COPD Research Articles

Serum lipopolysaccharide associated with new-onset atrial fibrillation in patients with non-small-cell lung cancer a retrospective observational study.

Lipopolysaccharide (LPS) is related to atrial fibrillation (AF). But so far, the relationship between LPS and new-onset AF (NOAF) in patients with lung cancer is unrevealed. This study was to investigate the association between LPS and NOAF in patients after lung cancer surgery. This was a single-center retrospective clinical observational study. Patients diagnosed with non-small-cell lung cancer (NSCLC) were enrolled. All patients receiving lung cancer surgery and at least 24 h electrocardiogram (ECG) examination was recorded during the hospitalization. The incidence of NOAF in this study was 34/406 (8.4%). The univariate analysis showed that NOAF was associated with age, intraoperative blood transfusion (IBT), chronic obstructive pulmonary disorder (COPD), and LPS. After adjusting risk factors, it was found that age, IBT and LPS (OR, 1.031; 95% CI: 1.001-1.042; P = 0.002) were still risk factors for NOAF. The area under curve (AUC) value was 0.709 for the LPS. When the LPS was added to the conventional model, the Net reclassification index (NRI) and integrated discrimination index (IDI) were improved significantly. Elevated LPS is associated with an increased risk of NOAF in patients after lung cancer surgery. LPS contributed to the discrimination of the NOAF risk model and improved it markedly.

Predicting unplanned admissions to hospital in older adults using routinely recorded general practice data: development and validation of a prediction model.

Unplanned admissions to hospital represent a hazardous event for older people. Timely identification of high-risk individuals using a prediction tool may facilitate preventive interventions. To develop and validate an easy-to-use prediction model for unplanned admissions to hospital in community-dwelling older adults using readily available data to allow rapid bedside assessment by GPs. This was a retrospective study using the general practice electronic health records of 243 324 community-dwelling adults aged ≥65 years linked with national administrative data to predict unplanned admissions to hospital within 6 months. The dataset was geographically split into a development (n = 142 791/243 324, 58.7%) and validation (n = 100 533/243 324, 41.3%) sample to predict unplanned admissions to hospital within 6 months. The performance of three different models was evaluated with increasingly smaller selections of candidate predictors (optimal, readily available, and easy-to-use models). Logistic regression was used with backward selection for model development. The models were validated internally and externally. Predictive performance was assessed by area under the curve (AUC) and calibration plots. In both samples, 7.6% (development cohort: n = 10 839/142 791, validation cohort: n = 7675/100 533) had ≥1 unplanned hospital admission within 6 months. The discriminative ability of the three models was comparable and remained stable after geographic validation. The easy-to-use model included age, sex, prior admissions to hospital, pulmonary emphysema, heart failure, and polypharmacy. Its discriminative ability after validation was AUC 0.72 (95% confidence interval = 0.71 to 0.72). Calibration plots showed good calibration. The models showed satisfactory predictive ability. Reducing the number of predictors and geographic validation did not have an impact on predictive performance, demonstrating the robustness of the model. An easy-to-use tool has been developed in this study that may assist GPs in decision making and with targeted preventive interventions.

Downregulation of Mirlet7 miRNA family promotes Tc17 differentiation and emphysema via de-repression of RORγt.

Environmental air irritants including nanosized carbon black (nCB) can drive systemic inflammation, promoting chronic obstructive pulmonary disease (COPD) and emphysema development. The let-7 microRNA (Mirlet7 miRNA) family is associated with IL-17-driven T cell inflammation, a canonical signature of lung inflammation. Recent evidence suggests the Mirlet7 family is downregulated in patients with COPD, however, whether this repression conveys a functional consequence on emphysema pathology has not been elucidated. Here, we show that overall expression of the Mirlet7 clusters, Mirlet7b/Mirlet7c2 and Mirlet7a1/Mirlet7f1/Mirlet7d, are reduced in the lungs and T cells of smokers with emphysema as well as in mice with cigarette smoke (CS)- or nCB-elicited emphysema. We demonstrate that loss of the Mirlet7b/Mirlet7c2 cluster in T cells predisposed mice to exaggerated CS- or nCB-elicited emphysema. Furthermore, ablation of the Mirlet7b/Mirlet7c2 cluster enhanced CD8+IL17a+ T cells (Tc17) formation in emphysema development in mice. Additionally, transgenic mice overexpressing Mirlet7g in T cells are resistant to Tc17 and CD4+IL17a+ T cells (Th17) development when exposed to nCB. Mechanistically, our findings reveal the master regulator of Tc17/Th17 differentiation, RAR-related orphan receptor gamma t (RORγt), as a direct target of Mirlet7 in T cells. Overall, our findings shed light on the Mirlet7/RORγt axis with Mirlet7 acting as a molecular brake in the generation of Tc17 cells and suggest a novel therapeutic approach for tempering the augmented IL-17-mediated response in emphysema.

Downregulation of Mirlet7 miRNA family promotes Tc17 differentiation and emphysema via de-repression of RORγt

Environmental air irritants including nanosized carbon black (nCB) can drive systemic inflammation, promoting chronic obstructive pulmonary disease (COPD) and emphysema development. The let-7 microRNA (Mirlet7 miRNA) family is associated with IL-17-driven T cell inflammation, a canonical signature of lung inflammation. Recent evidence suggests the Mirlet7 family is downregulated in patients with COPD, however, whether this repression conveys a functional consequence on emphysema pathology has not been elucidated. Here, we show that overall expression of the Mirlet7 clusters, Mirlet7b/Mirlet7c2 and Mirlet7a1/Mirlet7f1/Mirlet7d, are reduced in the lungs and T cells of smokers with emphysema as well as in mice with cigarette smoke (CS)- or nCB-elicited emphysema. We demonstrate that loss of the Mirlet7b/Mirlet7c2 cluster in T cells predisposed mice to exaggerated CS- or nCB-elicited emphysema. Furthermore, ablation of the Mirlet7b/Mirlet7c2 cluster enhanced CD8+IL17a+ T cells (Tc17) formation in emphysema development in mice. Additionally, transgenic mice overexpressing Mirlet7g in T cells are resistant to Tc17 and CD4+IL17a+ T cells (Th17) development when exposed to nCB. Mechanistically, our findings reveal the master regulator of Tc17/Th17 differentiation, RAR-related orphan receptor gamma t (RORγt), as a direct target of Mirlet7 in T cells. Overall, our findings shed light on the Mirlet7/RORγt axis with Mirlet7 acting as a molecular brake in the generation of Tc17 cells and suggest a novel therapeutic approach for tempering the augmented IL-17-mediated response in emphysema.

Deflamin Attenuated Lung Tissue Damage in an Ozone-Induced COPD Murine Model by Regulating MMP-9 Catalytic Activity.

Chronic obstructive pulmonary disease (COPD) is comprised of histopathological alterations such as pulmonary emphysema and peribronchial fibrosis. Matrix metalloproteinase 9 (MMP-9) is one of the key enzymes involved in both types of tissue remodeling during the development of lung damage. In recent studies, it was demonstrated that deflamin, a protein component extracted from Lupinus albus, markedly inhibits the catalytic activity of MMP-9 in experimental models of colon adenocarcinoma and ulcerative colitis. Therefore, in the present study, we investigated for the first time the biological effect of deflamin in a murine COPD model induced by chronic exposure to ozone. Ozone exposure was carried out in C57BL/6 mice twice a week for six weeks for 3 h each time, and the treated group was orally administered deflamin (20 mg/kg body weight) after each ozone exposure. The histological results showed that deflamin attenuated pulmonary emphysema and peribronchial fibrosis, as evidenced by H&E and Masson's trichrome staining. Furthermore, deflamin administration significantly decreased MMP-9 activity, as assessed by fluorogenic substrate assay and gelatin zymography. Interestingly, bioinformatic analysis reveals a plausible interaction between deflamin and MMP-9. Collectively, our findings demonstrate the therapeutic potential of deflamin in a COPD murine model, and suggest that the attenuation of the development of lung tissue damage occurs by deflamin-regulated MMP-9 catalytic activity.

Mechanical and morphological characterization of the emphysematous lung tissue

Irreversible alveolar airspace enlargement is the main characteristic of pulmonary emphysema, which has been extensively studied using animal models. While the alterations in lung mechanics associated with these morphological changes have been documented in the literature, the study of the mechanical behavior of parenchymal tissue from emphysematous lungs has been poorly investigated. In this work, we characterize the mechanical and morphological properties of lung tissue in elastase-induced emphysema rat models under varying severity conditions. We analyze the non-linear tissue behavior using suitable hyperelastic constitutive models that enable to compare different non-linear responses in terms of hyperelastic material parameters. We further analyze the effect of the elastase dose on alveolar morphology and tissue material parameters and study their connection with respiratory-system mechanical parameters. Our results show that while the lung mechanical function is not significantly influenced by the elastase treatment, the tissue mechanical behavior and alveolar morphology are markedly affected by it. We further show a strong association between alveolar enlargement and tissue softening, not evidenced by respiratory-system compliance. Our findings highlight the importance of understanding tissue mechanics in emphysematous lungs, as changes in tissue properties could detect the early stages of emphysema remodeling. Statement of significanceGas exchange is vital for life and strongly relies on the mechanical function of the lungs. Pulmonary emphysema is a prevalent respiratory disease where alveolar walls are damaged, causing alveolar enlargement that induces harmful changes in the mechanical response of the lungs. In this work, we study how the mechanical properties of lung tissue change during emphysema. Our results from animal models show that tissue properties are more sensitive to alveolar enlargement due to emphysema than other mechanical properties that describe the function of the whole respiratory system.

Abstract PO3-17-07: Real-world experience with trastuzumab deruxtecan in patients with breast cancer: 6 month-interim analysis of an all-patient postmarketing surveillance in Japan

Abstract Background: Trastuzumab deruxtecan (T-DXd) is an anti-human epidermal growth factor receptor 2 (HER2) antibody-drug conjugate. T-DXd has shown great efficacy in HER2-positive breast cancer, hence receiving approval in Japan in March 2020. In Japan, all-patient postmarketing surveillance (PMS) is underway to evaluate the risk of interstitial lung disease/pneumonitis (ILD/p) in patients with breast cancer treated with T-DXd. Due to the limited generalizability of results from clinical trials, there is a need for more information about ILD/p in a real-world setting. Herein we present an interim analysis of the large-scale all-patient PMS. Methods: This is an observational, multicenter, all-patient PMS (jRCT1080225197) with an observation period of 18 months that enrolled all patients treated with T-DXd for recurrent/advanced HER2-positive breast cancer. Patients who initiated T-DXd treatment between May 2020 (launch date of T-DXd) and May 2021 were included in the interim analysis to ensure the observation period of 6 months from the initial treatment of T-DXd. This interim analysis is based on safety data from the first 6 months of 1204 patients. Data collected includes baseline characteristics and information on ILD/p. All potential ILD/p (identified based on the AE terms) reported by physicians were adjudicated by an independent ILD adjudication committee. The incidence of ILD/p was calculated from adjudicated drug-related ILD/p. Results: The interim analysis set included 1204 patients with median age of 60 years. Three of the 1204 patients (0.2%) received T-DXd as a first-line treatment, 30 (2.5%) as second-line, 1159 (96.3%) as third- line or later treatment. At baseline, 105 (8.7%) of patients had an Eastern Cooperative Oncology Group performance status (ECOG PS) 2 or greater, 8 (0.7%) had severe renal impairment (15≤ creatinine clearance (CLcr) < 30 mL/min), 4 (0.3%) had end-stage renal disease (CLcr < 15 mL/min), 5 (0.4%) had severe liver impairment (total bilirubin >4.5 mg/dL), and 32 (2.7%) had comorbid ILD/radiation pneumonitis. Those were defined as exclusion criteria in clinical trials of T-DXd. The median dose at the start of administration of T-DXd was 5.4 mg/kg (range:2.7-5.4). During the first 6 months from the initial treatment, T-DXd was discontinued in 403 (33.5%) of the 1204 patients. The most common reasons for discontinuation were disease progression in 232 (57.6%) of the discontinued 403 patients followed by ILD/p in 97 (24.1%) of the 403 patients. In the first 6 months, the incidence of all grade, grade ≥3, and grade 5 ILD/p were 8.2% (n=99), 1.7% (n=20) and 0.4% (n=5), respectively. The incidence of ILD/p stratified by baseline characteristics identified as potential risk factors of drug-related ILD/p is shown in Table. Conclusion: This is the first report demonstrating real-world experience with T-DXd in Japan. The interim analysis revealed useful information including patient and treatment profiles of T-DXd and the incidence of ILD/p during the first 6 months from the initial treatment in a real-world setting in Japan. The final analysis of the ongoing PMS is warranted for further evaluation. Incidence of interstitial lung disease/pneumonitis by patient baseline characteristics XX XX ILD/p: interstitial lung disease/pneumonitis, 95% CI: 95% confidence interval, CLCr: creatinine clearance using the Cockcroft-Gault equation * includes ILD/p, pulmonary fibrosis, radiation pneumonitis, chronic obstructive pulmonary disease, emphysema, and Asthma (Source: Powell CA, Modi S, Iwata H, et al. Pooled analysis of drug-related interstitial lung disease and/or pneumonitis in nine trastuzumab deruxtecan monotherapy studies. ESMO Open 2022;7(4):100554) Citation Format: Junji Tsurutani, Hideki Mizutani, Ayumi Tanabe. Real-world experience with trastuzumab deruxtecan in patients with breast cancer: 6 month-interim analysis of an all-patient postmarketing surveillance in Japan [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-17-07.

ROBUST QUANTIFICATION OF PERCENT EMPHYSEMA ON CT VIA DOMAIN ATTENTION: THE MULTI-ETHNIC STUDY OF ATHEROSCLEROSIS (MESA) LUNG STUDY.

Robust quantification of pulmonary emphysema on computed tomography (CT) remains challenging for large-scale research studies that involve scans from different scanner types and for translation to clinical scans. Although the domain shifts in different CT scanners are subtle compared to shifts existing in other modalities (e.g., MRI) or cross-modality, emphysema is highly sensitive to it. Such subtle difference limits the application of general domain adaptation methods, such as image translation-based methods, as the contrast difference is too subtle to be distinguished. Existing studies have explored several directions to tackle this challenge, including density correction, noise filtering, regression, hidden Markov measure field (HMMF) model-based segmentation, and volume-adjusted lung density. Despite some promising results, previous studies either required a tedious workflow or eliminated opportunities for downstream emphysema subtyping, limiting efficient adaptation on a large-scale study. To alleviate this dilemma, we developed an end-to-end deep learning framework based on an existing HMMF segmentation framework. We first demonstrate that a regular UNet cannot replicate the existing HMMF results because of the lack of scanner priors. We then design a novel domain attention block, a simple yet efficient cross-modal block to fuse image visual features with quantitative scanner priors (a sequence), which significantly improves the results.

Intraclass comparison of inhaled corticosteroids for the risk of pneumonia in chronic obstructive pulmonary airway disorder: a network meta-analysis and meta-regression.

Inhalational corticosteroids (ICS) were observed to increase the pneumonia risk in chronic obstructive pulmonary airway disorder (COPD). However, it is unknown whether any differences exist between the drugs within the ICS class. This study aimed to evaluate the risk of pneumonia associated with different ICS and identify factors that predict pneumonia in patients with moderate-to-severe COPD using a network meta-analysis. Electronic databases (Medline, Cochrane CENTRAL and Google Scholar) were searched for trials comparing ICS in COPD patients. The outcomes were pneumonia and serious pneumonia. Odds ratios (OR) with 95% confidence interval (95% CI) were estimated. Meta-regression was used to identify the predictors. The strength of evidence was graded using the Grading of Recommendations, Assessment, Development, and Evaluations approach. Sixty-six studies (103,347 participants) were included. Fluticasone (OR: 1.46; 95% CI: 1.26, 1.7), mometasone (OR: 2.2; 95% CI: 1.05, 4.6), and beclometasone (OR: 1.7; 95% CI: 1.1, 2.6) were observed with an increased pneumonia risk compared to placebo. Fluticasone (OR: 1.5; 95% CI: 1.3, 1.7) was observed with an increased risk of serious pneumonia. High doses (OR: 1.2; 95% CI: 1.03, 1.4), BMI ≥ 25kg/m2 (OR: 1.6; 95% CI: 1.1, 2.2), and history of exacerbations in the preceding year predicted the pneumonia risk. Evidence strength was moderate. ICS class differences in pneumonia risk were observed in terms of pooled effect estimates but it is unlikely that any clinically relevant differences exist. Risk-benefit analysis supports ICS use in moderate-severe COPD.

Explicate molecular landscape of combined pulmonary fibrosis and emphysema through explainable artificial intelligence: a comprehensive analysis of ILD and COPD interactions using RNA from whole lung homogenates.

Combined pulmonary fibrosis and emphysema (CPFE) presents a unique challenge in respiratory disorders, merging features of interstitial lung disease (ILD) and chronic obstructive pulmonary disease (COPD). Using the random forest algorithm, our study thoroughly examines the molecular details of CPFE. Analyzing gene expression datasets from GSE47460 (ILD: 254, COPD: 220, control: 108), we identify key genes namely ADRB2, CDH3, IRS2, MATN3, CD38, PDIA4, VEGFC, and among twenty others, crucial in airway regulation, lung function, and apoptosis, shaping the complex pathogenesis of CPFE. Additionally, miRNAs (hsa-mir-101-3p, hsa-mir-1343-3p, hsa-mir-27a-3p, and miR-16-5p) showcase regulatory impacts on CPFE-related molecular pathways. Our machine learning model unveils these intricate interactions, offering a comprehensive insight into CPFE's molecular mechanisms. This research not only pinpoints potential therapeutic targets and biomarkers but also opens avenues for innovative approaches in managing CPFE, linking ILD and COPD within this complex respiratory condition.

Anti-inflammatory effect of Anadenanthera colubrina var. cebil (Griseb.) Altschul in experimental elastase-induced pulmonary emphysema in rats

Ethnopharmacological relevanceMedicinal plants have shown promise in the search for new treatments of pulmonary emphysema. Anadenanthera colubrina, a species native to the Caatinga biome in northeastern Brazil, is widely recognized and traditionally employed in the treatment of pulmonary diseases. Many studies corroborate popular knowledge about the medicinal applications of A. colubrina, which has demonstrated a remarkable variety of pharmacological properties, however, its anti-inflammatory and antioxidant properties are highlighted. Aim of the studyThe objective of this study was to investigate the anti-inflammatory potential of the crude hydroethanolic extract of A. colubrina var. cebil (Griseb.) Altschul on pulmonary emphysema in rats as well as to determine its potential genotoxic and cytotoxic effects using the micronucleus assay. Materials and methodsThe stem bark of the plant was collected in Pimenteiras-PI and sample was extracted by maceration using 70% ethanol. A portion of the extract underwent phytochemical analyses using TLC and HPLC. In this study, 8-week-old, male Wistar rats weighing approximately ±200 g was utilized following approval by local ethics committee for animal experimentation (No. 718/2022). Pulmonary emphysema was induced through orotracheal instillation of elastase, and treatment with A. colubrina extract or dexamethasone (positive control) concomitantly during induction. Twenty-eight days after the initiation of the protocol, plasma was used for cytokine measurement. Bronchoalveolar lavage (BAL) was used for leukocyte count. After euthanasia, lung samples were processed for histological analysis and quantification of oxidative stress markers. The micronucleus test was performed by evaluating the number of polychromatic erythrocytes (PCE) with micronuclei (MNPCE) to verify potential genotoxic effects of A. colubrina. A differential count of PCE and normochromatic erythrocytes (NCE) was performed to verify the potential cytotoxicity of the extract. Parametric data were subjected to normality analysis and subsequently to analysis of variance and Tukey or Dunnett post-test, non-parametric data were treated using the Kruskal-Wallis test with Dunn's post-test for unpaired samples. P value < 0.05 were considered significant. ResultsThe A. colubrina extract did not show a significant increase in the number of MNPCE (p > 0.05), demonstrating low genotoxicity. No changes were observed in the PCE/NCE ratio of treated animals, compared with the vehicle, suggesting low cytotoxic potential of the extract. A significant reduction (p < 0.05) in neutrophilic inflammation was observed in the lungs of rats treated with the extract, evidenced by presence of these cells in both the tissue and BAL. The extract also demonstrated pulmonary antioxidant activity, with a significant decrease (p < 0.05) in myeloperoxidase, malondialdehyde, and nitrite levels. TNFα, IL-1β, and IL-6 levels, as well as alveolar damage, were significantly reduced in animals treated with A. colubrina extract. Phytochemical analyses identified the presence of phenolic compounds and hydrolysable tannins in the A. colubrina extract. ConclusionsThe findings of this study highlights the safety of the hydroethanolic extract of Anadenanthera colubrina, and demonstrates its potential as a therapeutic approach in the treatment of emphysema. The observed properties of this medicinal plant provide an optimistic outlook in the development of therapies for the treatment of pulmonary emphysema.

Pulmonary interstitial emphysema and spontaneous pneumomediastinum are more prevalent in sighthounds than other dog breeds undergoing thoracic CT.

Spontaneous pneumomediastinum is an uncommon condition described in veterinary medicine with concurrent respiratory disease. It can be caused by the Macklin effect, which is when gas leaks from the alveoli into the surrounding interstitial lung tissue. Pulmonary interstitial emphysema (PIE) is the presence of gas within the pulmonary vascular sheaths and indicates the presence of the Macklin effect. In the authors' experience, spontaneous pneumomediastinum and PIE are more prevalent in sighthound dogs than in other breeds and are often considered incidental findings. This retrospective, observational, cross-sectional study compared the prevalence of PIE and subsequent pneumomediastinum in sighthound with other purebred dogs. It characterized the appearance of PIE in CT and analyzed a possible association with concomitant pulmonary pathologies or with the use of general anesthesia. Medical records and thoracic CTs of sighthounds and nonsighthound dogs from two institutions were reviewed. A total of 256 dogs, comprising 127 sighthounds and 129 other purebred dogs, were included. The prevalence of PIE and pneumomediastinum was statistically higher in sighthound (14.2%) compared with other nonsighthound dogs (2.2%). There was no statistical association between the presence of PIE and pneumomediastinum with different age and weight groups or with sex. There was no statistical difference in the prevalence of PIE and pneumomediastinum between dogs with and without pulmonary pathology or in dogs undergoing CT with sedation or general anesthesia. Spontaneous pneumomediastinum in sighthounds is more prevalent than in other breeds, and its prevalence is not associated with the presence of pulmonary pathology or the use of general anesthesia.

Pulmonary Interstitial Emphysema in an Infant with Critical Congenital Heart Defect Associated with TNNC1 Gene Mutation and 22q11.2 Microdeletion: A Case Report

Pulmonary Interstitial Emphysema in an Infant with Critical Congenital Heart Defect Associated with TNNC1 Gene Mutation and 22q11.2 Microdeletion: A Case Report

Detection of early pulmonary emphysema by multi-contrast x-ray Talbot-Lau interferometer.

Pulmonary emphysema is a part of chronic obstructive pulmonary disease, which is an irreversible chronic respiratory disease. In order to avoid further damage to lung tissue, early diagnosis and treatment of pulmonary emphysema is essential. Early pulmonary emphysema diagnosis is difficult with conventional radiographic imaging. Recently, x-ray phase contrast imaging has proved to be an effective and promising imaging strategy for soft tissue, due to its high sensitivity and multi-contrast. The aim of this study is to diagnose pulmonary emphysema early utilizing an x-ray Talbot-Lau interferometer (TLI). We successfully established the mouse model of emphysema by porcine pancreatic elastase treatment, and then used the established x-ray TLI to perform imaging experiments on the mice with different treatment time. The traditional absorption CT and phase contrast CT were obtained simultaneously through TLI. The CT results and histopathology of mice lung in different treatment time were quantitatively analyzed. By imaging mice lungs, it can be found that phase contrast has higher sensitivity than absorption contrast in early pulmonary emphysema. The results show that the phase contrast signal could distinguish the pulmonary emphysema earlier than the conventional attenuation signal, which can be consistent with histological images. Through the quantitative analysis of pathological section and phase contrast CT, it can be found that there is a strong linear correlation. In this study, we quantitatively analyze mean linear intercept of histological sections and CT values of mice. The results show that the phase contrast signal has higher imaging sensitivity than the attenuation signal. X-ray TLI multi-contrast imaging is proved as a potential diagnostic method for early pulmonary emphysema in mice.

Development and Application of a Virtual Imaging Trial Framework for Longitudinal Quantification of Emphysema in CT.

Pulmonary emphysema is a progressive lung disease that requires accurate evaluation for optimal management. This task, possible using quantitative CT, is particularly challenging as scanner and patient attributes change over time, negatively impacting the CT-derived quantitative measures. Efforts to minimize such variations have been limited by the absence of ground truth in clinical data, thus necessitating reliance on clinical surrogates, which may not have one-to-one correspondence to CT-based findings. This study aimed to develop the first suite of human models with emphysema at multiple time points, enabling longitudinal assessment of disease progression with access to ground truth. A total of 14 virtual subjects were modeled across three time points. Each human model was virtually imaged using a validated imaging simulator (DukeSim), modeling an energy-integrating CT scanner. The models were scanned at two dose levels and reconstructed with two reconstruction kernels, slice thicknesses, and pixel sizes. The developed longitudinal models were further utilized to demonstrate utility in algorithm testing and development. Two previously developed image processing algorithms (CT-HARMONICA, EmphysemaSeg) were evaluated. The results demonstrated the efficacy of both algorithms in improving the accuracy and precision of longitudinal quantifications, from 6.1±6.3% to 1.1±1.1% and 1.6±2.2% across years 0-5. Further investigation in EmphysemaSeg identified that baseline emphysema severity, defined as >5% emphysema at year 0, contributed to its reduced performance. This finding highlights the value of virtual imaging trials in enhancing the explainability of algorithms. Overall, the developed longitudinal human models enabled ground-truth based assessment of image processing algorithms for lung quantifications.

Evaluation of pulmonary imaging data by radiography in children with bronchopulmonary dysplasia

Introduction. According to specialized literature, X-rays are also used in the diagnosis and suspicion of chronic bronchopulmonary disease (bronchopulmonary dysplasia (BPD), in premature children. Material and methods. The study included 105 premature babies who were divided into the study group – premature babies with bronchopulmonary dysplasia (BPD) and the control group – premature babies without BPD. Data were statistically analyzed using Microsoft Excel, MedCalc, SPSS and Contingency Table Analysis as a method of evaluating the performance of a diagnostic test. Results. Radiological changes of discoidal atelectasis type in subjects with BPD were detected in 49.1% in the basic group versus 13.5% in the control group (χ2 = 15.431; p &lt; 0.0001), subsegmental ones 47.2% vs 25.0% (χ2 = 5.586; p = 0.018); pulmonary emphysema areas 62.3% vs 5.8% (χ2 = 37.182; p &lt; 0.0001), opaque fibrosis sectors 50.9% vs 11.5% (χ2 = 18.911; p &lt; 0.0001); signs of pulmonary hypertransparency 47.2% vs 1.9% (χ2 = 28.843; p &lt; 0.0001); microcystic formations 41.5% vs 5.8% (χ2 = 18.482; p &lt; 0.0001). Depending on the severity degrees of BPD, changes such as discoidal atelectasis were noted, in those with mild grade – 50% medium grade – 38.5%, severe grade – 56.3% (χ2 = 16.502; p &lt; 0.001), subsegmental atelectasis 41.7%, vs 38.5% (χ2 = 7.956; p = 0.047), pulmonary emphysema areas 58.3%, vs 38.5%, vs 87.5% (χ2 = 45.138; p &lt; 0.0001); microcystic formations, 33.3%, vs 53.8%, vs 43.8% (χ2 = 20.502; p &lt; 0.0001). Conclusions. The changes recorded on radiological examination in mild, moderate, and severe cases of BPD in premature babies are of the type discoidal atelectasis, areas of emphysema, opaque sectors of fibrosis, pulmonary hypertransparency, microcystic formations.

Smoking Related Diseases, Combined Pulmonary Emphysema, and Fibrosis

Smoking Related Diseases, Combined Pulmonary Emphysema, and Fibrosis

(1266) - Bilateral Lung Transplantation for Pulmonary Emphysema Associated with Cutis Laxa

(1266) - Bilateral Lung Transplantation for Pulmonary Emphysema Associated with Cutis Laxa

Advanced Diagnostic Tools in Hypothermia-Related Fatalities-A Pathological Perspective.

Although classical gross features are known in hypothermia victims, they lack specific diagnosis features. The aim of our study was to reveal specific brain and lung pathological features in a group of hypothermia-related fatalities. The study group comprised 107 cases from our files associated with hypothermia. Routine hematoxylin-eosin (H&E) staining and postmortem immunohistochemistry were performed. The microscopic cerebral exam revealed diffuse perineuronal and perivascular edema, gliosis, mononuclear cell infiltration, acute brain injuries, focal neuronal ischemia, lacunar infarction, and variable hemorrhages. Variable alveolar edema, pulmonary emphysema, intra-alveolar and/or pleural hemorrhage, and bronchopneumonia, as well as other pre-existing lesions, were identified in lung tissue samples. Glial cells displayed S100β expression, while neurons showed moderate Hsp70 immunopositivity. Alveolar basal membranes exhibited diffuse ICAM-1 positive expression, while ICAM-1 and AQP-1 positivity was observed in the alveolar septum vascular endothelium. Statistical analysis revealed a significant correlation between S100β and Hps70 immunoexpression and cerebral pathological features, between ICAM-1 immunoexpression and alveolar edema and pulmonary emphysema, and between AQP-1 immunoexpression and pulmonary emphysema. Our results add supplementary data to brain and lung pathological findings in hypothermia-related fatalities, with potential therapeutic value in hypothermia patients.

Astaxanthin attenuates cigarette smoke-induced small airway remodeling via the AKT1 signaling pathway

BackgroundAstaxanthin (AXT) is a keto-carotenoid with a variety of biological functions, including antioxidant and antifibrotic effects. Small airway remodeling is the main pathology of chronic obstructive pulmonary disease (COPD) and is caused by epithelial-to-mesenchymal transition (EMT) and fibroblast differentiation and proliferation. Effective therapies are still lacking. This study aimed to investigate the role of AXT in small airway remodeling in COPD and its underlying mechanisms.MethodsFirst, the model of COPD mice was established by cigarette smoke (CS) exposure combined with intraperitoneal injection of cigarette smoke extract (CSE). The effects of AXT on the morphology of CS combined with CSE -induced emphysema, EMT, and small airway remodeling by using Hematoxylin-eosin (H&E) staining, immunohistochemical staining, and western blot. In addition, in vitro experiments, the effects of AXT on CSE induced-EMT and fibroblast function were further explored. Next, to explore the specific mechanisms underlying the protective effects of AXT in COPD, potential targets of AXT in COPD were analyzed using network pharmacology. Finally, the possible mechanism was verified through molecular docking and in vitro experiments.ResultsAXT alleviated pulmonary emphysema, EMT, and small airway remodeling in a CS combined with CSE -induced mouse model. In addition, AXT inhibited the EMT process in airway cells and the differentiation and proliferation of fibroblasts. Mechanistically, AXT inhibited myofibroblast activation by directly binding to and suppressing the phosphorylation of AKT1. Therefore, our results show that AXT protects against small airway remodeling by inhibiting AKT1.ConclusionsThe present study identified and illustrated a new food function of AXT, indicating that AXT could be used in the therapy of COPD-induced small airway remodeling.