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- Bousquet, J, et al.
(författare)
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Severe chronic allergic (and related) diseases: a uniform approach--a MeDALL--GA2LEN--ARIA position paper
- 2012
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Ingår i: International archives of allergy and immunology. - : S. Karger AG. - 1423-0097 .- 1018-2438. ; 158:3, s. 216-231
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Tidskriftsartikel (refereegranskat)abstract
- Concepts of disease severity, activity, control and responsiveness to treatment are linked but different. Severity refers to the loss of function of the organs induced by the disease process or to the occurrence of severe acute exacerbations. Severity may vary over time and needs regular follow-up. Control is the degree to which therapy goals are currently met. These concepts have evolved over time for asthma in guidelines, task forces or consensus meetings. The aim of this paper is to generalize the approach of the uniform definition of severe asthma presented to WHO for chronic allergic and associated diseases (rhinitis, chronic rhinosinusitis, chronic urticaria and atopic dermatitis) in order to have a uniform definition of severity, control and risk, usable in most situations. It is based on the appropriate diagnosis, availability and accessibility of treatments, treatment responsiveness and associated factors such as comorbidities and risk factors. This uniform definition will allow a better definition of the phenotypes of severe allergic (and related) diseases for clinical practice, research (including epidemiology), public health purposes, education and the discovery of novel therapies.
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- Chung, KF, et al.
(författare)
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International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma
- 2014
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Ingår i: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 43:2, s. 343-373
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Tidskriftsartikel (refereegranskat)abstract
- Severe or therapy-resistant asthma is increasingly recognised as a major unmet need. A Task Force, supported by the European Respiratory Society and American Thoracic Society, reviewed the definition and provided recommendations and guidelines on the evaluation and treatment of severe asthma in children and adults.A literature review was performed, followed by discussion by an expert committee according to the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach for development of specific clinical recommendations.When the diagnosis of asthma is confirmed and comorbidities addressed, severe asthma is defined as asthma that requires treatment with high dose inhaled corticosteroids plus a second controller and/or systemic corticosteroids to prevent it from becoming “uncontrolled” or that remains “uncontrolled” despite this therapy. Severe asthma is a heterogeneous condition consisting of phenotypes such as eosinophilic asthma. Specific recommendations on the use of sputum eosinophil count and exhaled nitric oxide to guide therapy, as well as treatment with anti-IgE antibody, methotrexate, macrolide antibiotics, antifungal agents and bronchial thermoplasty are provided.Coordinated research efforts for improved phenotyping will provide safe and effective biomarker-driven approaches to severe asthma therapy.
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- Frix, AN, et al.
(författare)
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Heterogeneity in the use of biologics for severe asthma in Europe: a SHARP ERS study
- 2022
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Ingår i: ERJ open research. - : European Respiratory Society (ERS). - 2312-0541. ; 8:4
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Tidskriftsartikel (refereegranskat)abstract
- Treatment with biologics for severe asthma is informed by international and national guidelines and defined by national regulating bodies, but how these drugs are used in real-life is unknown.Materials and methodsThe European Respiratory Society (ERS) SHARP Clinical Research Collaboration conducted a three-step survey collecting information on asthma biologics use in Europe. Five geographically distant countries defined the survey questions, focusing on seven end-points: biologics availability and financial issues, prescription and administration modalities, inclusion criteria, continuation criteria, switching biologics, combining biologics and evaluation of corticosteroid toxicity. The survey was then sent to SHARP National Leads of 28 European countries. Finally, selected questions were submitted to a broad group of 263 asthma experts identified by national societies.ResultsAvailability of biologics varied between countries, with 17 out of 28 countries having all five existing biologics. Authorised prescribers (pulmonologists and other specialists) also differed. In-hospital administration was the preferred deliverance modality. While exacerbation rate was used as an inclusion criterion in all countries, forced expiratory volume in 1 s was used in 46%. Blood eosinophils were an inclusion criterion in all countries for interleukin-5 (IL-5)-targeted and IL-4/IL-13-targeted biologics, with varying thresholds. There were no formally established criteria for continuing biologics. Reduction in exacerbations represented the most important benchmark, followed by improvement in asthma control and quality of life. Only 73% (191 out of 263) of surveyed clinicians assessed their patients for corticosteroid-induced toxicity.ConclusionOur study reveals important heterogeneity in the use of asthma biologics across Europe. To what extent this impacts on clinical outcomes relevant to patients and healthcare services needs further investigation.
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- Kroes, JA, et al.
(författare)
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Evaluation of real-world mepolizumab use in severe asthma across Europe: the SHARP experience with privacy-preserving federated analysis
- 2023
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Ingår i: ERJ open research. - : European Respiratory Society (ERS). - 2312-0541. ; 9:2
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Tidskriftsartikel (refereegranskat)abstract
- An objective of the Severe Heterogeneous Asthma Registry, Patient-centered (SHARP) is to produce real-world evidence on a pan-European scale by linking non-standardized, patient-level registry-data. Mepolizumab has shown clinical efficacy in RCTs and prospective real-world studies and could therefore serve as a proof of principle for this novel approach.AimTo harmonize data from 10 national severe asthma registries and characterize patients receiving mepolizumab, assess its effectiveness on annual exacerbations and maintenance oral glucocorticoid (OCS) use, and evaluate treatment patterns.MethodsIn this observational cohort study, registry data (5871 patients) were extracted for harmonization. Where harmonization was possible, patients who initiated mepolizumab between 1-1-2016 and 31-12-2021 were examined. Changes of a 12 (range 11–18) months period in frequent (≥2) exacerbations, maintenance OCS use and dose were analyzed in a privacy-preserving manner using meta-analysis of generalized estimating equation parameters. Periods before and during the COVID-19 pandemic were analyzed separately.ResultsIn 912 patients who fulfilled selection criteria mepolizumab significantly reduced frequent exacerbations (OR;95%CI: 0.18;0.13–0.25), maintenance OCS use (OR;95%CI: 0.75;0.61–0.92) and dose (mean; 95%CI: −3.93 mg·day−1; −5.24–2.62) in the Pre-Pandemic group, with similar trends in the Pandemic group. Marked heterogeneity was observed between registries in patient characteristics and mepolizumab treatment patterns.ConclusionsBy harmonizing patient-level registry data and applying federated analysis, SHARP demonstrated the real-wold effectiveness of mepolizumab on asthma exacerbations and maintenance OCS use in severe asthma patients across Europe, consistent with previous evidence. This paves the way for future pan-European real-world severe asthma studies using patient-level data in a privacy-proof manner.
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- Mikus, MS, et al.
(författare)
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Plasma proteins elevated in severe asthma despite oral steroid use and unrelated to Type-2 inflammation
- 2022
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Ingår i: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 59:2
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Tidskriftsartikel (refereegranskat)abstract
- Asthma phenotyping requires novel biomarker discovery.ObjectivesTo 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).MethodsAn 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.ResultsIn 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.ConclusionsThe 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.
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- Shaw, DE, et al.
(författare)
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Clinical and inflammatory characteristics of the European U-BIOPRED adult severe asthma cohort
- 2015
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Ingår i: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 46:5, s. 1308-1321
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Tidskriftsartikel (refereegranskat)abstract
- U-BIOPRED is a European Union consortium of 20 academic institutions, 11 pharmaceutical companies and six patient organisations with the objective of improving the understanding of asthma disease mechanisms using a systems biology approach.This cross-sectional assessment of adults with severe asthma, mild/moderate asthma and healthy controls from 11 European countries consisted of analyses of patient-reported outcomes, lung function, blood and airway inflammatory measurements.Patients with severe asthma (nonsmokers, n=311; smokers/ex-smokers, n=110) had more symptoms and exacerbations compared to patients with mild/moderate disease (n=88) (2.5 exacerbations versus 0.4 in the preceding 12 months; p<0.001), with worse quality of life, and higher levels of anxiety and depression. They also had a higher incidence of nasal polyps and gastro-oesophageal reflux with lower lung function. Sputum eosinophil count was higher in severe asthma compared to mild/moderate asthma (median count 2.99% versus 1.05%; p=0.004) despite treatment with higher doses of inhaled and/or oral corticosteroids.Consistent with other severe asthma cohorts, U-BIOPRED is characterised by poor symptom control, increased comorbidity and airway inflammation, despite high levels of treatment. It is well suited to identify asthma phenotypes using the array of “omic” datasets that are at the core of this systems medicine approach.
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