Publications
298 results found
Coughlin S, Parrott H, Wells C, et al., 2021, Acceptability of Home Spirometry in Children with Asthma: The NuvoAir Platform, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Bush A, Levy M, Fleming L, 2021, Steroid-filled rant: or another fashion accessory?, ARCHIVES OF DISEASE IN CHILDHOOD, Vol: 106, Pages: 211-+, ISSN: 0003-9888
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- Citations: 2
Jamalzadeh A, Makhecha S, Irving S, et al., 2021, FROM HOSPITAL TO HOME: VIRTUALLY OBSERVED ADMINISTRATION OF BIOLOGICS IN CHILDREN WITH SEVERE ASTHMA DURING COVID-19, Publisher: BMJ PUBLISHING GROUP, Pages: A138-A139, ISSN: 0040-6376
Van Riper M, Knafl GJ, Barbieri-Figueiredo MDC, et al., 2021, Measurement of Family Management in Families of Individuals With Down Syndrome: A Cross-Cultural Investigation, JOURNAL OF FAMILY NURSING, Vol: 27, Pages: 8-22, ISSN: 1074-8407
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- Citations: 1
Fleming L, 2021, Diagnosing, Monitoring and Treating Asthma, Encyclopedia of Respiratory Medicine, Second Edition, Pages: 270-287, ISBN: 9780081027233
Asthma is the most common long term condition in childhood, yet the frequency with which it is diagnosed belies the complexity and heterogeneity of asthma and the challenges in management. Although most children respond well to low levels of inhaled steroids a significant proportion experience frequent attacks and symptoms which impact on their quality of life. Advances have been made in recent years in understanding the underlying pathobiology of childhood asthma, particularly in those with severe asthma, affording the opportunity for more effective targeted treatments. This article will discuss the important considerations in diagnosing childhood asthma, explore the underlying pathophysiology, describe phenotypes of asthma and how they can be used to direct treatment and finally discuss the key components of asthma monitoring.
Andersson CK, Iwasaki J, Cook J, et al., 2020, Impaired airway epithelial cell wound-healing capacity is associated with airway remodelling following RSV infection in severe preschool wheeze, ALLERGY, Vol: 75, Pages: 3195-3207, ISSN: 0105-4538
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- Citations: 12
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
Makhecha S, Chan A, Jamalzadeh A, et al., 2020, Novel electronic adherence monitoring devices in children with asthma: a mixed methods study, BMJ Open Respiratory Research, Vol: 7, ISSN: 2052-4439
Introduction Adherence monitoring to inhaled corticosteroids is an essential component of asthma management. Electronic monitoring devices (EMD) provide objective data on date, time and number of actuations. However, most give no information on inhalation. Novel EMD (NEMD) platforms have the potential to monitor both activation and inhalation.Aim To assess the feasibility of NEMDs, in terms of usability, acceptability to patients and healthcare professionals and accuracy.Methods This was an open-label, prospective, mixed-methods, pragmatic randomised study. Children with asthma attending specialist tertiary care were randomised to one of four NEMD: Remote Directly Observed Therapy (R-DOT), Hailie Smartinhaler, INhaler Compliance Assessment device (INCA) and the Rafi-tone App. Following monitoring, participants were invited to focus groups or one-to-one interviews. Usability and acceptability were evaluated using themes identified from the focus groups and interviews. Adherence accuracy was determined using adherence data from each NEMD.Results Thirty-five children were recruited; 18 (51%), (11 males, median age 13.5 (7–16) years) completed monitoring, 14 (78%) provided feedback. Participants identified various features such as ease of use and minimal effort as desirable criteria for an NEMD. The Hailie and INCA fulfilled these criteria and were able to record both actuation and inhalation. Negative themes included a ‘Big Brother’ effect and costs.Conclusion There was no ‘one size fits all’, as participants identified advantages and disadvantages for each NEMD. Devices that can easily calculate adherence to activation and inhalation have the potential to have greatest utility in clinical practice. Each NEMD has different functionality and therefore choice of platform should be determined by the needs of the patient and healthcare professional.
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
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.
Liu NM, Carlsen KCL, Cunningham S, et al., 2020, First analysis of the Severe Paediatric Asthma Collaborative in Europe registry, ERJ OPEN RESEARCH, Vol: 6
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- Citations: 3
Pijnenburg MW, Fleming L, 2020, Advances in understanding and reducing the burden of severe asthma in children, LANCET RESPIRATORY MEDICINE, Vol: 8, Pages: 1032-1044, ISSN: 2213-2600
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- Citations: 57
Bingham Y, Fleming L, Sanghani N, et al., 2020, Electronic monitoring of adherence to inhaled corticosteroids in preschool children with wheeze, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Wells C, Cartwright M, Hirani S, et al., 2020, Identifying predictors for referral to a physiotherapy service for children with difficult asthma, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Bingham Y, Sanghani N, Cook J, et al., 2020, Electronic adherence monitoring identifies severe preschool wheezers who are steroid responsive., Pediatric Pulmonology, Vol: 55, Pages: 2254-2260, ISSN: 1099-0496
Little is known about adherence to inhaled corticosteroids (ICS) in preschool children with troublesome wheeze. Children with aeroallergen senitization, or those reporting multiple trigger wheeze (MTW), are more likely to respond to ICS. We hypothesized that adherence to ICS and symptom control are only positively related in atopic children, or those reporting MTW. Patients aged 1 to 5 years with recurrent wheeze prescribed ICS were recruited from a tertiary respiratory clinic. Clinical phenotype and aeroallergen senitization were determined, and adherence assessed using an electronic monitoring device (Smartinhaler). Symptom control (test for respiratory and asthma control in kids [TRACK]), quality of life (PACQLQ), airway inflammation (offline exhaled nitric oxide) were assessed at baseline and follow-up. Forty-eight children (mean age 3.7 years; SD, 1.2) were monitored for a median of 112 (interquartile range [IQR], 91-126) days. At baseline n = 29 reported episodic viral wheeze and n = 19 reported MTW. Twenty-four out of 48 (50%) wheezers had suboptimal ICS adherence (<80%). Median adherence was 64% (IQR, 38-84). There was a significant increase in TRACK and PACQLQ in the group as a whole, unrelated to adherence. In subgroup analysis only atopic wheezers with moderate or good adherence ≥ 60% had a significant increase in TRACK. There was no relationship between clinical phenotype, and adherence or TRACK. In this pilot study, overall adherence to ICS was suboptimal and was positively related to symptom control in atopic wheezers only. Assessments of adherence are important in preschool troublesome wheezers before therapy escalation to help identify those with an ICS responsive phenotype.
Hew M, Menzies-Gow A, Hull JH, et al., 2020, Systematic assessment of difficult-to-treat asthma: principles and perspectives, Journal of Allergy and Clinical Immunology: In Practice, Vol: 8, Pages: 2222-2233, ISSN: 2213-2198
Difficult-to-treat asthma affects a minority of adults and children with asthma but represents a challenging mix of misdiagnosis, multimorbidity, inadequate self-management, severe airway pathobiology, and treatment complications. Management of these patients extends beyond asthma pharmacotherapy, because multiple other patient-related domains need to be addressed as well. Such complexity can hinder adequate clinical assessment even when performed in specialist practice. Systematic assessment undertaken by specialized multidisciplinary teams brings a broad range of resources to bear on patients with difficult-to-treat asthma. Although the concept of systematic assessment is not new, practices vary considerably and implementation is not universal. Nevertheless, assessment protocols are already in place in several institutions worldwide, and outcomes after such assessments have been highly encouraging. This review discusses the rationale, components, and benefits of systematic assessment, outlining its clinical utility and the available evidence for improved outcomes. It describes a range of service configurations and assessment approaches, drawing examples from severe asthma centers around the world to highlight common essential elements. It also provides a framework for establishing such services and discusses practical considerations for implementation.
Jochmann A, Artusio L, Sharifian H, et al., 2020, Fluctuation-based clustering reveals phenotypes of patients with different asthma severity, ERJ OPEN RESEARCH, Vol: 6
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- Citations: 1
Irving S, Fleming L, Ahmad F, et al., 2020, Lung clearance index and steroid response in pediatric severe asthma, PEDIATRIC PULMONOLOGY, Vol: 55, Pages: 890-898, ISSN: 8755-6863
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- Citations: 8
Turner P, Fleming L, Saglani S, et al., 2020, Safety of live attenuated influenza vaccine in children with moderate-severe asthma, Journal of Allergy and Clinical Immunology, Vol: 145, Pages: 1157-1164.e6, ISSN: 0091-6749
Background:Live attenuated influenza vaccine (LAIV) is recommended for annual influenza vaccination in children from age 2 years. However, some guidelines recommend against its use in children with asthma or recurrent wheeze due to concerns over its potential to induce wheezing. Objective: To assess the safety of LAIV in children with moderate-severe asthma, and in preschool children with recurrent wheeze. Methods: Prospective, multi-center, open label, phase IV intervention studyin 14 specialist UK clinics.LAIV was administered under medical supervision, with follow-up of asthma symptoms 72 hours and 4 weeks late, using validated questionnaires.Clinical Trials.gov registration NCT02866942, EU Clinical Trials registration 2016-002352-24. Results: 478 young people (median 9.3, range 2–18 years) with physician-diagnosed asthma or recurrent wheeze were recruited, including 208 (44%) prescribed high-dose inhaled corticosteroids and 122 (31%) with severe asthma.There was no significant change in asthma symptoms in the 4 weeks following administration (median change 0, P=.26, McNemar’s test), with no impact of level of baseline asthma control/symptoms in predicting either a worsening of asthma or exacerbation following LAIV using a regression model. 47 subjects (14.7%, 95%CI 11% to 19.1%) reported a severe asthma exacerbation in the four weeks following immunization, requiring short course of systemic corticosteroids; in four cases, this occurred within 72 hours of vaccine. No association with asthma severity, baseline lung function or asthma control was identified.Conclusions: LAIV appears to be well-tolerated in the vast majority of children with asthma or recurrent wheeze, includingthosewhose asthma is categorized as severe or poorly controlled
Hellen R, Dhonncha EN, Havelin A, et al., 2020, An audit of pain scores with conventional and white light topical 5-methyl aminolaevulinic acid photodynamic therapy for superficial basal cell carcinoma and squamous cell carcinoma in situ, PHOTODERMATOLOGY PHOTOIMMUNOLOGY & PHOTOMEDICINE, Vol: 36, Pages: 161-162, ISSN: 0905-4383
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- Citations: 3
Levy ML, Fleming L, 2020, Asthma reviews in children: what have we learned?, THORAX, Vol: 75, Pages: 98-99, ISSN: 0040-6376
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- Citations: 4
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.
Selby L, Fleming LJ, 2020, Management of Medication Side Effects and Complications, SEVERE ASTHMA IN CHILDREN AND ADOLESCENTS: MECHANISMS AND MANAGEMENT, Editors: Forno, Saglani, Publisher: SPRINGER INTERNATIONAL PUBLISHING AG, Pages: 183-211, ISBN: 978-3-030-27433-7
Selby L, Saglani S, Bush A, et al., 2019, ADHERENCE, AIRWAY INFLAMMATION AND ADRENAL FUNCTION IN A COHORT OF PAEDIATRIC ASTHMA PATIENTS, Winter Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A43-A43, ISSN: 0040-6376
Bingham Y, Moreiras J, Goldring S, et al., 2019, USE OF PATHOLOGICAL PHENOTYPE TO DETERMINE OPTIMAL MANAGEMENT FOR MODERATE TO SEVERE PRESCHOOL WHEEZE, Winter Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A44-A44, ISSN: 0040-6376
Makhecha S, Chan AHY, Pearce CJ, et al., 2019, ASSESSMENT OF NOVEL ELECTRONIC ADHERENCE MONITORING DEVICES IN CHILDREN WITH ASTHMA, Winter Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A179-A179, ISSN: 0040-6376
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- Citations: 1
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.
Fleming L, Heaney L, 2019, Severe asthma-perspectives from adult and pediatric pulmonology, Frontiers in Pediatrics, Vol: 7, Pages: 389-389, ISSN: 2296-2360
Both adults and children with severe asthma represent a small proportion of the asthma population; however, they consume disproportionate resources. For both groups it is important to confirm the diagnosis of severe asthma and ensure that modifiable factors such as adherence have, as far as possible, been addressed. Most children can be controlled on inhaled corticosteroids and long term oral corticosteroid use is rare, in contrast to adults where steroid related morbidity accounts for a large proportion of the costs of severe asthma. Atopic sensitization is very common in children with severe asthma as are other atopic conditions such as allergic rhinitis and hay fever which can impact on asthma control. In adults, the role of allergic driven disease, even in those with co-existent evidence of sensitization, is unclear. There is currently an exciting pipeline of novel biologicals, particularly directed at Type 2 inflammation, which afford the possibility of improved asthma control and reduced treatment side effects for people with asthma. However, not all drugs will work for all patients and accurate phenotyping is essential. In adults the terms T2 high and T2 low asthma have been coined to describe groups of patients based on the presence/absence of eosinophilic inflammation and T-helper 2 (TH2) cytokines. Bronchoscopic studies in children with severe asthma have demonstrated that these children are predominantly eosinophilic but the cytokine patterns do not fit the T2 high paradigm suggesting other steroid resistant pathways are driving the eosinophilic inflammation. It remains to be seen whether treatments developed for adult severe asthma will be effective in children and which biomarkers will predict response.
Selby L, Saglani S, Bush A, et al., 2019, Assessment of adrenal function using low and standard dose synacthen tests in a cohort of paediatric asthma patients, International Congress of the European-Respiratory-Society (ERS), Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
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