Publications
1032 results found
Di Stefano A, Gnemmi I, Dossena F, et al., 2022, Bone Morphogenic Proteins and their antagonists in the lower airways of stable COPD patients, 2022 ERS International Congress, Publisher: European Respiratory Society, ISSN: 0903-1936
Thorsen J, Stokholm J, Rasmussen MA, et al., 2022, Asthma and Wheeze Severity and the Oropharyngeal Microbiota in Children and Adolescents, ANNALS OF THE AMERICAN THORACIC SOCIETY, Vol: 19, Pages: 2031-2043, ISSN: 1546-3222
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- Citations: 4
Kliment CR, Gosens R, 2022, Chymase-1: a “MAST”-er switch in COPD?, European Respiratory Journal, Vol: 60, Pages: 2201356-2201356, ISSN: 0903-1936
Hashemian SM, Mortaz E, Shafigh N, et al., 2022, Effectiveness of Borage plus syrup (BPS) on COVID-19 patients in intensive care units, Frontiers in Nutrition, Vol: 9, Pages: 1-7, ISSN: 2296-861X
Introduction: COVID-19 (coronovirus disease-2019) still causes a high rate of death globally with no definite curative treatment described. The traditional plant Borage (Borago officinalis L.) is a good source of gamma-linolenic (GLA). We hypothesized that Borage plus syrup (BPS) would be beneficial in severe COVID-19 patients within an intensice care unit (ICU) setting. Methods: A pilot single centre, randomized trial with no placebo was undertaken. 60 PCR-positive severe COVID-19 participants admitted to ICU from June 2020- Dec 2020 at Masih Daneshvari Hospital Tehran-Iran gave informed consent. The participants were randomly assigned to either Borage Plus Syrup (BPS, 5ml for 5 days) (n=30) or standard care (IFN- and favipiravir) as a control group (n=30). Pao2/Fio2, serum ferritin, CRP, bilirubin, IL-6, TNF-α, ALT, AST, PCT and serum IL-8 was measured upon admission and on release. Results: All the measured parameters decreased significantly with BPS treatment . In the control group, most parameters significantly improved apart from AST and PCT. In addition, the suppression of serum TNF levels in the BPS group was greater than that seen in the control group (P≤0.05). Moreover, the length of ICU stay was significantly lower in the BPS group compared with the control group (P≤0.05). Conclusion: Our study shows that addition of BPS to the standard treatment regime of COVID-19 patients in ICU improved outcomes and reduced the length of ICU treatment. Natural products could be considered as new approaches for reducting the harmful consequences of COVID-19.
Mumby S, Kermani NZ, Garnett JP, et al., 2022, CEACAM5 is an IL-13-regulated epithelial gene that mediates transcription in type-2 (T2) high severe asthma, ALLERGY, Vol: 77, Pages: 3463-3466, ISSN: 0105-4538
Xuan S, Li Y, Wu Y, et al., 2022, Langerin-expressing dendritic cells in pulmonary immune-related diseases, Frontiers of Medicine, Vol: 9, ISSN: 1673-7342
Dendritic cells (DCs) are "frontline" immune cells dedicated to antigen presentation. They serve as an important bridge connecting innate and adaptive immunity, and express various receptors for antigen capture. DCs are divided into various subclasses according to their differential expression of cell surface receptors and different subclasses of DCs exhibit specific immunological characteristics. Exploring the common features of each sub-category has became the focus of many studies. There are certain amounts of DCs expressing langerin in airways and peripheral lungs while the precise mechanism by which langerin+ DCs drive pulmonary disease is unclear. Langerin-expressing DCs can be further subdivided into numerous subtypes based on the co-expressed receptors, but here, we identify commonalities across these subtypes that point to the major role of langerin. Better understanding is required to clarify key disease pathways and determine potential new therapeutic approaches.
Kermani NZ, Macis G, Bakke PS, et al., 2022, Radiomics for severe asthma phenotyping and endotyping, ERS International Congress 2022, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, Pages: 1-2, ISSN: 0903-1936
Shi Y, Kermani NZ, Faiz A, et al., 2022, Altered airway epithelial cell landscape in U-BIOPRED severe asthma, 2022 ERS International Congress, Publisher: European Respiratory Society, Pages: 1-2, ISSN: 0903-1936
Koranteng J, Zounemat-Kermani N, Badi Y, et al., 2022, Expression of eosinophil-associated gene signatures in U-BIOPRED severe asthma, 2022 ERS International Congress, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, Pages: 1-2, ISSN: 0903-1936
Versi A, Xaverius IF, Abdel-Aziz M, et al., 2022, Sputum metagenomics of U-BIOPRED asthma cohort: link to severity and granulocytic inflammation, ERS International Congress 2022, Publisher: European Respiratory Society, Pages: 1-2, ISSN: 0903-1936
Abdel-Aziz M, Thorsen J, Hashimoto S, et al., 2022, Identification of oropharyngeal microbiome-driven asthma and wheezing clusters in children, 2022 ERS International Congress, Publisher: European Respiratory Society, Pages: 1-3, ISSN: 0903-1936
Song W, Zounemat-Kermani N, Guo Y, et al., 2022, Transcriptomic analysis of cellular senescence signatures in severe asthma, ERS International Congress 2022, Publisher: European Respiratory Society, Pages: 1-2, ISSN: 0903-1936
Faiz A, Boedijono FS, Timens W, et al., 2022, The regulation of IL33 following smoking cessation, 2022 ERS International Congress, Publisher: European Respiratory Society, Pages: 1-2, ISSN: 0903-1936
Iemoli E, Ortolani VGR, Preziosi D, et al., 2022, Failure of desensitization with Pfizer-BioNTech COVID-19 vaccine in two asthmatic patients., Eur Ann Allergy Clin Immunol, Vol: 54, Pages: 240-241, ISSN: 1764-1489
Since December 2020, in various countries of the world, many cases of severe allergic reactions after administration of PfizerBioNTech COVID-19 vaccine, were reported. A great concern has arisen among the doctors who administer the vaccine and the allergic patients who undergo vaccinations. In Italy guidelines were published in order to stratify the risk in the allergic population. In mRNA vaccines, the component currently suspected of causing allergic reactions is the polyethylene glycol excipient (PEG or macrogol). In patients who have shown an immediate allergic reaction to vaccine and who are negative to skin tests for PEG, desensitization with the same vaccine is proposed. In this paper we describe two cases of asthma after the first COVID vaccine administration in which desensitization has failed.
Sanchez-Ovando S, Pavlidis S, Kermani NZ, et al., 2022, Pathways linked to unresolved inflammation and airway remodelling characterize the transcriptome in two independent severe asthma cohorts, Respirology, Vol: 27, Pages: 730-738, ISSN: 1323-7799
Background and objectiveSevere asthma (SA) is a heterogeneous disease. Transcriptomic analysis contributes to the understanding of pathogenesis necessary for developing new therapies. We sought to identify and validate mechanistic pathways of SA across two independent cohorts.MethodsTranscriptomic profiles from U-BIOPRED and Australian NOVocastrian Asthma cohorts were examined and grouped into SA, mild/moderate asthma (MMA) and healthy controls (HCs). Differentially expressed genes (DEGs), canonical pathways and gene sets were identified as central to SA mechanisms if they were significant across both cohorts in either endobronchial biopsies or induced sputum.ResultsThirty-six DEGs and four pathways were shared across cohorts linking to tissue remodelling/repair in biopsies of SA patients, including SUMOylation, NRF2 pathway and oxidative stress pathways. MMA presented a similar profile to HCs. Induced sputum demonstrated IL18R1 as a shared DEG in SA compared with healthy subjects. We identified enrichment of gene sets related to corticosteroid treatment; immune-related mechanisms; activation of CD4+ T cells, mast cells and IL18R1; and airway remodelling in SA.ConclusionOur results identified differentially expressed pathways that highlight the role of CD4+ T cells, mast cells and pathways linked to ongoing airway remodelling, such as IL18R1, SUMOylation and NRF2 pathways, as likely active mechanisms in the pathogenesis of SA.
Adcock I, Badi Y, salcman B, et al., 2022, IL1RAP expression and the enrichment of IL-33 activation signatures in severe neutrophilic asthma, Allergy, Vol: 78, Pages: 156-167, ISSN: 0105-4538
Background:Interleukin (IL)-33 is an upstream regulator of type 2 (T2) eosinophilic inflammation and has been proposed as a key driver of some asthma phenotypes.Objective:To derive gene signatures from in vitro studies of IL-33-stimulated cells and use these to determine IL-33-associated enrichment patterns in asthma.Methods:Signatures downstream of IL-33 stimulation were derived from our in vitro study of human mast cells and from public datasets of in vitro stimulated human basophils, type 2 innate lymphoid cells (ILC2), regulatory T cells (Treg) and endothelial cells. Gene Set Variation Analysis (GSVA) was used to probe U-BIOPRED and ADEPT sputum transcriptomics to determine enrichment scores (ES) for each signature according to asthma severity, sputum granulocyte status and previously defined molecular phenotypes.Results:IL-33-activated gene signatures were cell-specific with little gene overlap. Individual signatures, however, were associated with similar signalling pathways (TNF, NF-κB, IL-17 and JAK/STAT signalling) and immune cell differentiation pathways (Th17, Th1 and Th2 differentiation). ES for IL-33-activated gene signatures were significantly enriched in asthmatic sputum, particularly in patients with neutrophilic and mixed granulocytic phenotypes. IL-33 mRNA expression was not elevated in asthma whereas the expression of mRNA for IL1RL1, the IL-33 receptor, was up-regulated in the sputum of severe eosinophilic asthma. The mRNA expression for IL1RAP, the IL1RL1 co-receptor, was greatest in severe neutrophilic and mixed granulocytic asthma.Conclusions:IL-33-activated gene signatures are elevated in neutrophilic and mixed granulocytic asthma corresponding with IL1RAP co-receptor expression. This suggests incorporating T2-low asthma in anti-IL-33 trials.
Mortaz E, Movassaghi M, Bassir A, et al., 2022, Evaluation of myeloid-derived suppressor cells in the blood of Iranian COVID-19 patients, Iranian Journal Of Allergy, Asthma and Immunology, Vol: 21, Pages: 467-477, ISSN: 1735-1502
The cytokine storm and lymphopenia are reported in coronavirus disease 2019 (COVID-19). Myeloid-derived suppressive cells (MDSCs) exist in two different forms, granulocyte (G-MDSCs) and monocytic (M-MDSCs), that both suppress T-cell function. In COVID-19, the role of chemokines such as interleukin (IL)-8 in recruiting MDSCs is unclear. A recent report has correlated IL-8 and MDSCs with poor clinical outcomes in melanoma patients. In the current study, we evaluated the frequency of MDSCs and their correlation with serum IL-8 levels in severe COVID-19 patients from Iran. Thirty-seven severe patients (8 on ventilation, 29 without ventilation), thirteen moderate COVID-19 patients, and eight healthy subjects participated in this study between 10th April 2020 and 9th March 2021. Clinical and biochemical features, serum, and whole blood were obtained. CD14, CD15, CD11b, and HLA-DR expression on MDSCs was measured by flow cytometry. COVID-19 patients compared to healthy subjects had a greater frequency of M-MDSCs (12.7±13.3% vs 0.19±0.20%,), G-MDSCs (15.8±12.6% vs 0.35±0.40%,) and total-MDSCs (27.5±17.3% vs 0.55±0.41%,). M-MDSC (16.8±15.8% vs 5.4±4.8%,) and total-MDSC (33.3±18.5% vs 17.3±13.3%) frequency was higher in non- ventilated compared to moderate COVID-19 subjects. Serum IL-8 levels were higher in patients with COVID-19 than in normal healthy subjects (6.4±7.8 vs. 0.10±00 pg/mL). Ventilated patients (15.7±6.7 pg/mL), non-ventilated patients (5.7±2.7 pg/mL) and moderate patients (2.8±3.0 pg/mL) had significantly different levels of IL-8. A negative correlation was found between the frequency of G-MDSCs and the international normalized ratio (INR) test (r=-0.39), and between the frequency of total-MDSCs and oxygen saturation (%) (r=-0.39). COVID-19 patients with severe non-ventilated disease had the highest levels of M-MDSCs. In addition to systemic MDSC
Di Stefano A, Dossena F, Gnemmi I, et al., 2022, Decreased humoral immune response in the bronchi of rapid decliners with chronic obstructive pulmonary disease., Respiratory Research, Vol: 23, Pages: 1-13, ISSN: 1465-9921
BACKGROUND: Identification of COPD patients with a rapid decline in FEV1 is of particular interest for prognostic and therapeutic reasons. OBJECTIVE: To determine the expression of markers of inflammation in COPD patients with rapid functional decline in comparison to slow or no decliners. METHODS: In COPD patients monitored for at least 3 years (mean ± SD: 5.8 ± 3 years) for lung functional decline, the expression and localization of inflammatory markers was measured in bronchial biopsies of patients with no lung functional decline (FEV1% + 30 ± 43 ml/year, n = 21), slow (FEV1% ml/year, - 40 ± 19, n = 14) and rapid decline (FEV1% ml/year, - 112 ± 53, n = 15) using immunohistochemistry. ELISA test was used for polymeric immunoglobulin receptor (pIgR) quantitation "in vitro". RESULTS: The expression of secretory IgA was significantly reduced in bronchial epithelium (p = 0.011) and plasma cell numbers was significantly reduced in the bronchial lamina propria (p = 0.017) of rapid decliners compared to no decliners. Bronchial inflammatory cell infiltration, CD4, CD8, CD68, CD20, NK, neutrophils, eosinophils, mast cells, pIgR, was not changed in epithelium and lamina propria of rapid decliners compared to other groups. Plasma cells/mm2 correlated positively with scored total IgA in lamina propria of all patients. "In vitro" stimulation of 16HBE cells with LPS (10 μg/ml) and IL-8 (10 ng/ml) induced a significant increase while H2O2 (100 μM) significantly decreased pIgR epithelial expression. CONCLUSION: These data show an impaired humoral immune response in rapid decliners with COPD, marked by reduced epithelial secretory IgA and plasma cell numbers in the bronchial lamina propria. These findings may help in the prognosti
Luecken MD, Zaragosi L-E, Madissoon E, et al., 2022, The discovAIR project: a roadmap towards the Human Lung Cell Atlas, European Respiratory Journal, Vol: 60, Pages: 1-11, ISSN: 0903-1936
The Human Cell Atlas (HCA) consortium aims to establish an atlas of all organs in the healthy human body at single-cell resolution to increase our understanding of basic biological processes that govern development, physiology and anatomy, and to accelerate diagnosis and treatment of disease. The Lung Biological Network of the HCA aims to generate the Human Lung Cell Atlas as a reference for the cellular repertoire, molecular cell states and phenotypes, and cell–cell interactions that characterise normal lung homeostasis in healthy lung tissue. Such a reference atlas of the healthy human lung will facilitate mapping the changes in the cellular landscape in disease. The discovAIR project is one of six pilot actions for the HCA funded by the European Commission in the context of the H2020 framework programme. discovAIR aims to establish the first draft of an integrated Human Lung Cell Atlas, combining single-cell transcriptional and epigenetic profiling with spatially resolving techniques on matched tissue samples, as well as including a number of chronic and infectious diseases of the lung. The integrated Human Lung Cell Atlas will be available as a resource for the wider respiratory community, including basic and translational scientists, clinical medicine, and the private sector, as well as for patients with lung disease and the interested lay public. We anticipate that the Human Lung Cell Atlas will be the founding stone for a more detailed understanding of the pathogenesis of lung diseases, guiding the design of novel diagnostics and preventive or curative interventions.
Marshall DC, Al Omari O, Goodall R, et al., 2022, Trends in prevalence, mortality, and disability-adjusted life-years relating to chronic obstructive pulmonary disease in Europe: an observational study of the global burden of disease database, 2001-2019, BMC Pulmonary Medicine, Vol: 22, Pages: 1-11, ISSN: 1471-2466
IntroductionChronic Obstructive Pulmonary Disease (COPD) is associated with significant mortality and well-defined aetiological factors. Previous reports indicate that mortality from COPD is falling worldwide. This study aims to assess the burden of COPD using prevalence, mortality, and disability-adjusted life years (DALYs) between 2001 and 2019 in 28 European countries (the European Union and the United Kingdom).MethodsWe extracted COPD data from the Global Burden of Disease database based on the International Classification of Diseases versions 10 (J41, 42, 43, 44 and 47). Age-standardised prevalence rates (ASPRs), age-standardised mortality rates (ASMRs), and DALYs were analysed for European countries by sex for each year (2001–2019) and reported per 100,000 population. We used Joinpoint regression analysis to quantify changing trends in the burden of COPD.ResultsIn 2019, the median ASPR across Europe was 3230/100,000 for males and 2202/100,000 for females. Between 2001 and 2019, the median percentage change in ASPR was − 9.7% for males and 4.3% for females. 23/28 countries demonstrated a decrease in ASPRs in males, and 11/28 demonstrated a decrease in females. The median percentage change in ASMR between 2001 and 2019 was − 27.5% for males and − 10.4% for females. 25/28 and 19/28 countries demonstrated a decrease in ASMR in males and females, respectively.ConclusionIn the EU between 2001 and 2019 COPD prevalence has overall increased in females but continues to decrease in males and in some countries, female prevalence now exceeds that of males. COPD mortality in the EU has decreased overall between 2001 and 2019; however, this decrease is not universal, particularly in females, and therefore remains a substantial source of amenable mortality.
Lakhdar R, Mumby S, Abubakar-Waziri H, et al., 2022, Lung toxicity of particulates and gaseous pollutants using <i>ex-vivo</i> airway epithelial cell culture systems, ENVIRONMENTAL POLLUTION, Vol: 305, ISSN: 0269-7491
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- Citations: 5
Adcock I, Mumby S, 2022, Recent evidence from omic analysis for redox signalling and mitochondrial oxidative stress in COPD, Journal of Inflammation, Vol: 19, ISSN: 1476-9255
COPD is driven by exogenous and endogenous oxidative stress derived from inhaled cigarette smoke, air pollution and reactive oxygen species from dysregulated mitochondria in activated inflammatory cells within the airway and lung. This is compounded by the loss in antioxidant defences including FOXO and NRF2 and other antioxidant transcription factors together with various key enzymes that attenuate oxidant effects. Oxidative stress enhances inflammation; airway remodelling including fibrosis and emphysema; post-translational protein modifications leading to autoantibody generation; DNA damage and cellular senescence. Recent studies using various omics technologies in the airways, lungs and blood of COPD patients has emphasised the importance of oxidative stress, particularly that derived from dysfunctional mitochondria in COPD and its role in immunity, inflammation, mucosal barrier function and infection. Therapeutic interventions targeting oxidative stress should overcome the deleterious pathologic effects of COPD if targeted to the lung. We require novel, more efficacious antioxidant COPD treatments among which mitochondria-targeted antioxidants and Nrf2 activators are promising.
Nucera F, Mumby S, Paudel KR, et al., 2022, Role of oxidative stress in the pathogenesis of COPD, Minerva Medica, Vol: 113, Pages: 370-404, ISSN: 0026-4806
Chronic inhalation of cigarette smoke is a prominent cause of chronic obstructive pulmonary disease (COPD) and provides an important source of exogenous oxidants. In addition, several inflammatory and structural cells are a source of endogenous oxidants in the lower airways of COPD patients, even in former smokers. This suggests that oxidants play a key role in the pathogenesis of COPD. This oxidative stress is counterbalanced by the protective effects of the various endogenous antioxidant defenses of the lower airways. A large amount of data from animal models and patients with COPD have shown that both the stable phase of the disease, and during exacerbations, have increased oxidative stress in the lower airways compared with age-matched smokers with normal lung function. Thus, counteracting the increased oxidative stress may produce clinical benefits in COPD patients. Smoking cessation is currently the most effective treatment of COPD patients and reduces oxidative stress in the lower airways. In addition, many drugs used to treat COPD have some antioxidant effects, however, it is still unclear if their clinical efficacy is related to pharmacological modulation of the oxidant/antioxidant balance. Several new antioxidant compounds are in development for the treatment of COPD.
Reinke SN, Naz S, Chaleckis R, et al., 2022, Urinary metabotype of severe asthma evidences decreased carnitine metabolism independent of oral corticosteroid treatment in the U-BIOPRED study, European Respiratory Journal, Vol: 59, Pages: 1-17, ISSN: 0903-1936
Introduction Asthma is a heterogeneous disease with poorly defined phenotypes. Patients with severe asthma often receive multiple treatments including oral corticosteroids (OCS). Treatment may modify the observed metabotype, rendering it challenging to investigate underlying disease mechanisms. Here, we aimed to identify dysregulated metabolic processes in relation to asthma severity and medication.Methods Baseline urine was collected prospectively from healthy participants (n=100), patients with mild-to-moderate asthma (n=87) and patients with severe asthma (n=418) in the cross-sectional U-BIOPRED cohort; 12–18-month longitudinal samples were collected from patients with severe asthma (n=305). Metabolomics data were acquired using high-resolution mass spectrometry and analysed using univariate and multivariate methods.Results A total of 90 metabolites were identified, with 40 significantly altered (p<0.05, false discovery rate <0.05) in severe asthma and 23 by OCS use. Multivariate modelling showed that observed metabotypes in healthy participants and patients with mild-to-moderate asthma differed significantly from those in patients with severe asthma (p=2.6×10−20), OCS-treated asthmatic patients differed significantly from non-treated patients (p=9.5×10−4), and longitudinal metabotypes demonstrated temporal stability. Carnitine levels evidenced the strongest OCS-independent decrease in severe asthma. Reduced carnitine levels were associated with mitochondrial dysfunction via decreases in pathway enrichment scores of fatty acid metabolism and reduced expression of the carnitine transporter SLC22A5 in sputum and bronchial brushings.Conclusions This is the first large-scale study to delineate disease- and OCS-associated metabolic differences in asthma. The widespread associations with different therapies upon the observed metabotypes demonstrate the need to evaluate potential modulating effects on a treatment- and metabolite-speci
Michaeloudes C, Abubakar-Waziri H, Lakhdar R, et al., 2022, Molecular mechanisms of oxidative stress in asthma, Molecular Aspects of Medicine, Vol: 85, ISSN: 0098-2997
The lungs are exposed to reactive oxygen species oxygen (ROS) produced as a result of inhalation of oxygen, as well as smoke and other air pollutants. Cell metabolism and the NADPH oxidases (Nox) generate low levels of intracellular ROS that act as signal transduction mediators by inducing oxidative modifications of histones, enzymes and transcription factors. Redox signalling is also regulated by localised production and sensing of ROS in mitochondria, the endoplasmic reticulum (ER) and inside the nucleus. Intracellular ROS are maintained at low levels through the action of a battery of enzymatic and non-enzymatic antioxidants. Asthma is a heterogeneous airway inflammatory disease with different immune endotypes; these include atopic or non-atopic Th2 type immune response associated with eosinophilia, or a non-Th2 response associated with neutrophilia. Airway remodelling and hyperresponsiveness accompany the inflammatory response in asthma. Over-production of ROS resulting from infiltrating immune cells, particularly eosinophils and neutrophils, and a concomitant impairment of antioxidant responses lead to development of oxidative stress in asthma. Oxidative stress is augmented in severe asthma and during exacerbations, as well as by air pollution and obesity, and causes oxidative damage of tissues promoting airway inflammation and hyperresponsiveness. Furthermore, deregulated Nox activity, mitochondrial dysfunction, ER stress and/or oxidative DNA damage, resulting from exposure to irritants, inflammatory mediators or obesity, may lead to redox-dependent changes in cell signalling. ROS play a central role in airway epithelium-mediated sensing, development of innate and adaptive immune responses, and airway remodelling and hyperresponsiveness. Nonetheless, antioxidant compounds have proven clinically ineffective as therapeutic agents for asthma, partly due to issues with stability and in vivo metabolism of these compounds. The compartmentalised nature of ROS product
Chung KF, Wenzel SE, Brozek JL, et al., 2022, International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma (vol 43, pg 343, 2014), EUROPEAN RESPIRATORY JOURNAL, Vol: 59, ISSN: 0903-1936
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Mortaz E, Garssen J, Adcock IM, 2022, Do Low-density Granulocytes Induce Lymphopenia in Patients with COVID-19?, IRANIAN JOURNAL OF ALLERGY ASTHMA AND IMMUNOLOGY, Vol: 21, Pages: 369-373, ISSN: 1735-1502
Uwagboe I, Adcock IM, Lo Bello F, et al., 2022, New drugs under development for COPD, MINERVA MEDICA, Vol: 113, Pages: 471-496, ISSN: 0026-4806
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Li C, Zhang H, Wei L, et al., 2022, Role of TRPA1/TRPV1 in acute ozone exposure induced murine model of airway inflammation and bronchial hyperresponsiveness, Journal of Thoracic Disease, Vol: 14, ISSN: 2072-1439
Background: Transient receptor potential (TRP) ankyrin 1 (TRPA1) and vanilloid 1 (TRPV1) mediatethe development of lung injury and inflammation. This study investigated the role and mechanism of theTRPA1/TRPV1 pathway in airway inflammation and bronchial hyperresponsiveness (BHR) induced byacute ozone exposure.Methods: C57BL/6 mice (8–10 weeks) were intraperitoneally injected with phosphate buffered saline(PBS), A967079 (TRPA1 inhibitor) or AMG9810 (TRPV1 inhibitor) 1 h before or after ozone exposure(2.5 ppm, 3 h). BHR, cell counts in bronchoalveolar lavage (BAL) fluid, oxidative stress biomarkers,inflammatory cytokines, TRPA1 and TPRV1 protein levels, mitochondrial dynamics- and mitophagy-relatedprotein levels, and activities of mitochondrial respiratory chain (MRC) in lung were measured.Results: The preventive treatment effect was similar to the therapeutic treatment effect. Both A967079 andAMG9810 intervention suppressed BHR, inflammatory cytokines, total BAL fluid cells, malondialdehyde(MDA) levels and inflammatory cytokines mRNA including Substance P (SP), Keratinocyte-DerivedChemokine (KC), interleukin18 (IL-18) and chemokine (C-X-C motif) ligand 8 (CXCL8) expression, andenhanced reduced glutathione (GSH)/oxidized glutathione (GSSG) levels compared with ozone-exposedmice. A967079 and AMG9810 intervention inhibited dynamin-related protein (DRP1), mitochondrial fissionfactor (MFF), Parkinson protein 2 E3 ubiquitin protein ligase (PARK2) and Sequestosome 1 (SQSTM1)/p62expression, increased Optic atrophy 1 (OPA1), mitofusin 2 (MFN2) and PTEN-induced putative kinase 1(PINK1) expression, and up-regulated the activities of MRC complex III and V in lung tissue.Conclusions: The results show that both TRPA1 and TRPV1 pathways are involved in acute ozoneexposure-induced airway inflammation and BHR and influence oxidative stress, mitochondrial qualitycontrol and MRC activity, which could be a potential target for clinical therapy of respiritory disease
Masfufa IW, Chung KF, Adcock I, 2022, Clinical characteristic of severe asthma patients with JAK-STAT pathway activation, IFCC WorldLab Congress, Publisher: ELSEVIER, Pages: S32-S32, ISSN: 0009-8981
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