Publications
298 results found
Pearce C, Chan A, Horne R, et al., 2018, "IT'S LIKE TRYING TO FIT A PIECE INTO AN ALREADY NOT WORKING PUZZLE": NON ADHERENCE TO INHALED CORTICOSTEROIDS IN YOUNG PEOPLE WITH PROBLEMATIC ASTHMA: A QUALITATIVE STUDY, Publisher: SPRINGER, Pages: S191-S191, ISSN: 1070-5503
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- Citations: 2
Pearce CJ, Chan A, Horne R, et al., 2018, WHAT ARE THE EFFECTIVE ASPECTS OF ADHERENCE INTERVENTIONS FOR INHALED CORTICOSTEROIDS IN CHILDREN WITH ASTHMA?: A SYSTEMATIC REVIEW, Publisher: SPRINGER, Pages: S166-S166, ISSN: 1070-5503
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- Citations: 1
Emma R, Bansal AT, Kolmert J, et al., 2018, Enhanced oxidative stress in smoking and ex-smoking severe asthma in the U-BIOPRED cohort, PLoS ONE, Vol: 13, ISSN: 1932-6203
Oxidative stress is believed to be a major driver of inflammation in smoking asthmatics. The U-BIOPRED project recruited a cohort of Severe Asthma smokers/ex-smokers (SAs/ex) and non-smokers (SAn) with extensive clinical and biomarker information enabling characterization of these subjects. We investigated oxidative stress in severe asthma subjects by analysing urinary 8-iso-PGF2α and the mRNA-expression of the main pro-oxidant (NOX2; NOSs) and anti-oxidant (SODs; CAT; GPX1) enzymes in the airways of SAs/ex and SAn. All the severe asthma U-BIOPRED subjects were further divided into current smokers with severe asthma (CSA), ex-smokers with severe asthma (ESA) and non-smokers with severe asthma (NSA) to deepen the effect of active smoking. Clinical data, urine and sputum were obtained from severe asthma subjects. A bronchoscopy to obtain bronchial biopsy and brushing was performed in a subset of subjects. The main clinical data were analysed for each subset of subjects (urine-8-iso-PGF2α; IS-transcriptomics; BB-transcriptomics; BBr-transcriptomics). Urinary 8-iso-PGF2α was quantified using mass spectrometry. Sputum, bronchial biopsy and bronchial brushing were processed for mRNA expression microarray analysis. Urinary 8-iso-PGF2α was increased in SAs/ex, median (IQR) = 31.7 (24.5–44.7) ng/mmol creatinine, compared to SAn, median (IQR) = 26.6 (19.6–36.6) ng/mmol creatinine (p< 0.001), and in CSA, median (IQR) = 34.25 (24.4–47.7), vs. ESA, median (IQR) = 29.4 (22.3–40.5), and NSA, median (IQR) = 26.5 (19.6–16.6) ng/mmol creatinine (p = 0.004). Sputum mRNA expression of NOX2 was increased in SAs/ex compared to SAn (probe sets 203922_PM_s_at fold-change = 1.05 p = 0.006; 203923_PM_s_at fold-change = 1.06, p = 0.003; 233538_PM_s_at fold-change = 1.06, p = 0.014). The mRNA expression of antioxidant enzymes were similar between the two severe asthma cohorts in all airway samples. NOS2 mRNA expression was decreased in b
Pavlidis S, Guo Y, Sun K, et al., 2018, Weighted Gene Co-expression Network Analysis of blood paediatric samples from the U-BIOPRED study identifies oxidative stress association with asthma severity, 28th International Congress of the European-Respiratory-Society (ERS), Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Alahmadi F, Simpson A, Gomez C, et al., 2018, Measures of adherence in patients with severe asthma prescribed systemic steroids in the U-BIOPRED cohort, 28th International Congress of the European-Respiratory-Society (ERS), Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
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- Citations: 3
Selby L, Beresford F, Saglani S, et al., 2018, Emotional distress in children with problematic severe asthma is associated with parental anxiety and depression, 28th International Congress of the European-Respiratory-Society (ERS), Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
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- Citations: 3
Schofield JPR, Bigler J, Boedigheimer M, et al., 2018, Topological data analysis (TDA) of U-BIOPRED paediatric peripheral blood gene expression identified asthma phenotypes characterised by alternative splicing of glucocorticoid receptor (GR) mRNA, 28th International Congress of the European-Respiratory-Society (ERS), Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
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- Citations: 2
Shaw D, Bansal AT, Riley J, et al., 2018, Late Breaking Abstract - Longitudinal analysis of variation in clinical features from the U-BIOPRED severe asthma cohort, 28th International Congress of the European-Respiratory-Society (ERS), Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Hashimoto S, Brinkman P, Lefaudeux D, et al., 2018, Unsupervised and externally validated clinical cluster analysis from the U-BIOPRED paediatric cohorts, 28th International Congress of the European-Respiratory-Society (ERS), Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
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- Citations: 1
Mcmurray A, Fleming L, Cunningham S, 2018, Defining acute asthma severity - how do worldwide asthma guidelines compare?, 28th International Congress of the European-Respiratory-Society (ERS), Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Hellen R, Dhonncha EN, Havelin A, et al., 2018, An audit comparing pain scores during conventional and white light topical 5 methyl aminolaevulinic acid photodynamic therapy for superficial basal cell carcinoma and squamous cell carcinoma <i>in situ</i>, 98th Annual Meeting of the British-Association-of-Dermatologists (BAD), Publisher: WILEY, Pages: 56-56, ISSN: 0007-0963
Stewart AC, Gannon KN, Beresford F, et al., 2018, Adolescent and caregivers' experiences of electronic adherence assessment in paediatric problematic severe asthma, Journal of Child Health Care, Vol: 22, Pages: 238-250, ISSN: 1367-4935
This study explored the experiences of adolescents and their caregivers regarding adherence to inhaled corticosteroids which are assessed through an electronic monitoring device (EMD). These devices are increasingly being used for assessing medication adherence, yet there is little information about patient's experience of these tools. Semi-structured interviews were conducted with eight adolescents with severe asthma, aged 11-15 years, who were electronically monitored as part of their care, along with their caregivers. Interviews were analysed using thematic analysis. Three themes were identified: 'they were trying to help me get better', 'checking up and catching out' and 'who is responsible?' The themes highlighted differences in priorities between participant groups, the impact of monitoring on the healthcare relationship and the dilemma of transferring responsibility for asthma management to adolescents. The findings suggest it is important for healthcare professionals to engage with patient's preferences and priorities when introducing EMDs.
Castro-Rodriguez JA, Saglani S, Rodriguez-Martinez CE, et al., 2018, The relationship between inflammation and remodeling in childhood asthma: a systematic review, Pediatric Pulmonology, Vol: 53, Pages: 824-835, ISSN: 1099-0496
OBJECTIVES: We aimed to perform a systematic review of all studies with direct measurements of both airway inflammation and remodeling in the subgroup of children with repeated wheezing and/or persistent asthma severe enough to warrant bronchoscopy, to address whether airway inflammation precedes remodeling or is a parallel process, and also to assess the impact of remodeling on lung function. METHODS: Four databases were searched up to June 2017. Two independent reviewers screened the literature and extracted relevant data. RESULTS: We found 526 references, and 39 studies (2390 children under 18 years old) were included. Airway inflammation (eosinophilic/neutrophilic) and remodeling were not present in wheezers at a mean age of 12 months, but in older pre-school children (mean 2.5 years), remodeling (mainly increased reticular basement membrane [RBM] thickness and increased area of airway smooth muscle) and also airway eosinophilia was reported. This was worse in school-age children. RBM thickness was similar in atopic and non-atopic preschool wheezers. Airway remodeling was correlated with lung function in seven studies, with FeNO in three, and with HRCT-scan in one. Eosinophilic inflammation was not seen in patients without remodeling. There were no invasive longitudinal or intervention studies. CONCLUSION: The relationship between inflammation and remodeling in children cannot be determined. Failure to demonstrate eosinophilic inflammation in the absence of remodeling is contrary to the hypothesis that inflammation causes these changes. We need reliable, non-invasive markers of remodeling in particular if this is to be addressed.
Burg D, Schofield JPR, Brandsma J, et al., 2018, Large-scale label-free quantitative mapping of the sputum proteome, Journal of Proteome Research, Vol: 17, Pages: 2072-2091, ISSN: 1535-3893
Analysis of induced sputum supernatant is a minimally invasive approach to study the epithelial lining fluid and, thereby, provide insight into normal lung biology and the pathobiology of lung diseases. We present here a novel proteomics approach to sputum analysis developed within the U-BIOPRED (unbiased biomarkers predictive of respiratory disease outcomes) international project. We present practical and analytical techniques to optimize the detection of robust biomarkers in proteomic studies. The normal sputum proteome was derived using data-independent HDMSE applied to 40 healthy nonsmoking participants, which provides an essential baseline from which to compare modulation of protein expression in respiratory diseases. The "core" sputum proteome (proteins detected in ≥40% of participants) was composed of 284 proteins, and the extended proteome (proteins detected in ≥3 participants) contained 1666 proteins. Quality control procedures were developed to optimize the accuracy and consistency of measurement of sputum proteins and analyze the distribution of sputum proteins in the healthy population. The analysis showed that quantitation of proteins by HDMSE is influenced by several factors, with some proteins being measured in all participants' samples and with low measurement variance between samples from the same patient. The measurement of some proteins is highly variable between repeat analyses, susceptible to sample processing effects, or difficult to accurately quantify by mass spectrometry. Other proteins show high interindividual variance. We also highlight that the sputum proteome of healthy individuals is related to sputum neutrophil levels, but not gender or allergic sensitization. We illustrate the importance of design and interpretation of disease biomarker studies considering such protein population and technical measurement variance.
Liu NM, van Aalderen W, Carlsen KCL, et al., 2018, Severe Paediatric Asthma Collaborative in Europe (SPACE): protocol for a European registry, Breathe, Vol: 14, Pages: 93-98, ISSN: 2073-4735
The development of new asthma biologics and receptor blockers for the treatment of paediatric severe asthma raises challenges. It is unclear whether there are sufficient children in Europe to recruit into randomised placebo-controlled trials to establish efficacy and safety in this age group.In February 2016, the European Respiratory Society funded a clinical research collaboration entitled “Severe Paediatric Asthma Collaborative in Europe” (SPACE). We now report the SPACE protocol for a prospective pan-European observational study of paediatric severe asthma. Inclusion criteria are: 1) age 6–17 years, 2) severe asthma managed at a specialised centre for ≥6 months, 3)clinical and spirometry evidence of asthma, and 4) reaching a pre-defined treatment threshold. The exclusion criterion is the presence of conditions which mimic asthma symptoms. Eligible children will be prospectively recruited into a registry, recording demographics, comorbidities, quality of life, family history, neonatal history, smoking history, asthma background, investigations, and treatment. Follow-up will provide longitudinal data on asthma control and treatment changes.The SPACE registry, by identifying well-phenotyped children eligible for clinical trials, and the amount of overlap in eligibility criteria, will inform the design of European trials in paediatric severe asthma, and facilitate observational research where data from single centres are limited.
Fleming L, 2018, Sputum: Infection and inflammation, 17th International Congress of Pediatric Pulmonology, Publisher: Wiley, Pages: S39-S40, ISSN: 1099-0496
Fleming L, 2018, Exercise-induced laryngeal obstruction, 17th International Congress of Pediatric Pulmonology, Publisher: Wiley, Pages: S37-S38, ISSN: 1099-0496
Liu NM, van Aalderen W, Carlsen KCL, et al., 2018, Severe Paediatric Asthma Collaborative in Europe (SPACE): protocol for a European registry., Breathe (Sheff), Vol: 14, Pages: 93-98, ISSN: 1810-6838
The development of new asthma biologics and receptor blockers for the treatment of paediatric severe asthma raises challenges. It is unclear whether there are sufficient children in Europe to recruit into randomised placebo-controlled trials to establish efficacy and safety in this age group. In February 2016, the European Respiratory Society funded a clinical research collaboration entitled "Severe Paediatric Asthma Collaborative in Europe" (SPACE). We now report the SPACE protocol for a prospective pan-European observational study of paediatric severe asthma. Inclusion criteria are: 1) age 6-17 years, 2) severe asthma managed at a specialised centre for ≥6 months, 3)clinical and spirometry evidence of asthma, and 4) reaching a pre-defined treatment threshold. The exclusion criterion is the presence of conditions which mimic asthma symptoms. Eligible children will be prospectively recruited into a registry, recording demographics, comorbidities, quality of life, family history, neonatal history, smoking history, asthma background, investigations, and treatment. Follow-up will provide longitudinal data on asthma control and treatment changes. The SPACE registry, by identifying well-phenotyped children eligible for clinical trials, and the amount of overlap in eligibility criteria, will inform the design of European trials in paediatric severe asthma, and facilitate observational research where data from single centres are limited.
Chan AHY, De Simoni A, Wileman V, et al., 2018, Digital interventions to improve adherence to maintenance medication in asthma, Cochrane Database of Systematic Reviews, Vol: 2018, ISSN: 1469-493X
© 2018 The Cochrane Collaboration. This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To determine the effectiveness of digital adherence interventions for improving adherence to maintenance treatments in asthma.
De Meulder B, Lefaudeux D, Bansal AT, et al., 2018, A computational framework for complex disease stratification from multiple large-scale datasets, BMC Systems Biology, Vol: 12, ISSN: 1752-0509
BACKGROUND: Multilevel data integration is becoming a major area of research in systems biology. Within this area, multi-'omics datasets on complex diseases are becoming more readily available and there is a need to set standards and good practices for integrated analysis of biological, clinical and environmental data. We present a framework to plan and generate single and multi-'omics signatures of disease states. METHODS: The framework is divided into four major steps: dataset subsetting, feature filtering, 'omics-based clustering and biomarker identification. RESULTS: We illustrate the usefulness of this framework by identifying potential patient clusters based on integrated multi-'omics signatures in a publicly available ovarian cystadenocarcinoma dataset. The analysis generated a higher number of stable and clinically relevant clusters than previously reported, and enabled the generation of predictive models of patient outcomes. CONCLUSIONS: This framework will help health researchers plan and perform multi-'omics big data analyses to generate hypotheses and make sense of their rich, diverse and ever growing datasets, to enable implementation of translational P4 medicine.
Takahashi K, Pavlidis S, Ng Kee Kwong F, et al., 2018, Sputum proteomics and airway cell transcripts of current and ex-smokers with severe asthma in U-BIOPRED: an exploratory analysis, European Respiratory Journal, Vol: 51, ISSN: 0903-1936
Background: Severe asthma patients with a significant smoking history have airflow obstruction with reported neutrophilia. We hypothesise that multi1omic analysis will enable the definition of smoking and ex1smoking severe asthma molecular phenotypes.Methods The U1BIOPRED severe asthma patients containing current1smokers (CSA), ex1smokers (ESA), non1smokers (NSA) and healthy non1smokers (NH) was examined. Blood and sputum cell counts, fractional exhaled nitric oxide and spirometry were obtained. Exploratory proteomic analysis of sputum supernatants and transcriptomic analysis of bronchial brushings, biopsies and sputum cells was performed. Results Colony stimulating factor (CSF)2 protein levels were increased in CSA sputum supernatants with azurocidin 1, neutrophil elastase and CXCL8 upregulated in ESA. Phagocytosis and innate immune pathways were associated with neutrophilic inflammation in ESA. Gene Set Variation Analysis of bronchial epithelial cell transcriptome from CSA showed enrichment of xenobiotic metabolism, oxidative stress and endoplasmic reticulum stress compared to other groups. CXCL5 and matrix metallopeptidase 12 genes were upregulated in ESA and the epithelial protective genes, mucin 2 and cystatin SN, were downregulated. Conclusion Despite little difference in clinical characteristics, CSA were distinguishable from ESA subjects at the sputum proteomic level with CSA having increased CSF2 expression and ESA patients showed sustained loss of epithelial barrier processes.
Rosenthal R, Berger W, Bronsky E, et al., 2018, Tri-nasal triamcinolone acetonide nasal spray 200 and 400 μg qd versus placebo and nasacort triamcinolone acetonide nasal aerosol 440 μg qd in patients suffering from seasonal allergic rhinitis during the grass season, AMERICAN JOURNAL OF RHINOLOGY, Vol: 12, Pages: 427-433, ISSN: 1050-6586
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- Citations: 9
Fleming L, 2018, Asthma exacerbation prediction: recent insights, Current Opinion in Allergy and Clinical Immunology, Vol: 18, Pages: 117-123, ISSN: 1473-6322
PURPOSE OF REVIEW: Asthma attacks are frequent in children with asthma and can lead to significant adverse outcomes including time off school, hospital admission and death. Identifying children at risk of an asthma attack affords the opportunity to prevent attacks and improve outcomes. RECENT FINDINGS: Clinical features, patient behaviours and characteristics, physiological factors, environmental data and biomarkers are all associated with asthma attacks and can be used in asthma exacerbation prediction models. Recent studies have better characterized children at risk of an attack: history of a severe exacerbation in the previous 12 months, poor adherence and current poor control are important features which should alert healthcare professionals to the need for remedial action. There is increasing interest in the use of biomarkers. A number of novel biomarkers, including patterns of volatile organic compounds in exhaled breath, show promise. Biomarkers are likely to be of greatest utility if measured frequently and combined with other measures. To date, most prediction models are based on epidemiological data and population-based risk. The use of digital technology affords the opportunity to collect large amounts of real-time data, including clinical and physiological measurements and combine these with environmental data to develop personal risk scores. These developments need to be matched by changes in clinical guidelines away from a focus on current asthma control and stepwise escalation in drug therapy towards inclusion of personal risk scores and tailored management strategies including nonpharmacological approaches. SUMMARY: There have been significant steps towards personalized prediction models of asthma attacks. The utility of such models needs to be tested in the ability not only to predict attacks but also to reduce them.
Delimpoura V, Bostantzoglou C, Liu N, et al., 2018, Novel therapies for severe asthma in children and adults., Breathe (Sheff), Vol: 14, Pages: 59-62, ISSN: 1810-6838
The heterogeneous nature of asthma requires personalised treatments. Monoclonal antibody treatments showed good efficacy, and should be considered when symptoms are poorly controlled despite good inhaler technique, compliance and controlled comorbidities. http://ow.ly/UWpg30hImQh.
Delimpoura V, Bostantzoglou C, Liu N, et al., 2018, Novel therapies for severe asthma in children and adults, Breathe, Vol: 14, Pages: 59-62, ISSN: 1810-6838
Nagakumar P, Gambir N, Sanghani N, et al., 2018, Role of a prolonged inpatient admission when evaluating children with problematic severe asthma., European Respiratory Journal, Vol: 51, ISSN: 0903-1936
Belgrave D, Cassidy R, Custovic A, et al., 2018, Predictive Modelling Strategies to Understand Heterogeneous Manifestations of Asthma in Early Life, 16th IEEE International Conference on Machine Learning and Applications (ICMLA), Publisher: IEEE, Pages: 68-75
Wheezing is common among children and ~50% of those under 6 years of age are thought to experience at least one episode of wheeze. However, due to the heterogeneity of symptoms there are difficulties in treating and diagnosing these children. `Phenotype specific therapy' is one possible avenue of treatment, whereby we use significant pathology and physiology to identify and treat pre-schoolers with wheeze. By performing feature selection algorithms and predictive modelling techniques, this study will attempt to determine if it is possible to robustly distinguish patient diagnostic categories among pre-school children. Univariate feature analysis identified more objective variables and recursive feature elimination a larger number of subjective variables as important in distinguishing between patient categories. Predicative modelling saw a drop in performance when subjective variables were removed from analysis, indicating that these variables are important in distinguishing wheeze classes. We achieved 90%+ performance in AUC, sensitivity, specificity, and accuracy, and 80%+ in kappa statistic, in distinguishing ill from healthy patients. Developed in a synergistic statistical - machine learning approach, our methodologies propose also a novel ROC Cross Evaluation method for model post-processing and evaluation. Our predictive modelling's stability was assessed in computationally intensive Monte Carlo simulations.
Cook J, Martin-Alonso A, Sanghani N, et al., 2018, Children with Pre-School Wheeze Have Neutrophilic Airway Inflammation Associated with Bacteria and Viruses During Periods of Clinical Stability, International Conference of the American-Thoracic-Society, Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Jochmann A, Artusio L, Jamalzadeh A, et al., 2017, Electronic monitoring of adherence to inhaled corticosteroids: an essential tool in identifying severe asthma in children, European Respiratory Journal, Vol: 50, ISSN: 0903-1936
International guidelines recommend that severe asthma can only be diagnosed after contributory factors, including adherence, have been addressed. Accurate assessment of adherence is difficult in clinical practice. We hypothesised that electronic monitoring in children would identify nonadherence, thus delineating the small number with true severe asthma.Asthmatic children already prescribed inhaled corticosteroids were prospectively recruited and persistence of adherence assessed using electronic monitoring devices. Spirometry, airway inflammation and asthma control were measured at the start and end of the monitoring period.93 children (62 male; median age 12.4 years) were monitored for a median of 92 days. Median (range) monitored adherence was 74% (21-99%). We identified four groups: 1) good adherence during monitoring with improved control, 24% (likely previous poor adherence); 2) good adherence with poor control, 18% (severe therapy-resistant asthma); 3) poor adherence with good control, 26% (likely overtreated); and 4) poor adherence with poor control, 32%. No clinical parameter prior to monitoring distinguished these groups.Electronic monitoring is a useful tool for identifying children in whom a step up in treatment is indicated. Different approaches are needed in those who are controlled when adherent or who are nonadherent. Electronic monitoring is essential in a paediatric severe asthma clinic.
Irving S, Bingham Y, Bossley C, et al., 2017, Change in lung clearance index and exhaled nitric oxide as markers of systemic corticosteroid response in children with severe asthma, Winter Meeting of the British-Thoracic-Society, Publisher: BMJ Publishing Group, Pages: A44-A45, ISSN: 1468-3296
Introduction Children with severe therapy resistant asthma (STRA) have heterogeneous disease with variable response to steroids. Currently, spirometry (forced expiratory volume in 1 s (FEV1)) is most widely used to assess treatment response. We hypothesised lung clearance index (LCI) would more sensitively assess steroid response than FEV1 alone, using our multi-domain approach [JACI 2016;138:413–420] with the addition of LCI to measure response of distal airway disease.Methods 39 children with STRA were recruited during a clinically-indicated admission for bronchoscopy and intramuscular triamcinolone injection. Prior to triamcinolone, they performed LCI, spirometry, FeNO, and filled in the asthma control test (ACT). They were followed up at 4 weeks and these tests repeated. ACT was considered abnormal if <20, LCI if ≥7.1, FEV1 percent predicted below 80%, and FeNO if ≥24 parts per billion. Any domain which was abnormal at visit 2 was a non-response.Results 26/39 (67%) patients had at least a partial response, see Table. There was strongest concordance of Results between FeNO and LCI (70%). 11/39 (28%) of patients had a response in at least two domains, 4/39 (10%) at least three, and 1 patient responded in all four domains.Conclusions In this cohort, LCI, FeNO and FEV1 were equally likely to be abnormal at baseline. FeNO and LCI were most likely to respond, (36% and 33% respectively), whereas FEV1 was least responsive to systemic steroids. Using this multi-domain approach 67% improved over 4 weeks following treatment with systemic corticosteroid. The clinical significance of an LCI response remains to be determined. We speculate that this group may reflect a distal airway disease phenotype who may benefit from fine particle inhaled corticosteroids.
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