scholarly journals Anti-Interleukin Biologics for the treatment of the Atopic March Diseases

2021 ◽  
pp. 1-27
Author(s):  
Nightingale Syabbalo
Keyword(s):  
Atopic Dermatitis ◽  
Lung Function ◽  
Asthma Control ◽  
Eosinophilic Esophagitis ◽  
Cell Injury ◽  
Th2 Cells ◽  
Mucosal Inflammation ◽  
Eosinophilic Asthma ◽  
Atopic March ◽  
Iga Response

The atopic march refers to the natural history of allergic disorders as they develop from infancy to childhood. Classically, the atopic march begins with atopic dermatitis (AD), followed by food allergy, advancing to asthma, allergic rhinitis (AR), and finally to the fifth member eosinophilic esophagitis. The pathogenesis of the atopic march is complex, and involves genetic, immunological, and environmental factors. T helper type 2 (Th2) lymphocytes, and epithelial cells play a key role in the pathogenesis of the diseases in the atopic march. Th2 cells secrete cytokines, such as interleukin-5 (IL-5), IL-4, and IL-13, whereas, epithelial cell injury release alarmin cytokines, including IL-25, IL-33, and thymic stromal lymphopoietin (TSLP). Th2 cells and alarmin cytokines play an important role in the development of eczematous skin lesions, airway inflammation and remodeling, and oesophageal mucosal inflammation. Treatment of eosinophilic asthma and associated comorbid disorders is challenging, and requires a precision targeted approach with biologics. Dupilumab is a fully humanized IgG4 monoclonal antibody to the IL-4Rα, which mediates signaling to both IL-4 and IL-13, and blocks their immunopathological effects. Dupilumab is the only biologic that has been approved for the treatment of eosinophilic asthma, AD, and eosinophilic esophagitis. In patients with eosinophilic asthma treatment with dupilumab has been shown to improve asthma control, reduce exacerbations, and improve lung function. In patients with atopic dermatitis dupilumab has been demonstrated to improve the Eczema Area Severity Index (EASI) score, Investigator’s Global Assessment (IGA) response, SCORing Atopic Dermatitis (SCORAD) score, and the Peak Pruritus Numerical Rating (PNR) scale. Lebrikizumab and Tralokinumab (anti-IL-13) failed to show the expected results for the treatment of asthma, astoundingly, in several clinical trials they have been shown to significantly improvement EASI score, IGA response, SCORAD score, PNR scale, sleep architecture, and Dermatology Life Quality Index (DLQI). They have been granted First Tract Designation, and European Commission regulatory approval, respectively. Tezepelumab (anti-TSLP) is approved for the treatment of eosinophilic asthma, and has been shown to significantly reduce exacerbations, and improve asthma control, lung function, and HLQoL. However, tezepelumab did not meet the endpoints in phase II for the treatment of AD. Keywords: Atopic March; Atopic Dermatitis; Eosinophilic Asthma; Interleukin; Dupilumab; Tralokinumab

Significant improvement in lung function and asthma control after benralizumab treatment for severe refractory eosinophilic asthma

2020 ◽  
Vol 64 ◽  
pp. 101966
Author(s):  
Francesco Menzella ◽  
Patrizia Ruggiero ◽  
Carla Galeone ◽  
Chiara Scelfo ◽  
Diego Bagnasco ◽  
...  
Keyword(s):  
Lung Function ◽  
Asthma Control ◽  
Eosinophilic Asthma

scholarly journals Effectiveness of Benralizumab in Improving the Quality of Life of Severe Eosinophilic Asthmatic Patients: Our Real-Life Experience

2021 ◽  
Vol 12 ◽  
Author(s):  
Giulia Scioscia ◽  
Giovanna Elisiana Carpagnano ◽  
Carla Maria Irene Quarato ◽  
Donato Lacedonia ◽  
Sonia Santamaria ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Lung Function ◽  
Asthma Control ◽  
Severe Asthma ◽  
Life Experience ◽  
Real Life ◽  
Eosinophilic Inflammation ◽  
Eosinophilic Asthma ◽  
Severe Eosinophilic Asthma

Background: Severe eosinophilic asthma decreases lung function and causes worsen symptoms, often forcing recurrent maintenance corticosteroid use. The aim of our real-life study was to evaluate the effectiveness of an add-on treatment with benralizumab in patients with severe eosinophilic asthma, paying particular attention to the impact on their quality of life (QoL).Materials and methods: In this prospective study, 10 outpatients with severe eosinophilic asthma were added-on with benralizumab and followed-up in our severe asthma clinic after 12 and 24 weeks. At each patient visit, pre-bronchodilator FEV1 and inflammatory markers were recorded. Variations in asthma symptoms control and QoL perception was assessed by validated questionnaires.Results: All the subjects experienced a marked reduction of nocturnal and diurnal symptoms over time and were able to stop using OCS, as documented by the improvement in Asthma control test (ACT) and Asthma Control Questionnaire score. Similarly, we recorded a statistically significant increase in patient’s QoL perception in EQ-VAS, EQ-5D-3L and Asthma Quality of Life Questionnaire (AQLQ) assessment (p < 0.05). Simultaneously we recorded a significant reduction in eosinophilic inflammation, an improvement in pre-bronchodilator FEV1. These results appear to be in line with those already obtained in the previous randomized controlled trials (RCTs).Conclusion: Our 24-weeks real life experience supports the effectiveness of an add-on treatment with benralizumab in reducing eosinophilic inflammation and OCS-use, increasing lung function and improving control of nocturnal and diurnal symptoms, as well as restoring severe asthma patients to a better QoL.

scholarly journals Impact of baseline clinical asthma characteristics on the response to mepolizumab: a post hoc meta-analysis of two Phase III trials

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Catherine Lemiere ◽  
Camille Taillé ◽  
Jason Kihyuk Lee ◽  
Steven G. Smith ◽  
Stephen Mallett ◽  
...  
Keyword(s):  
Lung Function ◽  
Asthma Control ◽  
Clinical Characteristics ◽  
Meta Analysis ◽  
Phase Iii ◽  
Eosinophilic Asthma ◽  
Severe Eosinophilic Asthma ◽  
Clinically Significant ◽  
Post Hoc ◽  
Airway Reversibility

Abstract Background Severe asthma is associated with a broad range of phenotypes and clinical characteristics. This analysis assessed whether select baseline patient characteristics could prognosticate mepolizumab efficacy in severe eosinophilic asthma. Methods This was a post hoc meta-analysis of data from the Phase III MENSA (NCT01691521/MEA115588) and MUSCA (NCT02281318/200862) studies. Patients aged ≥ 12 years with severe eosinophilic asthma and a history of exacerbations were randomised to receive placebo (MENSA/MUSCA), mepolizumab 75 mg intravenously (MENSA) or 100 mg subcutaneously (SC) (MENSA/MUSCA) every 4 weeks for 32 (MENSA) or 24 (MUSCA) weeks. The primary endpoint was the annual rate of clinically significant exacerbations; other outcomes included the proportion of patients with no exacerbations and changes from baseline in pre-bronchodilator forced expiratory volume in 1 s (FEV1), St George’s Respiratory Questionnaire (SGRQ) total score and Asthma Control Questionnaire (ACQ)-5 score. Analyses were performed by baseline age of asthma onset (< 18 years; 18–40 years; ≥ 40 years); lung function (% predicted FEV1 ≤ 60; 60–80; > 80); airway reversibility (reversible [≥ 12% change in FEV1]; non-reversible [< 12% change in FEV1]); perennial and/or seasonal allergen sensitivity (yes/no); asthma control (uncontrolled [ACQ-5 score ≥ 1.5]; partial/complete control [ACQ-5 score < 1.5]). Results Overall, 936 patients received mepolizumab 100 mg SC or placebo. Across age at asthma onset, lung function and airway reversibility subgroups, mepolizumab reduced the rate of clinically significant exacerbations by 49–63% versus placebo. Improvements in lung function, SGRQ total score and ACQ-5 score were also seen with mepolizumab versus placebo across most age and lung function subgroups. Clinically significant exacerbations were reduced with mepolizumab versus placebo irrespective of season or allergen sensitivity; SGRQ total and ACQ-5 scores were generally improved across seasons. Conclusions Mepolizumab efficacy was consistent for patients with varying age at asthma onset, lung function, airway reversibility and allergen sensitivities at baseline. Our results indicate that mepolizumab is likely to be beneficial for patients with severe eosinophilic asthma with a broad range of baseline clinical characteristics; large-scale real-world studies are needed to confirm the external validity of these findings. Trial registration Post hoc meta-analysis of data from MENSA (NCT01691521/MEA115588) and MUSCA (NCT02281318/200862)

Active Eosinophilic Esophagitis is Associated with Increased Asthma Severity and Lower Lung Function in Children with Comorbid Asthma

2021 ◽  
Vol 147 (2) ◽  
pp. AB92
Author(s):  
Karyn Parsons ◽  
Katharine Guarnieri ◽  
Dawit Tadesse ◽  
Md Monir Hossain ◽  
Vincent Mukkada ◽  
...  
Keyword(s):  
Lung Function ◽  
Eosinophilic Esophagitis ◽  
Asthma Severity ◽  
Lower Lung

scholarly journals Classification of non-acute bronchial asthma according to allergy and eosinophil characteristics: a retrospective study

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Yi Jiang ◽  
Ruoli An ◽  
Li Cheng ◽  
Qianru Yue ◽  
Hanwei Zhang ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Lung Function ◽  
Allergic Asthma ◽  
Asthma Management ◽  
Effective Management ◽  
Sputum Cytology ◽  
Eosinophilic Asthma ◽  
Asthma Patients ◽  
Medical University

Abstract Background Investigating the endotypes of the different asthma phenotypes would help disease monitoring, prognosis determination, and improving asthma management standardization. This study aimed to classify asthma into four endotypes according to the allergic and eosinophilic characteristics and explore the phenotypes (clinical characteristics, pulmonary functions, and fractional expired nitric oxide (FeNO)) of each endotype. Methods This retrospective study included non-acute asthma patients treated at the First Hospital of Shanxi Medical University (05/2016–01/2018). The patients were classified into the eosinophilic allergic, eosinophilic non-allergic, non-eosinophilic allergic, and non-eosinophilic non-allergic asthma endotypes. Serum sIgE, lung function, FeNO, and induced sputum cytology were tested and compared among groups. Results Of the 171 included patients, 22 had eosinophilic allergic asthma, 17 had eosinophilic non-allergic asthma, 66 had non-eosinophilic allergic asthma, and 66 had non-eosinophilic non-allergic asthma. Lung function measurements (FEV1%, FEF25%, FEF50%, FEF75%, and FEF25–75%) showed that airway dysfunction was worse in eosinophilic non-allergic asthma than in the other three endotypes (all P < 0.001). In allergic asthma patients, eosinophilic asthma had worse airway dysfunction than non-eosinophilic asthma (all P < 0.05). Similar results were found in non-allergic asthma (all P < 0.01). The FeNO levels in eosinophilic allergic asthma were higher than in eosinophilic non-allergic and non-eosinophilic non-allergic asthma (both P = 0.001). Conclusions FeNO can objectively reflect eosinophilic airway inflammation in asthma. Endotypic classification of asthma patients regarding the allergic and eosinophilic characteristics is conducive to the effective management of patients with asthma.

scholarly journals Asthma Control Measures Are Not Associated with Decreased Lung Function in Obese Children with Severe Asthma

2020 ◽  
Author(s):  
C.N. Martin ◽  
A.A. Dooley ◽  
M. Gatti ◽  
N. Weinstein ◽  
E. Chorvinsky ◽  
...  
Keyword(s):  
Lung Function ◽  
Asthma Control ◽  
Severe Asthma ◽  
Control Measures ◽  
Obese Children

Late Breaking Abstract - Phase 2 trial evaluating the effects of dexpramipexole on blood eosinophils, lung function, and airway biomarkers in eosinophilic asthma

2021 ◽  
Author(s):  
Salman Siddiqui ◽  
Michael Bozik ◽  
Donald Archibald ◽  
Steven Dworetzky ◽  
James Mather ◽  
...  
Keyword(s):  
Lung Function ◽  
Phase 2 ◽  
Eosinophilic Asthma ◽  
Phase 2 Trial ◽  
Blood Eosinophils

L-Citrulline as Add-On Therapy to Increase Exhaled Nitric Oxide and Improve Lung Function and Asthma Control in Obese Asthmatics

2019 ◽  
Author(s):  
F. Holguin ◽  
S. Sharma ◽  
D.E. Winnica ◽  
K. Wasil ◽  
V.L. Smith ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Lung Function ◽  
Asthma Control ◽  
Exhaled Nitric Oxide ◽  
Improve Lung Function
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