Publications
1581 results found
Lee S-W, Huang Y-C, Lin C-Y, et al., 2021, Impact of Annual Exposure to Polycyclic Aromatic Hydrocarbons on Acute Exacerbation Frequency in Asthmatic Patients, JOURNAL OF ASTHMA AND ALLERGY, Vol: 14, Pages: 81-90, ISSN: 1178-6965
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- Citations: 3
Qiu M, Wei S, Lai Z, et al., 2020, Early radiologic and bronchoscopic changes after bronchial thermoplasty in patients with severe asthma, EXPERIMENTAL AND THERAPEUTIC MEDICINE, Vol: 20, ISSN: 1792-0981
Gorlanova O, Tischhauser E, Adcock IM, et al., 2020, Discordant use of short-acting beta(2) agonists in children and adults with severe, uncontrolled asthma from the U-BIOPRED cohort, Pediatric Pulmonology, Pages: 1-3, ISSN: 1099-0496
Abdel-Aziz MI, Brinkman P, Vijverberg SJH, et al., 2020, eNose breath prints as a surrogate biomarker for classifying patients with asthma by atopy, Journal of Allergy and Clinical Immunology, Vol: 146, Pages: 1045-1055, ISSN: 0091-6749
BACKGROUND: Electronic noses (eNoses) are emerging point-of-care tools that may help in the subphenotyping of chronic respiratory diseases such as asthma. OBJECTIVE: We aimed to investigate whether eNoses can classify atopy in pediatric and adult patients with asthma. METHODS: Participants with asthma and/or wheezing from 4 independent cohorts were included; BreathCloud participants (n = 429), Unbiased Biomarkers in Prediction of Respiratory Disease Outcomes adults (n = 96), Unbiased Biomarkers in Prediction of Respiratory Disease Outcomes pediatric participants (n = 100), and Pharmacogenetics of Asthma Medication in Children: Medication with Anti-Inflammatory Effects 2 participants (n = 30). Atopy was defined as a positive skin prick test result (≥3 mm) and/or a positive specific IgE level (≥0.35 kU/L) for common allergens. Exhaled breath profiles were measured by using either an integrated eNose platform or the SpiroNose. Data were divided into 2 training and 2 validation sets according to the technology used. Supervised data analysis involved the use of 3 different machine learning algorithms to classify patients with atopic versus nonatopic asthma with reporting of areas under the receiver operating characteristic curves as a measure of model performance. In addition, an unsupervised approach was performed by using a bayesian network to reveal data-driven relationships between eNose volatile organic compound profiles and asthma characteristics. RESULTS: Breath profiles of 655 participants (n = 601 adults and school-aged children with asthma and 54 preschool children with wheezing [68.2% of whom were atopic]) were included in this study. Machine learning models utilizing volatile organic compound profiles discriminated between atopic and nonatopic participants with areas under the receiver operating characteristic curves of at least 0.84 and 0.72 in the training and validation sets, respectively. The unsupervised approach revealed t
Xiao D, Chen Z, Wu S, et al., 2020, Prevalence and risk factors of small airway dysfunction, and association with smoking, in China: findings from a national cross-sectional study, LANCET RESPIRATORY MEDICINE, Vol: 8, Pages: 1081-1093, ISSN: 2213-2600
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- Citations: 55
Haji G, Wiegman C, Michaeloudes C, et al., 2020, Mitochondrial dysfunction in airways and quadriceps muscle of patients with Chronic Obstructive Pulmonary Disease, Respiratory Research, Vol: 21, ISSN: 1465-9921
BackgroundMitochondrial damage and dysfunction have been reported in airway and quadriceps muscle cells of patients with chronic obstructive pulmonary disease (COPD). We determined the concomitance of mitochondrial dysfunction in these cells in COPD.MethodsBronchial biopsies were obtained from never- and ex-smoker volunteers and COPD patients (GOLD Grade 2) and quadriceps muscle biopsies from the same volunteers in addition to COPD patients at GOLD Grade 3/4 for measurement of mitochondrial function.ResultsDecreased mitochondrial membrane potential (ΔΨm), increased mitochondrial reactive oxygen species (mtROS) and decreased superoxide dismutase 2 (SOD2) levels were observed in mitochondria isolated from bronchial biopsies from Grade 2 patients compared to healthy never- and ex-smokers. There was a significant correlation between ΔΨm and FEV1 (% predicted), transfer factor of the lung for carbon monoxide (TLCOC % predicted), 6-min walk test and maximum oxygen consumption. In addition, ΔΨm was also associated with decreased expression levels of electron transport chain (ETC) complex proteins I and II. In quadriceps muscle of Grade 2 COPD patients, a significant increase in total ROS and mtROS was observed without changes in ΔΨm, SOD2 or ETC complex protein expression. However, quadriceps muscle of GOLD Grade 3/4 COPD patients showed an increased mtROS and decreased SOD2 and ETC complex proteins I, II, III and V expression.ConclusionsMitochondrial dysfunction in the airways, but not in quadriceps muscle, is associated with airflow obstruction and exercise capacity in Grade 2 COPD. Oxidative stress-induced mitochondrial dysfunction in the quadriceps may result from similar disease processes occurring in the lungs.
Michaeloudes C, Seiffert J, Chen S, et al., 2020, Effect of silver nanospheres and nanowires on human airway smooth muscle cells: role of sulfidation, Nanoscale Advances, Vol: 2, Pages: 5635-5647, ISSN: 2516-0230
Background: The toxicity of inhaled silver nanoparticles on contractile and pro-inflammatory airway smooth muscle cells (ASMCs) that control airway calibre is unknown. We explored the oxidative activities and sulfidation processes of the toxic-inflammatory response. Method: Silver nanospheres (AgNSs) of 20 nm and 50 nm diameter and silver nanowires (AgNWs), short S-AgNWs, 1.5 μm and long L-AgNWs, 10 μm, both 72 nm in diameter were manufactured. We measured their effects on cell proliferation, mitochondrial reactive oxygen species (ROS) release and membrane potential, and also performed electron microscopic studies. Main results and findings: The greatest effects were observed for the smallest particles with the highest specific surface area and greatest solubility that were avidly internalised. ASMCs exposed to 20 nm AgNSs (25 μg mL−1) for 72 hours exhibited a significant decrease in DNA incorporation (−72.4%; p < 0.05), whereas neither the 50 nm AgNSs nor the s-AgNWs altered DNA synthesis or viability. There was a small reduction in ASMC proliferation for the smaller AgNS, although Ag+ at 25 μL mL−1 reduced DNA synthesis by 93.3% (p < 0.001). Mitochondrial potential was reduced by both Ag+ (25 μg mL−1) by 47.1% and 20 nm Ag NSs (25 μg mL−1) by 40.1% (*both at p < 0.05), but was not affected by 50 nm AgNSs and the AgNWs. None of the samples showed a change in ROS toxicity. However, malondialdehyde release, associated with greater total ROS, was observed for all AgNPs, to an extent following the geometric size (20 nm AgNS: 213%, p < 0.01; 50 nm AgNS: 179.5%, p < 0.01 and L-AgNWs by 156.2%, p < 0.05). The antioxidant, N-acetylcysteine, prevented the reduction in mitochondrial potential caused by 20 nm AgNSs. The smaller nanostructures were internalised and dissolved within the ASMCs with the formation of non-reactive silver sulphide (Ag2S) on their surface, but with very little uptake of L-AgNWs. When A
Kermani NZ, Pavlidis S, Xie J, et al., 2020, Instability of sputum molecular phenotypes in U-BIOPRED severe asthma, European Respiratory Journal, Vol: 57, Pages: 1-5, ISSN: 0903-1936
Roberts G, Fontanella S, Selby A, et al., 2020, Connectivity patterns between multiple allergen specific IgE antibodies and their association with severe asthma, Journal of Allergy and Clinical Immunology, Vol: 146, Pages: 821-830, ISSN: 0091-6749
BACKGROUND: Allergic sensitization is associated with severe asthma, but assessment of sensitization is not recommended by most guidelines. OBJECTIVE: We hypothesized that patterns of IgE responses to multiple allergenic proteins differ between sensitized participants with mild/moderate and severe asthma. METHODS: IgE to 112 allergenic molecules (components, c-sIgE) was measured using multiplex array among 509 adults and 140 school-age and 131 preschool children with asthma/wheeze from the Unbiased BIOmarkers for the PREDiction of respiratory diseases outcomes cohort, of whom 595 had severe disease. We applied clustering methods to identify co-occurrence patterns of components (component clusters) and patterns of sensitization among participants (sensitization clusters). Network analysis techniques explored the connectivity structure of c-sIgE, and differential network analysis looked for differences in c-sIgE interactions between severe and mild/moderate asthma. RESULTS: Four sensitization clusters were identified, but with no difference between disease severity groups. Similarly, component clusters were not associated with asthma severity. None of the c-sIgE were identified as associates of severe asthma. The key difference between school children and adults with mild/moderate compared with those with severe asthma was in the network of connections between c-sIgE. Participants with severe asthma had higher connectivity among components, but these connections were weaker. The mild/moderate network had fewer connections, but the connections were stronger. Connectivity between components with no structural homology tended to co-occur among participants with severe asthma. Results were independent from the different sample sizes of mild/moderate and severe groups. CONCLUSIONS: The patterns of interactions between IgE to multiple allergenic proteins are predictors of asthma severity among school children and adults with allergic asthma.
Ramu S, Calven J, Michaeloudes C, et al., 2020, TLR3/TAK1 signalling regulates rhinovirus-induced interleukin-33 in bronchial smooth muscle cells, ERJ OPEN RESEARCH, Vol: 6
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- Citations: 4
Wu S-M, Feng P-H, Chuang H-C, et al., 2020, Impaired lnc-IL7R modulatory mechanism of Toll-like receptors is associated with an exacerbator phenotype of chronic obstructive pulmonary disease, FASEB JOURNAL, Vol: 34, Pages: 13317-13332, ISSN: 0892-6638
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- Citations: 5
Orton CM, Garner JL, Shah TA, et al., 2020, Metered Cryospray Modulates Bronchial Epithelial Gene Expression in Patients with Chronic Obstructive Pulmonary Disease, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Marshall D, Salciccioli J, Dobson P, et al., 2020, European Trends in Chronic Obstructive Pulmonary Disease Mortality and Incidence rates 2001 to 2017, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Wang C-H, Huang Y-C, Lee C-L, et al., 2020, Impact of air pollutant of polycyclic aromatic hydrocarbons (PAHs) on the yearly decline of pulmonary in patients with asthma, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Sheng TF, Huang Y-C, Lee S-W, et al., 2020, Impact of PAHs exposure on exacerbation frequency in asthma using a new grid-scale simulation of PM2.5-PAHs distribution, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Melen E, Hallberg J, Backman H, et al., 2020, Spirometric phenotypes from early childhood to young adulthood - A CADSET (Chronic Airway Disease Early Stratification) study, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Wheelock C, Reinke S, Kolmert J, et al., 2020, Urinary metabolomics-profiling of the U-BIOPRED asthma study identified biochemical clusters associated with asthma severity, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Adcock IM, Sun K, Kermani NZ, et al., 2020, A CADSET WP4 transcriptomic analysis of Asthma and COPD overlap, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Tiotiu A, Badi Y, Kermani NZ, et al., 2020, Differential mast cell activation by transcriptomic signature analysis in the U-BIOPRED severe asthma cohort, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Wiegman CH, Li F, Ryffel B, et al., 2020, Oxidative Stress in Ozone-Induced Chronic Lung Inflammation and Emphysema: A Facet of Chronic Obstructive Pulmonary Disease, Frontiers in Immunology, Vol: 11
Prihandoko R, Kaur D, Wiegman CH, et al., 2020, Pathophysiological regulation of lung function by the free fatty acid receptor FFA4, Science Translational Medicine, Vol: 12, Pages: 1-13, ISSN: 1946-6234
Increased prevalence of inflammatory airway diseases including asthma and chronic obstructive pulmonary disease (COPD) together with inadequate disease control by current frontline treatments means that there is a need to define therapeutic targets for these conditions. Here, we investigate a member of the G protein-coupled receptor family, FFA4, that responds to free circulating fatty acids including dietary omega-3 fatty acids found in fish oils. We show that FFA4, although usually associated with metabolic responses linked with food intake, is expressed in the lung where it is coupled to Gq/11 signaling. Activation of FFA4 by drug-like agonists produced relaxation of murine airway smooth muscle mediated at least in part by the release of the prostaglandin E2 (PGE2) that subsequently acts on EP2 prostanoid receptors. In normal mice, activation of FFA4 resulted in a decrease in lung resistance. In acute and chronic ozone models of pollution-mediated inflammation and house dust mite and cigarette smoke-induced inflammatory disease, FFA4 agonists acted to reduce airway resistance, a response that was absent in mice lacking expression of FFA4. The expression profile of FFA4 in human lung was similar to that observed in mice, and the response to FFA4/FFA1 agonists similarly mediated human airway smooth muscle relaxation ex vivo. Our study provides evidence that pharmacological targeting of lung FFA4, and possibly combined activation of FFA4 and FFA1, has in vivo efficacy and might have therapeutic value in the treatment of bronchoconstriction associated with inflammatory airway diseases such as asthma and COPD.
Kolmert J, Gómez C, Balgoma D, et al., 2020, Urinary leukotriene E4 and prostaglandin D2 metabolites increase in adult and childhood severe asthma characterized by type-2 inflammation, American Journal of Respiratory and Critical Care Medicine, Vol: 203, Pages: 37-53, ISSN: 1073-449X
RATIONALE: New approaches are needed to guide personalized treatment of asthma. OBJECTIVE: To test if urinary eicosanoid metabolites can direct asthma phenotyping. METHODS: Urinary metabolites of prostaglandins (PGs), cysteinyl-leukotrienes (LTs) and isoprostanes were quantified in the Unbiased Biomarkers for the Prediction of Respiratory Diseases Outcomes (U-BIOPRED) study including 86 adults with mild-to-moderate asthma (MMA), 411 with severe asthma (SA), and 100 healthy controls (HC). Validation was performed internally in 302 SA subjects followed-up after 12-18 months, and externally in 95 adolescents with asthma. MEASUREMENT AND MAIN RESULTS: Metabolite levels in HC were unrelated to age, BMI and sex, except for the PGE2-pathway. Eicosanoid levels were generally greater in MMA relative to HC, with further elevations in SA. However, PGE2-metabolite levels were either the same or lower in male non-smoking asthmatics as in HC. Metabolite levels were unchanged in asthmatics adherent to oral corticosteroid treatment as documented by urinary prednisolone detection, whereas SA treated with omalizumab had lower levels of LTE4 and the PGD2 metabolite 2,3-dinor-11β-PGF2α. High levels of LTE4 and PGD2-metabolites were associated with lower lung-function, and increased levels of exhaled nitric oxide and eosinophil markers in blood, sputum and urine in U-BIOPRED and in adolescents with asthma. These type-2 (T2) asthma associations were reproduced in the follow-up visit of the U-BIOPRED study, and found to be as sensitive to detect T2 inflammation as the established biomarkers. CONCLUSIONS: Monitoring of urinary eicosanoids can identify T2 asthma and introduces a new non-invasive approach for molecular phenotyping of adult and adolescent asthma. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Niespodziana K, Borochova K, Pazderova P, et al., 2020, Toward personalization of asthma treatment according to trigger factors, JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, Vol: 145, Pages: 1529-1534, ISSN: 0091-6749
Asthma is a severe and chronic disabling disease affecting more than 300 million people worldwide. Although in the past few drugs for the treatment of asthma were available, new treatment options are currently emerging, which appear to be highly effective in certain subgroups of patients. Accordingly, there is a need for biomarkers that allow selection of patients for refined and personalized treatment strategies. Recently, serological chip tests based on microarrayed allergen molecules and peptides derived from the most common rhinovirus strains have been developed, which may discriminate 2 of the most common forms of asthma, that is, allergen- and virus-triggered asthma. In this perspective, we argue that classification of patients with asthma according to these common trigger factors may open new possibilities for personalized management of asthma.
Carlsten C, Salvi S, Wong GWK, et al., 2020, Personal strategies to minimise effects of air pollution on respiratory health: advice for providers, patients and the public, EUROPEAN RESPIRATORY JOURNAL, Vol: 55, ISSN: 0903-1936
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- Citations: 55
Khusial RJ, Honkoop PJ, Usmani O, et al., 2020, Effectiveness of myAirCoach: A mHealth Self-Management System in Asthma, JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE, Vol: 8, Pages: 1972-+, ISSN: 2213-2198
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- Citations: 23
Song W-J, Chung KF, 2020, Pharmacotherapeutic Options for Chronic Refractory Cough, EXPERT OPINION ON PHARMACOTHERAPY, Vol: 21, Pages: 1345-1358, ISSN: 1465-6566
Xie J, Zhang J, Zhang X, et al., 2020, Cough in hypereosinophilic syndrome: case report and literature review, BMC PULMONARY MEDICINE, Vol: 20, ISSN: 1471-2466
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- Citations: 6
Jolliffe DA, Stefanidis C, Wang Z, et al., 2020, Vitamin D metabolism is dysregulated in asthma and chronic obstructive pulmonary disease., American Journal of Respiratory and Critical Care Medicine, Vol: 202, Pages: 371-382, ISSN: 1073-449X
RATIONALE: Vitamin D deficiency is common in patients with asthma and COPD. Low 25-hydroxyvitamin D (25[OH]D) levels may represent a cause or a consequence of these conditions. OBJECTIVE: To determine whether vitamin D metabolism is altered in asthma or COPD. METHODS: We conducted a longitudinal study in 186 adults to determine whether the 25(OH)D response to six oral doses of 3 mg vitamin D3, administered over one year, differed between those with asthma or COPD vs. controls. Serum concentrations of vitamin D3, 25(OH)D3 and 1α,25-dihydroxyvitamin D3 (1α,25[OH]2D3) were determined pre- and post-supplementation in 93 adults with asthma, COPD or neither condition, and metabolite-to-parent compound molar ratios were compared between groups to estimate hydroxylase activity. Additionally, we analyzed fourteen datasets to compare expression of 1α,25[OH]2D3-inducible gene expression signatures in clinical samples taken from adults with asthma or COPD vs. controls. MEASUREMENTS AND MAIN RESULTS: The mean post-supplementation 25(OH)D increase in participants with asthma (20.9 nmol/L) and COPD (21.5 nmol/L) was lower than in controls (39.8 nmol/L; P=0.001). Compared with controls, patients with asthma and COPD had lower molar ratios of 25(OH)D3-to-vitamin D3 and higher molar ratios of 1α,25(OH)2D3-to-25(OH)D3 both pre- and post-supplementation (P≤0.005). Inter-group differences in 1α,25[OH]2D3-inducible gene expression signatures were modest and variable where statistically significant. CONCLUSIONS: Attenuation of the 25(OH)D response to vitamin D supplementation in asthma and COPD associated with reduced molar ratios of 25(OH)D3-to-vitamin D3 and increased molar ratios of 1α,25(OH)2D3-to-25(OH)D3 in serum, suggesting that vitamin D metabolism is dysregulated in these conditions.
Tan KS, Lim RL, Liu J, et al., 2020, Respiratory viral infections in exacerbation of chronic airway inflammatory diseases: novel mechanisms and insights from the upper airway epithelium., Front Cell Dev Biol, Vol: 8, Pages: 99-99, ISSN: 2296-634X
Respiratory virus infection is one of the major sources of exacerbation of chronic airway inflammatory diseases. These exacerbations are associated with high morbidity and even mortality worldwide. The current understanding on viral-induced exacerbations is that viral infection increases airway inflammation which aggravates disease symptoms. Recent advances in in vitro air-liquid interface 3D cultures, organoid cultures and the use of novel human and animal challenge models have evoked new understandings as to the mechanisms of viral exacerbations. In this review, we will focus on recent novel findings that elucidate how respiratory viral infections alter the epithelial barrier in the airways, the upper airway microbial environment, epigenetic modifications including miRNA modulation, and other changes in immune responses throughout the upper and lower airways. First, we reviewed the prevalence of different respiratory viral infections in causing exacerbations in chronic airway inflammatory diseases. Subsequently we also summarized how recent models have expanded our appreciation of the mechanisms of viral-induced exacerbations. Further we highlighted the importance of the virome within the airway microbiome environment and its impact on subsequent bacterial infection. This review consolidates the understanding of viral induced exacerbation in chronic airway inflammatory diseases and indicates pathways that may be targeted for more effective management of chronic inflammatory diseases.
George L, Taylor AR, Esteve-Codina A, et al., 2020, Blood eosinophil count and airway epithelial transcriptome relationships in COPD versus asthma, Allergy, Vol: 75, Pages: 370-380, ISSN: 0105-4538
BackgroundWhether the clinical or pathophysiologic significance of the “treatable trait” high blood eosinophil count in COPD is the same as for asthma remains controversial. We sought to determine the relationship between the blood eosinophil count, clinical characteristics and gene expression from bronchial brushings in COPD and asthma.MethodsSubjects were recruited into a COPD (emphysema versus airway disease [EvA]) or asthma cohort (Unbiased BIOmarkers in PREDiction of respiratory disease outcomes, U‐BIOPRED). We determined gene expression using RNAseq in EvA (n = 283) and Affymetrix microarrays in U‐BIOPRED (n = 85). We ran linear regression analysis of the bronchial brushings transcriptional signal versus blood eosinophil counts as well as differential expression using a blood eosinophil > 200 cells/μL as a cut‐off. The false discovery rate was controlled at 1% (with continuous values) and 5% (with dichotomized values).ResultsThere were no differences in age, gender, lung function, exercise capacity and quantitative computed tomography between eosinophilic versus noneosinophilic COPD cases. Total serum IgE was increased in eosinophilic asthma and COPD. In EvA, there were 12 genes with a statistically significant positive association with the linear blood eosinophil count, whereas in U‐BIOPRED, 1197 genes showed significant associations (266 positive and 931 negative). The transcriptome showed little overlap between genes and pathways associated with blood eosinophil counts in asthma versus COPD. Only CST1 was common to eosinophilic asthma and COPD and was replicated in independent cohorts.ConclusionDespite shared “treatable traits” between asthma and COPD, the molecular mechanisms underlying these clinical entities are predominately different.
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