Publications
224 results found
Brandsma J, Schofield JPR, Yang X, et al., 2023, Stratification of asthma by lipidomic profiling of induced sputum supernatant, Journal of Allergy and Clinical Immunology, Pages: 1-44, 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.
Levy ML, Bacharier LB, Bateman E, et al., 2023, Key recommendations for primary care from the 2022 Global Initiative for Asthma (GINA) update., NPJ Prim Care Respir Med, Vol: 33
The Global Initiative for Asthma (GINA) was established in 1993 by the World Health Organization and the US National Heart Lung and Blood Institute to improve asthma awareness, prevention and management worldwide. GINA develops and publishes evidence-based, annually updated resources for clinicians. GINA guidance is adopted by national asthma guidelines in many countries, adapted to fit local healthcare systems, practices, and resource availability. GINA is independent of industry, funded by the sale and licensing of its materials. This review summarizes key practical guidance for primary care from the 2022 GINA strategy report. It provides guidance on confirming the diagnosis of asthma using spirometry or peak expiratory flow. GINA recommends that all adults, adolescents and most children with asthma should receive inhaled corticosteroid (ICS)-containing therapy to reduce the risk of severe exacerbations, either taken regularly, or (for adults and adolescents with "mild" asthma) as combination ICS-formoterol taken as needed for symptom relief. For patients with moderate-severe asthma, the preferred regimen is maintenance-and-reliever therapy (MART) with ICS-formoterol. Asthma treatment is not "one size fits all"; GINA recommends individualized assessment, adjustment, and review of treatment. As many patients with difficult-to-treat or severe asthma are not referred early for specialist review, we provide updated guidance for primary care on diagnosis, further investigation, optimization and treatment of severe asthma across secondary and tertiary care. While the GINA strategy has global relevance, we recognize that there are special considerations for its adoption in low- and middle-income countries, particularly the current poor access to inhaled medications.
Ko FWS, Fleming L, 2023, Advancement of asthma management in the past decade, LANCET RESPIRATORY MEDICINE, Vol: 11, Pages: 15-17, ISSN: 2213-2600
Rattu A, Khaleva E, Brightling C, et al., 2022, Identifying and appraising outcome measures for severe asthma: a systematic review., Eur Respir J
BACKGROUND: Valid outcome measures are imperative to evaluate treatment response, yet the suitability of existing endpoints 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 2018-2020 (PROSPERO, CRD42020204437). 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 identify development and validation studies for these endpoints. 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" endpoints from the latter three domains. Only SAQ and C-ACT were developed with input from severe asthma patients. The certainty of evidence was "low" to "very low" for most "priority" endpoints across all measurement properties, and none fulfilled all quality standards. CONCLUSION: Only two outcome measures had robust developmental data for severe asthma. This review informed development of core outcome measures sets for severe asthma.
Thorsen J, Stokholm J, Rasmussen MA, et al., 2022, Asthma and Wheeze Severity and the Oropharyngeal Microbiota in Children and Adolescents., Ann Am Thorac Soc, Vol: 19, Pages: 2031-2043
Rationale: There is a major unmet need for improving the care of children and adolescents with severe asthma and wheeze. Identifying factors contributing to disease severity may lead to improved diagnostics, biomarkers, or therapies. The airway microbiota may be such a key factor. Objectives: To compare the oropharyngeal airway microbiota of children and adolescents with severe and mild/moderate asthma/wheeze. Methods: Oropharyngeal swab samples from school-age and preschool children in the European U-BIOPRED (Unbiased BIOmarkers in the PREDiction of respiratory disease outcomes) multicenter study of severe asthma, all receiving severity-appropriate treatment, were examined using 16S ribosomal RNA gene sequencing. Bacterial taxa were defined as amplicon sequence variants. Results: We analyzed 241 samples from four cohorts: A) 86 school-age children with severe asthma; B) 39 school-age children with mild/moderate asthma; C) 65 preschool children with severe wheeze; and D) 51 preschool children with mild/moderate wheeze. The most common bacteria were Streptococcus (mean relative abundance, 33.5%), Veillonella (10.3%), Haemophilus (7.0%), Prevotella (5.9%), and Rothia (5.5%). Age group (school-age vs. preschool) was associated with the microbiota in β-diversity analysis (F = 3.32, P = 0.011) and in a differential abundance analysis (28 significant amplicon sequence variants). Among all children, we found no significant difference in the microbiota between children with severe and mild/moderate asthma/wheeze in univariable β-diversity analysis (F = 1.99, P = 0.08, N = 241), but a significant difference in a multivariable model (F = 2.66, P = 0.035), including the number of exacerbations in the previous year. Age was also significant when expressed as a microbial maturity score (Spearman Rho, 0.39; P = 4.6 × 10-10); however, t
Wells C, Wilkinson N, Makhecha S, et al., 2022, ACCEPTABILITY AND FEASIBILITY PILOT OF CODESIGNED TELEHEALTH PHYSIOTHERAPY INTERVENTIONS FOR CHILDREN WITH ASTHMA AND DYSFUNCTIONAL BREATHING, Publisher: BMJ PUBLISHING GROUP, Pages: A130-A130, ISSN: 0040-6376
Pavlou B, Scotney E, Makariou I, et al., 2022, ACCEPTABILITY AND FEASIBILITY OF MEASURING BLOOD EOSINOPHILS USING A POINT-OF-CARE DEVICE IN CHILDREN WITH ASTHMA, Publisher: BMJ PUBLISHING GROUP, Pages: A130-A131, ISSN: 0040-6376
Chen PC, Irving SI, Fleming LF, 2022, AN ASSESSMENT OF SELF-PERFORMED HOME SPIROMETRY IN PAEDIATRIC ASTHMA PATIENTS, Publisher: BMJ PUBLISHING GROUP, Pages: A128-A129, ISSN: 0040-6376
Khaleva E, Rattu A, Brightling C, et al., 2022, Development of Core Outcome Measures sets for paediatric and adult Severe Asthma (COMSA)., Eur Respir J
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 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 (ACT) or Childhood-ACT while the adult COM includes the Severe Asthma Questionnaire and the 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.
Abdel-Aziz M, Thorsen J, Hashimoto S, et al., 2022, Identification of oropharyngeal microbiome-driven asthma and wheezing clusters in children, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Scotney E, Jayarathna R, Gupta L, et al., 2022, The role of cardiopulmonary exercise testing to evaluate exercise induced dyspnoea in asthmatic children, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Makariou I, Bush A, Saglani S, et al., 2022, Ethnic differences in daily FeNO response after systemic steroids in children with severe asthma, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Makariou I, Rhamie S, Bush A, et al., 2022, Peak inspiratory flow in children with exercise induced laryngeal obstruction, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Fowler S, Bhatt J, Brown S, et al., 2022, E-cigarette company tactics in sports advertising, LANCET RESPIRATORY MEDICINE, Vol: 10, Pages: 634-636, ISSN: 2213-2600
Hoda U, Pavlidis S, Bansal AT, et 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.
Duijts L, Fleming LJ, Bacharier LB, et 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
Robinson PD, Jayasuriya G, Haggie S, et 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.
Nichols A-L, Sonnappa-Naik M, Gardner L, et al., 2022, COVID-19 and delivery of difficult asthma services, ARCHIVES OF DISEASE IN CHILDHOOD, Vol: 107, ISSN: 0003-9888
Pearce CJ, Chan AHY, Jackson T, et 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
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Mikus MS, Kolmert J, Andersson L, et 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.
Reddel HK, Bacharier LB, Bateman ED, et 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
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- Citations: 6
Reddel HK, Bacharier LB, Bateman ED, et al., 2022, Global initiative for Asthma Strategy 2021: executive summary and rationale for key changes, EUROPEAN RESPIRATORY JOURNAL, Vol: 59, ISSN: 0903-1936
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- Citations: 54
Badi Y, Pavel AB, Pavlidis S, et 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.
Saglani S, Bingham Y, Balfour-Lynn I, et 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.
Reddel HK, Bacharier LB, Bateman ED, et 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
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- Citations: 26
Ko J, Jamalzadeh A, Makhecha S, et 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
De Simoni A, Fleming L, Holliday L, et 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
Reddel HK, Bacharier LB, Bateman ED, et 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.
Reddel HK, Bacharier LB, Bateman ED, et 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.
Saglani S, Bingham Y, Balfour-Lynn I, et al., 2021, Blood eosinophils in managing preschool wheeze: lessons learnt from a proof-of-concept trial
<jats:p id="p1">Background: Management of preschool wheeze is based predominantly onsymptom pattern. Objective: To determine whether personalising therapyusing blood eosinophils or airway bacterial infection results in fewerattacks compared to standard care. Methods: A proof-of-concept,randomised trial to investigate whether prescription of inhaledcorticosteroids (ICS) guided by blood eosinophils, or targetedantibiotics for airway bacterial infection, results in fewer unscheduledhealthcare visits (UHCV) compared to standard care. Children aged 1-5years with >2 wheeze attacks in the previous year werecategorised as episodic viral wheeze (EVW), or multiple trigger wheeze(MTW). The intervention group were prescribed ICS if blood eosinophils>3%, or targeted antibiotics if positive culture oninduced sputum/cough swab. The control group received standard care.Primary outcome: UHCV at 4 months. Results: 60 children, median age 36.5(range 14-61) months were randomised. Median blood eosinophils were 5.2(range 0-21)%, 27/60 (45%) children were atopic and 8/60 (13%) hadairway bacterial infection. There was no relationship between EVW, MTWand either blood eosinophils, atopic status, or infection. 67% in eachgroup were prescribed ICS. 15/30 control subjects and 16/30 interventiongroup had UHCV over 4 months, p=0.8. Time to first UHCV was similar.50% returned adherence monitors, in those, median ICS adherence was67%. There were no differences in any parameter between those that didand did not have an UHCV. Conclusion: Clinical phenotype was unrelatedto allergen sensitisation or blood eosinophils. ICS treatment determinedby blood eosinophils did not impact UHCV, but ICS adherence was poor.</jats:p>
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