Publications
298 results found
Barry T, Holliday M, Sparks J, et al., 2024, START CARE: a protocol for a randomised controlled trial of step-wise budesonide-formoterol reliever-based treatment in children., ERJ Open Res, Vol: 10, ISSN: 2312-0541
BACKGROUND: Asthma is the most common chronic childhood respiratory condition globally. Inhaled corticosteroid (ICS)-formoterol reliever-based regimens reduce the risk of asthma exacerbations compared with conventional short-acting β2-agonist (SABA) reliever-based regimens in adults and adolescents. The current limited evidence for anti-inflammatory reliever therapy in children means it is unknown whether these findings are also applicable to children. High-quality randomised controlled trials (RCTs) are needed. OBJECTIVE: The study aim is to determine the efficacy and safety of budesonide-formoterol reliever alone or maintenance and reliever therapy (MART) compared with standard therapy: budesonide or budesonide-formoterol maintenance, both with terbutaline reliever, in children aged 5 to 11 years with mild, moderate and severe asthma. METHODS: A 52-week, multicentre, open-label, parallel group, phase III, two-sided superiority RCT will recruit 400 children aged 5 to 11 years with asthma. Participants will be randomised 1:1 to either budesonide-formoterol 100/6 µg Turbuhaler reliever alone or MART; or budesonide or budesonide-formoterol Turbuhaler maintenance, with terbutaline Turbuhaler reliever. The primary outcome is moderate and severe asthma exacerbations as rate per participant per year. Secondary outcomes are asthma control, lung function, exhaled nitric oxide and treatment step change. Assessment of Turbuhaler technique and cost-effectiveness analysis are also planned. CONCLUSION: This will be the first RCT to compare the efficacy and safety of a step-wise budesonide-formoterol reliever alone or MART regimen with conventional inhaled ICS or ICS-long-acting β-agonist maintenance plus SABA reliever in children. The results will provide a much-needed evidence base for the treatment of asthma in children.
Levy ML, Beasley R, Bostock B, et al., 2024, A simple and effective evidence-based approach to asthma management: ICS-formoterol reliever therapy., Br J Gen Pract, Vol: 74, Pages: 86-89
Hine J, Fleming L, Judah G, et al., 2023, M17 PATIENT ENGAGEMENT WITH ADHERENCE TECHNOLOGY: LEARNINGS FROM THE ‘FINANCIAL INCENTIVES TO IMPROVE ASTHMA’ (FINA) STUDY, Pages: A269-A270, ISSN: 0040-6376
Background Digital interventions are acceptable and often effective for improving short-term medication adherence for children and young people (CYP) with asthma. Interventions using electronic monitoring devices (EMDs) can be supported by behaviour change techniques such as reminders and financial incentives. Most digital interventions require patient engagement; however, it is important to understand how patients engage to maximise effectiveness. As part of the feasibility assessment of the FINA study, a pilot RCT of a digital financial incentives intervention, patient engagement with EMDs and smartphone app was explored. Methods During the FINA study, CYP (aged 11–17 years old) with asthma monitored their adherence for 24-weeks using an EMD. Participants randomised to financial incentives intervention viewed their adherence (table and bar-graph) and their reward progress (totaliser, traffic-light calendar, and weekly notifications) through a smartphone app. Financial reward was delivered regularly (at 4-, 8- and 12-weeks) and relied upon real-time data; participants were advised to sync their EMD and app daily. Control group viewed their sensor syncing history only and were advised to sync their EMD and app weekly. All participants were requested to promptly report any problems to the research team. Patient engagement was explored using syncing data, technical issue reporting and research team involvement. Results 32 participants are enrolled in on-going trial (intervention, n=16); 84% have completed first 12-weeks. Technical problems were experienced by 13/16 intervention and 8/16 control participants; 12 of whom did not report these until research visit 2 (12-weeks, post-intervention). 7/16 intervention participants did not sync their EMD and app as advised and were reminded by research team at least once ahead of reward delivery; 1 participant only synced once throughout intervention. 14/16 control participants did not sync weekly. Discussion Limited pat
Versi A, Ivan FX, Abdel-Aziz MI, et al., 2023, Haemophilus influenzae and Moraxella catarrhalis in sputum of severe asthma with inflammasome and neutrophil activation, Allergy, Vol: 78, Pages: 2906-2920, ISSN: 0105-4538
BACKGROUND: Because of altered airway microbiome in asthma, we analysed the bacterial species in sputum of patients with severe asthma. METHODS: Whole genome sequencing was performed on induced sputum from non-smoking (SAn) and current or ex-smoker (SAs/ex) severe asthma patients, mild/moderate asthma (MMA) and healthy controls (HC). Data were analysed by asthma severity, inflammatory status and transcriptome-associated clusters (TACs). RESULTS: α-diversity at the species level was lower in SAn and SAs/ex, with an increase in Haemophilus influenzae and Moraxella catarrhalis, and Haemophilus influenzae and Tropheryma whipplei, respectively, compared to HC. In neutrophilic asthma, there was greater abundance of Haemophilus influenzae and Moraxella catarrhalis and in eosinophilic asthma, Tropheryma whipplei was increased. There was a reduction in α-diversity in TAC1 and TAC2 that expressed high levels of Haemophilus influenzae and Tropheryma whipplei, and Haemophilus influenzae and Moraxella catarrhalis, respectively, compared to HC. Sputum neutrophils correlated positively with Moraxella catarrhalis and negatively with Prevotella, Neisseria and Veillonella species and Haemophilus parainfluenzae. Sputum eosinophils correlated positively with Tropheryma whipplei which correlated with pack-years of smoking. α- and β-diversities were stable at one year. CONCLUSIONS: Haemophilus influenzae and Moraxella catarrhalis were more abundant in severe neutrophilic asthma and TAC2 linked to inflammasome and neutrophil activation, while Haemophilus influenzae and Tropheryma whipplei were highest in SAs/ex and in TAC1 associated with highest expression of IL-13 type 2 and ILC2 signatures with the abundance of Tropheryma whipplei correlating positively with sputum eosinophils. Whether these bacterial species drive the inflammatory response in asthma needs evaluation.
Salehian S, Fleming L, Saglani S, et al., 2023, Phenotype and endotype based treatment of preschool wheeze, EXPERT REVIEW OF RESPIRATORY MEDICINE, ISSN: 1747-6348
Kallis C, Morgan A, Fleming L, et al., 2023, Prevalence of poorly controlled asthma and factors associated with specialist referral in those with poorly controlled asthma in a paediatric asthma population, Journal of Asthma and Allergy, Vol: 16, Pages: 1065-1075, ISSN: 1178-6965
Background: Significant morbidity and mortality are associated with poor asthma control. The aim of this study was to determine factors associated with poor control and referral to specialist secondary care services.Methods: We used primary care data from the Clinical Practice Research Datalink Aurum (CPRD) linked with Hospital Episode Statistics (HES) records from 1st January 2007 to 31st December 2019. We selected patients aged 6– 17 years old. Poor control was defined as six or more prescriptions of short-acting beta-agonist (SABA) inhalers, two or more courses of oral corticosteroids (OCS), an Asthma Control test (ACT) or childhood ACT < 20, one hospital admission for asthma, or one visit to Accident & Emergency (A&E) department for asthma-related episodes in the 12 months following asthma diagnosis. Asthma severity was defined following GINA guidelines 2021.Results: About 17.6% of children aged between 6 and 17 years with active asthma had poor control. Severe asthma, eczema, food allergies, increased BMI and living in deprived areas were identified as risk factors for poor control. Among those with poor control, referral rates to specialist care were extremely low, only 2% overall. Those with severe asthma were three-times more likely to be referred than those with mild-to-moderate asthma [HRcrude = 4.04 (95% CI, 3.35– 4.87); HRadj = 2.72 (95% CI: 2.13– 3.49)]. Other factors associated with referral were food allergy and living in a more deprived area.Conclusion: Around 1 in 6 children and adolescents with active asthma are not achieving adequate control of their symptoms. Among the subset of 6– 17-year olds with poorly controlled asthma, timely referral for specialist advice in secondary care is rare, especially in those with so-called mild asthma who nevertheless are at significant risk for poor asthma outcomes.
Levy ML, Bateman ED, Allan K, et al., 2023, Global access and patient safety in the transition to environmentally friendly respiratory inhalers: the Global Initiative for Asthma perspective., Lancet, Vol: 402, Pages: 1012-1016
Warraich S, Bush A, Levy ML, et al., 2023, Regular (up to 10 puffs 4-hourly) inhaled salbutamol should be prescribed at discharge after an asthma attack: myth or maxim?, Breathe (Sheff), Vol: 19, ISSN: 1810-6838
Over the past 20 years, the concept of asthma weaning plans on discharge after an attack has crept into common practice, although the precise origin of these plans is unclear. High use of short-acting β2-agonists (SABAs) may result in tolerance to their bronchodilator effects, thus diminishing their efficacy, particularly when they are most needed at the time of an acute attack. Furthermore, key warning signs of a deterioration in asthma control may be masked and the weaning plan may encourage the over-use and over-reliance on SABAs. Side-effects from over-use may also occur, including lactic acidosis, downregulation of the β2-adrenoreceptor, increased allergen response and pro-inflammatory effects. The need for asthma education at discharge, a personal asthma action plan and vigilance about prescribing and ensuring adherence to maintenance therapy are definitely important. However, the current authors conclude that the benefit of prescribing regular salbutamol (up to 10 puffs every 4 h) at discharge after an acute asthma attack is a myth, and a very dangerous one.
Fleming L, Hine J, Bush A, et al., 2023, Patient financial incentives to improve asthma management: a systematic review, BMJ Open, Vol: 13, Pages: 1-9, ISSN: 2044-6055
Objectives The objectives of this systematic review are to identify studies that assess the effectiveness of patient-directed financial incentive interventions to improve asthma management behaviours, determine overall effectiveness of financial incentives, identify design characteristics of effective interventions and assess the impact on longer-term outcomes in the context of asthma.Design Systematic review with narrative synthesis.Data sources Electronic databases (MEDLINE, Embase, Global Health, PsycINFO, CINAHL, PubMed and Web of Science) and grey literature sources (NHS Digital, CORE, ProQuest, Clinical Trials Register and EU Clinical Trials Register) were searched in November 2021 and updated March 2023.Eligiblity criteria Eligible articles assessed financial incentives to improve asthma management behaviours (attendance at appointments, medication adherence, tobacco smoke/allergen exposure, inhaler technique and asthma education) for patients with asthma or parents/guardians of children with asthma. Eligible study design included randomised controlled, controlled or quasi-randomised trials and retrospective/prospective cohort, case-controlled or pilot/feasibility studies.Synthesis A narrative synthesis was conducted; eligible studies were grouped by asthma management behaviours and financial incentive framework domains.Results We identified 4268 articles; 8 met the inclusion criteria. The studies were from the USA (n=7) and the UK (n=1). Asthma management behaviours included attendance at appointments (n=4), reduction in smoke exposure (n=1) and medication adherence (n=3). Five studies demonstrated positive behaviour change, four of which were significant (attendance at appointments (n=3) showed significant differences between intervention and control: 73% and 49% in one study, 46.3% and 28.9% in another, and 35.7% and 18.9%, respectively; medication adherence (n=1) showed significant change from 80% during intervention to 33% post intervention). These four
Abdel-Aziz MI, Thorsen J, Hashimoto S, et al., 2023, Oropharyngeal Microbiota Clusters in Children with Asthma or Wheeze Associate with Allergy, Blood Transcriptomic Immune Pathways, and Exacerbation Risk, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 208, Pages: 142-154, ISSN: 1073-449X
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Brandsma J, Schofield JPR, Yang X, et al., 2023, Stratification of asthma by lipidomic profiling of induced sputum supernatant, Journal of Allergy and Clinical Immunology, Vol: 152, Pages: 117-125, ISSN: 0091-6749
BACKGROUND: Asthma is a chronic respiratory disease with significant heterogeneity in its clinical presentation and pathobiology. There is need for improved understanding of respiratory lipid metabolism in asthma patients and its relation to observable clinical features. OBJECTIVE: To perform a comprehensive, prospective, cross-sectional analysis of the lipid composition of induced sputum supernatant obtained from asthma patients with a range of disease severities, as well as healthy controls. METHODS: Induced sputum supernatant was collected from 211 asthmatic adults and 41 healthy individuals enrolled in the U-BIOPRED study. Sputum lipidomes were characterised by semi-quantitative shotgun mass spectrometry, and clustered using topological data analysis to identify lipid phenotypes. RESULTS: Shotgun lipidomics of induced sputum supernatant revealed a spectrum of nine molecular phenotypes, highlighting not just significant differences between the sputum lipidomes of asthmatics and healthy controls, but within the asthmatic population as well. Matching clinical, pathobiological, proteomic and transcriptomic data informed on the underlying disease processes. Sputum lipid phenotypes with higher levels of non-endogenous, cell-derived lipids were associated with significantly worse asthma severity, worse lung function, and elevated granulocyte counts. CONCLUSION: We propose a novel mechanism of increased lipid loading in the epithelial lining fluid of asthmatics, resulting from the secretion of extracellular vesicles by granulocytic inflammatory cells, which could reduce the ability of pulmonary surfactant to lower surface tension in asthmatic small airways, as well as compromise its role as an immune regulator. CLINICAL IMPLICATION: Immunomodulation of extracellular vesicle secretion in the lungs may provide a novel therapeutic target for severe asthma.
Yorgancıoğlu A, Reddel HK, GINA Board of Directors and GINA Science Committee, 2023, Global initiative for asthma: 30 years of promoting evidence-based asthma care., Allergy, Vol: 78, Pages: 1737-1739
Khaleva E, Rattu A, Brightling C, et al., 2023, Definitions of non-response and response to biological therapy for severe asthma: a systematic review, ERJ OPEN RESEARCH, Vol: 9
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- Citations: 2
Lajunen KT, Mayoral K, Alabdulkareem F, et al., 2023, Feasibility and Acceptability of Point-of-Care Blood Eosinophil Count Together With Lung Function in Wheezy Preschool Children, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Van Riper M, Cosgrove B, Fleming L, 2023, Adaptation at the Family Level in Families of Individuals With Down Syndrome: A Scoping Review, JOURNAL OF FAMILY NURSING, ISSN: 1074-8407
Rattu A, Khaleva E, Brightling C, et al., 2023, Identifying and appraising outcome measures for severe asthma: a systematic review, EUROPEAN RESPIRATORY JOURNAL, Vol: 61, ISSN: 0903-1936
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- Citations: 6
Khaleva E, Rattu A, Brightling C, et al., 2023, Development of Core Outcome Measures sets for paediatric and adult Severe Asthma (COMSA), European Respiratory Journal, Vol: 61, ISSN: 0903-1936
Background Effectiveness studies with biological therapies for asthma lack standardised outcome measures. The COMSA (Core Outcome Measures sets for paediatric and adult Severe Asthma) Working Group sought to develop Core Outcome Measures (COM) sets to facilitate better synthesis of data and appraisal of biologics in paediatric and adult asthma clinical studies.Methods COMSA utilised a multi-stakeholder consensus process among patients with severe asthma, adult and paediatric clinicians, pharmaceutical representatives, and health regulators from across Europe. Evidence included a systematic review of development, validity and reliability of selected outcome measures plus a narrative review and a pan-European survey to better understand patients’ and carers’ views about outcome measures. It was discussed using a modified GRADE (Grading of Recommendations Assessment, Development and Evaluation) Evidence to Decision framework. Anonymous voting was conducted using predefined consensus criteria.Results Both adult and paediatric COM sets include forced expiratory volume in 1 s (FEV1) as z-scores, annual frequency of severe exacerbations and maintenance oral corticosteroid use. Additionally, the paediatric COM set includes the Paediatric Asthma Quality of Life Questionnaire and Asthma Control Test or Childhood Asthma Control Test, while the adult COM set includes the Severe Asthma Questionnaire and Asthma Control Questionnaire-6 (symptoms and rescue medication use reported separately).Conclusions This patient-centred collaboration has produced two COM sets for paediatric and adult severe asthma. It is expected that they will inform the methodology of future clinical trials, enhance comparability of efficacy and effectiveness of biological therapies, and help assess their socioeconomic value. COMSA will inform definitions of non-response and response to biological therapy for severe asthma.
Levy ML, Bacharier LB, Bateman E, et al., 2023, Key recommendations for primary care from the 2022 Global Initiative for Asthma (GINA) update, NPJ PRIMARY CARE RESPIRATORY MEDICINE, Vol: 33
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- Citations: 16
Ko FWS, Fleming L, 2023, Advancement of asthma management in the past decade, The Lancet Respiratory Medicine, Vol: 11, Pages: 15-17, ISSN: 2213-2600
Scotney E, Fleming L, Saglani S, et al., 2023, Advances in the pathogenesis and personalised treatment of paediatric asthma., BMJ Med, Vol: 2
The diversity of pathology of severe paediatric asthma demonstrates that the one-size-fits-all approach characterising many guidelines is inappropriate. The term "asthma" is best used to describe a clinical syndrome of wheeze, chest tightness, breathlessness, and sometimes cough, making no assumptions about underlying pathology. Before personalising treatment, it is essential to make the diagnosis correctly and optimise basic management. Clinicians must determine exactly what type of asthma each child has. We are moving from describing symptom patterns in preschool wheeze to describing multiple underlying phenotypes with implications for targeting treatment. Many new treatment options are available for school age asthma, including biological medicines targeting type 2 inflammation, but a paucity of options are available for non-type 2 disease. The traditional reliever treatment, shortacting β2 agonists, is being replaced by combination inhalers containing inhaled corticosteroids and fast, longacting β2 agonists to treat the underlying inflammation in even mild asthma and reduce the risk of asthma attacks. However, much decision making is still based on adult data extrapolated to children. Better inclusion of children in future research studies is essential, if children are to benefit from these new advances in asthma treatment.
Thorsen J, Stokholm J, Rasmussen MA, et al., 2022, Asthma and Wheeze Severity and the Oropharyngeal Microbiota in Children and Adolescents, ANNALS OF THE AMERICAN THORACIC SOCIETY, Vol: 19, Pages: 2031-2043, ISSN: 1546-3222
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- Citations: 4
Pavlou B, Scotney E, Makariou I, et al., 2022, ACCEPTABILITY AND FEASIBILITY OF MEASURING BLOOD EOSINOPHILS USING A POINT-OF-CARE DEVICE IN CHILDREN WITH ASTHMA, Winter Meeting of the British-Thoracic-Society (BTS), Publisher: BMJ PUBLISHING GROUP, Pages: A130-A131, ISSN: 0040-6376
Chen PC, Irving SI, Fleming LF, 2022, AN ASSESSMENT OF SELF-PERFORMED HOME SPIROMETRY IN PAEDIATRIC ASTHMA PATIENTS, Winter Meeting of the British-Thoracic-Society (BTS), Publisher: BMJ PUBLISHING GROUP, Pages: A128-A129, ISSN: 0040-6376
Wells C, Wilkinson N, Makhecha S, et al., 2022, ACCEPTABILITY AND FEASIBILITY PILOT OF CODESIGNED TELEHEALTH PHYSIOTHERAPY INTERVENTIONS FOR CHILDREN WITH ASTHMA AND DYSFUNCTIONAL BREATHING, Winter Meeting of the British-Thoracic-Society (BTS), Publisher: BMJ PUBLISHING GROUP, Pages: A130-A130, ISSN: 0040-6376
Coppinger T, Burns C, O'Leary M, et al., 2022, Subjective wellbeing of Cork primary school children, IRISH EDUCATIONAL STUDIES, ISSN: 0332-3315
Scotney E, Jayarathna R, Gupta L, et al., 2022, The role of cardiopulmonary exercise testing to evaluate exercise induced dyspnoea in asthmatic children, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Abdel-Aziz M, Thorsen J, Hashimoto S, et al., 2022, Identification of oropharyngeal microbiome-driven asthma and wheezing clusters in children, 2022 ERS International Congress, Publisher: European Respiratory Society, Pages: 1-3, ISSN: 0903-1936
Makariou I, Bush A, Saglani S, et al., 2022, Ethnic differences in daily FeNO response after systemic steroids in children with severe asthma, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Makariou I, Rhamie S, Bush A, et al., 2022, Peak inspiratory flow in children with exercise induced laryngeal obstruction, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
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Hyams C, Nava G, Begier E, et al., 2022, Prospective cohort study of adults hospitalised with acute COPD exacerbations: SARS-CoV-2-associated patient characteristics and clinical outcomes, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
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