Lung imaging in COPD and asthma.

Chronic obstructive pulmonary disease (COPD) and asthma are common lung diseases with heterogeneous clinical presentations. Lung imaging allows evaluations of underlying pathophysiological changes and provides additional personalized approaches for disease management. This narrative review provides an overview of recent advances in chest imaging analysis using various modalities, such as computed tomography (CT), dynamic chest radiography, and magnetic resonance imaging (MRI). Visual CT assessment localizes emphysema subtypes and mucus plugging in the airways. Dedicated software quantifies the severity and spatial distribution of emphysema and the airway tree structure, including the central airway wall thickness, branch count and fractal dimension of the tree, and airway-to-lung size ratio. Nonrigid registration of inspiratory and expiratory CT scans quantifies small airway dysfunction, local volume changes and shape deformations in specific regions. Lung ventilation and diaphragm movement are also evaluated on dynamic chest radiography. Functional MRI detects regional oxygen transfer across the alveolus using inhaled oxygen and ventilation defects and gas diffusion into the alveolar-capillary barrier tissue and red blood cells using inhaled hyperpolarized 129Xe gas. These methods have the potential to determine local functional properties in the lungs that cannot be detected by lung function tests in patients with COPD and asthma. Further studies are needed to apply these technologies in clinical practice, particularly for early disease detection and tailor-made interventions, such as the efficient selection of patients likely to respond to biologics. Moreover, research should focus on the extension of healthy life expectancy in patients at higher risk and with established diseases.

Phase angle measured by bioelectrical impedance analysis in patients with chronic obstructive pulmonary disease: Associations with physical inactivity and frailty.

BACKGROUND: Factors associated with early-stage frailty (pre-frailty) in patients with chronic obstructive pulmonary disease (COPD) remain unestablished. In addition to skeletal muscle quantity, skeletal muscle dysfunction can be estimated using an angular metric from bioelectrical impedance analyzer (BIA), termed the phase angle, that reflects cell membrane reactance representing the structural stability. This study examined whether the phase angle was more closely associated with pre-frailty compared with skeletal muscle quantity in patients with COPD. METHODS: This cross-sectional analysis included stable smokers with and without COPD whose frailty status was assessed using the Japanese version of the Cardiovascular Health Study criteria. The phase angle and skeletal muscle index (SMI) were measured using BIA, and physical activity over one week was assessed using triaxial accelerometers. RESULTS: A total of 159 patients were categorized into robust, pre-frail, and frail groups (n = 38, 92, and 29, respectively). The phase angle was significantly smaller in the pre-frail and frail groups than in the robust group after adjusting for age, sex, height, body mass index, smoking history, and lung function. In contrast, SMI did not differ between the robust and pre-frail groups. When combining the pre-frail and frail groups into a non-robust group, 4.8° was determined as the cutoff phase angle value to identify non-robust status. A phase angle <4.8° was associated with shorter durations of moderate-intensity physical activity but not with light physical activity. CONCLUSIONS: A smaller phase angle was associated with pre-frailty and impaired moderate-intensity physical activity in smokers with and without COPD.

Lower skeletal muscle density and airway structure on computed tomography in asthma.

BACKGROUND: Lower skeletal muscle density may reflect muscle adiposity and metabolic dysregulation that potentially impair disease control and lung function independent of high body mass index (BMI) in patients with asthma. OBJECTIVE: To investigate whether the lower density of pectoralis muscles (PMs) and erector spinae muscles (ESMs) on chest computed tomography was associated with airway structural changes in patients with asthma. METHODS: Consecutive patients with asthma and healthy controls undergoing chest computed tomography were retrospectively analyzed. The ESM and PM density, areas of subcutaneous adipose tissue near the PM and epicardial adipose tissue, wall area percent of the airways, and airway fractal dimension (AFD) were quantified on computed tomography. RESULTS: The study included 179 patients with asthma (52% women) and 88 controls (47% women). All the controls were 60 years old or younger. The PM and ESM density in female patients with asthma who were 60 years old or younger were significantly lower than those in controls after adjustment for BMI. In female patients with asthma at all ages, lower PM and ESM density (but not subcutaneous or epicardial adipose tissue area) was associated with greater wall area percent of the airways and lower AFD after adjusting for age, height, BMI, smoking status, blood eosinophil count, and oral corticosteroid use. The only association between ESM density and AFD was found in male patients with asthma. CONCLUSION: Lower skeletal muscle density may be associated with airway wall thickening and less complexity of the airway luminal tree in female patients with asthma.

Increased adiposity-to-muscle ratio and severity of sinusitis affect quality of life in asthma: Computed tomographic analysis.

Background: Deteriorated sinusitis and increased adiposity relative to muscle mass may affect quality of life in patients with asthma. However, whether these effects are observed regardless of intrapulmonary pathology is unknown. Objectives: We evaluated the correlation of the cross-sectional ratio of abdominal visceral fat (VF) to erector spinae muscle (ESM) and sinus findings based on Lund-Mackey scoring system (LMS) on computed tomography (CT) with the impaired score of the Asthma Quality of Life Questionnaire (AQLQ), regardless of airway and parenchymal disease, in patients with asthma. Methods: We recruited participants from the Hokkaido-based severe asthma cohort who had completed AQLQ and CT examination at the entry. The participants were divided into high (highest) and low (other quartiles) groups on the bases of the extrapulmonary indices. Multivariate analysis examined the association of VF/ESM for the adiposity-to-muscle ratio and LMS with AQLQ after adjusting for the airway fractal dimension for airway index and percentage of low attenuation volume to lung volume for parenchymal index. Results: No significant differences were observed in VF/ESM and LMS in terms of sex. The AQLQ score in the high VF/ESM group and high LMS group was lower than those in low VF/ESM group and low LMS group (63 male and 100 female subjects). High VF/ESM (estimate [95% confidence interval] (-0.43 [-0.61, -0.25]) and high LMS scores (-0.22 [-0.41, -0.03]) were associated with low AQLQ scores when adjusted for age, body mass index, smoking status, blood eosinophil count, and intrapulmonary CT indices. Conclusions: Increased VF relative to ESM mass and high LMS may deteriorate asthma-related quality of life, regardless of presence of intrapulmonary disease.

Mucus plugging on computed tomography and the sputum microbiome in patients with asthma, chronic obstructive pulmonary disease, and asthma-COPD overlap.

BACKGROUND: Despite clinical implications, the pathogenesis of mucus plugging in asthma, chronic obstructive pulmonary disease (COPD), and asthma-COPD overlap (ACO) remains unclear. We hypothesized that distinct airway microbiomes might affect mucus plugging differently among ACO, asthma, and COPD and among different extents of airway eosinophilic inflammation. METHODS: The sputum microbiome, sputum cell differential count, and mucus plug score on computed tomography were cross-sectionally evaluated in patients with chronic airflow limitation. RESULTS: Patients with ACO, asthma, or COPD were enrolled (n = 56, 10, and 25). Higher mucus plug scores were associated with a greater relative abundance of the phylum Proteobacteria (rho = 0.29) only in patients with ACO and a greater relative abundance of the phylum Actinobacteria (rho = 0.46) only in patients with COPD. In multivariable models including only patients with ACO, the presence of mucus plugs was associated with a greater relative abundance of the phylum Proteobacteria and the genus Haemophilus, independent of smoking status, airflow limitation, and emphysema severity. Moreover, the mucus score was associated with a greater relative abundance of the genus Streptococcus (rho = 0.46) in patients with a high sputum eosinophil count (n = 22) and with that of the genus Haemophilus (rho = 0.46) in those with a moderate sputum eosinophil count (n = 26). CONCLUSIONS: The associations between mucus plugging and the microbiome in ACO differed from those in COPD and asthma. Greater relative abundances of the phylum Proteobacteria and genus Haemophilus may be involved in mucus plugging in patients with ACO and moderate airway eosinophilic inflammation.

Computed tomography mucus plugs and airway tree structure in patients with chronic obstructive pulmonary disease: Associations with airflow limitation, health-related independence and mortality.

BACKGROUND AND OBJECTIVE: Mucus plugs and underlying airway tree structure can affect airflow limitation and prognosis in patients with chronic obstructive pulmonary disease (COPD), but their relative roles are unclear. This study used two COPD cohorts to examine whether mucus plugs on computed tomography (CT) were associated with airflow limitation and clinical outcomes independent of other airway structural changes and emphysema. METHODS: Based on visual CT assessment, patients with mucus plugs in 0, 1-2 and ≥3 lung segments were assigned to no-, low- and high-mucus groups. Loss of health-related independence and mortality were prospectively recorded for 3 and 10 years in the Kyoto-Himeji and Hokkaido cohorts, respectively. The percentages of the wall area of the central airways (WA%), total airway count (TAC) and emphysema were quantified on CT. RESULTS: Of 199 and 96 patients in the Kyoto-Himeji and Hokkaido cohorts, 34% and 30%, respectively, had high mucus scores. In both cohorts, TAC was lower in the high-mucus group than in the no-mucus group, whereas their emphysema severity did not differ. High mucus score and low TAC were independently associated with airflow limitation after adjustment for WA% and emphysema. In multivariable models adjusted for WA% and emphysema, TAC, rather than mucus score, was associated with a greater rate of loss of independence, whereas high mucus score, rather than TAC, was associated with increased mortality. CONCLUSION: Mucus plugs and lower airway branch count on CT had distinct roles in airflow limitation, health-related independence and mortality in patients with COPD.

CT-derived vertebral bone mineral density is a useful biomarker to predict COVID-19 outcome.

The low vertebral bone computed tomography (CT) Hounsfield unit values measured on CT scans reflect low bone mineral density (BMD) and are known as diagnostic indicators for osteoporosis. The potential prognostic significance of low BMD defined by vertebral bone CT values for the coronavirus disease 2019 (COVID-19) remains unclear. This study aimed to assess the impact of BMD on the clinical outcome in Japanese patients with COVID-19 and evaluate the association between BMD and critical outcomes, such as high-flow nasal cannula, non-invasive and invasive positive pressure ventilation, extracorporeal membrane oxygenation, or death. We examined the effects of COVID-19 severity on the change of BMD over time. This multicenter retrospective cohort study enrolled 1132 inpatients with COVID-19 from the Japan COVID-19 Task Force database between February 2020 and September 2022. The bone CT values of the 4th, 7th, and 10th thoracic vertebrae were measured from chest CT images. The average of these values was defined as BMD. Furthermore, a comparative analysis was conducted between the BMD on admission and its value 3 months later. The low BMD group had a higher proportion of critical outcomes than did the high BMD group. In a subanalysis stratifying patients by epidemic wave according to onset time, critical outcomes were higher in the low BMD group in the 1st-4th waves. Multivariable logistic analysis of previously reported factors associated with COVID-19 severity revealed that low BMD, chronic kidney disease, and diabetes were independently associated with critical outcomes. At 3 months post-infection, patients with oxygen demand during hospitalization showed markedly decreased BMD than did those on admission. Low BMD in patients with COVID-19 may help predict severe disease after the disease onset. BMD may decrease over time in patients with severe COVID-19, and the impact on sequelae symptoms should be investigated in the future.

Investigation of predictors for in-hospital death or long-term hospitalization in community-acquired pneumonia with risk factors for aspiration.

Background: It is known that the mortality of pneumonia in patients with risk factors for aspiration is worse than that in those without these risk factors. However, it is still unknown which risk factors for aspiration predict prognosis. Therefore, we aimed to determine which risk factors for aspiration are associated with death or prolonged hospitalization. Methods: We prospectively followed patients with community-acquired pneumonia at a single hospital providing acute to chronic care in Japan until they died or were discharged. Patients at any risk of aspiration were included. The associations between pneumonia severity, individual risk factors for aspiration, and in-hospital death or prolonged hospitalization were investigated. Overall survival was estimated by the Kaplan - Meier method, and the factors associated with in-hospital death or prolonged hospitalization were investigated by multivariate analysis using factors selected by a stepwise method. Results: In total, 765 patients with pneumonia and risk factors for aspiration were recruited. One hundred and ten patients deceased, and 259 patients were hospitalized over 27 days. In-hospital death increased as the number of risk factors for aspiration increased. In the multivariate analysis, male, impaired consciousness, acidemia, elevated blood urea nitrogen, and bedridden status before the onset of pneumonia were associated with in-hospital death (odds ratio [OR]: 2.5, 2.5, 3.6, 3.1, and 2.6; 95% confidence interval [CI]: 1.6-4.1, 1.4-4.2, 1.6-8.0, 1.9-5.0, and 1.6-4.2 respectively). In the Cox regression analysis, these factors were also associated with in-hospital death. None of the vital signs at admission were associated. Tachycardia, elevated blood urea nitrogen, hyponatremia, and bedridden status were associated with hospitalization for >27 days (OR: 4.1, 2.3, 4.3, and 2.9; 95% CI: 1.3-12.9, 1.5-3.4, 2.0-9.4, and 2.0-4.0, respectively). Conclusions: Blood sampling findings and bedridden status are useful for predicting in-hospital mortality and long-term hospitalization in patients with pneumonia and any risk factor for aspiration.

Lung volume measurement using chest CT in COVID-19 patients: a cohort study in Japan.

OBJECTIVE: This study aimed to investigate the utility of CT quantification of lung volume for predicting critical outcomes in COVID-19 patients. METHODS: This retrospective cohort study included 1200 hospitalised patients with COVID-19 from 4 hospitals. Lung fields were extracted using artificial intelligence-based segmentation, and the percentage of the predicted (%pred) total lung volume (TLC (%pred)) was calculated. The incidence of critical outcomes and posthospitalisation complications was compared between patients with low and high CT lung volumes classified based on the median percentage of predicted TLCct (n=600 for each). Prognostic factors for residual lung volume loss were investigated in 208 patients with COVID-19 via a follow-up CT after 3 months. RESULTS: The incidence of critical outcomes was higher in the low TLCct (%pred) group than in the high TLCct (%pred) group (14.2% vs 3.3%, p<0.0001). Multivariable analysis of previously reported factors (age, sex, body mass index and comorbidities) demonstrated that CT-derived lung volume was significantly associated with critical outcomes. The low TLCct (%pred) group exhibited a higher incidence of bacterial infection, heart failure, thromboembolism, liver dysfunction and renal dysfunction than the high TLCct (%pred) group. TLCct (%pred) at 3 months was similarly divided into two groups at the median (71.8%). Among patients with follow-up CT scans, lung volumes showed a recovery trend from the time of admission to 3 months but remained lower in critical cases at 3 months. CONCLUSION: Lower CT lung volume was associated with critical outcomes, posthospitalisation complications and slower improvement of clinical conditions in COVID-19 patients.

Longitudinal assessment of interstitial lung abnormalities on CT in patients with COPD using artificial intelligence-based segmentation: a prospective observational study.

BACKGROUND: Interstitial lung abnormalities (ILAs) on CT may affect the clinical outcomes in patients with chronic obstructive pulmonary disease (COPD), but their quantification remains unestablished. This study examined whether artificial intelligence (AI)-based segmentation could be applied to identify ILAs using two COPD cohorts. METHODS: ILAs were diagnosed visually based on the Fleischner Society definition. Using an AI-based method, ground-glass opacities, reticulations, and honeycombing were segmented, and their volumes were summed to obtain the percentage ratio of interstitial lung disease-associated volume to total lung volume (ILDvol%). The optimal ILDvol% threshold for ILA detection was determined in cross-sectional data of the discovery and validation cohorts. The 5-year longitudinal changes in ILDvol% were calculated in discovery cohort patients who underwent baseline and follow-up CT scans. RESULTS: ILAs were found in 32 (14%) and 15 (10%) patients with COPD in the discovery (n = 234) and validation (n = 153) cohorts, respectively. ILDvol% was higher in patients with ILAs than in those without ILA in both cohorts. The optimal ILDvol% threshold in the discovery cohort was 1.203%, and good sensitivity and specificity (93.3% and 76.3%) were confirmed in the validation cohort. 124 patients took follow-up CT scan during 5 ± 1 years. 8 out of 124 patients (7%) developed ILAs. In a multivariable model, an increase in ILDvol% was associated with ILA development after adjusting for age, sex, BMI, and smoking exposure. CONCLUSION: AI-based CT quantification of ILDvol% may be a reproducible method for identifying and monitoring ILAs in patients with COPD.

Quantification of Airway Structures by Persistent Homology.

We propose two types of novel morphological metrics for quantifying the geometry of tubular structures on computed tomography (CT) images. We apply our metrics to identify irregularities in the airway of patients with chronic obstructive pulmonary disease (COPD) and demonstrate that they provide complementary information to the conventional metrics used to assess COPD, such as the tissue density distribution in lung parenchyma and the wall area ratio of the segmented airway. The three-dimensional shape of the airway and its abstraction as a rooted tree with the root at the trachea carina are automatically extracted from a lung CT volume, and the two metrics are computed based on a mathematical tool called persistent homology; treeH0 quantifies the distribution of branch lengths to assess the complexity of the tree-like structure and radialH0 quantifies the irregularities in the luminal radius along the airway. We show our metrics are associated with clinical outcomes.

Centrilobular emphysema and airway dysanapsis: factors associated with low respiratory function in younger smokers.

Background: Low respiratory function in young adulthood is one of the important factors in the trajectory leading to the future development of COPD, but its morphological characteristics are not well characterised. Methods: We retrospectively enrolled 172 subjects aged 40-49 years with ≥10 pack-years smoking history who underwent lung cancer screening by computed tomography (CT) and spirometry at two Japanese hospitals. Emphysema was visually assessed according to the Fleischner Society guidelines and classified into two types: centrilobular emphysema (CLE) and paraseptal emphysema (PSE). Airway dysanapsis was assessed with the airway/lung ratio (ALR), which was calculated by the geometric mean of the lumen diameters of the 14 branching segments divided by the cube root of total lung volume on a CT scan. Results: Among the subjects, CLE and PSE were observed in 20.9% and 30.8%, respectively. The mean ALR was 0.04 and did not differ between those with and without each type of emphysema. Multivariable regression analysis models adjusted for age, sex, body mass index and smoking status indicated that CLE and a low ALR were independently associated with lower forced expiratory volume in 1 s (FEV1)/forced vital capacity (estimate -1.64 (95% CI -2.68- -0.60) and 6.73 (95% CI 4.24-9.24), respectively) and FEV1 % pred (estimate -2.81 (95% CI -5.10- -0.52) and 10.9 (95% CI 5.36-16.4), respectively). Conclusions: CLE and airway dysanapsis on CT were independently associated with low respiratory function in younger smokers.

Associations of fractional exhaled nitric oxide with airway dimension and mucus plugs on ultra-high-resolution computed tomography in former smokers and nonsmokers with asthma.

BACKGROUND: Associations of fractional exhaled nitric oxide (FeNO) with airway wall remodeling and mucus plugs remain to be explored in smokers and nonsmokers with asthma. Ultra-high-resolution computed tomography (U-HRCT), which allows accurate structural quantification of airways >1 mm in diameter, was used in this study to examine whether higher FeNO was associated with thicker walls of the 3rd to 6th generation airways and mucus plugging in patients with asthma. METHODS: The retrospective analyses included consecutive former smokers and nonsmokers with asthma who underwent U-HRCT in a hospital. The ratio of wall area to summed lumen and wall area was calculated as the wall area percent (WA%). Mucus plugging was visually scored. RESULTS: Ninety-seven patients with asthma (including 59 former smokers) were classified into low (<20 ppb), middle (20-35 ppb), and high (>35 ppb) FeNO groups (n = 24, 26, and 47). In analysis including all patients and subanalysis including nonsmokers or former smokers, WA% in the 6th generation airways was consistently higher in the high FeNO group than in the low FeNO group, whereas WA% in the 3rd to 5th generation airways was not. In multivariable models, WA% in the 6th generation airways and the rate of mucus plugging were higher in the high FeNO group than in the low FeNO group after adjusting for age, sex, body mass index, smoking status, lung volume, and allergic rhinitis presence. CONCLUSIONS: Higher FeNO may reflect the inflammation and remodeling of relatively peripheral airways in asthma in both former smokers and nonsmokers.

Integrated assessment of computed tomography density in pectoralis and erector spinae muscles as a prognostic biomarker for coronavirus disease 2019.

BACKGROUND ＆ AIMS: Muscle quantification using chest computed tomography (CT) is a useful prognostic biomarker for coronavirus disease 2019 (COVID-19). However, no studies have evaluated the clinical course through comprehensive assessment of the pectoralis and erector spinae muscles. Therefore, we compared the impact of the areas and densities of these muscles on COVID-19 infection outcome. METHODS: This multicenter retrospective cohort study was conducted by the COVID-19 Task Force. A total of 1410 patients with COVID-19 were included, and data on the area and density of the pectoralis and erector spinae muscles on chest CT were collected. The impact of each muscle parameter on the clinical outcome of COVID-19 was stratified according to sex. The primary outcome was the percentage of patients with severe disease, including those requiring oxygen supplementation and those who died. Additionally, 167 patients were followed up for changes in muscle parameters at three months and for the clinical characteristics in case of reduced CT density. RESULTS: For both muscles, low density rather than muscle area was associated with COVID-19 severity. Regardless of sex, lower erector spinae muscle density was associated with more severe disease than pectoralis muscle density. The muscles were divided into two groups using the receiver operating characteristic curve of CT density, and the population was classified into four (Group A: high CT density for both muscles, Group B: low CT density for pectoralis and high for erector spinae muscle. Group C: high CT density for pectoralis and low for erector spinae muscle, Group D: low CT density for both muscles). In univariate analysis, Group D patients exhibited worse outcomes than Group A (OR: 2.96, 95% CI: 2.03-4.34 in men; OR: 3.02, 95% CI: 2.66-10.4 in women). Multivariate analysis revealed that men in Group D had a significantly more severe prognosis than those in Group A (OR: 1.82, 95% CI: 1.16-2.87). Moreover, Group D patients tended to have the highest incidence of other complications due to secondary infections and acute kidney injury during the clinical course. Longitudinal analysis of both muscle densities over three months revealed that patients with decreased muscle density over time were more likely to have severe cases than those who did not. CONCLUSIONS: Muscle density, rather than muscle area, predicts the clinical outcomes of COVID-19. Integrated assessment of pectoralis and erector spinae muscle densities demonstrated higher accuracy in predicting the clinical course of COVID-19 than individual assessments.

Aggregated eosinophils and neutrophils characterize the properties of mucus in chronic rhinosinusitis.

BACKGROUND: Airway obstruction caused by viscous mucus is an important pathophysiologic characteristic of persistent inflammation, which can result in organ damage. OBJECTIVE: We investigated the hypothesis that the biophysical characteristics of accumulating granulocytes affect the clinical properties of mucus. METHODS: Surgically acquired nasal mucus samples from patients with eosinophilic chronic rhinosinusitis and neutrophil-dominant, noneosinophilic chronic rhinosinusitis were evaluated in terms of computed tomography density, viscosity, water content, wettability, and protein composition. Isolated human eosinophils and neutrophils were stimulated to induce the formation of extracellular traps, followed by the formation of aggregates. The biophysical properties of the aggregated cells were also examined. RESULTS: Mucus from patients with eosinophilic chronic rhinosinusitis had significantly higher computed tomography density, viscosity, dry weight, and hydrophobicity compared to mucus from patients with noneosinophilic chronic rhinosinusitis. The levels of eosinophil-specific proteins in mucus correlated with its physical properties. Eosinophil and neutrophil aggregates showed physical and pathologic characteristics resembling those of mucus. Cotreatment with deoxyribonuclease and heparin, which slenderizes the structure of eosinophil extracellular traps, efficiently induced reductions in the viscosity and hydrophobicity of both eosinophil aggregates and eosinophilic mucus. CONCLUSIONS: The present study elucidated the pathogenesis of mucus stasis in infiltrated granulocyte aggregates from a novel perspective. These findings may contribute to the development of treatment strategies for eosinophilic airway diseases.

Artificial intelligence-based analysis of the spatial distribution of abnormal computed tomography patterns in SARS-CoV-2 pneumonia: association with disease severity.

BACKGROUND: The substantial heterogeneity of clinical presentations in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia still requires robust chest computed tomography analysis to identify high-risk patients. While extension of ground-glass opacity and consolidation from peripheral to central lung fields on chest computed tomography (CT) might be associated with severely ill conditions, quantification of the central-peripheral distribution of ground glass opacity and consolidation in assessments of SARS-CoV-2 pneumonia remains unestablished. This study aimed to examine whether the central-peripheral distributions of ground glass opacity and consolidation were associated with severe outcomes in patients with SARS-CoV-2 pneumonia independent of the whole-lung extents of these abnormal shadows. METHODS: This multicenter retrospective cohort included hospitalized patients with SARS-CoV-2 pneumonia between January 2020 and August 2021. An artificial intelligence-based image analysis technology was used to segment abnormal shadows, including ground glass opacity and consolidation. The area ratio of ground glass opacity and consolidation to the whole lung (GGO%, CON%) and the ratio of ground glass opacity and consolidation areas in the central lungs to those in the peripheral lungs (GGO(C/P)) and (CON(C/P)) were automatically calculated. Severe outcome was defined as in-hospital death or requirement for endotracheal intubation. RESULTS: Of 512 enrolled patients, the severe outcome was observed in 77 patients. GGO% and CON% were higher in patients with severe outcomes than in those without. Multivariable logistic models showed that GGO(C/P), but not CON(C/P), was associated with the severe outcome independent of age, sex, comorbidities, GGO%, and CON%. CONCLUSION: In addition to GGO% and CON% in the whole lung, the higher the ratio of ground glass opacity in the central regions to that in the peripheral regions was, the more severe the outcomes in patients with SARS-CoV-2 pneumonia were. The proposed method might be useful to reproducibly quantify the extension of ground glass opacity from peripheral to central lungs and to estimate prognosis.

Longitudinal changes in respiratory reactance in patients with COPD: associations with longitudinal change in air-trapping, exacerbations, and mortality.

INTRODUCTION: Air-trapping affects clinical outcomes in patients with chronic obstructive pulmonary disease (COPD) and may be detected by reactance at 5 Hz (X5) on respiratory oscillometry because X5 sensitively reflects the elasticity of the chest wall, airway and lung. However, the longitudinal association between X5 and air-trapping remains to be explored. This study aimed to test whether longitudinal changes in X5 could be associated with air-trapping progression, exacerbations, and mortality in patients with COPD. METHODS: In this prospective COPD observational study, the follow-up period consisted of the first 4 years to obtain longitudinal changes in X5 and residual volume (RV) and number of exacerbations and the remaining years (year 4 to 10) to test mortality. Patients were divided into large, middle, and small X5 decline groups based on the tertiles of longitudinal change in X5, and mortality after 4 years was compared between the groups. RESULTS: Patients with COPD (n = 114) were enrolled. The large X5 decline group (n = 38) showed a greater longitudinal change in RV and more exacerbations compared with the small X5 decline group (n = 39) in multivariable models adjusted for age, sex, body mass index, and smoking history. Long-term mortality after the 4-year follow-up was higher in the large X5 decline group than in the small X5 decline group (hazard ratio [95 % confidence interval] = 8.37[1.01, 69.0]) in the multivariable Cox proportional hazard model. CONCLUSION: Longitudinal changes in respiratory reactance could be associated with progressive air-trapping, exacerbation frequency, and increased mortality in patients with COPD.

Evaluation of Bone Mineral Density in Lung Transplant Recipients by Chest Computed Tomography.

INTRODUCTION: Lung transplantation (LT) recipients are at risk of bone mineral density (BMD) loss. Pre- and post-LT BMD loss has been reported in some cross-sectional studies; however, there are limited studies regarding the serial BMD change in LT recipients. The aim of this study was to investigate the serial BMD changes and the clinical characteristics associated with BMD decline. METHODS: This was a single-center, retrospective observational study. BMD was serially measured in thoracic vertebral bodies (Th4, 7, 10) using computed tomography (CT) before and 3 and 12 months after LT. The frequency of osteoporosis and factors associated with pre-LT osteoporosis and post-LT BMD loss were evaluated. The frequency of post-LT compression fracture and its associated factors were also analyzed. RESULTS: This study included 128 adult LT recipients. LT recipients had decreased BMD (151.8 ± 42.2 mg/mL) before LT compared with age-, sex-, and smoking index-matched controls (176.2 ± 35.7 mg/mL). The diagnosis of COPD was associated with pre-LT osteoporosis. LT recipients experience further BMD decline after transplantation, and the percentage of recipients classified as exhibiting osteoporosis increased from 20% at baseline to 43% at 12 months. Recipients who had been taking no or small doses of glucocorticoids before LT had rapid BMD loss after LT. Early bisphosphonate use (within 3 months) after LT attenuated BMD loss and decreased new-onset compression fracture. CONCLUSION: LT recipients are at high risk for BMD loss and compression fracture after LT. Early bisphosphonate use may decrease BMD loss and compression fracture.

Pharmacokinetics of GS-441524, the active metabolite of remdesivir, in patients receiving continuous renal replacement therapy: A case series.

Remdesivir plays a key role in the treatment of coronavirus disease in 2019 (COVID-19). Haemodialysis is sometimes required for hospitalised patients with COVID-19, and patients undergoing haemodialysis are at an increased risk of severe COVID-19. In the present study, we report the serum concentrations of GS-441524, the active metabolite of remdesivir, in four patients undergoing continuous renal replacement therapy (CRRT). Patient 1, a male aged 70s, received a loading dose of 200 mg remdesivir on day 1, followed by 100 mg remdesivir from day 2, according to the package insert as in non-haemodialysis patients. The mean trough serum concentration of GS-441524 was 783.5 ng/mL, which was approximately 7-fold higher than the mean for patients with an estimated glomerular filtration rate (eGFR) ≥ 60 mL/min. Patients 2-4 received a loading dose of 200 mg remdesivir on day 1, followed by 100 mg once every 2 days from day 2. The mean trough serum concentrations of GS-441524 were 302.2 ng/mL, 585.8 ng/mL and 677.3 ng/mL, respectively. These were 3 to 6-fold higher than the mean for patients with eGFR ≥60 mL/min. The target doses for patients 1, 2, 3, and 4 receiving CRRT were 13.6 mL/kg/h, 6.0-12.5 mL/kg/h, 20.1 mL/kg/h, and 15.1 mL/kg/h, respectively, using a polysulphone membrane. The package insert dose of remdesivir is an overdose for CRRT patients with a target dose of 10-20 mL/kg/h. In low-intensity CRRT, as in Japan, it may be necessary to extend the interval between the doses of remdesivir.