189 results found
Tanner N, Saglani S, Li AM, et al., 2021, Airway inflammation in severe asthmatics with acid gastro-oesophageal reflux, Thorax, ISSN: 0040-6376
The relationship between childhood asthma and gastro-oesophageal reflux (GOR) is contentious. Recent studies in adult asthmatics suggest that GOR is associated with worse control and differences in sputum proteomics related to epithelial integrity, systemic inflammation and host defence. We assessed 127 children with severe asthma undergoing bronchoscopy and pH study. There were no differences in asthma control or measures of airway inflammation or remodelling when those with acid GOR were compared with those without. These results suggest that acid GOR is not an important comorbidity in paediatric severe asthma.
Makhecha S, Jamalzadeh A, Irving S, et al., 2021, Paediatric severe asthma biologics service: from hospital to home, Archives of Disease in Childhood, Vol: 106, Pages: 900-902, ISSN: 0003-9888
Children with severe asthma may be treated with biologic agents normally requiring 2–4 weekly injections in hospital. In March 2020, due to COVID-19, we needed to minimise hospital visits. We assessed whether biologics could be given safely at home. The multidisciplinary team identified children to be considered for home administration. This was virtually observed using a video link, and home spirometry was also performed. Feedback was obtained from carers and young people. Of 23 patients receiving biologics, 16 (70%) families agreed to homecare administration, 14 administered by parents/patients and 2 by a local nursing team. Video calls for omalizumab were observed on 56 occasions, mepolizumab on 19 occasions over 4 months (April–July). Medication was administered inaccurately on 2/75 occasions without any adverse events. Virtually observed home biologic administration in severe asthmatic children, supported by video calls and home spirometry, is feasible, safe and is positively perceived by children and their families
Levy ML, Fleming L, Goldring S, et al., 2021, Piling Pelion upon Ossa: surely we already have enough non-evidence based ways of treating acute asthma?, ARCHIVES OF DISEASE IN CHILDHOOD, Vol: 106, Pages: 730-731, ISSN: 0003-9888
Jochmann A, Artusio L, Usemann J, et al., 2021, A 3-month period of electronic monitoring can provide important information to the healthcare team to assess adherence and improve asthma control, ERJ Open Research, Vol: 7, Pages: 1-4, ISSN: 2312-0541
Santos-Valente E, Buntrock-Döpke H, Abou Taam R, et al., 2021, Biologicals in childhood severe asthma: the European PERMEABLE survey on the status quo, ERJ Open Research, Vol: 7, ISSN: 2312-0541
Introduction: Severe asthma is a rare disease in children, for which three biologicals, anti-immunoglobulin E, anti-interleukin-5 and anti-IL4RA antibodies, are available in European countries. While global guidelines exist on who should receive biologicals, knowledge is lacking on how those guidelines are implemented in real life and which unmet needs exist in the field. In this survey, we aimed to investigate the status quo and identify open questions in biological therapy of childhood asthma across Europe. Methods: Structured interviews regarding experience with biologicals, regulations on access to the different treatment options, drug selection, therapy success and discontinuation of therapy were performed. Content analysis was used to analyse data. Results: We interviewed 37 experts from 25 European countries and Turkey and found a considerable range in the number of children treated with biologicals per centre. All participating countries provide public access to at least one biological. Most countries allow different medical disciplines to prescribe biologicals to children with asthma, and only a few restrict therapy to specialised centres. We observed significant variation in the time point at which treatment success is assessed, in therapy duration and in the success rate of discontinuation. Most participating centres intend to apply a personalised medicine approach in the future to match patients a priori to available biologicals. Conclusion: Substantial differences exist in the management of childhood severe asthma across Europe, and the need for further studies on biomarkers supporting selection of biologicals, on criteria to assess therapy response and on how/when to end therapy in stable patients is evident.
Alahmadi FH, Simpson AJ, Gomez C, et al., 2021, Medication adherence in patients with severe asthma prescribed oral corticosteroids in the U-BIOPRED cohort, Chest, Vol: 160, Pages: 53-64, ISSN: 0012-3692
BACKGROUND: Whilst estimates of sub-optimal adherence to oral corticosteroids in asthma range from 30 to 50%, no ideal method for measurement exists; the impact of poor adherence in severe asthma is likely to be particularly high. RESEARCH QUESTIONS: 1. What is the prevalence of suboptimal adherence detected using self-reporting and direct measures? 2. Is suboptimal adherence associated with disease activity? STUDY DESIGN AND METHODS: Data were included from individuals with severe asthma taking part in the U-BIOPRED study prescribed daily oral corticosteroids. Participants completed the MARS, a five-item questionnaire used to grade adherence on a scale from 1 to 5, and provided a urine sample for analysis of prednisolone and metabolites by liquid-chromatography mass spectrometry. RESULTS: Data from 166 participants were included in this study, mean (SD) age 54.2 (11.9) years, FEV1 65.1 (20.5) % predicted, 58% female. 37% completing the MARS reported sub-optimal adherence, and 43% with urinary corticosteroid data did not have detectable prednisolone or metabolites in their urine. Good adherence by both methods was detected in 35% participants who had both performed; adherence detection did not match between methods in 53%. Self-reported high-adherers had better asthma control and quality of life, whereas directly-measured high-adherers had lower blood eosinophils. INTERPRETATION: Low adherence is a common problem in severe asthma, whether measured directly or self-reported. We report poor agreement between the two methods suggesting some disassociation between self-assessment of medication adherence and regular oral corticosteroid use, which suggests that each approach may provide complementary information in clinical practice.
Saglani S, Robinson P, Fontanella S, et al., 2021, Recurrent severe preschool wheeze: From pre-specified diagnostic labels to underlying endotypes, American Journal of Respiratory and Critical Care Medicine, Vol: 204, Pages: 523-535, ISSN: 1073-449X
Rationale: Preschool wheezing is heterogeneous, but the underlying mechanisms are poorly understood. Objectives: To investigate lower airway inflammation and infection in preschool children with different clinical diagnoses undergoing elective bronchoscopy/bronchoalveolar lavage-BAL. Methods: We recruited 136 children aged 1-5 years (105 recurrent severe wheeze-RSW; 31 non-wheeze respiratory disorders-NWRD). RSW were assigned as episodic viral-EVW or multiple trigger wheeze-MTW. We compared lower airway inflammation/infection in different clinical diagnoses and undertook data-driven analyses to determine clusters of pathophysiological features, and investigated their relationships with pre-specified diagnostic labels. Measurements and Main Results: Blood eosinophils and allergic sensitization were significantly higher in RSW than NWRD. Blood neutrophils, BAL eosinophils and neutrophils, and positive bacterial culture and virus detection rates were similar between groups. However, pathogen distribution differed significantly, with higher detection of rhinovirus in RSW and Moraxella in sensitized RSW. EVW and MTW did not differ in blood/BAL inflammation, or bacterial/virus detection. Partition Around Medoids algorithm revealed 4 clusters of pathophysiological features: (1) Atopic (17.9%); (2) Non-atopic, low infection rate, high inhaled corticosteroids-ICS (31.3%); (3) Non-atopic, high infection rate (23.1%); and (4) Non-atopic, low infection rate, no ICS (27.6%). Cluster allocation differed significantly between RSW and NWRD (RSW evenly distributed across clusters, 60% of NWRD assigned to cluster 4, p<0.001). There was no difference in cluster membership between EVW and MTW. Cluster 1 was dominated by Moraxella detection (p=0.04) and Cluster 3 by Haemophilus/Staphylococcus/ Streptococcus (p=0.02). Conclusions: We identified four clusters of severe preschool wheeze distinguished using sensitization, peripheral eosinophilia, lower airway neutrophilia and bacteriolog
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
Agerskov N, Coughlin S, Parrott H, et al., 2021, Quality of Unsupervised Home Spirometry in Children with Asthma, 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
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
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
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
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.
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, 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
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
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
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
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
Levy ML, Fleming L, 2020, Asthma reviews in children: what have we learned?, THORAX, Vol: 75, Pages: 98-99, ISSN: 0040-6376
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.
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
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
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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