Publications
1584 results found
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.
Zein J, Gaston B, Bazeley P, et al., 2020, HSD3B1 genotype identifies glucocorticoid responsiveness in severe asthma, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 117, Pages: 2187-2193, ISSN: 0027-8424
Song W-J, Chung KF, 2020, Exploring the clinical relevance of cough hypersensitivity syndrome, EXPERT REVIEW OF RESPIRATORY MEDICINE, Vol: 14, Pages: 275-284, ISSN: 1747-6348
Ponzi E, Vineis P, Chung K, et al., 2020, Accounting for measurement error to assess the effect of air pollution on omics signals, PLoS One, Vol: 15, Pages: 1-16, ISSN: 1932-6203
Studies on the effects of air pollution and more generally environmental exposures onhealth require measurements of pollutants, which are affected by measurement error.This is a cause of bias in the estimation of parameters relevant to the study and canlead to inaccurate conclusions when evaluating associations among pollutants, diseaserisk and biomarkers. Although the presence of measurement error in such studies hasbeen recognized as a potential problem, it is rarely considered in applications andpractical solutions are still lacking. In this work, we formulate Bayesian measurementerror models and apply them to study the link between air pollution and omic signals.The data we use stem from the “Oxford Street II Study”, a randomized crossover trialin which 60 volunteers walked for two hours in a traffic-free area (Hyde Park) and in abusy shopping street (Oxford Street) of London. Metabolomic measurements were madein each individual as well as air pollution measurements, in order to investigate theassociation between short-term exposure to traffic related air pollution and perturbationof metabolic pathways. We implemented error-corrected models in a classical frameworkand used the flexibility of Bayesian hierarchical models to account for dependenciesamong omic signals, as well as among different pollutants. Models were implementedusing traditional Markov Chain Monte Carlo (MCMC) simulative methods as well asintegrated Laplace approximation. The inclusion of a classical measurement error termresulted in variable estimates of the association between omic signals and traffic relatedair pollution measurements, where the direction of the bias was not predictable a priori.The models were successful in including and accounting for different correlationstructures, both among omic signals and among different pollutant exposures. Ingeneral, more associations were identified when the correlation among omics and amongpollutants were modeled, and their number
Cruz AA, Riley JH, Barisal AT, et al., 2020, Asthma similarities across ProAR (Brazil) and U-BIOPRED (Europe) adult cohorts of contrasting locations, ethnicity and socioeconomic status, Respiratory Medicine, Vol: 161, Pages: 1-8, ISSN: 0954-6111
BackgroundAsthma prevalence is 339 million globally. ‘Severe asthma’ (SA) comprises subjects with uncontrolled asthma despite proper management.ObjectivesTo compare asthma from diverse ethnicities and environments.MethodsA cross-sectional analysis of two adult cohorts, a Brazilian (ProAR) and a European (U-BIOPRED). U-BIOPRED comprised of 311 non-smoking with Severe Asthma (SAn), 110 smokers or ex-smokers with SA (SAs) and 88 mild to moderate asthmatics (MMA) while ProAR included 544 SA and 452 MMA. Although these projects were independent, there were similarities in objectives and methodology, with ProAR adopting operating procedures of U-BIOPRED.ResultsAmong SA subjects, age, weight, proportion of former smokers and FEV1 pre-bronchodilator were similar. The proportion of SA with a positive skin prick tests (SPT) to aeroallergens, the scores of sino-nasal symptoms and quality of life were comparable. In addition, blood eosinophil counts (EOS) and the % of subjects with EOS > 300 cells/μl were not different. The Europeans with SA however, were more severe with a greater proportion of continuous oral corticosteroids (OCS), worse symptoms and more frequent exacerbations. FEV1/FVC pre- and post-bronchodilator were lower among the Europeans. The MMA cohorts were less comparable in control and treatment, but similar in the proportion of allergic rhinitis, gastroesophageal reflux disease and EOS >3%.ConclusionsProAR and U-BIOPRED cohorts, with varying severity, ethnicity and environment have similarities, which provide the basis for global external validation of asthma phenotypes. This should stimulate collaboration between asthma consortia with the aim of understanding SA, which will lead to better management.
Holguin F, Cardet JC, Chung KF, et al., 2020, Management of severe asthma: a European Respiratory Society/American Thoracic Society Guideline, European Respiratory Journal, Vol: 55, ISSN: 0903-1936
This document provides clinical recommendations for the management of severe asthma. Comprehensive evidence syntheses, including meta-analyses, were performed to summarise all available evidence relevant to the Task Force's questions. The evidence was appraised using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach and the results were summarised in evidence profiles. The evidence syntheses were discussed and recommendations formulated by a multidisciplinary Task Force of asthma experts, who made specific recommendations on 6 specific questions. After considering the balance of desirable and undesirable consequences, quality of evidence, feasibility, and acceptability of various interventions, the Task Force made the following recommendations: 1) Suggest using anti-IL5 and anti IL-5Rα for severe uncontrolled adult eosinophilic asthma phenotypes; 2) suggest using blood eosinophil cut-point of ≥150/μL to guide anti-IL5 initiation in adult patients with severe asthma; and 3) Suggest considering specific eosinophil (≥260/μL) and FeNO (≥19.5 ppb) cutoffs to identify adolescents or adults with the greatest likelihood or response to anti-IgE therapy; 4) Suggest using inhaled tiotropium for adolescents and adults with severe uncontrolled asthma despite GINA step 4-5 or NAEPP step 5 therapies; 5) Suggest a trial of chronic macrolide therapy to reduce asthma exacerbations in persistently symptomatic or uncontrolled patients on GINA step 5 or NAEPP step 5 therapies, irrespective of asthma phenotype; 6) Suggest using anti-IL4/13 for adult patients with severe eosinophilic asthma, and for those with severe corticosteroid-dependent asthma regardless of blood eosinophil levels. These recommendations should be reconsidered as new evidence becomes available.
van Bragt JJMH, Adcock IM, Bel EHD, et al., 2020, Characteristics and treatment regimens across ERS SHARP severe asthma registries, European Respiratory Journal, Vol: 55, ISSN: 0903-1936
Little is known about the characteristics and treatments of patients with severe asthma across Europe but both are likely to vary. This is the first study in the ERS Severe Heterogeneous Asthma Research collaboration, Patient-centred (SHARP) and it is designed to explore these variations. Therefore, we aimed to compare characteristics of patients in European severe asthma registries and treatments before starting biologicals. This was a cross-sectional retrospective analysis of aggregated data from 11 national severe asthma registries that joined SHARP with established patient databases. Analysis of data from 3233 patients showed many differences in characteristics and life style factors. Current smokers ranged from 0% (Poland, PL, Sweden, SE) to 9.5% (Belgium, BE), mean BMI ranged from 26.2 (Italy) to 30.6 kg·m-2 (UK) and the largest difference in mean pre-bronchodilator FEV1% pred. was 20.9% (Netherlands versus Hungary). Before starting biologicals patients were treated differently between countries: mean ICS dose ranged from 700 to 1335 µg·day-1 between those from Slovenia (SL) versus PL when starting anti-IL-5 antibody and from 772 to 1344 µg·day-1 in those starting anti-IgE (SL versus Spain). Maintenance OCS use ranged from 21.0% (BE) to 63.0% (SE) and from 9.1% (Denmark) to 56.1% (UK) in patients starting anti-IL-5 and anti-IgE, respectively. The severe asthmatic population in Europe is heterogeneous and differs in both clinical characteristics and treatment, often appearing not to comply with the current ERS/ATS guidelines definition of severe asthma. Treatment regimens before starting biologicals were different from inclusion criteria in clinical trials and varied between countries.
Michaeloudes C, Bhavsar PK, Mumby S, et al., 2020, Role of metabolic reprogramming in pulmonary innate immunity and Its impact on lung diseases, Journal of Innate Immunity, Vol: 12, Pages: 1-16, ISSN: 1662-811X
Lung innate immunity is the first line of defence against inhaled allergens, pathogens and environmental pollutants. Cellular metabolism plays a key role in innate immunity. Catabolic pathways, including glycolysis and fatty acid oxidation (FAO), are interconnected with biosynthetic and redox pathways. Innate immune cell activation and differentiation trigger extensive metabolic changes that are required to support their function. Pro-inflammatory polarisation of macrophages and activation of dendritic cells, mast cells and neutrophils are associated with increased glycolysis and a shift towards the pentose phosphate pathway and fatty acid synthesis. These changes provide the macromolecules required for proliferation and inflammatory mediator production and reactive oxygen species for anti-microbial effects. Conversely, anti-inflammatory macrophages use primarily FAO and oxidative phosphorylation to ensure efficient energy production and redox balance required for prolonged survival. Deregulation of metabolic reprogramming in lung diseases, such as asthma and chronic obstructive pulmonary disease, may contribute to impaired innate immune cell function. Understanding how innate immune cell metabolism is altered in lung disease may lead to identification of new therapeutic targets. This is important as drugs targeting a number of metabolic pathways are already in clinical development for the treatment of other diseases such as cancer.
Preston GW, Dagnino S, Ponzi E, et al., 2020, Relationships between airborne pollutants, serum albumin adducts and short-term health outcomes in an experimental crossover study, Chemosphere, Vol: 239, ISSN: 1879-1298
Exposure to air pollution can have both short-term and long-term effects on health. However, the relationships between specific pollutants and their effects can be obscured by characteristics of both the pollution and the exposed population. One way of elucidating the relationships is to link exposures and internal changes at the level of the individual. To this end, we combined personal exposure monitoring (59 individuals, Oxford Street II crossover study) with mass-spectrometry-based analyses of putative serum albumin adducts (fixed-step selected reaction monitoring). We attempted to infer adducts' identities using data from another, higher-resolution mass spectrometry method, and were able to detect a semi-synthetic standard with both methods. A generalised least squares regression method was used to test for associations between amounts of adducts and pollution measures (ambient concentrations of nitrogen dioxide and particulate matter), and between amounts of adducts and short-term health outcomes (measures of lung health and arterial stiffness). Amounts of some putative adducts (e.g., one with a positive mass shift of approximately 143Da) were associated with exposure to pollution (11 associations), and amounts of other adducts were associated with health outcomes (eight associations). Adducts did not appear to provide a link between exposures and short-term health outcomes.
, 2019, Kian Fan Chung, Elliot Israel and Peter G. Gibson (Editors). ERS Monograph Series. Severe Asthma. ERJ publications. Pub 2019. 360 pages. DOI: 10.1183/2312508X.erm8419. ISBN (electronic): 978-1-84984-104-7, Publisher: ERJ publications
Garcia JF, Xu B, Hui C, et al., 2019, REGULATION OF MITOCHONDRIAL TRANSFER BETWEEN AIRWAY SMOOTH MUSCLE CELLS (ASMCS): RELEVANCE TO COPD, Winter Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A48-A49, ISSN: 0040-6376
Chung KF, McGarvey L, Mazzone SB, 2019, Progress in cough hypersensitivity at the Tenth London International Cough Symposium 2018 (10th LICS 2018), PULMONARY PHARMACOLOGY & THERAPEUTICS, Vol: 59, ISSN: 1094-5539
- Author Web Link
- Cite
- Citations: 1
Lai K, Long L, Yi F, et al., 2019, Age and Sex Distribution of Chinese Chronic Cough Patients and Their Relationship With Capsaicin Cough Sensitivity, ALLERGY ASTHMA & IMMUNOLOGY RESEARCH, Vol: 11, Pages: 871-884, ISSN: 2092-7355
- Author Web Link
- Cite
- Citations: 25
Song W-J, Lee J-H, Kang Y, et al., 2019, Future Risks in Patients With Severe Asthma, ALLERGY ASTHMA & IMMUNOLOGY RESEARCH, Vol: 11, Pages: 763-778, ISSN: 2092-7355
- Author Web Link
- Cite
- Citations: 38
Östling J, van Geest M, Schofield JPR, et al., 2019, IL-17-high asthma with features of a psoriasis immunophenotype, Journal of Allergy and Clinical Immunology, Vol: 144, Pages: 1198-1213, ISSN: 0091-6749
BACKGROUND: The role of interleukin-17 immunity is well established in inflammatory diseases like psoriasis and inflammatory bowel disease but not in asthma where further study is required. OBJECTIVE: To undertake a deep-phenotyping study of asthmatics with up-regulated interleukin-17 immunity. METHODS: Whole genome transcriptomic analysis was performed using epithelial brushings, bronchial biopsies (91 asthmatics patients and 46 healthy controls) and whole blood samples (n=498) from the U-BIOPRED cohort. Gene signatures induced in vitro by interleukin-17 and interleukin-13 in bronchial epithelial cells were used to identify patients with interleukin-17-high and interleukin-13-high phenotypes of asthma. RESULTS: 22 out of 91 patients were identified with interleukin-17 and 9 patients with interleukin-13 gene signatures. The interleukin-17-high asthmatics were characterised by risk of frequent exacerbations, airway (sputum and mucosal) neutrophilia, decreased lung microbiota diversity and urinary biomarker evidence of activation of the thromboxane B2 pathway. In pathway analysis, the differentially expressed genes in interleukin-17-high patients were shared with those reported as altered in psoriasis lesions, and included genes regulating epithelial barrier function and defence mechanisms, such as interleukin-1β, interleukin-6, interleukin-8, and beta-defensin. CONCLUSION: The interleukin-17-high asthma phenotype, characterized by bronchial epithelial dysfunction, upregulated anti-microbial and inflammatory response, resembles the immunophenotype of psoriasis, including activation of the thromboxane B2 pathway which should be considered as a biomarker for this phenotype in further studies, including clinical trials targeting interleukin-17.
Budden KF, Shukla SD, Rehman SF, et al., 2019, Functional effects of the microbiota in chronic respiratory disease, Lancet Respiratory Medicine, Vol: 7, Pages: 907-920, ISSN: 2213-2600
The composition of the lung microbiome is increasingly well characterised, with changes in microbial diversity or abundance observed in association with several chronic respiratory diseases such as asthma, cystic fibrosis, bronchiectasis, and chronic obstructive pulmonary disease. However, the precise effects of the microbiome on pulmonary health and the functional mechanisms by which it regulates host immunity are only now beginning to be elucidated. Bacteria, viruses, and fungi from both the upper and lower respiratory tract produce structural ligands and metabolites that interact with the host and alter the development and progression of chronic respiratory diseases. Here, we review recent advances in our understanding of the composition of the lung microbiome, including the virome and mycobiome, the mechanisms by which these microbes interact with host immunity, and their functional effects on the pathogenesis, exacerbations, and comorbidities of chronic respiratory diseases. We also describe the present understanding of how respiratory microbiota can influence the efficacy of common therapies for chronic respiratory disease, and the potential of manipulation of the microbiome as a therapeutic strategy. Finally, we highlight some of the limitations in the field and propose how these could be addressed in future research.
Tay TR, Choo XN, Yii A, et al., 2019, Asthma phenotypes in a multi-ethnic Asian cohort, RESPIRATORY MEDICINE, Vol: 157, Pages: 42-48, ISSN: 0954-6111
- Author Web Link
- Cite
- Citations: 9
Zhang Q, Fu X, Zhu L, et al., 2019, Characteristics of severe asthma in China with one year follow-up: the C-BIOPRED study, International Congress of the European-Respiratory-Society (ERS), Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
van Bragt JJMH, Adcock IM, Anderson G, et al., 2019, Characteristics and treatment regimens across ERS SHARP severe asthma registries, International Congress of the European-Respiratory-Society (ERS), Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
- Author Web Link
- Cite
- Citations: 2
Kermani NZ, Pavlidis S, Riley JH, et al., 2019, Prediction of longitudinal inflammatory phenotypes using baseline sputum transcriptomics in UBIOPRED, EUROPEAN RESPIRATORY JOURNAL, Vol: 54, ISSN: 0903-1936
Yao X, Yan X, Jia M, et al., 2019, Increased METEORIN-LIKE (ML) expression promotes lung inflammation in asthma, EUROPEAN RESPIRATORY JOURNAL, Vol: 54, ISSN: 0903-1936
Khusial R, Honkoop PJ, Usmani O, et al., 2019, myAirCoach: mHealth assisted self-management in patients with uncontrolled asthma, a randomized control trial, International Congress of the European-Respiratory-Society (ERS), Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
- Author Web Link
- Cite
- Citations: 3
Wang C-H, Lo C-Y, He J-R, et al., 2019, Oxygen desaturation is associated with fibrocyte activation via epidermal growth factor receptor/hypoxia-inducible factor(HIF)-1a axis in COPD, International Congress of the European-Respiratory-Society (ERS), Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
- Author Web Link
- Cite
- Citations: 1
Ibrahim MIA, Brinkman P, Vijverberg S, et al., 2019, Microbiome-driven clusters in severe asthma derived from induced sputum: identification and stability over time, EUROPEAN RESPIRATORY JOURNAL, Vol: 54, ISSN: 0903-1936
Garcia JF, Mak J, Xu B, et al., 2019, Regulation of mitochondrial transfer between airway smooth muscle cells: relevance to COPD, International Congress of the European-Respiratory-Society (ERS), Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Perotin-Collard J-M, Schofield JP, Nicholas B, et al., 2019, Subtypes of eosinophilic asthma with discrete gene pathway phenotypes, EUROPEAN RESPIRATORY JOURNAL, Vol: 54, ISSN: 0903-1936
Badi Y, Pavel AB, Riley JH, et al., 2019, Is Fezakinumab, an anti-IL22 antibody, a putative novel therapy for a subset of severe asthma?, EUROPEAN RESPIRATORY JOURNAL, Vol: 54, ISSN: 0903-1936
Michaeloudes C, Garcia JF, Xu B, et al., 2019, Altered mitochondrial function in proliferating airway smooth muscle cells, International Congress of the European-Respiratory-Society (ERS), Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.