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The Yale Journal of Biology and Medicine Mar 2023: We aim to comprehensively describe the transcriptional activity and signaling of pulmonary parenchymal and immune cells before and after cardiopulmonary bypass (CPB)...
Integrated Analysis of Tracheobronchial Fluid from Before and After Cardiopulmonary Bypass Reveals Activation of the Integrated Stress Response and Altered Pulmonary Microvascular Permeability.
: We aim to comprehensively describe the transcriptional activity and signaling of pulmonary parenchymal and immune cells before and after cardiopulmonary bypass (CPB) by using a multi-omic approach coupled with functional cellular assays. We hypothesize that key signaling pathways from specific cells within the lung alter pulmonary endothelial cell function resulting in worsening or improving disease. : We collected serial tracheobronchial lavage samples from intubated patients less than 2-years-old undergoing surgery with CPB. Samples were immediately processed for single cell RNA sequencing (10x Genomics). Cell clustering, cell-type annotation, and visualization were performed, and differentially expressed genes (DEG) between serial samples were identified. Metabolomic and proteomic analyses were performed on the supernatant using mass spectrometry and a multiplex assay (SomaScan) respectively. Functional assays were done using electric cell-substrate impedance sensing to measure resistance across human pulmonary microvascular endothelial cells (HPMECs). : Analysis of eight patients showed a heterogeneous mixture of pulmonary parenchymal and immune cells. Cell clustering demonstrated time-dependent changes in the transcriptomic signature indicating altered cellular phenotypes after CPB. DEG analysis was represented by genes involved in host defense, innate immunity, and the mitochondrial respiratory transport chain. Ingenuity pathway analysis showed upregulation of the integrated stress response across all cell types after CPB. Metabolomic analysis demonstrated upregulation of ascorbate and aldarate metabolism. Unbiased proteomic analysis revealed upregulation of proteins involved in cytokine and chemokine pathways. Post-CPB patient supernatant improved HMPEC barrier function, suggesting a protective cellular response to CPB. : Children who undergo CPB for cardiac surgery have distinct cell populations, transcriptional activity, and metabolism that change over time. The response to ischemia-reperfusion injury in the lower airway of children appears to be protective, with the need to identify potential targets through future investigations.
Topics: Child; Humans; Child, Preschool; Cardiopulmonary Bypass; Endothelial Cells; Capillary Permeability; Proteomics; Lung
PubMed: 37009190
DOI: 10.59249/KFYZ8002 -
Journal of Visualized Experiments : JoVE Feb 2021Fetal tracheal occlusion (TO), an established treatment modality, promotes fetal lung growth and survival in severe congenital diaphragmatic hernia (CDH). Following TO,...
Fetal tracheal occlusion (TO), an established treatment modality, promotes fetal lung growth and survival in severe congenital diaphragmatic hernia (CDH). Following TO, retention of the secreted epithelial fluid increases luminal pressure and induces lung growth. Various animal models have been defined to understand the pathophysiology of CDH and TO. All have their own advantages and disadvantages such as the difficulty of the technique, the size of the animal, cost, high mortality rates, and the availability of genetic tools. Herein, a novel transuterine model of murine fetal TO is described. Pregnant mice were anesthetized, and the uterus exposed via a midline laparotomy. The trachea of selected fetuses were ligated with a single transuterine suture placed behind the trachea, one carotid artery, and one jugular vein. The dam was closed and allowed to recover. Fetuses were collected just before parturition. Lung to body weight ratio in TO fetuses was higher than that in control fetuses. This model provides researchers with a new tool to study the impact of both TO and increased luminal pressure on lung development.
Topics: Animals; Embryo, Mammalian; Female; Fetoscopy; Fetus; Hernias, Diaphragmatic, Congenital; Lung; Mice; Models, Animal; Pregnancy; Trachea
PubMed: 33616107
DOI: 10.3791/61772 -
Computed Tomography-Guıded Tru-Cut Bıopsy in the Dıagnosıs of Lung Lesıons; Our Clınıcal Experience.Asian Pacific Journal of Cancer... Sep 2023CT-guided tru-cut biopsy, which is less invasive and cost-effective, is an important diagnostic tool with high accuracy in lesions located peripherally in the lung. In...
INTRODUCTION
CT-guided tru-cut biopsy, which is less invasive and cost-effective, is an important diagnostic tool with high accuracy in lesions located peripherally in the lung. In this article, CT-guided tru-cut biopsy experiences of thoracic surgeons are shared.
MATERIALS AND METHODS
CT-guided tru-cut biopsy was performed on 200 patients with suspected lung lesions in the thoracic surgery clinic. Diagnostic rates of biopsies, complications, factors affecting the development of complications, and complication management were examined.
RESULTS
The diagnostic rate of the biopsies was 88%. Pneumothorax developed in 19.5% and hemothorax in 1% after the procedure. There was a significant relationship between mass dimensions and total complication rates (p=0.017). The relationship between the distance among the pleura and the mass and the development of complications was significant (p<0.001). The relationship between the number of biopsies and the development of pneumothorax was significant (p=0.011). The relationship between the size of the mass and the development of pneumothorax was significant (p=0.011). In univariate binary logistic regression analysis, a significant correlation was found between the size of the mass and the development of total complications (odds ratio (OR)=0.356 (95% CI: (0.146-0.868), (p=0.023)).
DISCUSSION
In the diagnosis of lung lesions, CT-guided tru-cut biopsy is an effective diagnostic tool with high diagnostic power, with its less invasiveness, and lower cost. The increase in the lung parenchyma distance passed with the biopsy needle increased the likelihood of complications most significantly. The size of the mass and the number of biopsies also had significant effects on the development of complications.
Topics: Humans; Pneumothorax; Image-Guided Biopsy; Lung; Biopsy, Needle; Lung Neoplasms; Tomography, X-Ray Computed; Retrospective Studies
PubMed: 37774057
DOI: 10.31557/APJCP.2023.24.9.3059 -
Radiology Dec 2022Background The prevalence of chronic obstructive pulmonary disease (COPD) in women is fast approaching that in men, and women experience greater symptom burden. Although...
Background The prevalence of chronic obstructive pulmonary disease (COPD) in women is fast approaching that in men, and women experience greater symptom burden. Although sex differences in emphysema have been reported, differences in airways have not been systematically characterized. Purpose To evaluate whether structural differences in airways may underlie some of the sex differences in COPD prevalence and clinical outcomes. Materials and Methods In a secondary analyses of a multicenter study of never-, current-, and former-smokers enrolled from January 2008 to June 2011 and followed up longitudinally until November 2020, airway disease on CT images was quantified using seven metrics: airway wall thickness, wall area percent, and square root of the wall thickness of a hypothetical airway with internal perimeter of 10 mm (referred to as Pi10) for airway wall; and lumen diameter, airway volume, total airway count, and airway fractal dimension for airway lumen. Least-squares mean values for each airway metric were calculated and adjusted for age, height, ethnicity, body mass index, pack-years of smoking, current smoking status, total lung capacity, display field of view, and scanner type. In ever-smokers, associations were tested between each airway metric and postbronchodilator forced expiratory volume in 1 second (FEV)-to-forced vital capacity (FVC) ratio, modified Medical Research Council dyspnea scale, St George's Respiratory Questionnaire score, and 6-minute walk distance. Multivariable Cox proportional hazards models were created to evaluate the sex-specific association between each airway metric and mortality. Results In never-smokers ( = 420), men had thicker airway walls than women as quantified on CT images for segmental airway wall area percentage (least-squares mean, 47.68 ± 0.61 [standard error] vs 45.78 ± 0.55; difference, -1.90; = .02), whereas airway lumen dimensions were lower in women than men after accounting for height and total lung capacity (segmental lumen diameter, 8.05 mm ± 0.14 vs 9.05 mm ± 0.16; difference, -1.00 mm; < .001). In ever-smokers ( = 9363), men had greater segmental airway wall area percentage (least-squares mean, 52.19 ± 0.16 vs 48.89 ± 0.18; difference, -3.30; < .001), whereas women had narrower segmental lumen diameter (7.80 mm ± 0.05 vs 8.69 mm ± 0.04; difference, -0.89; < .001). A unit change in each of the airway metrics (higher wall or lower lumen measure) resulted in lower FEV-to-FVC ratio, more dyspnea, poorer respiratory quality of life, lower 6-minute walk distance, and worse survival in women compared with men (all < .01). Conclusion Airway lumen sizes quantified at chest CT were smaller in women than in men after accounting for height and lung size, and these lower baseline values in women conferred lower reserves against respiratory morbidity and mortality for equivalent changes compared with men. © RSNA, 2022
Topics: Female; Humans; Male; Quality of Life; Sex Characteristics; Forced Expiratory Volume; Pulmonary Disease, Chronic Obstructive; Tomography, X-Ray Computed; Lung; Dyspnea
PubMed: 35916677
DOI: 10.1148/radiol.212985 -
Fa Yi Xue Za Zhi Dec 2019Objective To investigate the differences of heart mass and lung mass in forensic autopsy cases and to explore their application value in forensic identification. Methods...
Objective To investigate the differences of heart mass and lung mass in forensic autopsy cases and to explore their application value in forensic identification. Methods The data from 1 614 autopsy cases accepted by center of Medico-legal Investigation of China Medical University between 2007 to 2016 were collected. The correlation of heart and lung mass with age, height, body weight, and body mass index (BMI), as well as differences in different causes of death were analyzed by GraphPad Prism 6.0 software. Results The heart mass and lung mass of males were higher than those of females (<0.05). The heart mass of males and females was positively correlated with age, height, body weight and body mass index (BMI) (<0.05). The heart mass of patients dying from sudden cardiac death (SCD) was significantly higher than those dying from other causes of death. The lung mass of patients dying from drowning and delayed treatment was higher than those dying from other causes of death (<0.05). Conclusion In forensic practice, measurement of the heart mass and lung mass has certain significance for differential diagnosis and diagnosis of different causes of death.
Topics: Autopsy; Cause of Death; China; Death, Sudden, Cardiac; Female; Forensic Pathology; Heart; Humans; Lung; Male; Organ Size
PubMed: 31970949
DOI: 10.12116/j.issn.1004-5619.2019.06.002 -
Scientific Reports Jun 2022The obesity-exacerbated asthma phenotype is characterized by more severe asthma symptoms and glucocorticoid resistance. The aim of this study was to standardize an...
The obesity-exacerbated asthma phenotype is characterized by more severe asthma symptoms and glucocorticoid resistance. The aim of this study was to standardize an obesity-exacerbated asthma model by a high glycemic level index (HGLI) diet and ovalbumin (OVA) sensitization and challenges in Wistar rats. Animals were divided into groups: control (Ctrl), obese (Ob), asthmatic (Asth), obese asthmatic (Ob + Asth) and obese asthmatic treated with dexamethasone (Ob + Asth + Dexa), and in vivo and in vitro functional and morphological parameters were measured. After HGLI consumption, there was an increase in body weight, fasting blood glucose, abdominal circumferences, body mass index and adiposity index. Respiratory function showed a reduction in pulmonary tidal volume and ventilation. In isolated tracheas, carbachol showed an increase in contractile efficacy in the Ob, Ob + Asth and Ob + Asth + Dexa, but mostly on Ob + Asth. Histological analysis of lungs showed peribronchovascular inflammation and smooth muscle hypertrophy and extracellular remodeling on Ob + Asth and Ob + Asth + Dexa. An obesity-exacerbated asthma model was successfully established. Therefore, this model allows further molecular investigations and the search for new therapies for the treatment and relief of symptoms of patients with obesity-induced resistant asthma.
Topics: Animals; Asthma; Humans; Lung; Models, Theoretical; Obesity; Rats; Rats, Wistar
PubMed: 35681069
DOI: 10.1038/s41598-022-13551-0 -
American Journal of Physiology.... Jun 2021Hypoxia at high altitude can constrain metabolism and performance and can elicit physiological adjustments that are deleterious to health and fitness. Hypoxic pulmonary...
Hypoxia at high altitude can constrain metabolism and performance and can elicit physiological adjustments that are deleterious to health and fitness. Hypoxic pulmonary hypertension is a particularly serious and maladaptive response to chronic hypoxia, which results from vasoconstriction and pathological remodeling of pulmonary arteries, and can lead to pulmonary edema and right ventricle hypertrophy. We investigated whether deer mice () native to high altitude have attenuated this maladaptive response to chronic hypoxia and whether evolved changes or hypoxia-induced plasticity in pulmonary vasculature might impact ventilation-perfusion (V-Q) matching in chronic hypoxia. Deer mouse populations from both high and low altitudes were born and raised to adulthood in captivity at sea level, and various aspects of lung function were measured before and after exposure to chronic hypoxia (12 kPa O, simulating the O pressure at 4,300 m) for 6-8 wk. In lowlanders, chronic hypoxia increased right ventricle systolic pressure (RVSP) from 14 to 19 mmHg ( = 0.001), in association with thickening of smooth muscle in pulmonary arteries and right ventricle hypertrophy. Chronic hypoxia also impaired V-Q matching in lowlanders (measured at rest using SPECT-CT imaging), as reflected by increased log SD of the perfusion distribution (log SD) from 0.55 to 0.86 ( = 0.031). In highlanders, chronic hypoxia had attenuated effects on RVSP and no effects on smooth muscle thickness, right ventricle mass, or V-Q matching. Therefore, evolved changes in lung function help attenuate maladaptive plasticity and contribute to hypoxia tolerance in high-altitude deer mice.
Topics: Acclimatization; Animals; Hypertension, Pulmonary; Hypoxia; Lung; Mice; Oxygen; Oxygen Consumption; Perfusion; Peromyscus
PubMed: 33826424
DOI: 10.1152/ajpregu.00282.2020 -
Advanced Drug Delivery Reviews Jan 2023Direct delivery to the lung via inhalation is arguably one of the most logical approaches to treat lung cancer using drugs. However, despite significant efforts and... (Review)
Review
Direct delivery to the lung via inhalation is arguably one of the most logical approaches to treat lung cancer using drugs. However, despite significant efforts and investment in this area, this strategy has not progressed in clinical trials. Imaging drug delivery is a powerful tool to understand and develop novel drug delivery strategies. In this review we focus on imaging studies of drug delivery by the inhalation route, to provide a broad overview of the field to date and attempt to better understand the complexities of this route of administration and the significant barriers that it faces, as well as its advantages. We start with a discussion of the specific challenges for drug delivery to the lung via inhalation. We focus on the barriers that have prevented progress of this approach in oncology, as well as the most recent developments in this area. This is followed by a comprehensive overview of the different imaging modalities that are relevant to lung drug delivery, including nuclear imaging, X-ray imaging, magnetic resonance imaging, optical imaging and mass spectrometry imaging. For each of these modalities, examples from the literature where these techniques have been explored are provided. Finally the different applications of these technologies in oncology are discussed, focusing separately on small molecules and nanomedicines. We hope that this comprehensive review will be informative to the field and will guide the future preclinical and clinical development of this promising drug delivery strategy to maximise its therapeutic potential.
Topics: Humans; Drug Delivery Systems; Lung; Pharmaceutical Preparations; Administration, Inhalation; Magnetic Resonance Imaging
PubMed: 36509173
DOI: 10.1016/j.addr.2022.114641 -
Journal of Healthcare Engineering 2021Fungal infections have become crucial factors that threaten the prognosis and survival of blood disease patients. Here, we aim to analyze the epidemiological...
Fungal infections have become crucial factors that threaten the prognosis and survival of blood disease patients. Here, we aim to analyze the epidemiological characteristics and early and advanced CT (computed tomography) manifestations of patients with invasive pulmonary fungal infections secondary to blood system diseases. 65 hospitalized patients from October 2018 to October 2020 with invasive pulmonary fungal infections secondary to blood diseases were enrolled. Blood diseases were recorded according to clinical and imaging data, and the serum galactomannan test (GM test) was conducted. Two senior radiologists analyzed the CT data and recorded the distribution of the lesions and CT signs. We analyzed and counted the first chest CT scan images of patients with nodule/mass type secondary to hematological diseases and invasive pulmonary fungal infection. The first CT nodules or mass-type lesions were statistically significant in nodule size, the number of lesions, distribution, and accompanying signs. Pulmonary fungal infection was common in both lungs during 7-day, 14-day, and 30-day follow-up CT. We also found that the nodular mass type was the main manifestation in the positive group of the GM test. Both the positive group and the negative group had the highest incidence of nodules. The incidence of air crescent signs in nodules or mass lesions in the positive group was higher than in the negative group, and the difference was statistically significant. To conclude, follow-up CT signs after antifungal treatment were highly sensitive to the early diagnosis of hematological diseases and secondary invasive pulmonary Eumycetes infection, which could be used for clinical treatment to provide help. GM test results were also related to CT manifestations such as air crescent sign, cavity, and halo sign.
Topics: Hematologic Diseases; Humans; Lung; Lung Diseases, Fungal; Tomography, X-Ray Computed
PubMed: 34630984
DOI: 10.1155/2021/3736108 -
American Journal of Physiology. Lung... Jun 2023Chronic lung disease is often accompanied by disabling extrapulmonary symptoms, notably skeletal muscle dysfunction and atrophy. Moreover, the severity of respiratory...
Chronic lung disease is often accompanied by disabling extrapulmonary symptoms, notably skeletal muscle dysfunction and atrophy. Moreover, the severity of respiratory symptoms correlates with decreased muscle mass and in turn lowered physical activity and survival rates. Previous models of muscle atrophy in chronic lung disease often modeled chronic obstructive pulmonary disease (COPD) and relied on cigarette smoke exposure and LPS stimulation, but these conditions independently affect skeletal muscle even without accompanying lung disease. Moreover, there is an emerging and pressing need to understand the extrapulmonary manifestations of long-term post-viral lung disease (PVLD) as found in COVID-19. Here, we examine the development of skeletal muscle dysfunction in the setting of chronic pulmonary disease caused by infection due to the natural pathogen Sendai virus using a mouse model of PVLD. We identify a significant decrease in myofiber size when PVLD is maximal at 49 days after infection. We find no change in the relative types of myofibers, but the greatest decrease in fiber size is localized to fast-twitch-type IIB myofibers based on myosin heavy chain immunostaining. Remarkably, all biomarkers of myocyte protein synthesis and degradation (total RNA, ribosomal abundance, and ubiquitin-proteasome expression) were stable throughout the acute infectious illness and chronic post-viral disease process. Together, the results demonstrate a distinct pattern of skeletal muscle dysfunction in a mouse model of long-term PVLD. The findings thereby provide new insights into prolonged limitations in exercise capacity in patients with chronic lung disease after viral infections and perhaps other types of lung injury. Our study used a mouse model of post-viral lung disease to study the impact of chronic lung disease on skeletal muscle. The model reveals a decrease in myofiber size that is selective for specific types of myofibers and an alternative mechanism for muscle atrophy that might be independent of the usual markers of protein synthesis and degradation. The findings provide a basis for new therapeutic strategies to correct skeletal muscle dysfunction in chronic respiratory disease.
Topics: Humans; COVID-19; Muscle, Skeletal; Lung; Pulmonary Disease, Chronic Obstructive; Muscular Atrophy
PubMed: 37130808
DOI: 10.1152/ajplung.00338.2022