ProfessorAndrewBush

Warraich S, Bush A, Levy ML, Fleming Let al., 2023, Regular (up to 10 puffs 4-hourly) inhaled salbutamol should be prescribed at discharge after an asthma attack: myth or maxim?, Breathe (Sheff), Vol: 19, ISSN: 1810-6838

Over the past 20 years, the concept of asthma weaning plans on discharge after an attack has crept into common practice, although the precise origin of these plans is unclear. High use of short-acting β2-agonists (SABAs) may result in tolerance to their bronchodilator effects, thus diminishing their efficacy, particularly when they are most needed at the time of an acute attack. Furthermore, key warning signs of a deterioration in asthma control may be masked and the weaning plan may encourage the over-use and over-reliance on SABAs. Side-effects from over-use may also occur, including lactic acidosis, downregulation of the β2-adrenoreceptor, increased allergen response and pro-inflammatory effects. The need for asthma education at discharge, a personal asthma action plan and vigilance about prescribing and ensuring adherence to maintenance therapy are definitely important. However, the current authors conclude that the benefit of prescribing regular salbutamol (up to 10 puffs every 4 h) at discharge after an acute asthma attack is a myth, and a very dangerous one.

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Mazulov O, Powell Z, Powell E, Bush AB, Chang AB, Kantar A, Grimwood K, Karadag Bet al., 2023, World Bronchiectasis Day: It is time for global action to promote equity of care, PEDIATRIC PULMONOLOGY, Vol: 58, Pages: 2183-2186, ISSN: 8755-6863

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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

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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, Bonnelykke K, Sorensen SJ, Kraneveld AD, Sterk PJ, Roberts G, Bisgaard H, Maitland-van der Zee AHet al., 2023, Oropharyngeal Microbiota Clusters in Children with Asthma or Wheeze Associate with Allergy, Blood Transcriptomic Immune Pathways, and Exacerbation Risk, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 208, Pages: 142-154, ISSN: 1073-449X

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Brandsma J, Schofield JPR, Yang X, 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.

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Ramsey B, Bush A, 2023, Cystic Fibrosis: From Tragedy to Triumph, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 208, Pages: 9-10, ISSN: 1073-449X

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Davies J, Southern KW, Barben J, Goldring S, Kneen R, Southward S, Rajeev Y, Bush Aet al., 2023, Raised intracranial pressure in three children with cystic fibrosis receiving elexacaftor-tezacaftor-ivacaftor modulator therapy, American Journal of Respiratory and Critical Care Medicine, Vol: 208, Pages: 103-105, ISSN: 1073-449X

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Gilbert C, Bennett KM, Brown C, Bush Aet al., 2023, Experiences of UK-based adult transition services for interstitial lung disease in childhood: "There's a lot less cushioning", PEDIATRIC PULMONOLOGY, Vol: 58, Pages: 1993-1999, ISSN: 8755-6863

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Bush A, 2023, Basic clinical management of preschool wheeze, PEDIATRIC ALLERGY AND IMMUNOLOGY, Vol: 34, ISSN: 0905-6157

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Basile U, Santini G, Napodano C, Macis G, Pocino K, Gulli F, Malerba M, Bush A, Adcock IM, Montuschi Pet al., 2023, Elevated serum polyclonal immunoglobulin free light chains in patients with severe asthma, Frontiers in Pharmacology, Vol: 14, Pages: 1-14, ISSN: 1663-9812

Background: Inflammation plays a pivotal role in the pathophysiology of asthma. Free light chains (FLC) can cause inflammation by mast cell antigen-activation. Serum immunoglobulin (Ig) FLC κ, but not λ, were shown elevated in adult males with asthma. We sought to investigate if serum Ig FLC concentrations are affected by asthma severity and their relationships with inflammatory outcomes. Methods: By using immunoassays, we measured serum κ and λ Ig FLCs in 24 severe persistent asthma patients, 15 patients with moderate persistent asthma, 15 steroid-naïve mild persistent asthma patients and 20 healthy control subjects in a cross-sectional observational study. Total and specific serum IgE concentrations, fractional exhaled nitric oxide (FENO), lung function, peripheral blood eosinophils and neutrophils, and C reactive protein (CRP) were also measured. Results: Serum κ FLC concentrations were elevated in severe asthma patients compared mild asthma patients (p < 0.05) and healthy subjects (p < 0.05). Serum λ FLCs were higher in severe asthma patients than in healthy subjects (p < 0.05) and correlated with blood eosinophil counts (percentage, κ: r = 0.51, p = 2.9678-6; λ: r = 0.42, p = 1.7377-4; absolute values, κ: r = 0.45, p = 6.1284-5; λ: r = 0.38, p = 7.8261-4), but not with total or specific serum IgE. In severe asthma patients, serum Ig FLC correlated with serum CRP (κ: r = 0.33; p = 0.003; λ: r = 0.38, p = 8.8305-4) and blood neutrophil cell counts (percentage, κ: r = 0.31; p = 0.008; λ: r = 0.29, p = 0.01; absolute values, κ: r = 0.40; p = 3.9176-4; λ: r = 0.40, p = 4.5479-4), were elevated in subjects with blood eosinophilia (≥300 cells/µL) (n = 13) compared with non-eosinophilic subjects (n = 10) (κ: 19.2 ± 1.2 mg/L versus 12.1 ± 1.3 mg/L, p < 0.001; λ: 27.2 ± 2.6 mg/L versus 16.8 &plu

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Bush A, Martinez FJ, Brochard LJ, Chotirmall SH, Han MKet al., 2023, AJRCCM: Strength in Breadth., Am J Respir Crit Care Med, Vol: 207, Pages: 1111-1112

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Bush A, Martinez FJ, Brochard LJ, Chotirmall SH, Han MKet al., 2023, <i>AJRCCM</i>: Strength in Breadth, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 207, Pages: 1111-1112, ISSN: 1073-449X

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Khaleva E, Rattu A, Brightling C, Bush A, Bourdin A, Bossios A, Chung KF, Chaudhuri R, Coleman C, Djukanovic R, Dahlen S-E, Exley A, Fleming L, Fowler SJ, Gupta A, Hamelmann E, Koppelman GH, Melen 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 RESEARCH, Vol: 9

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Lajunen KT, Mayoral K, Alabdulkareem F, Irving S, Fleming L, Sonnappa S, Bush A, Saglani Set al., 2023, Feasibility and Acceptability of Point-of-Care Blood Eosinophil Count Together With Lung Function in Wheezy Preschool Children, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X

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Bousquet J, Melén E, Haahtela T, Koppelman GH, Togias A, Valenta R, Akdis CA, Czarlewski W, Rothenberg M, Valiulis A, Wickman M, Akdis M, Aguilar D, Bedbrook A, Bindslev-Jensen C, Bosnic-Anticevich S, Boulet LP, Brightling CE, Brussino L, Burte E, Bustamante M, Canonica GW, Cecchi L, Celedon JC, Chaves Loureiro C, Costa E, Cruz AA, Erhola M, Gemicioglu B, Fokkens WJ, Garcia-Aymerich J, Guerra S, Heinrich J, Ivancevich JC, Keil T, Klimek L, Kuna P, Kupczyk M, Kvedariene V, Larenas-Linnemann DE, Lemonnier N, Lodrup Carlsen KC, Louis R, Makela M, Makris M, Maurer M, Momas I, Morais-Almeida M, Mullol J, Naclerio RN, Nadeau K, Nadif R, Niedoszytko M, Okamoto Y, Ollert M, Papadopoulos NG, Passalacqua G, Patella V, Pawankar R, Pham-Thi N, Pfaar O, Regateiro FS, Ring J, Rouadi PW, Samolinski B, Sastre J, Savouré M, Scichilone N, Shamji MH, Sheikh A, Siroux V, Sousa-Pinto B, Standl M, Sunyer J, Taborda-Barata L, Toppila-Salmi S, Torres MJ, Tsiligianni I, Valovirta E, Vandenplas O, Ventura MT, Weiss S, Yorgancioglu A, Zhang L, Abdul Latiff AH, Aberer W, Agache I, Al-Ahmad M, Alobid I, Ansotegui IJ, Arshad SH, Asayag E, Barbara C, Baharudin A, Battur L, Bennoor KS, Berghea EC, Bergmann KC, Bernstein D, Bewick M, Blain H, Bonini M, Braido F, Buhl R, Bumbacea RS, Bush A, Calderon M, Calvo-Gil M, Camargos P, Caraballo L, Cardona V, Carr W, Carreiro-Martins P, Casale T, Cepeda Sarabia AM, Chandrasekharan R, Charpin D, Chen YZ, Cherrez-Ojeda I, Chivato T, Chkhartishvili E, Christoff G, Chu DK, Cingi C, Correia de Sousa J, Corrigan C, Custovic A, D'Amato G, Del Giacco S, De Blay F, Devillier P, Didier A, do Ceu Teixeira M, Dokic D, Douagui H, Doulaptsi M, Durham S, Dykewicz M, Eiwegger T, El-Sayed ZA, Emuzyte R, Fiocchi A, Fyhrquist N, Gomez RM, Gotua M, Guzman MA, Hagemann J, Hamamah S, Halken S, Halpin DMG, Hofmann M, Hossny E, Hrubiško M, Irani C, Ispayeva Z, Jares E, Jartti T, Jassem E, Julge K, Just J, Jutel M, Kaidashev I, Kalayci O, Kalyoncu AF, Kardas P, Kirenga B, Kraxner Het al., 2023, Rhinitis associated with asthma is distinct from rhinitis alone: The ARIA-MeDALL hypothesis, Allergy, Vol: 78, Pages: 1169-1203, ISSN: 0105-4538

Asthma, rhinitis, and atopic dermatitis (AD) are interrelated clinical phenotypes that partly overlap in the human interactome. The concept of "one-airway-one-disease," coined over 20 years ago, is a simplistic approach of the links between upper- and lower-airway allergic diseases. With new data, it is time to reassess the concept. This article reviews (i) the clinical observations that led to Allergic Rhinitis and its Impact on Asthma (ARIA), (ii) new insights into polysensitization and multimorbidity, (iii) advances in mHealth for novel phenotype definitions, (iv) confirmation in canonical epidemiologic studies, (v) genomic findings, (vi) treatment approaches, and (vii) novel concepts on the onset of rhinitis and multimorbidity. One recent concept, bringing together upper- and lower-airway allergic diseases with skin, gut, and neuropsychiatric multimorbidities, is the "Epithelial Barrier Hypothesis." This review determined that the "one-airway-one-disease" concept does not always hold true and that several phenotypes of disease can be defined. These phenotypes include an extreme "allergic" (asthma) phenotype combining asthma, rhinitis, and conjunctivitis. Rhinitis alone and rhinitis and asthma multimorbidity represent two distinct diseases with the following differences: (i) genomic and transcriptomic background (Toll-Like Receptors and IL-17 for rhinitis alone as a local disease; IL-33 and IL-5 for allergic and non-allergic multimorbidity as a systemic disease), (ii) allergen sensitization patterns (mono- or pauci-sensitization versus polysensitization), (iii) severity of symptoms, and (iv) treatment response. In conclusion, rhinitis alone (local disease) and rhinitis with asthma multimorbidity (systemic disease) should be considered as two distinct diseases, possibly modulated by the microbiome, and may be a model for understanding the epidemics of chronic and autoimmune diseases.

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Zar HJ, Bush A, 2023, Early childhood lower respiratory tract infection: a key determinant of premature adult respiratory mortality, LANCET, Vol: 401, Pages: 1135-1137, ISSN: 0140-6736

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Khaleva E, Rattu A, Brightling C, Bush A, Bossios A, Bourdin A, Chung KF, Chaudhuri R, Coleman C, Dahlen S-E, Djukanovic R, Deschildre A, Fleming L, Fowler SJ, Gupta A, Hamelmann E, Hashimoto S, Hedlin G, Koppelman GH, Melen 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, Dahlen 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, Vilarnau SR, Principe S, Rutjes N, Saglani S, Seddon P, Singer F, Staudinger H, Turner S, Vijverberg S, Winders T, Yasinska V, Roberts Get al., 2023, Development of Core Outcome Measures sets for paediatric and adult Severe Asthma (COMSA), European Respiratory Journal, Vol: 61, ISSN: 0903-1936

Background Effectiveness studies with biological therapies for asthma lack standardised outcome measures. The COMSA (Core Outcome Measures sets for paediatric and adult Severe Asthma) Working Group sought to develop Core Outcome Measures (COM) sets to facilitate better synthesis of data and appraisal of biologics in paediatric and adult asthma clinical studies.Methods COMSA utilised a multi-stakeholder consensus process among patients with severe asthma, adult and paediatric clinicians, pharmaceutical representatives, and health regulators from across Europe. Evidence included a systematic review of development, validity and reliability of selected outcome measures plus a narrative review and a pan-European survey to better understand patients’ and carers’ views about outcome measures. It was discussed using a modified GRADE (Grading of Recommendations Assessment, Development and Evaluation) Evidence to Decision framework. Anonymous voting was conducted using predefined consensus criteria.Results Both adult and paediatric COM sets include forced expiratory volume in 1 s (FEV1) as z-scores, annual frequency of severe exacerbations and maintenance oral corticosteroid use. Additionally, the paediatric COM set includes the Paediatric Asthma Quality of Life Questionnaire and Asthma Control Test or Childhood Asthma Control Test, while the adult COM set includes the Severe Asthma Questionnaire and Asthma Control Questionnaire-6 (symptoms and rescue medication use reported separately).Conclusions This patient-centred collaboration has produced two COM sets for paediatric and adult severe asthma. It is expected that they will inform the methodology of future clinical trials, enhance comparability of efficacy and effectiveness of biological therapies, and help assess their socioeconomic value. COMSA will inform definitions of non-response and response to biological therapy for severe asthma.

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Martinez FJ, Bush A, Brochard L, Han MK, Chotirmall SHet al., 2023, Introducing "Viewpoint: Turning the Air Blue", AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 207, Pages: 803-803, ISSN: 1073-449X

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Bush A, 2023, Giving a voice to the voiceless: end of life second opinions, ARCHIVES OF DISEASE IN CHILDHOOD, Vol: 108, ISSN: 0003-9888

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Ullmann N, Bush A, Piacentini G, Santamaria F, Cutrera Ret al., 2023, Editorial: Difficult and severe asthma in children, volume II, FRONTIERS IN PEDIATRICS, Vol: 11, ISSN: 2296-2360

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Bush A, Nicholson AG, 2023, Cancer or Not Cancer: That Is the Question, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 207, Pages: 511-513, ISSN: 1073-449X

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Ring AM, Schwerk N, Kiper N, Aslan AT, Aurora P, Ayats R, Azevedo I, Bandeira T, Carlens J, Castillo-Corullon S, Cobanoglu N, Elnazir B, Emiralioglu N, Eyuboglu TS, Fayon M, Gursoy TR, Hogg C, Kotz K, Karadag B, Latalova V, Krenke K, Lange J, Manali ED, Osona B, Papiris S, Proesmann M, Reix P, Roditis L, Rubak S, Rumman N, Snijders D, Stehling F, Weiss L, Yalcin E, Zirek F, Bush A, Clement A, Griese M, Buchvald FF, Nathan N, Nielsen KGet al., 2023, Diffuse alveolar haemorrhage in children: an international multicentre study, ERJ OPEN RESEARCH, Vol: 9

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Nkereuwem E, Agbla S, Sallahdeen A, Owolabi O, Sillah AK, Genekah M, Tunkara A, Kandeh S, Jawara M, Saidy L, Bush A, Togun T, Kampmann Bet al., 2023, Reduced lung function and health-related quality of life after treatment for pulmonary tuberculosis in Gambian children: a cross-sectional comparative study, THORAX, Vol: 78, Pages: 281-287, ISSN: 0040-6376

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• Citations: 9

Makrinioti H, Zhu Z, Camargo CA, Fainardi V, Hasegawa K, Bush A, Saglani Set al., 2023, Application of Metabolomics in Obesity-Related Childhood Asthma Subtyping: A Narrative Scoping Review, METABOLITES, Vol: 13

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Bush A, Holguin F, Porsbjerg C, Saglani Set al., 2023, Asthma: Closing in on the Biology of a Complex Life-course Disease, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 207, Pages: 375-376, ISSN: 1073-449X

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Cousins M, Hart K, Kotecha SJ, Henderson AJ, Watkins WJ, Bush A, Kotecha Set al., 2023, Characterising airway obstructive, dysanaptic and PRISm phenotypes of prematurity-associated lung disease, THORAX, ISSN: 0040-6376

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• Citations: 2

Di Cicco M, Ghezzi M, Kantar A, Song W-J, Bush A, Peroni D, D'Auria Eet al., 2023, Pediatric obesity and severe asthma: Targeting pathways driving inflammation, PHARMACOLOGICAL RESEARCH, Vol: 188, ISSN: 1043-6618

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• Citations: 4

Canny A, Donaghy E, Murray V, Campbell L, Stonham C, Bush A, McKinstry B, Milne H, Pinnock H, Daines Let al., 2023, Patient views on asthma diagnosis and how a clinical decision support system could help: A qualitative study, HEALTH EXPECTATIONS, Vol: 26, Pages: 307-317, ISSN: 1369-6513

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Bush A, 2023, Differing effects of mepolizumab across the life course, LANCET RESPIRATORY MEDICINE, Vol: 11, Pages: 123-125, ISSN: 2213-2600

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Bush A, 2023, Too Little, Too Late: Adult Lung Disease Cannot Be Prevented by Interventions in Adult Life, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 207, Pages: 124-126, ISSN: 1073-449X

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• Citations: 2