Imperial College London

DrLouiseFleming

Faculty of MedicineNational Heart & Lung Institute

Honorary Senior Research Fellow
 
 
 
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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

277 results found

Fleming L, Hine J, Bush A, Judah G, Di Simoni A, Griffiths C, Lee Bet 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

Journal article

Levy ML, Bateman ED, Allan K, Bacharier LB, Bonini M, Boulet L-P, Bourdin A, Brightling C, Brusselle G, Buhl R, Chakaya MJ, Cruz AA, Drazen J, Ducharme FM, Duijts L, Fleming L, Inoue H, Ko FWS, Krishnan JA, Masekela R, Mortimer K, Pitrez P, Salvi S, Sheikh A, Reddel HK, Yorgancıoğlu Aet al., 2023, Global access and patient safety in the transition to environmentally friendly respiratory inhalers: the Global Initiative for Asthma perspective., Lancet

Journal article

Abdel-Aziz MI, Thorsen J, Hashimoto S, Vijverberg SJH, Neerincx AH, Brinkman P, van Aalderen W, Stokholm J, Rasmussen MA, Roggenbuck-Wedemeyer M, Vissing NH, Mortensen MS, Brejnrod AD, Fleming LJ, Murray CS, Fowler SJ, Frey U, Bush A, Singer F, Hedlin G, Nordlund B, Shaw DE, Chung KF, Adcock IM, Djukanovic R, Auffray C, Bansal AT, Sousa AR, Wagers SS, Chawes BL, Bønnelykke K, Sørensen SJ, Kraneveld AD, Sterk PJ, Roberts G, Bisgaard H, Maitland-van der Zee AH, U-BIOPRED Study Groupet al., 2023, Oropharyngeal Microbiota Clusters in Children with Asthma or Wheeze Associate with Allergy, Blood Transcriptomic Immune Pathways, and Exacerbation Risk., Am J Respir Crit Care Med, Vol: 208, Pages: 142-154

Rationale: Children with preschool wheezing or school-age asthma are reported to have airway microbial imbalances. Objectives: To identify clusters in children with asthma or wheezing using oropharyngeal microbiota profiles. Methods: Oropharyngeal swabs from the U-BIOPRED (Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes) pediatric asthma or wheezing cohort were characterized using 16S ribosomal RNA gene sequencing, and unsupervised hierarchical clustering was performed on the Bray-Curtis β-diversity. Enrichment scores of the Molecular Signatures Database hallmark gene sets were computed from the blood transcriptome using gene set variation analysis. Children with severe asthma or severe wheezing were followed up for 12-18 months, with assessment of the frequency of exacerbations. Measurements and Main Results: Oropharyngeal samples from 241 children (age range, 1-17 years; 40% female) revealed four taxa-driven clusters dominated by Streptococcus, Veillonella, Rothia, and Haemophilus. The clusters showed significant differences in atopic dermatitis, grass pollen sensitization, FEV1% predicted after salbutamol, and annual asthma exacerbation frequency during follow-up. The Veillonella cluster was the most allergic and included the highest percentage of children with two or more exacerbations per year during follow-up. The oropharyngeal clusters were different in the enrichment scores of TGF-β (transforming growth factor-β) (highest in the Veillonella cluster) and Wnt/β-catenin signaling (highest in the Haemophilus cluster) transcriptomic pathways in blood (all q values <0.05). Conclusions: Analysis of the oropharyngeal microbiota of children with asthma or wheezing identified four clusters with distinct clinical characteristics (phenotypes) that associate with risk for exacerbation and transcriptomic pathways involved in airway remodeling. This suggests that further exploration of the oropharyngeal microbiota

Journal article

Brandsma J, Schofield JPR, Yang X, Strazzeri F, Barber C, Goss VM, Koster G, Bakke PS, Caruso M, Chanez P, Dahlén S-E, Fowler SJ, Horváth I, Krug N, Montuschi P, Sanak M, Sandström T, Shaw DE, Chung KF, Singer F, Fleming LJ, Adcock IM, Pandis I, Bansal AT, Corfield J, Sousa AR, Sterk PJ, Sánchez-García RJ, Skipp PJ, Postle AD, Djukanović R, U-BIOPRED Study Groupet 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.

Journal article

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

Journal article

Khaleva E, Rattu A, Brightling C, Bush A, Bourdin A, Bossios A, Chung KF, Chaudhuri R, Coleman C, Djukanovic R, Dahlén S-E, Exley A, Fleming L, Fowler SJ, Gupta A, Hamelmann E, Koppelman GH, Melén E, Mahler V, Seddon P, Singer F, Porsbjerg C, Ramiconi V, Rusconi F, Yasinska V, Roberts Get al., 2023, Definitions of non-response and response to biological therapy for severe asthma: a systematic review., ERJ Open Res, Vol: 9, ISSN: 2312-0541

BACKGROUND: Biologics have proven efficacy for patients with severe asthma but there is lack of consensus on defining response. We systematically reviewed and appraised methodologically developed, defined and evaluated definitions of non-response and response to biologics for severe asthma. METHODS: We searched four bibliographic databases from inception to 15 March 2021. Two reviewers screened references, extracted data, and assessed methodological quality of development, measurement properties of outcome measures and definitions of response based on COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN). A modified GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach and narrative synthesis were undertaken. RESULTS: 13 studies reported three composite outcome measures, three asthma symptoms measures, one asthma control measure and one quality of life measure. Only four measures were developed with patient input; none were composite measures. Studies utilised 17 definitions of response: 10 out of 17 (58.8%) were based on minimal clinically important difference (MCID) or minimal important difference (MID) and 16 out of 17 (94.1%) had high-quality evidence. Results were limited by poor methodology for the development process and incomplete reporting of psychometric properties. Most measures rated "very low" to "low" for quality of measurement properties and none met all quality standards. CONCLUSIONS: This is the first review to synthesise evidence about definitions of response to biologics for severe asthma. While high-quality definitions are available, most are MCIDs or MIDs, which may be insufficient to justify continuation of biologics in terms of cost-effectiveness. There remains an unmet need for universally accepted, patient-centred, composite definitions to aid clinical decision making and comparability of responses to biologics.

Journal article

Scotney E, Fleming L, Saglani S, Sonnappa S, Bush Aet al., 2023, Advances in the pathogenesis and personalised treatment of paediatric asthma, BMJ Medicine, Vol: 2, Pages: e000367-e000367

<jats:p>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.</jats:p>

Journal article

Rattu A, Khaleva E, Brightling C, Dahlén S-E, Bossios A, Fleming L, Chung KF, Melén E, Djukanovic R, Chaudhuri R, Exley A, Koppelman GH, Bourdin A, Rusconi F, Porsbjerg C, Coleman C, Williams C, Nielsen H, Davin E, Taverner P, Romagosa Vilarnau S, Roberts G, 3TR Consortium Respiratory Work Packageet al., 2023, Identifying and appraising outcome measures for severe asthma: a systematic review., Eur Respir J, Vol: 61

BACKGROUND: Valid outcome measures are imperative to evaluate treatment response, yet the suitability of existing end-points for severe asthma is unclear. This review aimed to identify outcome measures for severe asthma and appraise the quality of their measurement properties. METHODS: A literature search was performed to identify "candidate" outcome measures published between 2018 and 2020. A modified Delphi exercise was conducted to select "key" outcome measures within healthcare professional, patient, pharmaceutical and regulatory stakeholder groups. Initial validation studies for "key" measures were rated against modified quality criteria from COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN). The evidence was discussed at multi-stakeholder meetings to ratify "priority" outcome measures. Subsequently, four bibliographic databases were searched from inception to 20 July 2020 to identify development and validation studies for these end-points. Two reviewers screened records, extracted data, assessed their methodological quality and graded the evidence according to COSMIN. RESULTS: 96 outcome measures were identified as "candidates", 55 as "key" and 24 as "priority" for severe asthma, including clinical, healthcare utilisation, quality of life, asthma control and composite. 32 studies reported measurement properties of 17 "priority" end-points from the latter three domains. Only the Severe Asthma Questionnaire and Childhood Asthma Control Test were developed with input from severe asthma patients. The certainty of evidence was "low" to "very low" for most "priority" end-points across all measurement properties and none fulfilled all quality standards. CONCLUSIONS: Only two outcome measures had robust developmental data for severe asthma. This review informed development of core outcome measures sets for severe asthma.

Journal article

Khaleva E, Rattu A, Brightling C, Bush A, Bossios A, Bourdin A, Chung KF, Chaudhuri R, Coleman C, Dahlén S-E, Djukanovic R, Deschildre A, Fleming L, Fowler SJ, Gupta A, Hamelmann E, Hashimoto S, Hedlin G, Koppelman GH, Melén E, Murray CS, Pilette C, Porsbjerg C, Pike KC, Rusconi F, Williams C, Ahrens B, Alter P, Anckers F, van den Berge M, Blumchen K, Brusselle G, Clarke GW, Cunoosamy D, Dahlén B, Dixey P, Exley A, Frey U, Gaillard EA, Giovannini-Chami L, Grigg J, Hartenstein D, Heaney LG, Karadag B, Kaul S, Kull I, Licari A, Maitland-van der Zee AH, Mahler V, Schoos A-MM, Nagakumar P, Negus J, Nielsen H, Paton J, Pijnenburg M, Ramiconi V, Romagosa Vilarnau S, Principe S, Rutjes N, Saglani S, Seddon P, Singer F, Staudinger H, Turner S, Vijverberg S, Winders T, Yasinska V, Roberts G, COMSA Working Group in the 3TR Consortiumet al., 2023, Development of Core Outcome Measures sets for paediatric and adult Severe Asthma (COMSA)., Eur Respir J, Vol: 61

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.

Journal article

Levy ML, Bacharier LB, Bateman E, Boulet L-P, Brightling C, Buhl R, Brusselle G, Cruz AA, Drazen JM, Duijts L, Fleming L, Inoue H, Ko FWS, Krishnan JA, Mortimer K, Pitrez PM, Sheikh A, Yorgancioglu A, Reddel HKet al., 2023, Key recommendations for primary care from the 2022 Global Initiative for Asthma (GINA) update, NPJ PRIMARY CARE RESPIRATORY MEDICINE, Vol: 33

Journal article

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

Journal article

Thorsen J, Stokholm J, Rasmussen MA, Roggenbuck-Wedemeyer M, Vissing NH, Mortensen MS, Brejnrod AD, Fleming L, Bush A, Roberts G, Singer F, Frey U, Hedlin G, Nordlund B, Murray CS, Abdel-Aziz M, Hashimoto S, van Aalderen W, Maitland-van der Zee AH, Shaw D, Fowler SJ, Sousa A, Sterk PJ, Chung KF, Adcock IM, Djukanovic R, Auffray C, Bansal AT, Wagers S, Chawes B, Bonnelykke K, Sorensen SJ, Bisgaard Het 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

Journal article

Chen PC, Irving SI, Fleming LF, 2022, AN ASSESSMENT OF SELF-PERFORMED HOME SPIROMETRY IN PAEDIATRIC ASTHMA PATIENTS, Publisher: BMJ PUBLISHING GROUP, Pages: A128-A129, ISSN: 0040-6376

Conference paper

Wells C, Wilkinson N, Makhecha S, Hall P, Jamalzadeh A, Sonnappa S, Fleming L, Bush A, Saglani Set al., 2022, ACCEPTABILITY AND FEASIBILITY PILOT OF CODESIGNED TELEHEALTH PHYSIOTHERAPY INTERVENTIONS FOR CHILDREN WITH ASTHMA AND DYSFUNCTIONAL BREATHING, Publisher: BMJ PUBLISHING GROUP, Pages: A130-A130, ISSN: 0040-6376

Conference paper

Pavlou B, Scotney E, Makariou I, Bingham Y, Jamalzadeh A, Hall P, Jackman C, Bush A, Sonnappa S, Fleming L, Saglani Set al., 2022, ACCEPTABILITY AND FEASIBILITY OF MEASURING BLOOD EOSINOPHILS USING A POINT-OF-CARE DEVICE IN CHILDREN WITH ASTHMA, Publisher: BMJ PUBLISHING GROUP, Pages: A130-A131, ISSN: 0040-6376

Conference paper

Makariou I, Rhamie S, Bush A, Saglani S, Fleming L, Sonnappa Set al., 2022, Peak inspiratory flow in children with exercise induced laryngeal obstruction, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936

Conference paper

Abdel-Aziz M, Thorsen J, Hashimoto S, Vijverberg SJH, Neerincx AH, Brinkman P, Aalderen W, Stokholm J, Roggenbuck-Wedemeyer M, Vissing NH, Mortensen MS, Brejnrod AD, Fleming LJ, Murray CS, Fowler SJ, Frey U, Bush A, Singer F, Hedlin G, Nordlund B, Shaw DE, Chung KF, Adcock IM, Djukanovic R, Auffray C, Bansal AT, Sousa AR, Wagers SS, Chawes BL, Bonnelykke K, Sorensen SJ, Kraneveld AD, Sterk PJ, Roberts G, Bisgaard H, Maitland-Van der Zee AHet 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

Conference paper

Makariou I, Bush A, Saglani S, Fainardi V, Bossley CJ, Fleming Let 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

Conference paper

Scotney E, Jayarathna R, Gupta L, Bush A, Saglani S, Fleming L, Sonnappa Set 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

Conference paper

Fowler S, Bhatt J, Brown S, Fleming L, Mayell S, Sinha I, Bush Aet al., 2022, E-cigarette company tactics in sports advertising, LANCET RESPIRATORY MEDICINE, Vol: 10, Pages: 634-636, ISSN: 2213-2600

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, Pages: 1-17, ISSN: 0903-1936

Rationale Asthma phenotyping requires novel biomarker discovery.Objectives To identify plasma biomarkers associated with asthma phenotypes by application of a new proteomic panel to samples from two well-characterised cohorts of severe (SA) and mild-to-moderate (MMA) asthmatics, COPD subjects and healthy controls (HCs).Methods An antibody-based array targeting 177 proteins predominantly involved in pathways relevant to inflammation, lipid metabolism, signal transduction and extracellular matrix was applied to plasma from 525 asthmatics and HCs in the U-BIOPRED cohort, and 142 subjects with asthma and COPD from the validation cohort BIOAIR. Effects of oral corticosteroids (OCS) were determined by a 2-week, placebo-controlled OCS trial in BIOAIR, and confirmed by relation to objective OCS measures in U-BIOPRED.Results In U-BIOPRED, 110 proteins were significantly different, mostly elevated, in SA compared to MMA and HCs. 10 proteins were elevated in SA versus MMA in both U-BIOPRED and BIOAIR (alpha-1-antichymotrypsin, apolipoprotein-E, complement component 9, complement factor I, macrophage inflammatory protein-3, interleukin-6, sphingomyelin phosphodiesterase 3, TNF receptor superfamily member 11a, transforming growth factor-β and glutathione S-transferase). OCS treatment decreased most proteins, yet differences between SA and MMA remained following correction for OCS use. Consensus clustering of U-BIOPRED protein data yielded six clusters associated with asthma control, quality of life, blood neutrophils, high-sensitivity C-reactive protein and body mass index, but not Type-2 inflammatory biomarkers. The mast cell specific enzyme carboxypeptidase A3 was one major contributor to cluster differentiation.Conclusions The plasma proteomic panel revealed previously unexplored yet potentially useful Type-2-independent biomarkers and validated several proteins with established involvement in the pathophysiology of SA.

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

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

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

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