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Background: Asthma is associated with accelerated rate of FEV 1 decline., Objective: To determine predictive factors associated with accelerated FEV 1 decline in adult asthma and evaluate sputum cytokines as potential biomarkers for airflow decline., Methods: We recruited 125 asthmatics evaluated at the asthma clinic of Liège and reevaluated them at least 5 years later. Clinical, functional and inflammatory characteristics were compared between patients with accelerated decline (FEV 1 decline > 0.85% pred.y -1 ) and others. Predictive factors were highlighted with linear regression analysis. Sputum EGF, VEGF, FGF, IL5, IL8, TGF-β, and IgE levels were measured in 58 of these patients at both visits by Human XL cytokine Luminex Performance assay and Elisa., Results: Post-BD FEV 1 decline was 0.06 ± 2.44% pred.y -1 in the overall population. Median (IQR) time between visits was 66 (62 - 86) months. The multivariable analysis showed that an increase in blood eosinophils over time (Δ BEC) (Reg. Coef. (95%CI): 0.002 (0.001 to 0.004), p = 0.005)) and onset of asthma (0.04 (0.003 to 0.07), p = 0.036) were independently associated with FEV 1 decline. IL8 levels measured at baseline were higher (499 (408-603) pg/ml, p = 0.0040) in patients with accelerated decline compared to others (143 (88-308) pg/ml)., Conclusion: In this study, we have confirmed that an increase in blood eosinophil counts over a follow-up of at least 5 years and later onset of asthma are associated with accelerated annual FEV 1 decline. Moreover, high sputum IL8 levels could be a risk factor for accelerated decline in asthma patients., Competing Interests: Declarations. Conflict of interests: Graff S, Moermans C, Gerday S, Henket M, Paulus P, and Guissard F have nothing to disclose. Prof. LOUIS reports grants and personal fees from GSK, grants and personal fees from AZ, grants and personal fees from Novartis, grants from Chiesi, outside the submitted work. Prof. Schleich reports grants and personal fees from GSK, grants from AZ, grants and personal fees from Chiesi, outside the submitted work. Ethical Approval: CHU Liège: 2008/181. Informed Consent: Informed consent was obtained from all individual participants included in the study. Consent for Publication: Not applicable., (© 2024. The Author(s).)

Background: Although asthma is often seen as an eosinophilic disease associated with atopy, patients with noneosinophilic asthma represent a substantial part of the population with asthma., Objective: To apply an unsupervised clustering method in a cohort of 588 patients with noneosinophilic asthma (sputum eosinophils < 3%) recruited from an asthma clinic of a secondary care center., Methods: Our cluster analysis of the whole cohort identified 2 subgroups as cluster 1 (n = 417) and cluster 2 (n = 171)., Results: Cluster 1 comprised a predominantly female group with late disease onset, a low proportion of atopy (24%), and a substantial smoking history (53%). In this cluster, treatment burden was low (<50% of inhaled corticosteroid users); asthma control and quality of life were poor, with median Asthma Control Test, Asthma Control Questionnaire, and Asthma Quality of Life scores of 16, 1.7, and 4.5, respectively, whereas lung function was preserved with a median postbronchodilation forced expiratory volume in 1 second of 93% predicted. Cluster 2 was a predominantly male group, almost exclusively comprising patients with atopy (99%) with early disease onset and a moderate treatment burden (median inhaled corticosteroids dose 800 µg/d equivalent beclomethasone). In cluster 2, asthma was partially controlled, with median Asthma Control Test and Asthma Control Questionnaire scores reaching 18 and 1.3, respectively, and lung function well preserved with a median postbronchodilation of 95% predicted. Although systemic and airway neutrophilic inflammation was the dominant pattern in cluster 1, cluster 2 essentially comprised paucigranulocytic asthma with moderately elevated fraction exhaled nitric oxide., Conclusion: Noneosinophilic asthma splits into 2 clusters distinguishing by disease onset, atopic status, smoking history, systemic and airway inflammation, and disease control and quality of life., Competing Interests: Disclosures Dr Louis reports an educational grant and lecture fees from GlaxoSmithKline, a research grant and advisory board fees from AZ, a research grant from Chiesi, and a research grant and advisory board fees from Novartis, outside the submitted work. Dr Schleich reports lecture and advisory board fees from GlaxoSmithKline, AZ, Chiesi, and Novartis outside of the submitted work., (Copyright © 2024 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Several clinical trials have demonstrated that anti-IL-5(R) biologics were able to improve lung function, asthma control and chronic oral corticosteroid exposure and reduce exacerbations among eosinophilic asthmatic patients. However, a certain variability in clinical responses to anti-IL-5(R) biologics was brought to light. Our study aimed at evaluating the role of baseline sputum eosinophils in identifying super-responders to mepolizumab and benralizumab. Our study reinforces the importance to examine sputum eosinophils in patients suffering from severe asthma before starting a biologic as it is associated with the intensity of response to mepolizumab and benralizumab., Competing Interests: Competing interests: GERDAY Sara, GRAFF Sophie, MOERMANS Catherine, GUISSARD Françoise, PAULUS Virginie and HENKET Monique declare no competing interests. LOUIS Renaud reports grants from GSK, Astrazeneca, Chiesi; royalties from patent AU2016328384, CA2997506, EP 3337393, US2020345266; consulting fees from Astrazeneca; lecture payments from GSK, Chiesi; participation on a data safety monitoring board or advisory board for Astrazeneca ANDHI in practice study and leadership or fiduciary role in other board, society, committee or advocacy group for ERS task force on guidelines on asthma diagnosis, outside the submitted work. SCHLEICH Florence reports grants from GSK, Astrazeneca, Chiesi; consulting fees from GSK, Astrazeneca, Sanofi; lecture payments from GSK, Astrazeneca, Teva, Chiesi and Amgen and support for attending meetings/travel from Chiesi, outside the submitted work., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Staphylococcus aureus enterotoxins (SE) may act as superantigens and induce an intense T-cell activation, causing local production of polyclonal IgE and resultant eosinophil activation., Objective: To assess whether asthma with sensitization to SE but not to common aeroallergens (AAs) displays different inflammatory characteristics., Methods: We conducted a prospective study on a series of 110 consecutive patients with asthma recruited from the University Asthma Clinic of Liège. We compared clinical, functional, and inflammatory characteristics of this general population of patients with asthma categorized into 4 groups according to sensitization to AAs and/or SE. We also compared sputum supernatant cytokines in patients sensitized to SE or not., Results: Patients with asthma sensitized only to AAs represented 30%, while 29% were sensitized to both AAs and SE. One-fifth of the population had no specific IgE. Sensitization to SE but not to AA (21%) was associated with later onset of disease, higher rate of exacerbations, nasal polyps, and more severe airway obstruction. As for airway type 2 biomarkers, patients presenting with specific IgE against SE displayed higher fractional exhaled nitric oxide, sputum IgE, and sputum IL-5 levels but not IL-4. We confirm that the presence of specific IgE against SE is associated with elevated serum IgE to levels well above those observed in patients sensitized only to AAs., Conclusions: Our study suggests that asthma specialists should measure specific IgE against SE during the phenotyping process because it may allow the identification of a subgroup of patients with more asthma exacerbations, more nasal polyposis and chronic sinusitis, lower lung function, and more intense type 2 inflammation., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Atopic asthma is one of the most common asthma phenotypes and is generally opposed to the non-atopic counterpart. There have been very few large-scale studies comparing atopic and non-atopic asthmatics in terms of systemic and airway inflammation across the age spectrum., Methods: Here, we have undertaken a retrospective study investigating 1626 patients (924 atopic and 702 non-atopic asthmatics) recruited from our university asthma clinic who underwent extensive clinical investigations including induced sputum. Atopy was defined by any positive specific IgE to common aeroallergens (>0,35 kU/L). We performed direct comparisons between the groups and sought to appreciate the influence of age on the airway and systemic inflammatory components. The study was approved by the ethics committee of the University Hospital of Liege (Ref. 2016/276). Informed consents were obtained from healthy subjects., Results: Atopic asthmatics were younger (P  < .001), had a higher male/female ratio (P  < .001), an earlier disease onset (P  < .001) and a greater proportion of treated rhinitis (P  < .001) while non-atopic asthmatics had greater smoke exposure (P  < .001), lower FEV 1 /FVC ratio ( P  = .01) and diffusing capacity ( P  < .001). There was no difference between the 2 groups regarding FEV 1 (% predicted), asthma control, asthma quality of life and exacerbations in the previous 12 months. Regarding inflammation, atopic patients had higher FeNO levels (median = 28 ppb, P  < .001), were more eosinophilic both in blood (median = 2.8%, P  < .001) and in sputum (median = 2.2%, P  < .001) while non-atopic patients displayed greater blood (median = 57%, P  = .01) and sputum (median = 58.8%, P  = .01) neutrophilic inflammation. However, stratifying patients by age showed that non-atopic asthmatics above 50 years old became equally eosinophilic in the sputum (P  = .07), but not in the blood, as compared to atopic patients. Likewise, FeNO rose in non-atopic patients after 50 years old but remained, however, lower than in atopic patients., Conclusions: We conclude that, while sharing many features, atopic group still differentiates from non-atopic asthmatics by demographics, functional and inflammatory profiles. When atopic asthmatics showed a constant eosinophilic pattern across the age spectrum, non-atopic asthmatics were found to be neutrophilic before the age of 50 but eosinophilic above 50 years old., Competing Interests: SG, FG, VP, MH: no competing interests. FS reports grants from GSK, Astrazeneca, Teva, Chiesi and Novartis; consulting fees from GSK, Astrazeneca, Amgen, Chiesi and Novartis; lecture payments from GSK, Astrazeneca, Teva, Chiesi and Novartis, outside the submitted work. RL reports grants from GSK, AZ, Novartis, Chiesi and Teva; royalties from patent AU2016328384, CA2997506, EP 3337393, US2020345266; consulting fees and lecture payments from GSK, AZ, Novartis, Sanofi and Chiesi, outside the submitted work., (© 2022 The Authors.)

Asthma is the most prevalent chronic inflammatory airway disease worldwide. The gut microbiota possesses an important link with the development of the immunity in youth and a dysregulation of the gut flora was implicated in the asthmatic disease emergence. Moreover, a dysregulation of the intestinal microbiota exists in asthmatic individual. Probiotics are micro-organisms that can regulate our microbiome conferring potential beneficial effects on health. Thereby, their use in asthma prevention and treatment is attractive and could lead to new therapeutic perspectives. Indeed, they are well tolerated and safe and possess anti-inflammatory and immunoregulatory properties. This article is intended to update the current state of knowledge regarding the use of probiotics in the context of asthma.

Background: Eosinophilic inflammation has long been associated with asthma. Looking at systemic and airway eosinophilia, we have recently identified a group of patients exhibiting diffuse eosinophilic inflammation. Among the mechanisms governing eosinophilic inflammation, IgE-mediated mast cell activation is a key event leading to eosinophilia in atopic asthmatics., Methods: We conducted a retrospective study on our asthma clinic database containing more than 1500 patients and identified 205 asthmatics with successful sputum induction and concordant eosinophilic phenotype. This phenotype was defined as a sputum eosinophil count≥3% and a blood eosinophils concentration≥400cells/mm 3 . IgE-high atopic phenotype was characterized by the presence of at least one positive specific IgE (>0.35kU/L) to common aeroallergens and a raised total serum IgE (≥113kU/L)., Results: The largest group of asthmatics displaying concordant eosinophilic phenotype had a raised total serum IgE and atopy (45%). IgE-low non-atopic concordant eosinophilic asthma was a predominantly late onset disease, exhibited a more intense airway eosinophilic inflammation (P<0.05), required more often maintenance treatment with oral corticosteroids (P<0.05) but, surprisingly, had a reduced level of bronchial hyperresponsiveness to methacholine (P<0.05) despite similar baseline airway calibre impairment., Conclusion: The more severe airway eosinophilic inflammation in IgE-low non-atopic asthmatics despite similar treatment with ICS and a higher burden of OCS points to a certain corticosteroid resistance in this asthma phenotype., (Copyright © 2020 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)