Imperial College London

DrLouiseFleming

Faculty of MedicineNational Heart & Lung Institute

Reader in Paediatric Respiratory Medicine
 
 
 
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Contact

 

+44 (0)20 7352 8121 ext 2938l.fleming

 
 
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Location

 

Department of Respiratory PaediaRoyal BromptonRoyal Brompton Campus

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Summary

 

Publications

Publication Type
Year
to

208 results found

Fowler S, Bhatt J, Brown S, Fleming L, Mayell S, Sinha I, Bush Aet al., 2022, E-cigarette company tactics in sports advertising., Lancet Respir Med, Vol: 10, Pages: 634-636

Journal article

Hoda U, Pavlidis S, Bansal AT, Takahashi K, Hu S, Ng Kee Kwong F, Rossios C, Sun K, Bhavsar P, Loza M, Baribaud F, Chanez P, Fowler SJ, Horvath I, Montuschi P, Singer F, Musial J, Dahlen B, Krug N, Sandstrom T, Shaw DE, Lutter R, Fleming LJ, Howarth PH, Caruso M, Sousa AR, Corfield J, Auffray C, De Meulder B, Lefaudeux D, Dahlen S-E, Djukanovic R, Sterk PJ, Guo Y, Adcock IM, Chung KFet al., 2022, Clinical and transcriptomic features of persistent exacerbation-prone severe asthma in U-BIOPRED cohort, Clinical and Translational Medicine, Vol: 12, ISSN: 2001-1326

Background: Exacerbation-prone asthma is a feature of severe disease. Yet, the basis for its persistency remains unclear. Objectives: To determine the clinical and transcriptomic features of the frequent-exacerbator (FE) and of persistent FEs (PFE) in U-BIOPRED cohort. Methods: We compared features of FE (≥2 exacerbations in past year) to infrequent exacerbators (IE, <2 exacerbations) and of PFE with repeat ≥2 exacerbations during the following year to persistent IE (PIE). Transcriptomic data in blood, bronchial and nasal epithelial brushings, bronchial biopsies and sputum cells were analysed by gene set variation analysis for 103 gene signatures.Results: Of 317 patients, 62.4 % were FE of whom 63.6% were PFE, while 37.6% were IE of whom 61.3% were PIE. Using multivariate analysis, FE was associated with short-acting beta-agonist use, sinusitis and daily oral corticosteroid use, while PFE with eczema, short-acting beta-agonist use and asthma control index. CEA Cell Adhesion Molecule 5 (CEACAM5) was the only differentially-expressed transcript in bronchial biopsies between PE and IE. There were no differentially-expressed genes in the other 4 compartments. There were higher expression scores for Type 2 , T-helper type-17 and Type 1 pathway signatures together with those associated with viral infections in bronchial biopsies from FE compared to IE, while higher expression scores of Type 2, Type 1 and steroid insensitivity pathway signatures in bronchial biopsies of PFE compared to PIE.Conclusion: FE group and its PFE subgroup are associated with poor asthma control while expressing higher Type 1 and Type 2 activation pathways compared to IE and PIE, respectively.

Journal article

Duijts L, Fleming LJ, Bacharier LB, Pitrez PM, Reddel HKet al., 2022, Global Initiative for Asthma 2021: Asthma in Preschool Children and Short-Acting beta(2)-Agonist-Only Treatment Reply, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 205, Pages: 974-975, ISSN: 1073-449X

Journal article

Robinson PD, Jayasuriya G, Haggie S, Uluer AZ, Gaffin JM, Fleming Let al., 2022, Issues affecting young people with asthma through the transition period to adult care, Paediatric Respiratory Reviews, Vol: 41, ISSN: 1526-0542

Asthma is among the most common medical conditions affecting children and young people, with adolescence a recognised period of increased risk, overrepresented in analyses examining recent increasing asthma mortality rates. Asthma may change significantly during this period and management also occurs in the context of patients seeking increased autonomy and self-governance whilst navigating increasing academic and social demands. A number of disease factors can destabilise asthma during adolescence including: increased rates of anaphylaxis, anxiety, depression, obesity, and, in females, an emerging resistance to corticosteroids and the pro-inflammatory effects of oestrogen. Patient factors such as smoking, vaping, poor symptom recognition, treatment non-adherence and variable engagement with health services contribute to difficult to treat asthma. Significant deficiencies in the current approach to transition have been identified by a recent EAACI task force, and subsequent asthma-specific recommendations, published in 2020 provide an important framework moving forward. As with other chronic conditions, effective transition programmes plan ahead, engage with adolescents and their families to identify the patients' management priorities and the current challenges they are experiencing with treatment. Transition needs may vary significantly across asthma patients and for more complex asthma may include dedicated transition clinics involving multidisciplinary care requiring input including, amongst others, allergy and immunology, psychological medicine, respiratory physicians and scientists and nurse specialists. Across different global regions, barriers to treatment may vary but need to be elicited and an individualised approach taken to optimising asthma care which is sustainable within the local adult healthcare system.

Journal article

Nichols A-L, Sonnappa-Naik M, Gardner L, Richardson C, Orr N, Jamalzadeh A, Moore-Crouch R, Makhecha S, Wells C, Hall P, Bush A, Fleming L, Saglani S, Sonnappa Set al., 2022, COVID-19 and delivery of difficult asthma services, ARCHIVES OF DISEASE IN CHILDHOOD, Vol: 107, ISSN: 0003-9888

Journal article

Pearce CJ, Chan AHY, Jackson T, Fleming L, Foot H, Bush A, Horne Ret al., 2022, Features of successful interventions to improve adherence to inhaled corticosteroids in children with asthma: A narrative systematic review, PEDIATRIC PULMONOLOGY, Vol: 57, Pages: 822-847, ISSN: 8755-6863

Journal article

Mikus MS, Kolmert J, Andersson L, Ostling J, Knowles RG, Gomez C, Ericsson M, Thorngren J-O, Khoonsari PE, Dahlen B, Kupczyk M, De Meulder B, Auffray C, Bakke PS, Beghe B, Bel EH, Caruso M, Chanez P, Chawes B, Fowler SJ, Gaga M, Geiser T, Gjomarkaj M, Horvath I, Howarth PH, Johnston SL, Joos G, Krug N, Montuschi P, Musial J, Nizankowska-Mogilnicka E, Olsson HK, Papi A, Rabe KF, Sandstrom T, Shaw DE, Siafakas NM, Uhlen M, Riley JH, Bates S, Middelveld RJM, Wheelock CE, Chung KF, Adcock IM, Sterk PJ, Djukanovic R, Nilsson P, Dahlen S-E, James Aet al., 2022, Plasma proteins elevated in severe asthma despite oral steroid use and unrelated to Type-2 inflammation, EUROPEAN RESPIRATORY JOURNAL, Vol: 59, ISSN: 0903-1936

Journal article

Reddel HK, Bacharier LB, Bateman ED, Brightling CE, Brusselle GG, Buhl R, Cruz AA, Duijts L, Drazen JM, FitzGerald JM, Fleming LJ, Inoue H, Ko FW, Krishnan JA, Levy ML, Lin J, Mortimer K, Pitrez PM, Sheikh A, Yorgancioglu AA, Boulet L-Pet al., 2022, Global initiative for Asthma Strategy 2021: executive summary and rationale for key changes, EUROPEAN RESPIRATORY JOURNAL, Vol: 59, ISSN: 0903-1936

Journal article

Badi Y, Pavel AB, Pavlidis S, Riley J, Bates S, Zounemat Kermani N, Knowles R, Kolmert J, Wheelock C, Worsley S, Uddin M, Alving K, Bakke P, Behndig A, Caruso M, Chanez P, Fleming L, Fowler S, Frey U, Howarth P, Horvath I, Krug N, Maitland van der Zee A, Montuschi P, Roberts G, Sanak M, Shaw D, Singer F, Sterk P, Djukanovic R, Dahlen S-E, Guo Y, Chung KF, Guttman-Yassky E, Adcock IM, on behalf of theU-BIOPRED Study Groupet al., 2022, Mapping atopic dermatitis and anti–IL-22 response signatures to type 2–low severe neutrophilic asthma, Journal of Allergy and Clinical Immunology, Vol: 149, Pages: 89-101, ISSN: 0091-6749

Background:Transcriptomic changes in patients who respond clinically to biological therapies may identify responses in other tissues or diseases.Objective:We sought to determine whether a disease signature identified in atopic dermatitis (AD) is seen in adults with severe asthma and whether a transcriptomic signature for patients with AD who respond clinically to anti–IL-22 (fezakinumab [FZ]) is enriched in severe asthma.Methods:An AD disease signature was obtained from analysis of differentially expressed genes between AD lesional and nonlesional skin biopsies. Differentially expressed genes from lesional skin from therapeutic superresponders before and after 12 weeks of FZ treatment defined the FZ-response signature. Gene set variation analysis was used to produce enrichment scores of AD and FZ-response signatures in the Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes asthma cohort.Results:The AD disease signature (112 upregulated genes) encompassing inflammatory, T-cell, TH2, and TH17/TH22 pathways was enriched in the blood and sputum of patients with asthma with increasing severity. Patients with asthma with sputum neutrophilia and mixed granulocyte phenotypes were the most enriched (P < .05). The FZ-response signature (296 downregulated genes) was enriched in asthmatic blood (P < .05) and particularly in neutrophilic and mixed granulocytic sputum (P < .05). These data were confirmed in sputum of the Airway Disease Endotyping for Personalized Therapeutics cohort. IL-22 mRNA across tissues did not correlate with FZ-response enrichment scores, but this response signature correlated with TH22/IL-22 pathways.Conclusions:The FZ-response signature in AD identifies severe neutrophilic asthmatic patients as potential responders to FZ therapy. This approach will help identify patients for future asthma clinical trials of drugs used successfully in other chronic diseases.

Journal article

Reddel HK, Bacharier LB, Bateman ED, Brightling CE, Brusselle GG, Buhl R, Cruz AA, Duijts L, Drazen JM, FitzGerald JM, Fleming LJ, Inoue H, Ko FW, Krishnan JA, Levy ML, Lin J, Mortimer K, Pitrez PM, Sheikh A, Yorgancioglu AA, Boulet L-Pet al., 2022, Global Initiative for Asthma Strategy 2021. Executive Summary and Rationale for Key Changes, ARCHIVOS DE BRONCONEUMOLOGIA, Vol: 58, Pages: 35-51, ISSN: 0300-2896

Journal article

Saglani S, Bingham Y, Balfour-Lynn I, Goldring S, Gupta A, Banya W, Moreiras J, Fleming L, Bush A, Rosenthal Met al., 2022, Blood eosinophils in managing preschool wheeze: Lessons learnt from a proof-of-concept trial, Pediatric Allergy and Immunology, Vol: 33, Pages: 1-8, ISSN: 0905-6157

BackgroundManagement of preschool wheeze is based predominantly on symptom patterns.ObjectiveTo determine whether personalizing therapy using blood eosinophils or airway bacterial infection results in fewer attacks compared with standard care.MethodsA proof-of-concept, randomized trial to investigate whether the prescription of inhaled corticosteroids (ICS) guided by blood eosinophils, or targeted antibiotics for airway bacterial infection, results in fewer unscheduled healthcare visits (UHCVs) compared with standard care. Children aged 1–5 years with ≥2 wheeze attacks in the previous year were categorized as episodic viral wheeze (EVW) or multiple trigger wheeze (MTW). The intervention group was prescribed ICS if blood eosinophils ≥3%, or targeted antibiotics if there is positive culture on induced sputum/cough swab. The control group received standard care. The primary outcome was UHCV at 4 months.Results60 children, with a median age of 36.5 (range 14–61) months, were randomized. Median blood eosinophils were 5.2 (range 0–21)%, 27 of 60 (45%) children were atopic, and 8 of 60 (13%) had airway bacterial infection. There was no relationship between EVW, MTW and either blood eosinophils, atopic status or infection. 67% in each group were prescribed ICS. 15 of 30 control subjects and 16 of 30 patients in the intervention group had UHCV over 4 months (p = .8). The time to first UHCV was similar. 50% returned adherence monitors; in those, median ICS adherence was 67%. There were no differences in any parameter between those who did and did not have an UHCV.ConclusionClinical phenotype was unrelated to allergen sensitization or blood eosinophils. ICS treatment determined by blood eosinophils did not impact UHCV, but ICS adherence was poor.

Journal article

Reddel HK, Bacharier LB, Bateman ED, Brightling CE, Brusselle GG, Buhl R, Cruz AA, Duijts L, Drazen JM, FitzGerald JM, Fleming LJ, Inoue H, Ko FW, Krishnan JA, Levy ML, Lin J, Mortimer K, Pitrez PM, Sheikh A, Yorgancioglu AA, Boulet L-Pet al., 2021, Global Initiative for Asthma Strategy 2021: Executive Summary and Rationale for Key Changes, JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE, Vol: 10, Pages: S1-S18, ISSN: 2213-2198

Journal article

Ko J, Jamalzadeh A, Makhecha S, Saglani S, Bush A, Fleming Let al., 2021, REAL LIFE EXPERIENCE WITH MEPOLIZUMAB AND COMPARISON WITH OMALIZUMAB IN CHILDREN WITH SEVERE ASTHMA, Publisher: BMJ PUBLISHING GROUP, Pages: A176-A177, ISSN: 0040-6376

Conference paper

De Simoni A, Fleming L, Holliday L, Horne R, Priebe S, Bush A, Sheikh A, Griffiths Cet al., 2021, Electronic reminders and rewards to improve adherence to inhaled asthma treatment in adolescents: a non-randomised feasibility study in tertiary care., BMJ Open, Vol: 11, Pages: 1-11, ISSN: 2044-6055

OBJECTIVE: To test the feasibility and acceptability of a short-term reminder and incentives intervention in adolescents with low adherence to asthma medications. METHODS: Mixed-methods feasibility study in a tertiary care clinic. Adolescents recruited to a 24-week programme with three 8-weekly visits, receiving electronic reminders to prompt inhaled corticosteroid (ICS) inhalation through a mobile app coupled with electronic monitoring devices (EMD). From the second visit, monetary incentives based on adherence of ICS inhalation: £1 per dose, maximum £2 /day, up to £112/study, collected as gift cards at the third visit. End of study interviews and questionnaires assessing perceptions of asthma and ICS, analysed using the Perceptions and Practicalities Framework. PARTICIPANTS: Adolescents (11-18 years) with documented low ICS adherence (<80% by EMD), and poor asthma control at the first clinic visit. RESULTS: 10 out of 12 adolescents approached were recruited (7 males, 3 females, 12-16 years). Eight participants provided adherence measures up to the fourth visits and received rewards. Mean study duration was 281 days, with 7/10 participants unable to attend their fourth visit due to COVID-19 lockdown. Only 3/10 participants managed to pair the app/EMD up to the fourth visit, which was associated with improved ICS adherence (from 0.51, SD 0.07 to 0.86, SD 0.05). Adherence did not change in adolescents unable to pair the app/EMD. The intervention was acceptable to participants and parents/guardians. Exit interviews showed that participants welcomed reminders and incentives, though expressed frustration with app/EMD technological difficulties. Participants stated the intervention helped through reminding ICS doses, promoting self-monitoring and increasing motivation to take inhalers. CONCLUSIONS: An intervention using electronic reminders and incentives through an app coupled with an EMD was feasible and acceptable to adolescents with asthma

Journal article

Reddel HK, Bacharier LB, Bateman ED, Brightling CE, Brusselle GG, Buhl R, Cruz AA, Duijts L, Drazen JM, FitzGerald JM, Fleming LJ, Inoue H, Ko FW, Krishnan JA, Levy ML, Lin J, Mortimer K, Pitrez PM, Sheikh A, Yorgancioglu AA, Boulet L-Pet al., 2021, Global Initiative for Asthma (GINA) Strategy 2021 - Executive summary and rationale for key changes., Respirology, ISSN: 1323-7799

The Global Initiative for Asthma (GINA) Strategy Report provides clinicians with an annually updated evidence-based strategy for asthma management and prevention, which can be adapted for local circumstances (e.g., medication availability). This article summarizes key recommendations from GINA 2021, and the evidence underpinning recent changes. GINA recommends that asthma in adults and adolescents should not be treated solely with short-acting beta2-agonist (SABA), because of the risks of SABA-only treatment and SABA overuse, and evidence for benefit of inhaled corticosteroids (ICS). Large trials show that as- needed combination ICS-formoterol reduces severe exacerbations by ≥60% in mild asthma compared with SABA alone, with similar exacerbation, symptom, lung function and inflammatory outcomes as daily ICS plus as-needed SABA. Key changes in GINA 2021 include division of the treatment figure for adults and adolescents into two tracks. Track 1 (preferred) has low-dose ICS-formoterol as the reliever at all steps: as-needed only in Steps 1-2 (mild asthma), and with daily maintenance ICS-formoterol (maintenance-and-reliever therapy, MART) in Steps 3-5. Track 2 (alternative) has as-needed SABA across all steps, plus regular ICS (Step 2) or ICS-long-acting beta2-agonist (LABA) (Steps 3-5). For adults with moderate-to-severe asthma, GINA makes additional recommendations in Step 5 for add-on long-acting muscarinic antagonists and azithromycin, with add-on biologic therapies for severe asthma. For children 6-11 years, new treatment options are added at Steps 3-4. Across all age-groups and levels of severity, regular personalized assessment, treatment of modifiable risk factors, self-management education, skills training, appropriate medication adjustment and review remain essential to optimize asthma outcomes. This article is protected by copyright. All rights reserved.

Journal article

Reddel HK, Bacharier LB, Bateman ED, Brightling CE, Brusselle GG, Buhl R, Cruz AA, Duijts L, Drazen JM, FitzGerald JM, Fleming LJ, Inoue H, Ko FW, Krishnan JA, Levy ML, Lin J, Mortimer K, Pitrez PM, Sheikh A, Yorgancioglu AA, Boulet L-Pet al., 2021, Global Initiative for Asthma (GINA) strategy 2021 - executive summary and rationale for key changes., American Journal of Respiratory and Critical Care Medicine, Vol: 205, Pages: 17-35, ISSN: 1073-449X

The Global Initiative for Asthma (GINA) Strategy Report provides clinicians with an annually updated evidence-based strategy for asthma management and prevention, which can be adapted for local circumstances (e.g., medication availability). This article summarizes key recommendations from GINA 2021, and the evidence underpinning recent changes. GINA recommends that asthma in adults and adolescents should not be treated solely with short-acting beta2-agonist (SABA), because of the risks of SABA-only treatment and SABA overuse, and evidence for benefit of inhaled corticosteroids (ICS). Large trials show that as-needed combination ICS-formoterol reduces severe exacerbations by ≥60% in mild asthma compared with SABA alone, with similar exacerbation, symptom, lung function and inflammatory outcomes as daily ICS plus as-needed SABA. Key changes in GINA 2021 include division of the treatment figure for adults/adolescents into two tracks. Track 1 (preferred) has low-dose ICS-formoterol as the reliever at all steps: as-needed only in Steps 1-2 (mild asthma), and with daily maintenance ICS formoterol (maintenance-and-reliever therapy, MART) in Steps 3-5. Track 2 (alternative) has as-needed SABA across all steps, plus regular ICS (Step 2) or ICS-long-acting beta2-agonist (LABA) (Steps 3-5). For adults with moderate-to-severe asthma, GINA makes additional recommendations in Step 5 for add-on long-acting muscarinic antagonists and azithromycin, with add-on biologic therapies for severe asthma. For children 6-11 years, new treatment options are added at Steps 3-4. Across all age-groups and levels of severity, regular personalized assessment, treatment of modifiable risk factors, self-management education, skills training, appropriate medication adjustment and review remain essential to optimize asthma outcomes.

Journal article

Golebski K, Dankelman LHM, Bjorkander S, Bonnelykke K, Brinkman P, Deschildre A, van Dijk YE, Fleming L, Grigg J, Hamelmann E, Hashimoto S, Kabesch M, Klevebro S, Maitland-van der Zee A-H, Merid SK, Nieto A, Niggel J, Nilsson C, Potocnik U, Roberts G, Rusconi F, Saglani S, Valente E, van Drunen C, Wang G, Melen E, Vijverberg SJHet al., 2021, Expert meeting report: towards a joint European roadmap to address the unmet needs and priorities of paediatric asthma patients on biologic therapy, ERJ OPEN RESEARCH, Vol: 7

Journal article

Tanner N, Saglani S, Li AM, Bush A, Fleming Let al., 2021, Airway inflammation in severe asthmatics with acid gastro-oesophageal reflux, Thorax, Vol: 77, Pages: 398-399, 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.

Journal article

Makhecha S, Jamalzadeh A, Irving S, Hall P, Sonnappa S, Saglani S, Bush A, Fleming Let 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

Journal article

Levy ML, Fleming L, Goldring S, Bush Aet 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

Journal article

Jochmann A, Artusio L, Usemann J, Jamalzadeh A, Bush A, Frey U, Fleming LJet 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

Journal article

Santos-Valente E, Buntrock-Döpke H, Abou Taam R, Arasi S, Bakirtas A, Lozano Blasco J, Bønnelykke K, Craiu M, Cutrera R, Deschildre A, Elnazir B, Fleming L, Frey U, Gappa M, Nieto García A, Skamstrup Hansen K, Hanssens L, Jahnz-Rozyk K, Jesenak M, Kerzel S, Kopp MV, Koppelman GH, Krivec U, MacLeod KA, Mäkelä M, Melén E, Mezei G, Moeller A, Moreira A, Pohunek P, Minić P, Rutjes NWP, Sammut P, Schwerk N, Szépfalusi Z, Turkalj M, Tzotcheva I, Ulmeanu A, Verhulst S, Xepapadaki P, Niggel J, Vijverberg S, Maitland-van der Zee AH, Potočnik U, Reinartz SM, van Drunen CM, Kabesch Met 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.

Journal article

Alahmadi FH, Simpson AJ, Gomez C, Ericsson M, Thörngren J-O, Wheelock C, Shaw DE, Fleming LJ, Roberts G, Riley J, Bates S, Sousa AR, Knowles R, Bansal AT, Corfield J, Pandis I, Sun K, Bakke PS, Caruso M, Chanez P, Dahlén B, Horvath I, Krug N, Montuschi P, Singer F, Wagers S, Adcock IM, Djukanovic R, Chung KF, Sterk PJ, Dahlen S-E, Fowler SJ, U-BIOPRED Study Groupet 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.

Journal article

Saglani S, Robinson P, Fontanella S, Ananth S, Martin Alonso A, Cook J, Kaya-de Vries D, Polo Silveira L, Gregory L, Lloyd C, Fleming L, Bush A, Custovic Aet 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

Journal article

Agerskov N, Coughlin S, Parrott H, Saglani S, Sonnappa S, Fleming Let al., 2021, Quality of unsupervised home spirometry in children with asthma, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, Pages: 1-1, ISSN: 1073-449X

Rationale: Spirometry is a standard test that is used to support clinical decision making in patients with asthma.Laboratory spirometry is associated with high quality data but is performed only when patients attend thehospital. Hand-held spirometry can be performed regularly at home allowing clinical trends to be identified. It isunclear whether children perform these tests regularly and achieve adequate quality when unsupervised bytrained personnel. The goal of this study was to evaluate adherence to, and quality of, home spirometry inpaediatric asthma patients using NuvoAir Home. Methods: A retrospective analysis of data from 39 paediatricasthma patients (age, 13±3.3) using the NuvoAir Home platform, from the Royal Brompton Hospital (London,UK), was performed. The platform consists of a smartphone application, Bluetooth spirometer, and clinicianportal that allows patient data to be shared with their healthcare team. The built-in coaching system on the Appprovides feedback to patients on the quality of spirometry (2017 ATS) and tips on how to improve during futuretests. Patients were provided instructions on how to use the NuvoAir Home platform by a specialist respiratoryphysiologist using remote consultation. All sessions were performed in the home setting. Children were asked toperform tests prior to clinical review (1 to 3 monthly). Data were analysed for patients that had used the in-homesolution for at least 90 days. Assessment of session quality was completed over 30 day intervals, analyzing theoverall session grade, FEV1 and FVC percent predicted. All data were analysed anonymously, with informedconsent from the study participants. Results: A total of 517 sessions, performed over a period of 210 days wereanalysed. 288 (55.7%) of the sessions were of acceptable quality (grade A-C, at least 2 attempts <200 mL FEV1and FVC variability). A higher proportion (76.9%) of sessions performed in the last 30 days of the study were ofacceptable quality, compar

Conference paper

Coughlin S, Parrott H, Wells C, Saglani S, Sonnappa S, Fleming Let 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

Conference paper

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

Journal article

Jamalzadeh A, Makhecha S, Irving S, Bush A, Saglani S, Sonnappa S, Hall P, Moore-Crouch R, Kargbo A, Baynton L, Fleming Let 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

Conference paper

Gorlanova O, Tischhauser E, Adcock IM, Chung KF, Fleming L, Meier D, Sterk PJ, Roberts G, Roberts A, Singer F, Sousa AR, Uddin M, Frey Uet 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

Journal article

Makhecha S, Chan A, Jamalzadeh A, Fleming Let 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.

Journal article

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