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IScience Jun 2024remains one of the deadliest infectious agents globally. Amidst efforts to control TB, long treatment duration, drug toxicity, and resistance underscore the need for...
remains one of the deadliest infectious agents globally. Amidst efforts to control TB, long treatment duration, drug toxicity, and resistance underscore the need for novel therapeutic strategies. Despite advances in understanding the interplay between microbiome and disease in humans, the specific role of the microbiome in predicting disease susceptibility and discriminating infection status in tuberculosis still needs to be fully investigated. We investigated the impact of infection and -specific IFNγ immune responses on airway microbiome diversity by performing TB GeneXpert and QuantiFERON-GOLD assays during the follow-up phase of a longitudinal HIV-Lung Microbiome cohort of individuals recruited from two large independent cohorts in rural Uganda. rather than IFNγ immune response mainly drove a significant reduction in airway microbiome diversity. A microbiome signature comprising , , , and accurately discriminated active TB from Latent TB and uninfected individuals.
PubMed: 38904070
DOI: 10.1016/j.isci.2024.110142 -
Frontiers in Cellular and Infection... 2024The gut microbiota plays a vital role in the development of sepsis and in protecting against pneumonia. Previous studies have demonstrated the existence of the gut-lung...
BACKGROUND
The gut microbiota plays a vital role in the development of sepsis and in protecting against pneumonia. Previous studies have demonstrated the existence of the gut-lung axis and the interaction between the gut and the lung, which is related to the prognosis of critically ill patients; however, most of these studies focused on chronic lung diseases and influenza virus infections. The purpose of this study was to investigate the effect of faecal microbiota transplantation (FMT) on -related pulmonary infection via the gut-lung axis and to compare the effects of FMT with those of traditional antibiotics to identify new therapeutic strategies.
METHODS
We divided the mice into six groups: the blank control (PBS), pneumonia-derived sepsis (KP), pneumonia-derived sepsis + antibiotic (KP + PIP), pneumonia-derived sepsis + faecal microbiota transplantation(KP + FMT), antibiotic treatment control (KP+PIP+PBS), and pneumonia-derived sepsis+ antibiotic + faecal microbiota transplantation (KP + PIP + FMT) groups to compare the survival of mice, lung injury, inflammation response, airway barrier function and the intestinal flora, metabolites and drug resistance genes in each group.
RESULTS
Alterations in specific intestinal flora can occur in the gut of patients with pneumonia-derived sepsis caused by . Compared with those in the faecal microbiota transplantation group, the antibiotic treatment group had lower levels of proinflammatory factors and higher levels of anti-inflammatory factors but less amelioration of lung pathology and improvement of airway epithelial barrier function. Additionally, the increase in opportunistic pathogens and drug resistance-related genes in the gut of mice was accompanied by decreased production of favourable fatty acids such as acetic acid, propionic acid, butyric acid, decanoic acid, and secondary bile acids such as chenodeoxycholic acid 3-sulfate, isodeoxycholic acid, taurodeoxycholic acid, and 3-dehydrocholic acid; the levels of these metabolites were restored by faecal microbiota transplantation. Faecal microbiota transplantation after antibiotic treatment can gradually ameliorate gut microbiota disorder caused by antibiotic treatment and reduce the number of drug resistance genes induced by antibiotics.
CONCLUSION
In contrast to direct antibiotic treatment, faecal microbiota transplantation improves the prognosis of mice with pneumonia-derived sepsis caused by by improving the structure of the intestinal flora and increasing the level of beneficial metabolites, fatty acids and secondary bile acids, thereby reducing systemic inflammation, repairing the barrier function of alveolar epithelial cells, and alleviating pathological damage to the lungs. The combination of antibiotics with faecal microbiota transplantation significantly alleviates intestinal microbiota disorder, reduces the selection for drug resistance genes caused by antibiotics, and mitigates lung lesions; these effects are superior to those following antibiotic monotherapy.
Topics: Animals; Gastrointestinal Microbiome; Klebsiella Infections; Klebsiella pneumoniae; Mice; Fecal Microbiota Transplantation; Anti-Bacterial Agents; Lung; Sepsis; Prognosis; Disease Models, Animal; Humans; Male; Mice, Inbred C57BL
PubMed: 38903943
DOI: 10.3389/fcimb.2024.1392376 -
BMJ Open Respiratory Research Jun 2024Asthma is a heterogeneous disease with a prevalence and severity that differs between male and female patients. (Observational Study)
Observational Study
BACKGROUND
Asthma is a heterogeneous disease with a prevalence and severity that differs between male and female patients.
QUESTION
What are differences between male and female patients with asthma with regard to asthma control, lung function, inflammation and exacerbations?
METHODS
We performed a post hoc analysis in the ATLANTIS (Assessment of Small Airways Involvement in Asthma) study, an observational cohort study including patients with asthma from nine countries with a follow-up of 1 year during which patients were characterised with measures of large and small airway function, questionnaires, inflammation and imaging. We compared differences in baseline characteristics and longitudinal outcomes between male and female patients with asthma.
RESULTS
773 patients were enrolled; 450 (58%) of these were female. At baseline, female patients with asthma were in higher Global Initiative for Asthma (GINA) steps (p=0.042), had higher Asthma Control Questionnaire 6 (F: 0.83; M: 0.66, p<0.001) and higher airway resistance as reflected by uncorrected impulse oscillometry outcomes (ie, R-R: F: 0.06; M: 0.04 kPa/L/s, p=0.002). Male patients with asthma had more severe airway obstruction (forced expiratory volume in 1 s/forced vital capacity % predicted: F: 91.95; M: 88.33%, p<0.01) and more frequently had persistent airflow limitation (F: 27%; M: 39%, p<0.001). Blood neutrophils were significantly higher in female patients (p=0.014). With Cox regression analysis, female sex was an independent predictor for exacerbations.
INTERPRETATION
We demonstrate that female patients are in higher GINA steps, exhibit worse disease control, experience more exacerbations and demonstrate higher airway resistance compared with male patients. The higher exacerbation risk was independent of GINA step and blood eosinophil level. Male patients, in turn, have a higher prevalence of persistent airflow limitation and more severe airflow obstruction. These findings show sex can affect clinical phenotyping and outcomes in asthma.
TRIAL REGISTRATION NUMBER
NCT02123667.
Topics: Humans; Asthma; Female; Male; Middle Aged; Adult; Sex Factors; Lung; Disease Progression; Forced Expiratory Volume; Respiratory Function Tests; Severity of Illness Index; Vital Capacity; Airway Resistance; Aged; Cohort Studies; Surveys and Questionnaires
PubMed: 38901877
DOI: 10.1136/bmjresp-2024-002316 -
Annals of Intensive Care Jun 2024The objective was to compare sevoflurane, a volatile sedation agent with potential bronchodilatory properties, with propofol on respiratory mechanics in critically ill...
BACKGROUND
The objective was to compare sevoflurane, a volatile sedation agent with potential bronchodilatory properties, with propofol on respiratory mechanics in critically ill patients with COPD exacerbation.
METHODS
Prospective study in an ICU enrolling critically ill intubated patients with severe COPD exacerbation and comparing propofol and sevoflurane after 1:1 randomisation. Respiratory system mechanics (airway resistance, PEEPi, trapped volume, ventilatory ratio and respiratory system compliance), gas exchange, vitals, safety and outcome were measured at inclusion and then until H48. Total airway resistance change from baseline to H48 in both sevoflurane and propofol groups was the main endpoint.
RESULTS
Sixteen patients were enrolled and were sedated for 126 h(61-228) in the propofol group and 207 h(171-216) in the sevoflurane group. At baseline, airway resistance was 21.6cmH2O/l/s(19.8-21.6) in the propofol group and 20.4cmH2O/l/s(18.6-26.4) in the sevoflurane group, (p = 0.73); trapped volume was 260 ml(176-290) in the propofol group and 73 ml(35-126) in the sevoflurane group, p = 0.02. Intrinsic PEEP was 1.5cmH2O(1-3) in both groups after external PEEP optimization. There was neither early (H4) or late (H48) significant difference in airway resistance and respiratory mechanics parameters between the two groups.
CONCLUSIONS
In critically ill patients intubated with COPD exacerbation, there was no significant difference in respiratory mechanics between sevoflurane and propofol from inclusion to H4 and H48.
PubMed: 38888818
DOI: 10.1186/s13613-024-01311-4 -
Chemosphere Jun 2024Biodiesel, a renewable diesel fuel that can be created from almost any natural fat or oil, is promoted as a greener and healthier alternative to commercial mineral...
BACKGROUND
Biodiesel, a renewable diesel fuel that can be created from almost any natural fat or oil, is promoted as a greener and healthier alternative to commercial mineral diesel without the supporting experimental data to back these claims. The aim of this research was to assess the health effects of acute exposure to two types of biodiesel exhaust, or mineral diesel exhaust or air as a control in mice. Male BALB/c mice were exposed for 2-hrs to diluted exhaust obtained from a diesel engine running on mineral diesel, Tallow biodiesel or Canola biodiesel. A room air exposure group was used as a control. Twenty-four hours after exposure, a variety of respiratory related end point measurements were assessed, including lung function, responsiveness to methacholine and airway and systemic immune responses.
RESULTS
Tallow biodiesel exhaust exposure resulted in the greatest number of significant effects compared to Air controls, including increased airway hyperresponsiveness (178.1 ± 31.3% increase from saline for Tallow biodiesel exhaust exposed mice compared to 155.8 ± 19.1 for Air control), increased airway inflammation (63463 ± 13497 cells/mL in the bronchoalveolar lavage of Tallow biodiesel exhaust exposed mice compared to 40561 ± 11800 for Air exposed controls) and indications of immune dysregulation. In contrast, exposure to Canola biodiesel exhaust resulted in fewer significant effects compared to Air controls with a slight increase in airway resistance at functional residual capacity and indications of immune dysregulation. Exposure to mineral diesel exhaust resulted in significant effects between that of the two biodiesels with increased airway hyperresponsiveness and indications of immune dysregulation.
CONCLUSION
These data show that a single, brief exposure to biodiesel exhaust can result in negative health impacts in a mouse model, and that the biological effects of exposure change depending on the feedstock used to make the biodiesel.
PubMed: 38880256
DOI: 10.1016/j.chemosphere.2024.142621 -
Journal of Translational Medicine Jun 2024Gut microbiota (GM) have been implicated as important regulators of gastrointestinal symptom which is commonly occurred along with respiratory influenza A virus (IAV)...
BACKGROUND
Gut microbiota (GM) have been implicated as important regulators of gastrointestinal symptom which is commonly occurred along with respiratory influenza A virus (IAV) infection, suggesting the involvement of the gut-to-lung axis in a host's response to IAV. IAV primarily destroys airway epithelium tight junctions (TJs) and consequently causes acute respiratory disease syndrome. It is known that GM and their metabolism produce an anti-influenza effect, but their role in IAV-induced airway epithelial integrity remains unknown.
METHODS
A mouse model of IAV infection was established. GM were analyzed using 16S rRNA gene sequencing, and short-chain fatty acids (SCFAs) levels were measured. GM depletion and fecal microbiota transplantation (FMT) were conducted to validate the role of GM in IAV infection. A pair-feeding experiment was conducted to reveal whether IAV-induced GM dysbiosis is attributed to impaired food intake. Furthermore, human bronchial epithelial (HBE) cells were cocultured with IAV in the presence or absence of acetate. TJs function was analyzed by paracellular permeability and transepithelial electronic resistance (TEER). The mechanism of how acetate affects TJs integrity was evaluated in HBE cells transfected with G protein-coupled receptor 43 (GPR43) short hairpin RNA (shRNA).
RESULTS
IAV-infected mice exhibited lower relative abundance of acetate-producing bacteria (Bacteroides, Bifidobacterium, and Akkermansia) and decreased acetate levels in gut and serum. These changes were partly caused by a decrease in food consumption (due to anorexia). GM depletion exacerbated and FMT restored IAV-induced lung inflammatory injury. IAV infection suppressed expressions of TJs (occludin, ZO-1) leading to disrupted airway epithelial barrier function as evidenced by decreased TEER and increased permeability. Acetate pretreatment activated GPR43, partially restored IAV-induced airway epithelial barrier function, and reduced inflammatory cytokines levels (TNF-α, IL-6, and IL-1β). Such protective effects of acetate were absent in HBE cells transfected with GPR43 shRNA. Acetate and GPR43 improved TJs in an AMP-activated protein kinase (AMPK)-dependent manner.
CONCLUSION
Collectively, our results demonstrated that GM protected airway TJs by modulating GPR43-AMPK signaling in IAV-induced lung injury. Therefore, improving GM dysbiosis may be a potential therapeutic target for patients with IAV infection.
Topics: Animals; Tight Junctions; Gastrointestinal Microbiome; Acetates; Humans; Lung Injury; Orthomyxoviridae Infections; Mice, Inbred C57BL; Influenza A virus; Fecal Microbiota Transplantation; Receptors, G-Protein-Coupled; Mice; Epithelial Cells; Dysbiosis; Fatty Acids, Volatile
PubMed: 38879538
DOI: 10.1186/s12967-024-05376-4 -
Scientific Reports Jun 2024Myxovirus resistance (Mx) proteins are products of interferon stimulated genes (ISGs) and Mx proteins of different species have been reported to mediate antiviral...
Myxovirus resistance (Mx) proteins are products of interferon stimulated genes (ISGs) and Mx proteins of different species have been reported to mediate antiviral activity against a number of viruses, including influenza A viruses (IAV). Ferrets are widely considered to represent the 'gold standard' small animal model for studying pathogenesis and immunity to human IAV infections, however little is known regarding the antiviral activity of ferret Mx proteins. Herein, we report induction of ferret (f)Mx1/2 in a ferret lung cell line and in airway tissues from IAV-infected ferrets, noting that fMx1 was induced to higher levels that fMx2 both in vitro and in vivo. Overexpression confirmed cytoplasmic expression of fMx1 as well as its ability to inhibit infection and replication of IAV, noting that this antiviral effect of fMx1was modest when compared to cells overexpressing either human MxA or mouse Mx1. Together, these studies provide the first insights regarding the role of fMx1 in cell innate antiviral immunity to influenza viruses. Understanding similarities and differences in the antiviral activities of human and ferret ISGs provides critical context for evaluating results when studying human IAV infections in the ferret model.
Topics: Animals; Myxovirus Resistance Proteins; Ferrets; Influenza A virus; Humans; Orthomyxoviridae Infections; Virus Replication; Antiviral Agents; Cell Line; Mice; Immunity, Innate; Lung
PubMed: 38866913
DOI: 10.1038/s41598-024-63314-2 -
Frontiers in Veterinary Science 2024To compare the cardiopulmonary effects of apneustic anesthesia ventilation (AAV) and conventional mechanical ventilation (CMV) in anesthetized pigs and to describe a new...
OBJECTIVE
To compare the cardiopulmonary effects of apneustic anesthesia ventilation (AAV) and conventional mechanical ventilation (CMV) in anesthetized pigs and to describe a new mode of ventilation for anesthetized veterinary species.
STUDY DESIGN
Randomized, crossover design without washout.
ANIMALS
Twelve healthy, female white Landrace pigs.
METHODS
Following ketamine-midazolam premedication and anesthetic induction with propofol, the trachea was intubated, and each pig was positioned in dorsal recumbency. Anesthesia was maintained with propofol and sufentanil infusions. Pigs were instrumented and their lungs were sequentially ventilated with each mode, in random order, for 1 h according to predefined criteria [fraction of inspired oxygen (FiO) = 0.21, 10 mL kg tidal volume (V), and arterial carbon dioxide tension (PaCO) within 40-45 mmHg]. Cardiopulmonary data were collected at baseline, 30 and 60 min. In 8 pigs, thoracic computed tomography (CT) was performed following the 60 min time point for each mode of ventilation and images were analyzed to quantify lung aeration. The effects of ventilation mode, time, and order were analyzed using repeated measures ANOVA. Paired -tests were used to compare lung aeration between modes. Significance was defined as < 0.05.
RESULTS
Data from 12 pigs were analyzed. A significant effect of mode was found for heart rate, mean arterial pressure (MAP), pulmonary artery occlusion pressure, cardiac index (CI), stroke volume index, systemic vascular resistance, pulmonary vascular resistance, oxygen delivery index (DOI), oxygen extraction ratio (OER), V, arterial oxygen tension, arterial hemoglobin saturation, PaCO, end-tidal carbon dioxide tension, alveolar dead space (V/V), venous admixture ( ), mean airway pressure, and dynamic compliance index (CI). Order effects were also observed for some cardiovascular and respiratory variables. For the eight pigs that underwent thoracic CT, AAV resulted in significantly larger proportions of normally and hyperaerated lung while CMV resulted in larger proportions of hypoaerated and atelectatic lung.
CONCLUSIONS
In dorsally recumbent anesthetized pigs, ventilated with FiO = 0.21, both modes of ventilation supported adequate oxygenation while AAV resulted in higher CI, and lower V/V and , compared with CMV. AAV was also associated with lower MAP, CI, and DOI and higher OER compared with CMV. Further investigation of AAV in anesthetized animals is warranted.
PubMed: 38855412
DOI: 10.3389/fvets.2024.1378617 -
Cureus May 2024Subglottic stenosis (SGS) can be asymptomatic in cases with slow-growing granulomas. In this study, we report a case of SGS discovered during tracheal intubation for...
Subglottic stenosis (SGS) can be asymptomatic in cases with slow-growing granulomas. In this study, we report a case of SGS discovered during tracheal intubation for anesthesia induction. A 74-year-old woman was scheduled for surgery under general anesthesia for a left humeral fracture. Resistance was observed when the tracheal tube passed through the glottis, stopping the tube from advancing. We placed a laryngeal mask (LMA) to secure her airway and examined it using a bronchial fiber to detect circumferential stenosis of the subglottis due to granulation. The airway was secured using an LMA instead of intubation, and the patient was successfully managed under anesthesia. Asymptomatic SGS is difficult to detect preoperatively, and anesthesiologists may encounter unexpected intubation issues. LMA is an important tool for an effective strategy to manage intubation difficulties.
PubMed: 38832207
DOI: 10.7759/cureus.59543 -
Frontiers in Pediatrics 2024Although neonatal breathing patterns vary after perinatal asphyxia, whether they change during therapeutic hypothermia (TH) remains unclear. We characterized breathing...
INTRODUCTION
Although neonatal breathing patterns vary after perinatal asphyxia, whether they change during therapeutic hypothermia (TH) remains unclear. We characterized breathing patterns in infants during TH for hypoxic-ischemic encephalopathy (HIE) and normothermia after rewarming.
METHODS
In seventeen spontaneously breathing infants receiving TH for HIE and in three who did not receive TH, we analyzed respiratory flow and esophageal pressure tracings for respiratory timing variables, pulmonary mechanics and respiratory effort. Breaths were classified as braked (inspiratory:expiratory ratio ≥1.5) and unbraked (<1.5).
RESULTS
According to the expiratory flow shape braked breaths were chategorized into early peak expiratory flow, late peak expiratory flow, slow flow, and post-inspiratory hold flow (PiHF). The most braked breaths had lower rates, larger tidal volume but lower minute ventilation, inspiratory airway resistance and respiratory effort, except for the PiHF, which had higher resistance and respiratory effort. The braked pattern predominated during TH, but not during normothermia or in the uncooled infants.
CONCLUSIONS
We speculate that during TH for HIE low respiratory rates favor neonatal braked breathing to preserve lung volume. Given the generally low respiratory effort, it seems reasonable to leave spontaneous breathing unassisted. However, if the PiHF pattern predominates, ventilatory support may be required.
PubMed: 38832000
DOI: 10.3389/fped.2024.1383689