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BMC Veterinary Research May 2020Constitutive and inducible defenses protect the respiratory tract from bacterial infection. The objective of this study was to characterize the response to an...
BACKGROUND
Constitutive and inducible defenses protect the respiratory tract from bacterial infection. The objective of this study was to characterize the response to an aerosolized lysate of killed bacteria, as a basis for studying the regulation and in vivo effects of these inducible innate immune responses.
RESULTS
Bacterial lysate consisting of heat-killed and sonicated Staphylococcus aureus and Escherichia coli was aerosolized to 6 calves and systemic and pulmonary innate immune and inflammatory responses were measured in the first 24 h relative to baseline. Evaluated parameters included clinical parameters (body temperature and heart and respiratory rates), blood acute phase proteins and leukocyte counts, and leukocytes and proteins in bronchoalveolar lavage fluid. Mild clinical signs with increased heart rates and rectal temperatures developed following administration of the lysate, with resolution by 24 h. Serum haptoglobin and plasma fibrinogen concentrations were elevated at 24 h relative to baseline. Bronchoalveolar lavage fluid (BALF) had increased cellularity and increased proportion of neutrophils, as well as higher concentrations of interleukin (IL)-8, IL-10 and total protein at 24 h relative to baseline. Mass spectrometry identified 965 unique proteins in BALF: 19 proteins were increased and 26 proteins were decreased relative to baseline. The upregulated proteins included those involved in innate immunity including activation of complement, neutrophils and platelets. At postmortem examination, calves receiving higher doses of lysate had areas of lobular consolidation and interlobular edema. Histologically, neutrophils were present within bronchioles and to a lesser extent within alveoli. Calves receiving highest doses of lysate had patchy areas of neutrophils, hemorrhage and hyaline membranes within alveoli.
CONCLUSIONS
Aerosolization of bacterial lysate stimulated an innate immune response in lungs and airways, with alveolar damage observed at higher doses. Such a stimulus could be of value for investigating the effects of inducible innate immune responses on occurrence of disease, or for evaluating how stress, drugs or genetics affect these dynamic responses of the respiratory tract.
Topics: Acute-Phase Proteins; Aerosols; Animals; Body Temperature; Bronchoalveolar Lavage Fluid; Cattle; Escherichia coli; Heart Rate; Immunity, Innate; Leukocyte Count; Lung; Male; Respiratory Rate; Staphylococcus aureus
PubMed: 32471444
DOI: 10.1186/s12917-020-02383-7 -
American Journal of Physiology. Lung... Jun 2022Imatinib, a tyrosine kinase inhibitor, attenuates pulmonary edema and inflammation in lung injury. However, the physiological effects of this drug and their impact on...
Imatinib, a tyrosine kinase inhibitor, attenuates pulmonary edema and inflammation in lung injury. However, the physiological effects of this drug and their impact on outcomes are poorly characterized. Using serial computed tomography (CT), we tested the hypothesis that imatinib reduces injury severity and improves survival in ventilated rats. Hydrochloric acid (HCl) was instilled in the trachea (pH 1.5, 2.5 mL/kg) of anesthetized, intubated supine rats. Animals were randomized ( = 17 each group) to receive intraperitoneal imatinib or vehicle immediately prior to HCl. All rats then received mechanical ventilation. CT was performed hourly for 4 h. Images were quantitatively analyzed to assess the progression of radiological abnormalities. Injury severity was confirmed via hourly blood gases, serum biomarkers, bronchoalveolar lavage (BAL), and histopathology. Serial blood drug levels were measured in a subset of rats. Imatinib reduced mortality while delaying functional and radiological injury progression: out of 17 rats per condition, 2 control vs. 8 imatinib-treated rats survived until the end of the experiment ( = 0.02). Imatinib attenuated edema after lung injury ( < 0.05), and survival time in both groups was negatively correlated with increased lung mass ( = 0.70) as well as other physiological and CT parameters. Capillary leak (BAL protein concentration) was significantly lower in the treated group ( = 0.04). Peak drug concentration was reached after 70 min, and the drug half-life was 150 min. Imatinib decreased both mortality and lung injury severity in mechanically ventilated rats. Pharmacological inhibition of edema could be used during mechanical ventilation to improve the severity and outcome of lung injury.
Topics: Animals; Hydrochloric Acid; Imatinib Mesylate; Lung; Lung Injury; Pulmonary Edema; Rats; Respiration, Artificial
PubMed: 35438574
DOI: 10.1152/ajplung.00006.2022 -
Computational and Mathematical Methods... 2022This study retrospectively analyzed the clinical diagnosis, treatment process, and laboratory test data of patients with pulmonary cryptococcosis to improve the...
OBJECTIVE
This study retrospectively analyzed the clinical diagnosis, treatment process, and laboratory test data of patients with pulmonary cryptococcosis to improve the understanding and diagnosis and treatment ability of the disease.
METHODS
Patients with pulmonary cryptococcosis diagnosed in the First Affiliated Hospital of Dalian Medical University from October 2003 to July 2021 were selected, and their medical records were consulted. The general data, clinical manifestations, laboratory examinations, imaging characteristics, diagnosis, and treatment methods were studied. The software SPSS 22 was used for statistical analysis.
RESULTS
A total of 50 patients with pulmonary cryptococcosis were included in the study. The ratio of male to female was 1 : 1. The average age was 53.56 ± 11.99 years with a range of 27-82 years. Grouping the patients by age, with 10 years as an age group, we found that 40-60 years was the high-incidence age group. Two patients (4%) had a history of bird contact, and 18 patients (36%) had at least one underlying conditions. Hypertension and cough were the most common underlying condition and clinical manifestation, respectively. The main admission diagnoses were lung shadow (19/50, 38%) and chest/lung mass (15/50, 30%). In the imaging findings, the most common type of lesions was nodule/nodule shadow (29/69, 42.03%). Lesion distribution in the lower lobe, single lobe, and right lung was more frequent than that in the upper lobe, multilobes, and left lung, respectively. Burr sign (12/43, 27.91%) was the most common concomitant sign. Pulmonary ventilatory defect was found in 7 cases. Laboratory test results were largely nonspecific. The pathological examination showed granuloma, with 47 cases (94%) confirmed by postoperative biopsy. Two cases (4%) were confirmed by serology. One case (2%) was diagnosed with smear. 43 cases (86%) were treated with simple surgical resection, 6 cases (12%) were treated with antifungal drugs, and 1 case (2%) was transferred to another hospital for suspicion of pulmonary tuberculosis.
CONCLUSIONS
Pulmonary cryptococcosis is more common in the middle-aged and elderly, and the clinical specificity is low. It can occur in people with normal or impaired immune function. The main clinical and imaging manifestation is cough and pulmonary nodules, which are very easy 5to be misdiagnosed. Surgical resection is the primary treatment.
Topics: Adult; Aged; Aged, 80 and over; Child; Cough; Cryptococcosis; Female; Humans; Lung; Lung Diseases, Fungal; Male; Middle Aged; Retrospective Studies
PubMed: 35924106
DOI: 10.1155/2022/7981472 -
Radiology Feb 2023In the 3rd year of the SARS-CoV-2 pandemic, much has been learned about the long-term effects of COVID-19 pneumonia on the lungs. Approximately one-third of patients... (Review)
Review
In the 3rd year of the SARS-CoV-2 pandemic, much has been learned about the long-term effects of COVID-19 pneumonia on the lungs. Approximately one-third of patients with moderate-to-severe pneumonia, especially those requiring intensive care therapy or mechanical ventilation, have residual abnormalities at chest CT 1 year after presentation. Abnormalities range from parenchymal bands to bronchial dilation to frank fibrosis. Less is known about the long-term pulmonary vascular sequelae, but there appears to be a persistent, increased risk of venothromboembolic events in a small cohort of patients. Finally, the associated histologic abnormalities resulting from SARS-CoV-2 infection are similar to those seen in patients with other causes of acute lung injury.
Topics: Humans; COVID-19; SARS-CoV-2; Lung; Pneumonia; Thorax
PubMed: 36040336
DOI: 10.1148/radiol.221806 -
International Journal of Molecular... Sep 2021Advancements in cancer therapy increased the cancer free survival rates and reduced the malignant related deaths. Therapeutic options for patients with thoracic cancers... (Review)
Review
Advancements in cancer therapy increased the cancer free survival rates and reduced the malignant related deaths. Therapeutic options for patients with thoracic cancers include surgical intervention and the application of chemotherapy with ionizing radiation. Despite these advances, cancer therapy-related cardiopulmonary dysfunction (CTRCPD) is one of the most undesirable side effects of cancer therapy and leads to limitations to cancer treatment. Chemoradiation therapy or immunotherapy promote acute and chronic cardiopulmonary damage by inducing reactive oxygen species, DNA damage, inflammation, fibrosis, deregulation of cellular immunity, cardiopulmonary failure, and non-malignant related deaths among cancer-free patients who received cancer therapy. CTRCPD is a complex entity with multiple factors involved in this pathogenesis. Although the mechanisms of cancer therapy-induced toxicities are multifactorial, damage to the cardiac and pulmonary tissue as well as subsequent fibrosis and organ failure seem to be the underlying events. The available biomarkers and treatment options are not sufficient and efficient to detect cancer therapy-induced early asymptomatic cell fate cardiopulmonary toxicity. Therefore, application of cutting-edge multi-omics technology, such us whole-exome sequencing, DNA methylation, whole-genome sequencing, metabolomics, protein mass spectrometry and single cell transcriptomics, and 10 X spatial genomics, are warranted to identify early and late toxicity, inflammation-induced carcinogenesis response biomarkers, and cancer relapse response biomarkers. In this review, we summarize the current state of knowledge on cancer therapy-induced cardiopulmonary complications and our current understanding of the pathological and molecular consequences of cancer therapy-induced cardiopulmonary fibrosis, inflammation, immune suppression, and tumor recurrence, and possible treatment options for cancer therapy-induced cardiopulmonary toxicity.
Topics: Animals; Fibrosis; Humans; Immunomodulation; Inflammation; Lung; Myocardium; Neoplasms
PubMed: 34576287
DOI: 10.3390/ijms221810126 -
Annals of the New York Academy of... Nov 2020The threat from deliberate or accidental exposure to halogen gases is increasing, as is their industrial applications and use as chemical warfare agents. Biomarkers that...
The threat from deliberate or accidental exposure to halogen gases is increasing, as is their industrial applications and use as chemical warfare agents. Biomarkers that can identify halogen exposure, diagnose victims of exposure or predict injury severity, and enable appropriate treatment are lacking. We conducted these studies to determine and validate biomarkers of bromine (Br ) toxicity and correlate the symptoms and the extent of cardiopulmonary injuries. Unanesthetized rats were exposed to Br and monitored noninvasively for clinical scores and pulse oximetry. Animals were euthanized and grouped at various time intervals to assess brominated fatty acid (BFA) content in the plasma, lung, and heart using mass spectrometry. Bronchoalveolar lavage fluid (BALF) protein content was used to assess pulmonary injury. Cardiac troponin I (cTnI) was assessed in the plasma to evaluate cardiac injury. The blood, lung, and cardiac tissue BFA content significantly correlated with the clinical scores, tissue oxygenation, heart rate, and cardiopulmonary injury parameters. Total (free + esterified) bromostearic acid levels correlated with lung injury, as indicated by BALF protein content, and free bromostearic acid levels correlated with plasma cTnI levels. Thus, BFAs and cardiac injury biomarkers can identify Br exposure and predict the severity of organ damage.
Topics: Animals; Biomarkers; Bromine; Chemical Warfare Agents; Fatty Acids; Hydrocarbons, Brominated; Inhalation Exposure; Lung; Male; Myocardium; Rats; Rats, Sprague-Dawley; Troponin I
PubMed: 32645215
DOI: 10.1111/nyas.14422 -
Scientific Reports Mar 2023In patients with transfusion-dependent thalassemia (TDT), pulmonary function impairment has been reported but data are conflicting. Moreover, it remains unclear whether... (Observational Study)
Observational Study
In patients with transfusion-dependent thalassemia (TDT), pulmonary function impairment has been reported but data are conflicting. Moreover, it remains unclear whether pulmonary dysfunction is associated with iron overload. This study aimed to evaluate the pulmonary function in patients with TDT and to investigate the associations between pulmonary dysfunction and iron overload. It was a retrospective observational study. 101 patients with TDT were recruited for lung function tests. The most recent ferritin levels (pmol/L) and the magnetic resonance imaging (MRI) measurements of the myocardial and liver iron status, as measured by heart and liver T2* relaxation time (millisecond, ms) respectively, were retrieved from the computerized medical records. Only data within 12 months from the lung function measurement were included in the analysis. The serum ferritin, and the cardiac and liver T2* relaxation time were the surrogate indexes of body iron content. The threshold of abnormality in lung function was defined as under 80% of the predicted value. 101 subjects were recruited with a mean age of 25.1 years (standard deviation (SD) 7.9 years). Thirty-eight (38%) and five (5%) demonstrated restrictive and obstructive lung function deficits, respectively. A weak correlation of FVC %Predicted and TLC %Predicted with MRI myocardial T2* relaxation time (rho = 0.32, p = 0.03 and rho = 0.33, p = 0.03 respectively) was observed. By logistic regression, MRI cardiac T2* relaxation time was negatively associated with restrictive lung function deficit (B - 0.06; SE 0.03; Odds ratio 0.94; 95% confidence interval (CI) 0.89-0.99; p = 0.023) after adjusting for age, sex and body mass index. Restrictive pulmonary function deficit was commonly observed in patients with TDT, and the severity potentially correlates with myocardial iron content. Monitoring of lung function in this group of patients, particularly for those with iron overload, is important.
Topics: Humans; Adult; Thalassemia; Iron Overload; Iron; Lung; Ferritins
PubMed: 36871083
DOI: 10.1038/s41598-023-30784-9 -
Cells Aug 2023Club Cell Secretory Protein (CC16) plays many protective roles within the lung; however, the complete biological functions, especially regarding the pulmonary epithelium...
Club Cell Secretory Protein (CC16) plays many protective roles within the lung; however, the complete biological functions, especially regarding the pulmonary epithelium during infection, remain undefined. We have previously shown that CC16-deficient (CC16) mouse tracheal epithelial cells (MTECs) have enhanced Mp burden compared to CC16-sufficient (WT) MTECs; therefore, in this study, we wanted to further define how the pulmonary epithelium responds to infection in the context of CC16 deficiency. Using mass spectrometry and quantitative proteomics to analyze proteins secreted apically from MTECs grown at an air-liquid interface, we investigated the protective effects that CC16 elicits within the pulmonary epithelium during (Mp) infection. When challenged with Mp, WT MTECs have an overall reduction in apical protein secretion, whereas CC16 MTECs have increased apical protein secretion compared to their unchallenged controls. Following Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) assessment, many of the proteins upregulated from CC16 MTECS (unchallenged and during Mp infection) were related to airway remodeling, which were not observed by WT MTECs. These findings suggest that CC16 may be important in providing protection within the pulmonary epithelium during respiratory infection with Mp, which is the major causative agent of community-acquired pneumoniae.
Topics: Animals; Mice; Epithelial Cells; Epithelium; Lung; Pneumonia, Mycoplasma; Proteins; Uteroglobin; Mice, Knockout
PubMed: 37566063
DOI: 10.3390/cells12151984 -
BMJ Case Reports Mar 2021Bronchopulmonary sequestration is a rare congenital pulmonary abnormality of the lower airways, which includes an abnormal and non-functioning lung tissue not...
Bronchopulmonary sequestration is a rare congenital pulmonary abnormality of the lower airways, which includes an abnormal and non-functioning lung tissue not communicating with the tracheobronchial tree and having aberrant blood supply from systemic circulation with variable venous drainage. The incidence of sequestration is around 0.15%-6.4% of all congenital lung malformations.Common presenting features are cough and expectoration. Misdiagnosed cases may present with recurrent infections and haemoptysis. CT of the chest with contrast is the imaging modality of choice.This is a case report of a 32-year-old woman who presented with cough and haemoptysis. CT of the chest showed a multiloculated mass-like lesion in the left lower lobe with a feeding artery from coeliac plexus and venous drainage via the normal left pulmonary vein.Based on CT chest findings, diagnosis of intralobar pulmonary sequestration was made. The patient was reviewed by cardiothoracic surgeons and underwent surgical resection of the sequestrated lung.Common presenting features are cough and expectoration. Misdiagnosed cases may present with recurrent infections and haemoptysis. CT of the chest with contrast is the imaging modality of choice.
Topics: Adult; Bronchopulmonary Sequestration; Cough; Female; Hemoptysis; Humans; Lung; Tomography, X-Ray Computed
PubMed: 33653840
DOI: 10.1136/bcr-2020-239140 -
Respiratory Research May 2022Currently the only available therapies for fibrotic Interstitial Lung Disease are administered systemically, often causing significant side effects. Inhaled therapy...
BACKGROUND
Currently the only available therapies for fibrotic Interstitial Lung Disease are administered systemically, often causing significant side effects. Inhaled therapy could avoid these but to date there is no evidence that drug can be effectively delivered to distal, fibrosed lung. We set out to combine mass spectrometry and histopathology with rapid sample acquisition using transbronchial cryobiopsy to determine whether an inhaled drug can be delivered to fibrotic, distal lung parenchyma in participants with Interstitial Lung Disease.
METHODS
Patients with radiologically and multidisciplinary team confirmed fibrotic Interstitial Lung Disease were eligible for this study. Transbronchial cryobiopsies and endobronchial biopsies were taken from five participants, with Interstitial Lung Disease, within 70 min of administration of a single dose of nebulised ipratropium bromide. Thin tissue cryosections were analysed by Matrix Assisted Laser Desorption/Ionization-Mass Spectrometry imaging and correlated with histopathology. The remainder of the cryobiopsies were homogenised and analysed by Liquid Chromatography-tandem Mass Spectrometry.
RESULTS
Drug was detected in proximal and distal lung samples from all participants. Fibrotic regions were identified in research samples of four of the five participants. Matrix Assisted Laser Desorption/Ionization-Mass Spectrometry imaging showed co-location of ipratropium with fibrotic regions in samples from three participants.
CONCLUSIONS
In this proof of concept study, using mass spectrometry, we demonstrate for the first-time that an inhaled drug can deposit in distal fibrotic lung parenchyma in patients with Interstitial Lung Disease. This suggests that drugs to treat pulmonary fibrosis could potentially be administered by the inhaled route. Trial registration A prospective clinical study approved by London Camden and Kings Cross Research Ethics Committee and registered on clinicaltrials.gov (NCT03136120).
Topics: Humans; Lung; Lung Diseases, Interstitial; Mass Spectrometry; Prospective Studies; Pulmonary Fibrosis; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
PubMed: 35546672
DOI: 10.1186/s12931-022-02026-5