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- Bousquet, J, et al.
(author)
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Nrf2-interacting nutrients and COVID-19: time for research to develop adaptation strategies
- 2020
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In: Clinical and translational allergy. - : Wiley. - 2045-7022. ; 10:1, s. 58-
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Journal article (peer-reviewed)abstract
- There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPARγ:Peroxisome proliferator-activated receptor, NFκB: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2α:Elongation initiation factor 2α). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT1R axis (AT1R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity.
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- Bousquet, J., et al.
(author)
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Scaling up strategies of the chronic respiratory disease programme of the European Innovation Partnership on Active and Healthy Ageing (Action Plan B3: Area 5)
- 2016
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In: Clinical and Translational Allergy. - : Wiley. - 2045-7022. ; 6:1, s. 1-18
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Research review (peer-reviewed)abstract
- Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) focuses on the integrated care of chronic diseases. Area 5 (Care Pathways) was initiated using chronic respiratory diseases as a model. The chronic respiratory disease action plan includes (1) AIRWAYS integrated care pathways (ICPs), (2) the joint initiative between the Reference site MACVIA-LR (Contre les MAladies Chroniques pour un VIeillissement Actif) and ARIA (Allergic Rhinitis and its Impact on Asthma), (3) Commitments for Action to the European Innovation Partnership on Active and Healthy Ageing and the AIRWAYS ICPs network. It is deployed in collaboration with the World Health Organization Global Alliance against Chronic Respiratory Diseases (GARD). The European Innovation Partnership on Active and Healthy Ageing has proposed a 5-step framework for developing an individual scaling up strategy: (1) what to scale up: (1-a) databases of good practices, (1-b) assessment of viability of the scaling up of good practices, (1-c) classification of good practices for local replication and (2) how to scale up: (2-a) facilitating partnerships for scaling up, (2-b) implementation of key success factors and lessons learnt, including emerging technologies for individualised and predictive medicine. This strategy has already been applied to the chronic respiratory disease action plan of the European Innovation Partnership on Active and Healthy Ageing.
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- van Bragt, JJMH, et al.
(author)
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Characteristics and treatment regimens across ERS SHARP severe asthma registries
- 2020
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In: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 55:1
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Journal article (peer-reviewed)abstract
- Little is known about the characteristics and treatments of patients with severe asthma across Europe, but both are likely to vary. This is the first study in the European Respiratory Society Severe Heterogeneous Asthma Research collaboration, Patient-centred (SHARP) Clinical Research Collaboration and it is designed to explore these variations. Therefore, we aimed to compare characteristics of patients in European severe asthma registries and treatments before starting biologicals.This was a cross-sectional retrospective analysis of aggregated data from 11 national severe asthma registries that joined SHARP with established patient databases.Analysis of data from 3236 patients showed many differences in characteristics and lifestyle factors. Current smokers ranged from 0% (Poland and Sweden) to 9.5% (Belgium), mean body mass index ranged from 26.2 (Italy) to 30.6 kg·m−2 (the UK) and the largest difference in mean pre-bronchodilator forced expiratory volume in 1 s % predicted was 20.9% (the Netherlands versus Hungary). Before starting biologicals patients were treated differently between countries: mean inhaled corticosteroid dose ranged from 700 to 1335 µg·day−1 between those from Slovenia versus Poland when starting anti-interleukin (IL)-5 antibody and from 772 to 1344 µg·day−1 in those starting anti-IgE (Slovenia versus Spain). Maintenance oral corticosteroid use ranged from 21.0% (Belgium) to 63.0% (Sweden) and from 9.1% (Denmark) to 56.1% (the UK) in patients starting anti-IL-5 and anti-IgE, respectively.The severe asthmatic population in Europe is heterogeneous and differs in both clinical characteristics and treatment, often appearing not to comply with the current European Respiratory Society/American Thoracic Society guidelines definition of severe asthma. Treatment regimens before starting biologicals were different from inclusion criteria in clinical trials and varied between countries.
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- Heaney, Liam G., et al.
(author)
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Eosinophilic and Noneosinophilic Asthma : An Expert Consensus Framework to Characterize Phenotypes in a Global Real-Life Severe Asthma Cohort
- 2021
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In: Chest. - : Elsevier BV. - 0012-3692. ; 160:3, s. 814-830
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Journal article (peer-reviewed)abstract
- Background: Phenotypic characteristics of patients with eosinophilic and noneosinophilic asthma are not well characterized in global, real-life severe asthma cohorts. Research Question: What is the prevalence of eosinophilic and noneosinophilic phenotypes in the population with severe asthma, and can these phenotypes be differentiated by clinical and biomarker variables? Study Design and Methods: This was an historical registry study. Adult patients with severe asthma and available blood eosinophil count (BEC) from 11 countries enrolled in the International Severe Asthma Registry (January 1, 2015-September 30, 2019) were categorized according to likelihood of eosinophilic phenotype using a predefined gradient eosinophilic algorithm based on highest BEC, long-term oral corticosteroid use, elevated fractional exhaled nitric oxide, nasal polyps, and adult-onset asthma. Demographic and clinical characteristics were defined at baseline (ie, 1 year before or closest to date of BEC). Results: One thousand seven hundred sixteen patients with prospective data were included; 83.8% were identified as most likely (grade 3), 8.3% were identified as likely (grade 2), and 6.3% identified as least likely (grade 1) to have an eosinophilic phenotype, and 1.6% of patients showed a noneosinophilic phenotype (grade 0). Eosinophilic phenotype patients (ie, grades 2 or 3) showed later asthma onset (29.1 years vs 6.7 years; P < .001) and worse lung function (postbronchodilator % predicted FEV1, 76.1% vs 89.3%; P = .027) than those with a noneosinophilic phenotype. Patients with noneosinophilic phenotypes were more likely to be women (81.5% vs 62.9%; P = .047), to have eczema (20.8% vs 8.5%; P = .003), and to use anti-IgE (32.1% vs 13.4%; P = .004) and leukotriene receptor antagonists (50.0% vs 28.0%; P = .011) add-on therapy. Interpretation: According to this multicomponent, consensus-driven, and evidence-based eosinophil gradient algorithm (using variables readily accessible in real life), the severe asthma eosinophilic phenotype was more prevalent than previously identified and was phenotypically distinct. This pragmatic gradient algorithm uses variables readily accessible in primary and specialist care, addressing inherent issues of phenotype heterogeneity and phenotype instability. Identification of treatable traits across phenotypes should improve therapeutic precision.
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- Perez-de-Llano, Luis, et al.
(author)
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Impact of pre-biologic impairment on meeting domain-specific biologic responder definitions in patients with severe asthma
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In: Annals of Allergy, Asthma and Immunology. - 1081-1206.
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Journal article (peer-reviewed)abstract
- Background: There is little agreement on clinically useful criteria for identifying real-world responders to biologic treatments for asthma. Objective: To investigate the impact of pre-biologic impairment on meeting domain-specific biologic responder definitions in adults with severe asthma. Methods: This was a longitudinal, cohort study across 22 countries participating in the International Severe Asthma Registry (https://isaregistries.org/) between May 2017 and January 2023. Change in 4 asthma domains (exacerbation rate, asthma control, long-term oral corticosteroid [LTOCS] dose, and lung function) was assessed from biologic initiation to 1 year post-treatment (minimum 24 weeks). Pre- to post-biologic changes for responders and nonresponders were described along a categorical gradient for each domain derived from pre-biologic distributions (exacerbation rate: 0 to 6+/y; asthma control: well controlled to uncontrolled; LTOCS: 0 to >30 mg/d; percent-predicted forced expiratory volume in 1 second [ppFEV1]: <50% to ≥80%). Results: Percentage of biologic responders (ie, those with a category improvement pre- to post-biologic) varied by domain and increased with greater pre-biologic impairment, increasing from 70.2% to 90.0% for exacerbation rate, 46.3% to 52.3% for asthma control, 31.1% to 58.5% for LTOCS daily dose, and 35.8% to 50.6% for ppFEV1. The proportion of patients having improvement post-biologic tended to be greater for anti–IL-5/5R compared with for anti-IgE for exacerbation, asthma control, and ppFEV1 domains, irrespective of pre-biologic impairment. Conclusion: Our results provide realistic outcome-specific post-biologic expectations for both physicians and patients, will be foundational to inform future work on a multidimensional approach to define and assess biologic responders and response, and may enhance appropriate patient selection for biologic therapies. Trial Registration: The ISAR database has ethical approval from the Anonymous Data Ethics Protocols and Transparency (ADEPT) committee (ADEPT0218) and is registered with the European Union Electronic Register of Post-Authorization studies (ENCEPP/DSPP/23720). The study was designed, implemented, and reported in compliance with the European Network Centres for Pharmacoepidemiology and Pharmacovigilance (ENCEPP) Code of Conduct (EUPAS38288) and with all applicable local and international laws and regulation, and registered with ENCEPP (https://www.encepp.eu/encepp/viewResource.htm?id=38289). Governance was provided by ADEPT (registration number: ADEPT1220).
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