Publications
1584 results found
Yang Z, Lin Y, Wang S, et al., 2021, Urinary Amino-Polycyclic Aromatic Hydrocarbons in Urban Residents: Finding a Biomarker for Residential Exposure to Diesel Traffic, ENVIRONMENTAL SCIENCE & TECHNOLOGY, Vol: 55, Pages: 10569-10577, ISSN: 0013-936X
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- Citations: 8
Zein JG, McManus JM, Sharifi N, et al., 2021, Benefits of Airway Androgen Receptor Expression in Human Asthma, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 204, Pages: 285-293, ISSN: 1073-449X
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- Citations: 20
Chen J-Y, Cheng W-H, Lee K-Y, et al., 2021, Abnormal ADAM17 expression causes airway fibrosis in chronic obstructive asthma., Biomed Pharmacother, Vol: 140
Patients with chronic obstructive asthma (COA) develop airflow obstruction caused by subepithelial fibrosis. Although a disintegrin and metalloproteinase 17 (ADAM17) has been implicated in lung inflammation and tissue fibrosis, its role in airway fibrosis in COA has not been explored. Here, we found marked overexpression of ADAM17, phosphorylated ADAM17, and connective tissue growth factor (CTGF) in human airway fibroblasts from COA patients, compared with those of normal subjects. Similarly, levels of ADAM17, CTGF, α-smooth muscle actin (α-SMA), and collagen were increased in endobronchial biopsies from COA patients, but not in controls. In an ovalbumin-challenge asthma model, airway fibrosis was inhibited in ADAM17f/f/Cre+ mice compared to control mice. TGF-β- and thrombin-induced fibrotic protein expression was reduced by ADAM17 small interfering (si)RNA, TAPI-0 (an ADAM17 inhibitor), and EGFR siRNA. In addition, exogenous HB-EGF reversed fibrotic response in ADAM17 knockdown human lung fibroblasts. ADAM17 causes subepithelial fibrosis through regulation of enhanced extracellular matrix production and fibroblast differentiation and is the common pathway for airway fibrosis mediated by TGF-β and thrombin through an aberrant ADAM17/EGFR signalling pathway.
Chung KF, Zhang Q, Xie J, et al., 2021, Serum pregnancy-associated plasma protein A (PAPPA) as a predictor of eosinophilic Type-2 high asthma
Wang Z, Lai Z, Zhang X, et al., 2021, Altered gut microbiome compositions are associated with he severity of asthma, JOURNAL OF THORACIC DISEASE, Vol: 13, Pages: 4322-4338, ISSN: 2072-1439
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- Citations: 5
An J, Do AR, Kang HY, et al., 2021, Genome-wide association study of Korean asthmatics: a comparison with UK asthmatics, Allergy, asthma & immunology research, Vol: 13, Pages: 609-622, ISSN: 2092-7363
PurposeAlthough genome-wide association studies (GWASs) represent the most powerful approach for identifying genes that influence asthma, to date, no studies have established genetic susceptibility to asthma in the Korean population. This study aimed to identify genetic variants associated with adult Korean asthmatics and compare them with the significant single nucleotide polymorphisms (SNPs) of UK asthmatics from the UK Biobank.MethodsPatients were defined as having asthma if they were diagnosed by a doctor or taking medications for asthma. Controls were defined as individuals without asthma or chronic obstructive pulmonary disease. We performed quality control, genotype imputation, GWAS, and PrediXcan analyses. In the GWAS, a P value of < 5 × 10−8 was considered significant. We compared significant SNPs between Korean and UK patients with asthma.ResultsA total of 1,386 asthmatic patients and 5,205 controls were analyzed. The SNP rs1770, located near the human leukocyte antigen (HLA)-DQB1, was the most significant SNP (P = 4.5 × 10−10). In comparison with 24 SNPs in a GWAS of UK asthmatics, six SNPs were significant with the same odds ratio (OR) direction, including signals related to type 2 inflammation (e.g., IL1RL1, TSLP, and GATA3) and mucus plugging (e.g., MUC5AC). HLA-DQA1 showed an opposite OR direction. The HLA-DQB1 gene demonstrated significantly imputed mRNA expression in the lung tissue and whole blood.ConclusionsThe SNP rs1770 of HLA-DQB1 was the most significant in Korean asthmatics. Similarities and discrepancies were found in the genetic variants between Korean and UK asthmatics. GWAS of Korean asthmatics should be replicated and compared with those of GWAS of other ethnicities.
Nguyen TT, Ho S-C, Lu Y-H, et al., 2021, Higher alveolar deposition of particulate matter in emphysematous lobes of COPD, ERJ OPEN RESEARCH, Vol: 7
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- Citations: 4
Xu M, Wang X, Xu L, et al., 2021, Chronic lung inflammation and pulmonary fibrosis after multiple intranasal instillation of PM<sub>2</sub><sub>.5</sub> in mice, ENVIRONMENTAL TOXICOLOGY, Vol: 36, Pages: 1434-1446, ISSN: 1520-4081
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- Citations: 25
Chung KF, 2021, More Data on Risks and Outcomes of COVID-19 in Asthma, COPD, and Bronchiectasis, JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE, Vol: 9, Pages: 2656-2657, ISSN: 2213-2198
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- Citations: 4
Alahmadi FH, Simpson AJ, Gomez C, et al., 2021, Medication adherence in patients with severe asthma prescribed oral corticosteroids in the U-BIOPRED cohort, Chest, Vol: 160, Pages: 53-64, ISSN: 0012-3692
BACKGROUND: Whilst estimates of sub-optimal adherence to oral corticosteroids in asthma range from 30 to 50%, no ideal method for measurement exists; the impact of poor adherence in severe asthma is likely to be particularly high. RESEARCH QUESTIONS: 1. What is the prevalence of suboptimal adherence detected using self-reporting and direct measures? 2. Is suboptimal adherence associated with disease activity? STUDY DESIGN AND METHODS: Data were included from individuals with severe asthma taking part in the U-BIOPRED study prescribed daily oral corticosteroids. Participants completed the MARS, a five-item questionnaire used to grade adherence on a scale from 1 to 5, and provided a urine sample for analysis of prednisolone and metabolites by liquid-chromatography mass spectrometry. RESULTS: Data from 166 participants were included in this study, mean (SD) age 54.2 (11.9) years, FEV1 65.1 (20.5) % predicted, 58% female. 37% completing the MARS reported sub-optimal adherence, and 43% with urinary corticosteroid data did not have detectable prednisolone or metabolites in their urine. Good adherence by both methods was detected in 35% participants who had both performed; adherence detection did not match between methods in 53%. Self-reported high-adherers had better asthma control and quality of life, whereas directly-measured high-adherers had lower blood eosinophils. INTERPRETATION: Low adherence is a common problem in severe asthma, whether measured directly or self-reported. We report poor agreement between the two methods suggesting some disassociation between self-assessment of medication adherence and regular oral corticosteroid use, which suggests that each approach may provide complementary information in clinical practice.
Lo C-Y, Huang Y-C, Huang H-Y, et al., 2021, Increased Th1 Cells with Disease Resolution of Active Pulmonary Tuberculosis in Non-Atopic Patients, BIOMEDICINES, Vol: 9
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- Citations: 4
Chung KF, Togbe D, Ryffel B, 2021, Editorial: Ozone as a Driver of Lung Inflammation and Innate Immunity and as a Model for Lung Disease, FRONTIERS IN IMMUNOLOGY, Vol: 12, ISSN: 1664-3224
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- Citations: 6
Abdel-Aziz MI, Zounemat Kermani N, Neerincx AH, et al., 2021, Association of endopeptidases, involved in SARS-CoV-2 infection, with microbial aggravation in sputum of severe asthma, Allergy, Vol: 76, Pages: 1917-1921, ISSN: 0105-4538
Chen X-Y, Feng P-H, Han C-L, et al., 2021, Alveolar epithelial inter-alpha-trypsin inhibitor heavy chain 4 deficiency associated with senescence-regulated apoptosis by air pollution, ENVIRONMENTAL POLLUTION, Vol: 278, ISSN: 0269-7491
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- Citations: 11
Lin X, Lin Y, Lai Z, et al., 2021, Retrospective comparison of high-resolution computed tomography of eosinophilic granulomatosis with polyangiitis with severe asthma, ANNALS OF TRANSLATIONAL MEDICINE, Vol: 9, ISSN: 2305-5839
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- Citations: 6
Song W-J, Hui CKM, Hull JH, et al., 2021, Confronting COVID-19-associated cough and the post-COVID syndrome: role of viral neurotropism, neuroinflammation, and neuroimmune responses, LANCET RESPIRATORY MEDICINE, Vol: 9, Pages: 533-544, ISSN: 2213-2600
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- Citations: 121
Xie J, Chung KF, Lai K, 2021, Uncommon causes of chronic cough associated with airway eosinophilia, JOURNAL OF THORACIC DISEASE, Vol: 13, Pages: 3191-3196, ISSN: 2072-1439
Marwick JA, Stevenson CS, Chung KF, et al., 2021, Correction to: Research Cigarette Smoke Exposure Alters mSin3a and Mi-2α/β Expression; implications in the control of pro-inflammatory gene transcription and glucocorticoid function, Journal of Inflammation-London, Vol: 18, Pages: 1-2, ISSN: 1476-9255
Song W-J, Won H-K, Lee SY, et al., 2021, Patients' experiences of asthma exacerbation and management: a qualitative study of severe asthma, ERJ OPEN RESEARCH, Vol: 7
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- Citations: 11
Tiotiu A, Zounemat Kermani N, Badi Y, et al., 2021, Sputum macrophage diversity and activation in asthma: role of severity and inflammatory phenotype, Allergy, Vol: 76, Pages: 775-788, ISSN: 0105-4538
BACKGROUND: Macrophages control innate and acquired immunity but their role in severe asthma remains ill-defined. We investigated gene signatures of macrophage subtypes in the sputum of 104 asthmatics and 16 healthy volunteers from the U-BIOPRED cohort. METHODS: Forty-nine gene signatures (modules) for differentially stimulated macrophages, one to assess lung tissue-resident cells (TR-Mφ) and two for their polarization (classically- and alternatively-activated macrophages: M1 and M2 respectively) were studied using gene set variation analysis. We calculated enrichment scores (ES) across severity and previously identified asthma transcriptome-associated clusters (TACs). RESULTS: Macrophage numbers were significantly decreased in severe asthma compared to mild-moderate asthma and healthy volunteers. The ES for most modules were also significantly reduced in severe asthma except for 3 associated with inflammatory responses driven by TNF and Toll-like receptors via NF-κB, eicosanoid biosynthesis via the lipoxygenase pathway and IL-2 biosynthesis (all p<0.01). Sputum macrophage number and the ES for most macrophage signatures were higher in the TAC3 group compared to TAC1 and TAC2 asthmatics. However, a high enrichment was found in TAC1 for 3 modules showing inflammatory pathways linked to Toll-like and TNF receptor activation and arachidonic acid metabolism (p<0.001) and in TAC2 for the inflammasome- and interferon-signalling pathways (p<0.001). Data was validated in the ADEPT cohort. Module analysis provides additional information compared to conventional M1 and M2 classification. TR-Mφ were enriched in TAC3 and associated with mitochondrial function. CONCLUSIONS: Macrophage activation is attenuated in severe granulocytic asthma highlighting defective innate immunity except for specific subsets characterised by distinct inflammatory pathways.
Mazein A, Ivanova O, Balaur I, et al., 2021, AsthmaMap: An interactive knowledge repository for mechanisms of asthma, JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, Vol: 147, Pages: 853-856, ISSN: 0091-6749
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- Citations: 2
Kumar P, Kalaiarasan G, Porter AE, et al., 2021, An overview of methods of fine and ultrafine particle collection for physicochemical characterisation and toxicity assessments., Science of the Total Environment, Vol: 756, Pages: 1-22, ISSN: 0048-9697
Particulate matter (PM) is a crucial health risk factor for respiratory and cardiovascular diseases. The smaller size fractions, ≤2.5 μm (PM2.5; fine particles) and ≤0.1 μm (PM0.1; ultrafine particles), show the highest bioactivity but acquiring sufficient mass for in vitro and in vivo toxicological studies is challenging. We review the suitability of available instrumentation to collect the PM mass required for these assessments. Five different microenvironments representing the diverse exposure conditions in urban environments are considered in order to establish the typical PM concentrations present. The highest concentrations of PM2.5 and PM0.1 were found near traffic (i.e. roadsides and traffic intersections), followed by indoor environments, parks and behind roadside vegetation. We identify key factors to consider when selecting sampling instrumentation. These include PM concentration on-site (low concentrations increase sampling time), nature of sampling sites (e.g. indoors; noise and space will be an issue), equipment handling and power supply. Physicochemical characterisation requires micro- to milli-gram quantities of PM and it may increase according to the processing methods (e.g. digestion or sonication). Toxicological assessments of PM involve numerous mechanisms (e.g. inflammatory processes and oxidative stress) requiring significant amounts of PM to obtain accurate results. Optimising air sampling techniques are therefore important for the appropriate collection medium/filter which have innate physical properties and the potential to interact with samples. An evaluation of methods and instrumentation used for airborne virus collection concludes that samplers operating cyclone sampling techniques (using centrifugal forces) are effective in collecting airborne viruses. We highlight that predictive modelling can help to identify pollution hotspots in an urban environment for the efficient collection of PM mass. This review provides
Kermani NZ, Song W-J, Badi Y, et al., 2021, Correction to: Sputum ACE2, TMPRSS2 and FURIN gene expression in severe neutrophilic asthma., Respiratory Research, Vol: 22, Pages: 1-3, ISSN: 1465-9921
Mumby S, Perros F, Hui C, et al., 2021, Extracellular matrix degradation pathways and fatty acid metabolism regulate distinct pulmonary vascular cell types in Pulmonary Arterial Hypertension, Pulmonary Circulation, Vol: 11, Pages: 1-16, ISSN: 2045-8940
Pulmonary arterial hypertension (PAH) describes a group of diseases characterized by raised pulmonary vascular resistance, resulting from vascular remodelling in the pre-capillary resistance arterioles. Left untreated, patients die from right heart failure. Pulmonary vascular remodelling involves all cell types but to date the precise roles of the different cells is unknown. This study investigated differences in basal gene expression between PAH and controls using both human pulmonary microvascular endothelial (HPMEC) and pulmonary artery smooth muscle cells (HPASMC). HPMEC and HPASMC from PAH patients and controls were cultured to confluence, harvested and RNA extracted. Whole genome sequencing was performed and after transcript quantification and normalization, we examined differentially expressed genes (DEGs) and applied gene set enrichment analysis (GSEA) to the DEGs to identify putative activated pathways.HPMEC displayed 1008 significant (p≤0.0001) DEGs in PAH samples compared to controls. In HPASMC there were 229 significant (p≤0.0001) DEGs between PAH and controls. Pathway analysis revealed distinctive differences: HPMEC display down-regulation of extracellular matrix organisation, collagen formation and biosynthesis, focal- and cell- adhesion molecules suggesting severe endothelial barrier dysfunction and vascular permeability in PAH pathogenesis. In contrast pathways in HPASMC were mainly up-regulated, including those for fatty acid metabolism, biosynthesis of unsaturated fatty acids, cell-cell and adherens junction interactions suggesting a more energy-driven proliferative phenotype. This suggests that the two cell types play different mechanistic roles in PAH pathogenesis and further studies are required to fully elucidate the role each plays and the interactions between these cell types in vascular remodelling in disease progression.
Wilson SJ, Ward JA, Pickett HM, et al., 2021, Airway Elastin is increased in severe asthma and relates to proximal wall area: histological and computed tomography findings from the U-BIOPRED severe asthma study, CLINICAL AND EXPERIMENTAL ALLERGY, Vol: 51, Pages: 296-304, ISSN: 0954-7894
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- Citations: 7
Kermani N, Song W-J, Badi Y, et al., 2021, Sputum ACE2, TMPRSS2 and FURIN gene expression in severe neutrophilic asthma, Respiratory Research, Vol: 22, ISSN: 1465-9921
BackgroundPatients with severe asthma may have a greater risk of dying from COVID-19 disease. Angiotensin converting enzyme-2 (ACE2) and the enzyme proteases, transmembrane protease serine 2 (TMPRSS2) and FURIN, are needed for viral attachment and invasion into host cells.MethodsWe examined microarray mRNA expression of ACE2, TMPRSS2 and FURIN in sputum, bronchial brushing and bronchial biopsies of the European U-BIOPRED cohort. Clinical parameters and molecular phenotypes, including asthma severity, sputum inflammatory cells, lung functions, oral corticosteroid (OCS) use, and transcriptomic-associated clusters, were examined in relation to gene expression levels.ResultsACE2 levels were significantly increased in sputum of severe asthma compared to mild-moderate asthma. In multivariate analyses, sputum ACE2 levels were positively associated with OCS use and male gender. Sputum FURIN levels were significantly related to neutrophils (%) and the presence of severe asthma. In bronchial brushing samples, TMPRSS2 levels were positively associated with male gender and body mass index, whereas FURIN levels with male gender and blood neutrophils. In bronchial biopsies, TMPRSS2 levels were positively related to blood neutrophils. The neutrophilic molecular phenotype characterised by high inflammasome activation expressed significantly higher FURIN levels in sputum than the eosinophilic Type 2-high or the pauci-granulocytic oxidative phosphorylation phenotypes.ConclusionLevels of ACE2 and FURIN may differ by clinical or molecular phenotypes of asthma. Sputum FURIN expression levels were strongly associated with neutrophilic inflammation and with inflammasome activation. This might indicate the potential for a greater morbidity and mortality outcome from SARS-CoV-2 infection in neutrophilic severe asthma.
Abdel-Aziz MI, Brinkman P, Vijverberg SJH, et al., 2021, Sputum microbiome profiles identify severe asthma phenotypes of relative stability at 12-18 months, Journal of Allergy and Clinical Immunology, Vol: 147, Pages: 123-134, ISSN: 0091-6749
BACKGROUND: Asthma is a heterogeneous disease characterized by distinct phenotypes with associated microbial dysbiosis. OBJECTIVES: To identify severe asthma phenotypes based on sputum microbiome profiles and assess their stability after 12-18 months. Furthermore, to evaluate clusters' robustness after inclusion of an independent mild-to-moderate asthmatics. METHODS: In this longitudinal multicenter cohort study, sputum samples were collected for microbiome profiling from a subset of the U-BIOPRED adult patient cohort at baseline and after 12-18 months of follow-up. Unsupervised hierarchical clustering was performed using the Bray-Curtis β-diversity measure of microbial profiles. For internal validation, partitioning around medoids, consensus cluster distribution, bootstrapping and topological data analysis were applied. Follow-up samples were studied to evaluate within-patient clustering stability in severe asthmatics. Cluster robustness was evaluated by an independent mild-moderate asthma cohort. RESULTS: Data were available for 100 severe asthma subjects (median age: 55 yrs, 42% males). Two microbiome-driven clusters were identified, characterized by differences in asthma onset, smoking status, residential locations, percentage of blood and/or sputum neutrophils and macrophages, lung spirometry, and concurrent asthma medications (all p-values <.05). Cluster 2 patients displayed a commensal-deficient bacterial profile which was associated with worse asthma outcomes compared to cluster 1. Longitudinal clusters revealed high relative stability after 12-18 months in the severe asthmatics. Further inclusion of 24 independent mild-to-moderate asthmatics was consistent with the clustering assignments. CONCLUSION: Unbiased microbiome-driven clustering revealed two distinct robust severe asthma phenotypes, which exhibited relative overtime stability. This suggests that the sputum microbiome may serve as a biomarker for better characterizing asthma phenotypes.
Song WJ, Hull JH, Chung KF, 2021, Upper Airways: Assessment and Treatment for Cough, Diagnosis and Treatment of Chronic Cough, Pages: 29-36, ISBN: 9789813340282
Upper airway diseases involving the nose or throat areas are frequently observed in patients with chronic cough. However, the causal relationships with cough are controversial. Despite their frequent overlaps, evidence is largely lacking on how to assess and treat upper airway conditions in patients with chronic cough. This chapter summarizes clinical evidence on upper airways and cough, but also introduces a pragmatic clinical approach based on the evidence and the authors’ clinical experience.
Chung KF, 2021, Platelet-Activating Factor, Encyclopedia of Respiratory Medicine, Second Edition, Pages: 462-473, ISBN: 9780081027233
Platelet-activating factor (PAF) is a biologically active phospho lipid mediator of a family of alkylphosphoglycerides and has potent actions as a mediator of inflammation. PAF is metabolized by PAF acetylhydrolases. Low plasma PAF-acetylhydrolase activity has been associated with inflammatory disorders. It acts through a G-protein-coupled receptor linked to phospholipase A2 and C. PAF is produced by endothelial cells, macrophages, neutrophils, eosinophils, monocytes, and mast cells, and activates many inflammatory cells. PAF plays an important role in normal physiological homeostasis and in the primary response to inflammation and injury. It therefore has an inflammatory role in various lung conditions.
Dixey P, Abubakar-Waziri H, Raby K, et al., 2021, Adult Severe Asthma, Encyclopedia of Respiratory Medicine, Second Edition, Pages: 383-399, ISBN: 9780081027233
Severe asthma is “asthma which requires treatment with high dose inhaled corticosteroids plus a second controller (and/or systemic corticosteroids) to prevent it from becoming ‘uncontrolled’ or which remains ‘uncontrolled’ despite this therapy.” Asthma diagnosis and its severity requires systematic assessment of the underlying causative factors including suboptimal adherence to treatments and inhaler technique, comorbidities, risk factors and triggers. This is followed by asthma phenotyping using blood eosinophil counts and the fractional level of nitric oxide (FeNO) in exhaled breath to enable treatment with targeted anti-Type 2 inflammation-directed antibodies. Deeper molecular phenotyping of type 2 and non-type 2 airway inflammatory processes and elucidation of better selective biomarkers will lead to further precision medicine approaches linking mechanisms to treatable traits and biomarkers.
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