceae, which are alleged to metabolize fiber into short-chain fatty acids (SCFAs), increased at the family level with FMT and HFD. FMT and HFD attenuated emphysema development via local and systemic inhibition of inflammation and changes in gut microbiota composition, which could provide a new paradigm in COPD treatment.
The Continuing to Confront COPD International Patient Survey estimated the prevalence and burden of COPD across 12 countries. Using data from this survey we evaluated the economic impact of COPD.
...This cross-sectional, population-based survey questioned 4,343 subjects aged 40 years and older, fulfilling a case definition of COPD based on self-reported physician diagnosis or symptomatology. Direct cost measures were based on exacerbations of COPD (treated and those requiring emergency department visits and/or hospitalisation), contacts with healthcare professionals, and COPD medications. Indirect costs were calculated from work loss values using the Work Productivity and Activity Impairment scale. Combined direct and indirect costs estimated the total societal costs per patient.
The annual direct costs of COPD ranged from $504 (South Korea) to $9,981 (USA), with inpatient hospitalisations (5 countries) and home oxygen therapy (3 countries) being the key drivers of direct costs. The proportion of patients completely prevented from working due to their COPD ranged from 6% (Italy) to 52% (USA and UK) with 8 countries reporting this to be ≥20%. Total societal costs per patient varied widely from $1,721 (Russia) to $30,826 (USA) but a consistent pattern across countries showed greater costs among those with increased burden of COPD (symptoms, health status and more severe disease) and a greater number of comorbidities.
The economic burden of COPD is considerable across countries, and requires targeted resources to optimise COPD management encompassing the control of symptoms, prevention of exacerbations and effective treatment of comorbidities. Strategies to allow COPD patients to remain in work are important for addressing the substantial wider societal costs.
Abstract
Heterogeneous clinical manifestations and progression of chronic obstructive pulmonary disease (COPD) affect patient health risk assessment, stratification, and management. Pulmonary ...function tests are used to diagnose and classify the severity of COPD, but they cannot fully represent the type or range of pathophysiologic abnormalities of the disease. To evaluate whether deep radiomics from chest computed tomography (CT) images can predict mortality in patients with COPD, we designed a convolutional neural network (CNN) model for extracting representative features from CT images and then performed random survival forest to predict survival in COPD patients. We trained CNN-based binary classifier based on six-minute walk distance results (> 440 m or not) and extracted high-throughput image features (i.e., deep radiomics) directly from the last fully connected layer of it. The various sizes of fully connected layers and combinations of deep features were experimented using a discovery cohort with 344 patients from the Korean Obstructive Lung Disease cohort and an external validation cohort with 102 patients from Penang General Hospital in Malaysia. In the integrative analysis of discovery and external validation cohorts, with combining 256 deep features from the coronal slice of the vertebral body and two sagittal slices of the left/right lung, deep radiomics for survival prediction achieved concordance indices of 0.8008 (95% CI, 0.7642–0.8373) and 0.7156 (95% CI, 0.7024–0.7288), respectively. Deep radiomics from CT images could be used to predict mortality in COPD patients.
The comparative effectiveness of different inhaler therapies in mild-to-moderate asthma remains unclear. To assess this, we performed a systematic review and network meta-analysis of randomized ...controlled trials on the use of inhalers for mild-to-moderate asthma by searching PubMed, Cochrane, and Embase. A total of 29 trials including 43,515 patients and 12 types of inhaler therapies were included. For the prevention of severe and moderate-to-severe exacerbations, inhaled corticosteroid (ICS)/long-acting β2-agonist (LABA) as maintenance and reliever (SMART) showed the highest rank for effectiveness. As-needed ICS/LABA or short-acting β2-agonist (SABA) was similar to low-dose ICS and superior to as-needed SABA or LABA for the prevention of severe and moderate-severe exacerbations. As for lung function (FEV
), low-dose ICS/LABA had the highest rank; as-needed ICS/LABA was inferior to regular low-dose ICS but superior to placebo. Higher-dose ICS had a superior effect on the Asthma Control Questionnaire (ACQ) scores, and as-needed ICS/LABA and as-needed SABA or LABA had lower ranks in p-rankogram than did the regular use of low-dose ICS. As-needed ICS with LABA or SABA was more effective than a similar dose of regular ICS for preventing exacerbation in mild-to-moderate asthma. As-needed ICS showed some weakness in improving lung function and controlling asthma symptoms.
Bacterial infections are well known factors underlying acute exacerbations in bronchiectasis. However, viral infections may also contribute to acute exacerbations. We aimed to assess the rate of ...viral detection in acute exacerbations of bronchiectasis, and the associated clinical factors.
Diagnostic tests for viral and bacterial etiologies were performed in 792 patients with bronchiectasis who visited the emergency room or the respiratory care inpatient unit in a tertiary referral center in South Korea. All patients were diagnosed with bronchiectasis by chest computerized tomography and were prescribed antibiotics for a minimum of 3 days.
Viral pathogens were detected in 202 of the 792 enrolled patients (25.5%). The most common viral pathogen isolated was influenza A virus (24.8%), followed by rhinovirus (22.4%), influenza B virus (9.8%), respiratory syncytial virus B (8.9%), and human metapneumovirus (6.1%). In 145 patients, a viral, but not bacterial, pathogen was detected, whereas no pathogens were found in 443 patients with exacerbations. Multivariable analysis revealed that female sex and chronic heart disease as a comorbidity were positively associated with viral detection in acute exacerbations of patients with bronchiectasis, whereas the presence of radiographic infiltration was negatively associated.
Respiratory viruses were identified in approximately 25% of the acute exacerbations observed among patients with bronchiectasis. Of the viruses detected, influenza viruses and rhinovirus made up over 50%. More attention to viruses as possible causative pathogens for acute deteriorating symptoms in patients with bronchiectasis is warranted.
There are limited data regarding whether mortality is higher in patients with non cystic fibrosis bronchiectasis (bronchiectasis) than in those without bronchiectasis. Using 2005-2015 data from the ...Korean National Health Insurance Service, we evaluated hazard ratio (HR) for all-cause mortality in the bronchiectasis cohort relative to the matched cohort. The effect of comorbidities over the study period on the relative mortality was also assessed. All-cause mortality was significantly higher in the bronchiectasis cohort than in the matched cohort (2505/100,000 vs 2142/100,000 person-years, respectively; P < 0.001). Mortality risk was 1.15-fold greater in the bronchiectasis cohort than in the matched cohort (95% confidence interval CI 1.09-1.22); mortality was greatest among elderly patients (HR = 1.17, 95% CI 1.10-1.25) and men (HR = 1.19, 95% CI 1.10-1.29). Comorbidities over the study period significantly increased the risk of death in the bronchiectasis cohort relative to the matched cohort: asthma (adjusted HR = 1.20, 95% CI 1.11-1.30), chronic obstructive pulmonary disease (adjusted HR = 1.24, 95% CI 1.15-1.34), pneumonia (adjusted HR = 1.50, 95% CI 1.39-1.63), lung cancer (adjusted HR = 1.85, 95% CI 1.61-2.12), and cardiovascular disease (adjusted HR = 1.34, 95% CI 1.23-1.45). In contrast, there were no significant differences in the risk of death in patients without bronchiectasis-related comorbidities and the matched cohort, except in the case of non-tuberculous mycobacterial infection. In conclusion, all-cause mortality was higher in patients with bronchiectasis cohort than those without bronchiectasis, especially in elderly patients and men. Comorbidities over the study period played a major role in increasing mortality in patients with bronchiectasis relative to those without bronchiectasis.
Objectives
To apply radiomics analysis for overall survival prediction in chronic obstructive pulmonary disease (COPD), and evaluate the performance of the radiomics signature (RS).
Methods
This ...study included 344 patients from the Korean Obstructive Lung Disease (KOLD) cohort. External validation was performed on a cohort of 112 patients. In total, 525 chest CT-based radiomics features were semi-automatically extracted. The five most useful features for survival prediction were selected by least absolute shrinkage and selection operation (LASSO) Cox regression analysis and used to generate a RS. The ability of the RS for classifying COPD patients into high or low mortality risk groups was evaluated with the Kaplan-Meier survival analysis and Cox proportional hazards regression analysis.
Results
The five features remaining after the LASSO analysis were %LAA
−950
, AWT_Pi10_6
th
, AWT_Pi10_heterogeneity, %WA_heterogeneity, and VA
18mm
. The RS demonstrated a C-index of 0.774 in the discovery group and 0.805 in the validation group. Patients with a RS greater than 1.053 were classified into the high-risk group and demonstrated worse overall survival than those in the low-risk group in both the discovery (log-rank test, < 0.001; hazard ratio HR, 5.265) and validation groups (log-rank test, < 0.001; HR, 5.223). For both groups, RS was significantly associated with overall survival after adjustments for patient age and body mass index.
Conclusions
A radiomics approach for survival prediction and risk stratification in COPD patients is feasible, and the constructed radiomics model demonstrated acceptable performance. The RS derived from chest CT data of COPD patients was able to effectively identify those at increased risk of mortality.
Key Points
• A total of 525 chest CT-based radiomics features were extracted and the five radiomics features of %LAA
−950
, AWT_Pi10_6
th
, AWT_Pi10_heterogeneity, %WA_heterogeneity, and VA
18mm
were selected to generate a radiomics model.
• A radiomics model for predicting survival of COPD patients demonstrated reliable performance with a C-index of 0.774 in the discovery group and 0.805 in the validation group.
• Radiomics approach was able to effectively identify COPD patients with an increased risk of mortality, and patients assigned to the high-risk group demonstrated worse overall survival in both the discovery and validation groups.
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