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Frontiers in Dentistry 2023Enlarged adenoids can lead to obstruction of the nasopharyngeal airway and subsequent oral respiration. Oral breathing can cause dry mouth, dehydration in gingival...
Enlarged adenoids can lead to obstruction of the nasopharyngeal airway and subsequent oral respiration. Oral breathing can cause dry mouth, dehydration in gingival tissue, and resistance to plaque accumulation. This study aimed to evaluate the impact of tonsillectomy on oral health status, salivary pH and flow rate, and common complications caused by tonsillar hypertrophy in children. An analytical before-and-after study was conducted on 60 children aged 5-12 years who required tonsillectomy. We gathered data through a questionnaire and collected unstimulated saliva using the spitting method for five minutes. Salivary pH was measured by a pH meter and its volume was determined with a calibrated test tube. The plaque index, bleeding index and modified gingival index were determined using a disclosing tablet, Williams' probe and observational examination, respectively. All measurements were repeated one month after tonsillectomy. Paired t-test was used for data analysis. We found a significant increase in mean pH and salivary flow rate after tonsillectomy and observed a decrease in oral health indices among the children one month after surgery. Over half of the children who reported complications such as dry mouth, itchy nose and throat, snoring, night sweats, and sleep disturbances experienced complete recovery after tonsillectomy. Based on the results obtained in the present study, children with enlarged adenoids showed significant improvements in salivary pH, salivary flow rate, and oral health indices, one month after tonsillectomy.
PubMed: 37701649
DOI: 10.18502/fid.v20i24.13168 -
Respiratory Research Mar 2024Airway basal cells (BC) from patients with chronic obstructive pulmonary disease (COPD) regenerate abnormal airway epithelium and this was associated with reduced...
BACKGROUND
Airway basal cells (BC) from patients with chronic obstructive pulmonary disease (COPD) regenerate abnormal airway epithelium and this was associated with reduced expression of several genes involved in epithelial repair. Quercetin reduces airway epithelial remodeling and inflammation in COPD models, therefore we examined whether quercetin promotes normal epithelial regeneration from COPD BC by altering gene expression.
METHODS
COPD BC treated with DMSO or 1 µM quercetin for three days were cultured at air/liquid interface (ALI) for up to 4 weeks. BC from healthy donors cultured at ALI were used as controls. Polarization of cells was determined at 8 days of ALI. The cell types and IL-8 expression in differentiated cell cultures were quantified by flow cytometry and ELISA respectively. Microarray analysis was conducted on DMSO or 1 µM quercetin-treated COPD BC for 3 days to identify differentially regulated genes (DEG). Bronchial brushings obtained from COPD patients with similar age and disease status treated with either placebo (4 subjects) or 2000 mg/day quercetin (7 subjects) for 6 months were used to confirm the effects of quercetin on gene expression.
RESULTS
Compared to placebo-, quercetin-treated COPD BC showed significantly increased transepithelial resistance, more ciliated cells, fewer goblet cells, and lower IL-8. Quercetin upregulated genes associated with tissue and epithelial development and differentiation in COPD BC. COPD patients treated with quercetin, but not placebo showed increased expression of two developmental genes HOXB2 and ELF3, which were also increased in quercetin-treated COPD BC with FDR < 0.001. Active smokers showed increased mRNA expression of TGF-β (0.067) and IL-8 (22.0), which was reduced by 3.6 and 4.14 fold respectively after quercetin treatment.
CONCLUSIONS
These results indicate that quercetin may improve airway epithelial regeneration by increasing the expression of genes involved in epithelial development/differentiation in COPD.
TRIAL REGISTRATION
This study was registered at ClinicalTrials.gov on 6-18-2019. The study number is NCT03989271.
Topics: Humans; Quercetin; Interleukin-8; Dimethyl Sulfoxide; Pulmonary Disease, Chronic Obstructive; Bronchi; Epithelial Cells; Cells, Cultured; Transcription Factors; Homeodomain Proteins
PubMed: 38468259
DOI: 10.1186/s12931-024-02742-0 -
BMC Pulmonary Medicine Mar 2024Little attention has been paid to the pathophysiological changes in the natural history of chronic obstructive pulmonary disease (COPD). The destructions of the small...
BACKGROUND
Little attention has been paid to the pathophysiological changes in the natural history of chronic obstructive pulmonary disease (COPD). The destructions of the small airways were visualized on thoracic micro-computed tomography scan. We investigated whether small airway inflammation (SAI) was the risk for the development of COPD.
METHODS
A total of 1062 patients were enrolled and analyzed in the study. The partitioned airway inflammation was determined by exhaled nitric oxide (NO) of FnNO, FeNO, FeNO, and calculated CaNO. Both FeNO and CaNO were compared to detect the promising predictor for peripheral airway/alveolar inflammation in COPD. The correlation between exhaled NO and white cell classification was evaluated to determine the inflammation type during the development of COPD.
RESULTS
Exhaled NO levels (FnNO, FeNO, FeNO, and CaNO) were the highest in the COPD group compared with all other groups. Furthermore, compared with controls, exhaled NO levels (FeNO, FeNO, and CaNO) were also significantly higher in the emphysema, chronic bronchitis, and smoking groups. FeNO was found to be a promising predictor for peripheral airway/alveolar inflammation (area under the curve [AUC] of the receiver operating characteristic [ROC] curve, area under the curve [AUC] = 0.841) compared with CaNO (AUC ROC = 0.707) in COPD. FeNO was the main risk factor (adjusted odds ratio, 2.191; 95% CI, 1.797-2.671; p = 0.002) for the development of COPD. The blood eosinophil and basophil levels were correlated with FeNO and FeNO.
CONCLUSION
The complete airway inflammations were shown in COPD, whereas SAI was the main risk factor for the development of COPD, which might relate to eosinophil and basophil levels.
Topics: Humans; X-Ray Microtomography; Pulmonary Disease, Chronic Obstructive; Inflammation; Bronchitis, Chronic; Pulmonary Emphysema; Nitric Oxide
PubMed: 38443860
DOI: 10.1186/s12890-024-02911-3 -
Inflammation Research : Official... Nov 2023This study investigates the interactions between histaminergic system and glucocorticoid-induced leucin zipper (GILZ) in the inflammatory process and glucocorticoid...
INTRODUCTION
This study investigates the interactions between histaminergic system and glucocorticoid-induced leucin zipper (GILZ) in the inflammatory process and glucocorticoid modulation in lung fibrosis.
METHODS
Wild-type (WT) and GILZ Knock-Out (KO) mice were treated with bleomycin (0.05 IU) or saline, delivered by intra-tracheal injection. After surgery, mice received a continuous infusion of JNJ7777120 (JNJ, 2 mg/kg b.wt.) or vehicle for 21 days. Lung function was studied by measuring airway resistance to air insufflation through the analysis of pressure at airway opening (PAO). Lung samples were collected to evaluate the expression of histamine HR, Anx-A1, and p65-NF-kB, the activity of myeloperoxidase (MPO), and the production of pro-inflammatory cytokines.
RESULTS
Airway fibrosis and remodeling were assessed by measuring TGF-β production and α-SMA deposition. JNJ reduces PAO in WT but not in GILZ KO mice (from 22 ± 1 mm to 15 ± 0.5 and from 24 ± 1.5 to 19 ± 0.5 respectively), MPO activity (from 204 ± 3.13 pmol/mg to 73.88 ± 2.63 in WT and from 221 ± 4.46 pmol/mg to 107 ± 5.54 in GILZ KO), the inflammatory response, TGF-β production, and α-SMA deposition in comparison to WT and GILZ KO vehicle groups.
CONCLUSION
In conclusion, the role of HR and GILZ in relation to glucocorticoids could pave the way for innovative therapies to counteract pulmonary fibrosis.
Topics: Mice; Animals; Glucocorticoids; Pulmonary Fibrosis; Histamine; Transcription Factors; Anti-Inflammatory Agents; Receptors, Histamine; Transforming Growth Factor beta
PubMed: 37815550
DOI: 10.1007/s00011-023-01802-3 -
Tuberculosis and Respiratory Diseases Apr 2024: Bronchiectasis is a chronic respiratory disease that leads to airway inflammation, destruction, and airflow limitation, which reflects its severity. Impulse...
BACKGROUND
: Bronchiectasis is a chronic respiratory disease that leads to airway inflammation, destruction, and airflow limitation, which reflects its severity. Impulse oscillometry (IOS) is a non-invasive method that uses sound waves to estimate lung function and airway resistance. The aim of this study was to assess the usefulness of IOS in predicting the severity of bronchiectasis.
METHODS
: We retrospectively reviewed the IOS parameters and clinical characteristics in 145 patients diagnosed with bronchiectasis between March 2020 and May 2021. Disease severity was evaluated using the FACED score, and patients were divided into mild and moderate/severe groups.
RESULTS
: Forty-four patients (30.3%) were in the moderate/severe group, and 101 (69.7%) were in the mild group. Patients with moderate/severe bronchiectasis had a higher airway resistance at 5 Hz (R5), a higher difference between the resistance at 5 and 20 Hz (R5-R20), a higher resonant frequency (Fres), and a higher area of reactance (AX) than patients with mild bronchiectasis. R5 ≥0.43, resistance at 20 Hz (R20) ≥0.234, R5-R20 ≥28.3, AX ≥1.02, reactance at 5 Hz (X5) ≤-0.238, and Fres ≥20.88 revealed significant univariable relationships with bronchiectasis severity (p<0.05). Among these, only X5 ≤-0.238 exhibited a significant multivariable relationship with bronchiectasis severity (p=0.039). The receiver operating characteristic curve for predicting moderate- to-severe bronchiectasis of FACED score based on IOS parameters exhibited an area under the curve of 0.809.
CONCLUSION
: The IOS assessed by the disease severity of FACED score can effectively reflect airway resistance and elasticity in bronchiectasis patients and serve as valuable tools for predicting bronchiectasis severity.
PubMed: 38783483
DOI: 10.4046/trd.2023.0160 -
Food and Chemical Toxicology : An... Jan 2024Exposure to particulate matter is currently recognized as a serious aggravating factor of respiratory diseases. In this study, we investigated the effects of particulate...
Particulate matter-mediated oxidative stress induces airway inflammation and pulmonary dysfunction through TXNIP/NF-κB and modulation of the SIRT1-mediated p53 and TGF-β/Smad3 pathways in mice.
Exposure to particulate matter is currently recognized as a serious aggravating factor of respiratory diseases. In this study, we investigated the effects of particulate matter (PM) on the respiratory system in BALB/c mice and NCI-H292 cells. PM (0, 2.5, 5 and 20 mg/kg) was administered to mice by intra-tracheal instillation for 7 days. After a 7 day-repeated treatment of PM, we evaluated inflammatory cytokines/cell counts in bronchoalveolar lavage fluid (BALF) and conducted pulmonary histology and functional test. We also investigated the role of TXNIP/NF-κB and SIRT1-mediated p53 and TGF-β/Smad3 pathways in PM-induced airway inflammation and pulmonary dysfunction. PM caused a significant increase in pro-inflammatory cytokines, inflammatory cell counts in bronchoalveolar lavage fluid. PM-mediated oxidative stress down-regulated thioredoxin-1 and up-regulated thioredoxin-interacting protein and activation of nuclear factor-kappa B in the lung tissue and PM-treated NCI-H292 cells. PM suppressed sirtuin1 protein levels and increased p53 acetylation in PM-exposed mice and PM-treated NCI-H292 cells. In addition, PM caused inflammatory cell infiltration and the thickening of alveolar walls by exacerbating the inflammatory response in the lung tissue. PM increased levels of transforming growth factor-β, phosphorylation of Smad3 and activation of α-smooth muscle actin, and collagen type1A2 in PM-exposed mice and PM-treated NCI-H292 cells. In pulmonary function tests, PM exposure impaired pulmonary function resembling pulmonary fibrosis, characterized by increased resistance and elastance of the respiratory system, and resistance, elastance, and damping of lung tissues, whereas decreased compliance of the respiratory system, forced expired volume and forced vital capacity. Overall, PM-mediated oxidative stress caused airway inflammation and pulmonary dysfunction with pulmonary fibrosis via TXNIP pathway/NF-κB activation and modulation of the SIRT1-mediated TGF-β/Smad3 pathways. The results of this study can provide fundamental data on the potential adverse effects and underlying mechanism of pulmonary fibrosis caused by PM exposure as a public health concern. Due to the potential toxicity of PM, people with respiratory disease must be careful with PM exposure.
Topics: Animals; Humans; Mice; Carrier Proteins; Cytokines; Inflammation; Lung; NF-kappa B; Oxidative Stress; Particulate Matter; Pulmonary Fibrosis; Respiratory Tract Diseases; Sirtuin 1; Transforming Growth Factor beta; Tumor Suppressor Protein p53; Smad3 Protein
PubMed: 38013002
DOI: 10.1016/j.fct.2023.114201 -
Current Neuropharmacology 2024Rhythmic eupneic breathing in mammals depends on the coordinated activities of the neural system that sends cranial and spinal motor outputs to respiratory muscles.... (Review)
Review
Rhythmic eupneic breathing in mammals depends on the coordinated activities of the neural system that sends cranial and spinal motor outputs to respiratory muscles. These outputs modulate lung ventilation and adjust respiratory airflow, which depends on the upper airway patency and ventilatory musculature. Anesthetics are widely used in clinical practice worldwide. In addition to clinically necessary pharmacological effects, respiratory depression is a critical side effect induced by most general anesthetics. Therefore, understanding how general anesthetics modulate the respiratory system is important for the development of safer general anesthetics. Currently used volatile anesthetics and most intravenous anesthetics induce inhibitory effects on respiratory outputs. Various general anesthetics produce differential effects on respiratory characteristics, including the respiratory rate, tidal volume, airway resistance, and ventilatory response. At the cellular and molecular levels, the mechanisms underlying anesthetic-induced breathing depression mainly include modulation of synaptic transmission of ligand-gated ionotropic receptors (, γ-aminobutyric acid, N-methyl-D-aspartate, and nicotinic acetylcholine receptors) and ion channels (, voltage-gated sodium, calcium, and potassium channels, two-pore domain potassium channels, and sodium leak channels), which affect neuronal firing in brainstem respiratory and peripheral chemoreceptor areas. The present review comprehensively summarizes the modulation of the respiratory system by clinically used general anesthetics, including the effects at the molecular, cellular, anatomic, and behavioral levels. Specifically, analgesics, such as opioids, which cause respiratory depression and the "opioid crisis", are discussed. Finally, underlying strategies of respiratory stimulation that target general anesthetics and/or analgesics are summarized.
Topics: Animals; Humans; Anesthetics, General; Analgesics; Receptors, Nicotinic; Nervous System; Potassium Channels; Respiratory Insufficiency; Sodium; Mammals
PubMed: 37563812
DOI: 10.2174/1570159X21666230810110901 -
Respiratory Research Jul 2023Accumulating clinical evidence links Obstructive Sleep Apnea (OSA) with worse outcomes of asthma, but impact on airway function remains sparsely studied. We tested...
INTRODUCTION
Accumulating clinical evidence links Obstructive Sleep Apnea (OSA) with worse outcomes of asthma, but impact on airway function remains sparsely studied. We tested effects of Chronic Intermittent Hypoxia (CIH) - a hallmark of OSA - on airway hyperresponsiveness (AHR), in a rat model of chronic allergen-induced inflammation.
METHODS
Brown Norway rats were exposed to six weeks of CIH or normoxia (NORM) concurrent with weekly house dust mites (HDM) or saline (SAL) challenges. At endpoint, we assessed responses to seven Methacholine (Mch) doses (0, 4, 8, 16, 32, 64, 128 mg/mL) on a FlexiVent system (Scireq). Maximal (or plateau) responses (reactivity) for total respiratory system Resistance (R) and Elastance (E), Newtonian airway resistance (R a measure of central airways function) and tissue damping (G, a measure of distal airways function) were plotted.
RESULTS
HDM/CIH-treated animals demonstrated the highest reactivity to Mch in R and E compared to all other groups (HDM/NORM, SAL/CIH and SAL/NORM p < 0.05 for all comparisons, for doses 5-7 for R, and for doses 4-7 for E). The enhanced R response was due to an increase in G (doses 4-7, p < 0.05 for comparisons to all other groups), whereas R was not affected by CIH.
CONCLUSIONS
In rats chronically challenged with HDM, concurrent CIH exposure induces AHR primarily in the distal airways, which affects the respiratory system frequency-dependent elastic properties.
Topics: Rats; Animals; Pyroglyphidae; Allergens; Respiratory Hypersensitivity; Lung; Hypoxia; Methacholine Chloride; Inflammation; Sleep Apnea, Obstructive; Disease Models, Animal
PubMed: 37468919
DOI: 10.1186/s12931-023-02493-4 -
ESMO Open Aug 2023Ramucirumab plus erlotinib (RAM + ERL) demonstrated superior progression-free survival (PFS) over placebo + ERL (PBO + ERL) in the phase III RELAY study of patients... (Randomized Controlled Trial)
Randomized Controlled Trial
Ramucirumab plus erlotinib versus placebo plus erlotinib in previously untreated EGFR-mutated metastatic non-small-cell lung cancer (RELAY): exploratory analysis of next-generation sequencing results.
BACKGROUND
Ramucirumab plus erlotinib (RAM + ERL) demonstrated superior progression-free survival (PFS) over placebo + ERL (PBO + ERL) in the phase III RELAY study of patients with epidermal growth factor receptor (EGFR)-mutated metastatic non-small-cell lung cancer (EGFR+ mNSCLC; NCT02411448). Next-generation sequencing (NGS) was used to identify clinically relevant alterations in circulating tumor DNA (ctDNA) and explore their impact on treatment outcomes.
PATIENTS AND METHODS
Eligible patients with EGFR+ mNSCLC were randomized 1 : 1 to ERL (150 mg/day) plus RAM (10 mg/kg)/PBO every 2 weeks. Liquid biopsies were to be prospectively collected at baseline, cycle 4 (C4), and postdiscontinuation follow-up. EGFR and co-occurring/treatment-emergent (TE) genomic alterations in ctDNA were analyzed using Guardant360 NGS platform.
RESULTS
In those with valid baseline samples, detectable activating EGFR alterations in ctDNA (aEGFR+) were associated with shorter PFS [aEGFR+: 12.7 months (n = 255) versus aEGFR-: 22.0 months (n = 131); hazard ratio (HR) = 1.87, 95% confidence interval (CI) 1.42-2.51]. Irrespective of detectable/undetectable baseline aEGFR, RAM + ERL was associated with longer PFS versus PBO + ERL [aEGFR+: median PFS (mPFS) = 15.2 versus 11.1 months, HR = 0.63, 95% CI 0.46-0.85; aEGFR-: mPFS = 22.1 versus 19.2 months, HR = 0.80, 95% CI 0.49-1.30]. Baseline alterations co-occurring with aEGFR were identified in 69 genes, most commonly TP53 (43%), EGFR (other than aEGFR; 25%), and PIK3CA (10%). PFS was longer in RAM + ERL, irrespective of baseline co-occurring alterations. Clearance of baseline aEGFR by C4 was associated with longer PFS (mPFS = 14.1 versus 7.0 months, HR = 0.481, 95% CI 0.33-0.71). RAM + ERL improved PFS outcomes, irrespective of aEGFR mutation clearance. TE gene alterations were most commonly in EGFR [T790M (29%), other (19%)] and TP53 (16%).
CONCLUSIONS
Baseline aEGFR alterations in ctDNA were associated with shorter mPFS. RAM + ERL was associated with improved PFS outcomes, irrespective of detectable/undetectable aEGFR, co-occurring baseline alterations, or aEGFR+ clearance by C4. aEGFR+ clearance by C4 was associated with improved PFS outcomes. Monitoring co-occurring alterations and aEGFR+ clearance may provide insights into mechanisms of EGFR tyrosine kinase inhibitor resistance and the patients who may benefit from intensified treatment schedules.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Erlotinib Hydrochloride; ErbB Receptors; Lung Neoplasms; Protein Kinase Inhibitors; Mutation; High-Throughput Nucleotide Sequencing; Ramucirumab
PubMed: 37390764
DOI: 10.1016/j.esmoop.2023.101580 -
The Korean Journal of Physiology &... May 2024Cough is a common symptom of several respiratory diseases. However, frequent coughing from acute to chronic often causes great pain to patients. It may turn into cough...
Cough is a common symptom of several respiratory diseases. However, frequent coughing from acute to chronic often causes great pain to patients. It may turn into cough variant asthma, which seriously affects people's quality of life. For cough treatment, it is dominated by over-the-counter antitussive drugs, such as asmeton, but most currently available antitussive drugs have serious side effects. Thus, there is a great need for the development of new drugs with potent cough suppressant. BALB/c mice were used to construct mice model with cough to investigate the pharmacological effects of pectolinarigenin (PEC). Hematoxylin-eosin and Masson staining were used to assess lung injury and airway remodeling, and ELISA was used to assess the level of inflammatory factor release. In addition, inflammatory cell counts were measured to assess airway inflammation. Airway hyperresponsiveness assay was used to assess respiratory resistance in mice. Finally, we used Western blotting to explore the potential mechanisms of PEC. We found that PEC could alleviate lung tissue injury and reduce the release of inflammatory factors, inhibit of cough frequency and airway wall collagen deposition in mice model with cough. Meanwhile, PEC inhibited the Ras/ERK/c-Fos pathway to exhibit antitussive effect. Therefore, PEC may be a potential drug for cough suppression.
PubMed: 38682171
DOI: 10.4196/kjpp.2024.28.3.229