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Asthma is a chronic inflammatory disease that can lead to airways remodeling. Despite their well-known side-effects, oral corticosteroids (OCS) continue to be used to reduce exacerbations and control asthma symptoms in many patients. We describe two cases of uncontrolled severe asthma characterized by systemic clinical consequences of prolonged OCS use, such as diabetes, weight gain, and osteoporosis. Both patients were treated with Dupilumab. During follow-up both patients showed an improvement in asthma control and were able to gradually taper the OCS dose, thus reducing the clinical burden associated with hypercortisolism. Dupilumab was able to control both the inflammatory-induced "airway remodeling" as well as the OCS-induced "patient remodeling". [ABSTRACT FROM AUTHOR]

Background: Eosinophils have been divided into different subpopulations with distinct phenotypes based on CD62L expression. No data are available regarding the correlation between eosinophils subphenotypes and clinical severity of asthma, as well as the effect of anti‐IL‐5 therapy on these cells. The study investigates the correlation between blood CD62Llow inflammatory eosinophils (iEos) and clinical severity of severe eosinophilic asthma (SEA) and evaluates the impact of mepolizumab on iEos. Methods: 112 patients were screened and were divided in two groups: biological‐naive (n = 51) and biological‐treated patients (n = 61). The Biological‐naive patients were analyzed before treatment (Group A) and 19 out of 51 patients, were longitudinally analyzed before and after treatment with mepolizumab 100 mg s.c/4 weeks (Group B); 32 patients were excluded because they were being treated with other biological therapies. Blood eosinophils were analyzed by FACS and correlated with clinical scores. In vitro effect of IL‐5 and mepolizumab on CD62L expression was assessed. Results: A significant correlation between blood CD62Llow cells and clinical scores of asthma and nasal polyps, as well as the number of asthma exacerbations in the last year was shown in untreated patients. In longitudinally studied patients we observed a marked reduction of CD62Llow cells paralleled by an increase in the proportion of CD62Lbright cells, associated with clinical improvement of asthma control. In vitro, CD62L expression on eosinophils is modulated by IL‐5 and anti‐IL‐5. Conclusion: A positive correlation between CD62Llow iEos and the baseline clinical features of SEA with CRSwNP was shown. Furthermore mepolizumab restores the healthy balance among eosinophils sub‐phenotypes in SEA patients. [ABSTRACT FROM AUTHOR]

Primary antibody deficiencies (PAD) are an underestimated comorbidity in asthma and its treatment could improve disease control. a retrospective cohort of asthmatics, affected by IgG subclass deficiency or unclassified antibody deficiency and treated with low-dose intravenous immunoglobulin replacement therapy (IRT) was recruited. Demographic and clinical data, chest CT scan, blood eosinophils, atopy, chronic oral corticosteroid (OCS) therapy were evaluated at baseline. Asthma exacerbations, lower respiratory tract infections (LRTI), upper respiratory tract infections (URTI) and asthma-related hospitalizations were assessed after one and two years of IRT. 57 moderate-to-severe asthmatics were enrolled, mostly affected by T2 low asthma (39/57, 68.4%). After one year, IRT was effective in improving, irrespective of bronchiectasis, atopy, eosinophils and PAD type: 1) trough IgG (826.9 ± 221.3 vs 942.2 ± 195.1 mg/dl; p < 0.0001) and IgG subclasses (IgG1 355.4 ± 88.4 vs 466.7 ± 122.3, p < 0.0001; IgG2 300.1 ± 130.1 vs 347.6 ± 117.3, p < 0.0005) serum levels. 2) asthma exacerbations (6.4 ± 4.1 vs 2.4 ± 1.9, p < 0.0001), LRTI (4.3 ± 3.9 vs 1.3 ± 1.5, p < 0.0001) and hospitalization rate (0.26 ± 0.7 vs 0.05 ± 0.2, p < 0.01). These results persisted after 2 years of therapy. Estimated mean cumulative OCS exposure was reduced by 4500 mg over the 2-year period. low-dose IRT is effective in improving asthma control and lessening OCS burden in asthmatics affected by PAD. [ABSTRACT FROM AUTHOR]

Objective: Mepolizumab is an anti-IL-5 monoclonal antibody that has shown, in different trials, the capacity to induce a reduction of exacerbations, an improvement of asthma control and a significant oral corticosteroid (OCS)-sparing effect. At present, there is limited real-life data about its long-term effects. The aim of the study was to evaluate the long-term effects of mepolizumab in real-life.Methods: We conducted a 36-months single-center retrospective study in 51 patients suffering from severe eosinophilic asthma treated with mepolizumab 100 mg/4 weeks. Clinical outcomes (symptoms, annual asthma exacerbation rates) were monitored. Additionally, we estimated annualized OCS dosage before and after mepolizumab treatment. Mepolizumab retention rate in the follow-up period was also evaluated.Results: A significant decrease of the annual rate of asthma exacerbations in association with significant changes in asthma control was observed. Specifically, the exacerbation rate significantly fell from 5.1 ± 4 per person/year in the pre-mepolizumab treatment period to 0.8 ± 1.2 per person/year in the 12-follow-up. The clinical benefit was maintained throughout the study follow up period of 36 months. Mepolizumab treatment induced significant changes in both ACT and ACQ5 scores. The majority of patients (65.2%) experienced a more pronounced improvement of 50% or more in SNOT-22. A mean cumulative OCS exposure reduction of 5365.5 mg over a 3-year period for patients receiving mepolizumab was estimated. The drug retention rate was: 96% at 12 months; 93.7% at 18 months, 88.9% at 24 months and 82.3% at 36 months.Conclusions: Our real-life results confirm that mepolizumab treatment allows to control asthma symptoms, reduce exacerbations and OCS exposure in a significant and sustained manner. [ABSTRACT FROM AUTHOR]

Background: In mice models, eosinophils have been divided into different subpopulations with distinct phenotypes and functions, based on CD62L and CD101 patterns of membrane expression. Limited data are available in humans. Objective: To investigate eosinophils subpopulations in peripheral blood (PB) and nasal polyp tissue (NP) from severe eosinophilic asthma (SEA) patients plus concomitant chronic rhinosinusitis with nasal polyps (CRSwNP). Methods: We recruited 23 SEA patients (14 with CRSwNP); as controls, we enrolled 15 non‐severe asthma patients, 15 allergic rhinitis patients without asthma and 15 healthy donors. Eosinophils were isolated from PB and NP and analysed by FACS. Eotaxin‐3 and eotaxin‐1 mRNA expression in NP tissue was also evaluated. Results: A significantly higher percentage of circulating CD62Llow cells was observed in SEA, as compared with controls, expressing higher levels of CCR3, CD69 and lower levels of CD125 (IL‐5R), CRTH2, CD86 and CD28 in comparison with CD62Lbright cells. In NP, eosinophils showed a high proportion of CD62Llow phenotype, significantly greater than that observed in PB. Surface expression of IL‐3R, IL‐5R, CD69 and CD86 was significantly higher in CD62Llow eosinophils from NP than in those from blood. Moreover, eotaxin‐3 mRNA expression positively correlated with the percentage of CD62Llow cells in NP. Conclusion: Two different eosinophil subphenotypes can be identified in blood and NP of SEA patients, with a preferential accumulation of CD62Llow inflammatory cells in NP. [ABSTRACT FROM AUTHOR]

COVID-19 in severe asthmatic patients during ongoing treatment with biologicals targeting type 2 inflammation: Results from a multicenter Italian survey Keywords: asthma; biologics; infections; virus EN asthma biologics infections virus 871 874 4 03/09/21 20210301 NES 210301 To the Editor, Several reports describe an higher risk for viral infections in patients with asthma.1,2 Novel coronavirus disease (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that shows a predilection to infect the lower and upper airway tract, thus creating an higher clinical issue in asthmatic patients.3 Data about the prevalence and severity of COVID-19 in asthma patients are very scarce, and no conclusive evidence is available.4 Additional concerns about the effects of asthma medications on SARS-CoV-2 infection may arise, and data about severe asthma during ongoing biological treatment in COVID-19 pandemic are lacking. The four confirmed COVID-19 cases displayed a good control of asthma symptoms before SARS-CoV-2 infection, without asthma exacerbations during the last 3 months before illness. [Extracted from the article]

Biological agents (BAs) target molecules involved in disease mechanisms and have modified the natural history of several immune-mediated disorders. All BAs are immunogenic, resulting in the formation of antidrug antibodies (ADAs), which can neutralize drug activity leading to loss of response and potential relapse, or serious adverse events such as infusion hypersensitivity reactions. The production of ADAs is the result of a specific adaptive immune response in which T and B cells are involved. Factors conditioning the immunogenicity of BAs, including drug-, treatment- and patient-related factors are currently the subject of many studies. Among them, a lot of attention is dedicated to define the impact of BAs structure, the effect of targeting (soluble or membrane) molecules, the impact of interruption of therapy as well as the role of genetic (HLA and non-HLA) predisposing factors and disease activity. Knowledge of factors capable of influencing the immunogenicity of BAs may help to understand, in a predictive manner and at the single patient level, the presence of risk factors influencing the production of ADAs and their impact on clinical outcomes. [ABSTRACT FROM AUTHOR]

Hypereosinophilic syndrome (HES) encompasses a heterogeneous and complex group of different subtypes within the wider group of hypereosinophilic disorders. Despite increasing research interest, several unmet needs in terms of disease identification, pathobiology, phenotyping, and personalized treatment remain to be addressed. Also, the prospective burden of non-malignant HES and, more in general, HE disorders is currently unknown. On a practical note, shortening the diagnostic delay and the time to an appropriate treatment approach probably represents the most urgent issue, even in light of the great impact of HES on the quality of life of affected patients. The present document represents the first action that the Italian Society of Allergy, Asthma, and Clinical Immunology (SIAAIC) has finalized within a wider project aiming to establish a collaborative national network on HES (InHES-Italian Network on HES) for patients and physicians. The first step of the project could not but focus on defining a common language as well as sharing with all of the medical community an update on the most recent advances in the field. In fact, the existing literature has been carefully reviewed in order to critically integrate the different views on the topic and derive practical recommendations on disease identification and treatment approaches.

Background: Eosinophils have been divided into different subpopulations with distinct phenotypes based on CD62L expression. No data are available regarding the correlation between eosinophils subphenotypes and clinical severity of asthma, as well as the effect of anti-IL-5 therapy on these cells. The study investigates the correlation between blood CD62L low inflammatory eosinophils (iEos) and clinical severity of severe eosinophilic asthma (SEA) and evaluates the impact of mepolizumab on iEos., Methods: 112 patients were screened and were divided in two groups: biological-naive (n = 51) and biological-treated patients (n = 61). The Biological-naive patients were analyzed before treatment (Group A) and 19 out of 51 patients, were longitudinally analyzed before and after treatment with mepolizumab 100 mg s.c/4 weeks (Group B); 32 patients were excluded because they were being treated with other biological therapies. Blood eosinophils were analyzed by FACS and correlated with clinical scores. In vitro effect of IL-5 and mepolizumab on CD62L expression was assessed., Results: A significant correlation between blood CD62L low cells and clinical scores of asthma and nasal polyps, as well as the number of asthma exacerbations in the last year was shown in untreated patients. In longitudinally studied patients we observed a marked reduction of CD62L low cells paralleled by an increase in the proportion of CD62L bright cells, associated with clinical improvement of asthma control. In vitro, CD62L expression on eosinophils is modulated by IL-5 and anti-IL-5., Conclusion: A positive correlation between CD62L low iEos and the baseline clinical features of SEA with CRSwNP was shown. Furthermore mepolizumab restores the healthy balance among eosinophils sub-phenotypes in SEA patients., (© 2023 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: In mice models, eosinophils have been divided into different subpopulations with distinct phenotypes and functions, based on CD62L and CD101 patterns of membrane expression. Limited data are available in humans., Objective: To investigate eosinophils subpopulations in peripheral blood (PB) and nasal polyp tissue (NP) from severe eosinophilic asthma (SEA) patients plus concomitant chronic rhinosinusitis with nasal polyps (CRSwNP)., Methods: We recruited 23 SEA patients (14 with CRSwNP); as controls, we enrolled 15 non-severe asthma patients, 15 allergic rhinitis patients without asthma and 15 healthy donors. Eosinophils were isolated from PB and NP and analysed by FACS. Eotaxin-3 and eotaxin-1 mRNA expression in NP tissue was also evaluated., Results: A significantly higher percentage of circulating CD62L low cells was observed in SEA, as compared with controls, expressing higher levels of CCR3, CD69 and lower levels of CD125 (IL-5R), CRTH2, CD86 and CD28 in comparison with CD62L bright cells. In NP, eosinophils showed a high proportion of CD62L low phenotype, significantly greater than that observed in PB. Surface expression of IL-3R, IL-5R, CD69 and CD86 was significantly higher in CD62L low eosinophils from NP than in those from blood. Moreover, eotaxin-3 mRNA expression positively correlated with the percentage of CD62L low cells in NP., Conclusion: Two different eosinophil subphenotypes can be identified in blood and NP of SEA patients, with a preferential accumulation of CD62L low inflammatory cells in NP., (© 2022 John Wiley & Sons Ltd.)