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Inflammation Jun 2024Abstract-Obesity-related asthma is primarily characterized by nonallergic inflammation, with pathogenesis involving oxidative stress, metabolic imbalance, and...
Abstract-Obesity-related asthma is primarily characterized by nonallergic inflammation, with pathogenesis involving oxidative stress, metabolic imbalance, and immunoinflammatory mechanisms. M1 macrophages, which predominantly secrete pro-inflammatory factors, mediate insulin resistance and systemic metabolic inflammation in obese individuals. Concurrently, adenosine monophosphate-activated protein kinase (AMPK) serves as a critical regulator of intracellular energy metabolism and is closely associated with macrophage activation. However, their specific roles and associated mechanisms in obesity-related asthma remain to be explored. In this study, we investigated the macrophage polarization status and potential interventional mechanisms through obesity-related asthmatic models and lipopolysaccharide (LPS) -treated RAW264.7 cell with a comprehensive series of evaluations, including HE, PAS and Masson staining of lung histopathology, immunohistochemical staining, immunofluorescence technology, qRT-PCR, Western Blot, and ELISA inflammatory factor analysis. The results revealed M1 macrophage polarization in obesity-related asthmatic lung tissue alongside downregulation of AMPK expression. Under LPS stimulation, exogenous AMPK activation attenuated M1 macrophage polarization via the Janus kinase 2/ signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway. Additionally, in obesity-related asthmatic mice, AMPK activation was found to alleviate airway inflammation by regulating M1 macrophage polarization, the mechanism closely associated with the JAK2/STAT3 pathway. These findings not only advance our understanding of macrophage polarization in obesity-related asthma, but also provide new therapeutic targets for its treatment.
PubMed: 38886294
DOI: 10.1007/s10753-024-02070-x -
Computer Methods in Biomechanics and... Jun 2024Face cups form a vital component of breathing, assisting with devices that aid in artificial breathing for neonates. This study aims to evaluate the flow parameters in...
Face cups form a vital component of breathing, assisting with devices that aid in artificial breathing for neonates. This study aims to evaluate the flow parameters in the nasal cavity for two different types of face cups. The neonatal nasal cavity model was developed from CT scans using MIMICS 21.0. Two face cups, one hemispherical and the other anatomical shaped cups are developed around the nasal cavity and the airflow is simulated using ANSYS 2021 R2. Results are compared with a nasal-only model. At the nasal valve region, the highest velocity is seen for the nasal-only model which is 16.3% higher than that of the hemispherical face cup and 15.2% superior to the anatomical-shaped face cup. In addition, the decrease in pressure across the nasal-only model is 7.4 and 6.6% below that of the hemispherical cup and anatomical cup masks. The nasal resistance values across the nasal cavity are the lowest for the nasal-only model, 7.7 and 6.7% lower respectively than the hemispherical and anatomical-shaped cups. There were very minor changes in the flow parameters such as velocity, pressure and wall shear stress when comparing the hemispherical and anatomic-shaped masks for the airflow inside the nasal cavity.
PubMed: 38884320
DOI: 10.1080/10255842.2024.2367120 -
Indian Journal of Otolaryngology and... Jun 2024Tracheostomy is a surgical procedure in an emergency setting to relieve the upper airway obstruction by creating an opening in the anterior part of trachea. It can also...
Tracheostomy is a surgical procedure in an emergency setting to relieve the upper airway obstruction by creating an opening in the anterior part of trachea. It can also be done electively to wean off from a ventilator, during an elective surgery and clearance of pulmonary secretions. This study was a retrospective analysis of microbiological profile, antibiotic sensitivity & resistance pattern in patients with a tracheostomized wound. A retrospective review of the microbiological profiles of all adult patients who underwent a tracheostomy was conducted between May 2022 and May 2023 at our hospital. Based on the tracheostomy indications, patients were allocated under obstructed and non-obstructed group. Any patient with at least one positive sample was followed up quarterly for a year. The first culture result obtained was recorded at least one month following the last antibiotic dose in each quarter. Out of the 65 tracheal aspirate results obtained from 58 patients (mean age, 57.5 ± 16.48 years), the most common procedure and indications were surgical tracheostomy (72.4%) and non-obstructed causes (74.1%), respectively. Moreover, 47.7% of the culture results indicated , which showed significantly different proportions across the quarters ( = 0.006). Among obstructed patients, was the most common (35%), followed by methicillin-resistant (MRSA; 23.5%). The colonization was predominantly by gram negative bacteria Acinetobacter species, & and fungal species like followed by and non-Albicans candida.
PubMed: 38883486
DOI: 10.1007/s12070-024-04507-z -
The Journal of the Association of... May 2024Spirometry is used extensively, but airway oscillometry is gaining acceptance for evaluating obstructive airway disorders. Moderate persistent asthma requires daily... (Comparative Study)
Comparative Study
BACKGROUND
Spirometry is used extensively, but airway oscillometry is gaining acceptance for evaluating obstructive airway disorders. Moderate persistent asthma requires daily treatment with inhaled corticosteroids (ICS).
MATERIALS AND METHODS
We aimed to examine the relationship between airway oscillometry and lung volumes, which are the markers of lung physiology in obstructive airway disease and spirometry in the real-world clinical setting. A total of 72 adults with moderate persistent asthma followed up in our outpatient department from November 2021 to August 2022, and their clinical details and tests of spirometry, forced oscillation technique (FOT), and lung volumes by body plethysmography (BP) performed before and after bronchodilator administration were analyzed.
RESULTS
The mean age of the study population was 40 years, and the majority (57%) were females. FOT detected airflow limitation in 12 of the 31 patients with normal spirometry. BP detected abnormalities in more patients than both spirometry and FOT (91.6 vs 73.6%, < 0.001). Respiratory resistance 5 (R5) had a negative correlation with functional residual capacity (FRC) and total lung capacity (TLC). Reactance 5 (X5) correlated positively with inspiratory capacity (IC) and TLC and negatively with reserve volume (RV)/TLC ratio. A positive correlation was found between IC/TLC% and postbronchodilator X5 and between R5 and 19 and RV/TLC. R5 had a negative and X5 had a positive correlation with forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FEV1/FVC, and maximal mid expiratory flow rates (MMEF). ∇X5 had a negative correlation with FEV1, MMEF, and FEV1/FVC. Spirometry detected postbronchodilator responsiveness in more patients than FOT when only the R5 criterion was used and in a comparable number when the X5 criterion was added. ∇X5 and R5-R19/R5 declined significantly after bronchodilators.
CONCLUSION
We concluded that there is a moderate correlation between FOT and spirometry and lung volumes by BP. FOT and spirometry should be used together to identify airflow obstruction and postbronchodilator responsiveness in asthma. Lung volumes by BP identify more abnormalities in adults with asthma than both spirometry and FOT. Thresholds to define postbronchodilator responsiveness (PBDR) for ∇X5 and R5-R19 need to be defined.
Topics: Humans; Asthma; Female; Adult; Male; Spirometry; Middle Aged; Plethysmography, Whole Body; Oscillometry; Bronchodilator Agents; Lung Volume Measurements; Lung
PubMed: 38881107
DOI: 10.59556/japi.72.0520 -
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 -
Dental Clinics of North America Jul 2024Obstructive Sleep Apnea (OSA) is a common medical disorder and the most impacting sleep disturbance. OSA derive from the narrowing of the upper airway during sleep,... (Review)
Review
Obstructive Sleep Apnea (OSA) is a common medical disorder and the most impacting sleep disturbance. OSA derive from the narrowing of the upper airway during sleep, which result in recurrent episodes of ventilatory disturbances expressed by an increased airflow resistance (flow limitation and hypopneas) and often an absence of ventilation (apneas). The high heterogeneity in the clinical picture of OSA turns diagnostic and treatment challenging. In the last decade different phenotypes, referring to specific categories of patients that can be distinguished from others by features and related clinical meaningful attributes, were identified. Those phenotypes may predict clinically important outcomes as those deriving from MAD therapy.
Topics: Humans; Sleep Apnea, Obstructive; Mandibular Advancement; Phenotype
PubMed: 38879282
DOI: 10.1016/j.cden.2024.03.004 -
Journal of Asian Natural Products... Jun 2024One promising approach to overcome drug resistance in asthma treatments involves dual-target therapy, specifically targeting the β2 adrenergic receptor (β-AR) and...
One promising approach to overcome drug resistance in asthma treatments involves dual-target therapy, specifically targeting the β2 adrenergic receptor (β-AR) and muscarinic-3 acetylcholine receptor (MR). This study investigated the anti-asthma effects and dual-target mechanisms of glycyrrhizic acid, hesperidin, and platycodin D (GHP) from Zhisou San. GHP administration effectively attenuated OVA-induced inflammatory infiltration and overproduction of mucus in asthmatic mice. Additionally, GHP treatment significantly suppressed MR and promoted β-AR activation, resulting in the relaxation of tracheal smooth muscle. These findings concluded that GHP mitigated asthma by targeting β-AR and MR to ameliorate airway inflammation and modulate airway smooth muscle relaxation.
PubMed: 38874436
DOI: 10.1080/10286020.2024.2365442 -
Clinical Physiology and Functional... Jun 2024Expiratory flow limitation (EFL) during tidal breathing and lung hyperinflation have been identified as major decisive factors for disease status, prognosis and...
BACKGROUND
Expiratory flow limitation (EFL) during tidal breathing and lung hyperinflation have been identified as major decisive factors for disease status, prognosis and response to therapy in obstructive lung diseases.
AIM
To investigate the delta values between expiratory and inspiratory resistance and reactance, measured using respiratory oscillometry and its correlation with air trapping and symptoms in subjects with obstructive lung diseases.
METHODS
Four hundred and seventy-one subjects (96 with chronic obstructive pulmonary disease [COPD], 311 with asthma, 30 healthy smokers and 34 healthy subjects) were included. Spirometry, body plethysmography and respiratory oscillometry measurements were performed and the differences between the expiratory and inspiratory respiratory oscillometry values (as delta values) were calculated. Questionnaires regarding symptoms and quality of life were administered.
RESULTS
Patients with COPD and healthy smokers had an increased delta resistance at 5 Hz (R5) compared with patients with asthma (p < 0.0001 and p = 0.037, respectively) and healthy subjects (p = 0.0004 and p = 0.012, respectively). Patients with COPD also had higher values of ΔR5-R19 than healthy subjects (p = 0.0001) and patients with asthma (p < 0.0001). Delta reactance at 5 Hz (X5) was significantly more impaired in COPD patients than in asthma and healthy subjects (p < 0.0001 for all). There was a correlation between the ratio of residual volume and total lung capacity and ΔR5 (p = 0.0047; r = 0.32), ΔR5-R19 (p = 0.0002; r = 0.41) and ΔX5 (p < 0.0001; r = -0.44), for all subjects. ΔX5 correlated with symptoms in COPD, healthy smokers and patients with asthma. In addition, ΔR5 correlated with asthma symptoms.
CONCLUSION
EFL was most prominent in parameters measuring peripheral resistance and reactance and correlated with air trapping and airway symptoms.
PubMed: 38873744
DOI: 10.1111/cpf.12895 -
Pathology, Research and Practice Jun 2024Lung cancer (LC) is the leading cause of cancer-related mortality, and it is caused by many factors including cigarette smoking. Despite numerous treatment strategies...
Lung cancer (LC) is the leading cause of cancer-related mortality, and it is caused by many factors including cigarette smoking. Despite numerous treatment strategies for LC, its five-year survival is still poor (<20 %), attributable to treatment resistance and lack of early diagnosis and intervention. Importantly, LC incidence is higher in patients affected by chronic respiratory diseases (CRDs) such as asthma and chronic obstructive pulmonary disorder (COPD), and LC shares with other CRDs common pathophysiological features including chronic inflammation, oxidative stress, cellular senescence, and airway remodelling. Remodelling is a complex process resulting from the aberrant activation of tissue repair secondary to chronic inflammation, oxidative stress, and tissue damage observed in the airways of CRD patients, and it is characterized by irreversible airway structural and functional alterations, concomitantly with tissue fibrosis, epithelial-to-mesenchymal transition (EMT), excessive collagen deposition, and thickening of the basement membrane. Many processes involved in remodelling, particularly EMT, are also fundamental for LC pathogenesis, highlighting a potential connection between CRDs and LC. This provides rationale for the development of novel treatment strategies aimed at targeting components of the remodelling pathways. In this study, we tested the in vitro therapeutic activity of rat fecal microbiome extract (FME) on A549 human lung adenocarcinoma cells. We show that treatment with FME significantly downregulates the expression of six proteins whose function is at the forefront between airway remodelling and LC development: Snail, SPARC, MUC-1, Osteopontin, MMP-2, and HIF-1α. The results of this study, if confirmed by further investigations, provide proof-of-concept for a novel approach in the treatment of LC, focused on tackling the airway remodelling mechanisms underlying the increased susceptibility to develop LC observed in CRD patients.
PubMed: 38870713
DOI: 10.1016/j.prp.2024.155387