scholarly journals Eosinophils Target Therapy for Severe Asthma: Critical Points

2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
L. Brussino ◽  
E. Heffler ◽  
C. Bucca ◽  
S. Nicola ◽  
G. Rolla

Asthma is a chronic and heterogeneous disease, which is defined as severe disease whenever it requires treatment with a high dose of inhaled corticosteroids plus a second controller and/or systemic corticosteroids to prevent it from becoming ‘‘uncontrolled’’ or if it remains ‘‘uncontrolled’’ despite this therapy. Severe asthma is a heterogeneous condition consisting of phenotypes such as eosinophilic asthma, which is characterized by sputum eosinophilia, associated with mild to moderate increase in blood eosinophil count, frequently adult-onset, and associated with chronic rhinosinusitis with nasal polyps in half of the cases. Eosinophilic asthma is driven by T2 inflammation, characterized, among the others, by interleukin-5 production. IL-5 plays a key role in the differentiation, survival, migration, and activation of eosinophils, and it has become an appealing therapeutic target for eosinophilic asthma. In recent years two monoclonal antibodies (mepolizumab and reslizumab) directed against IL-5 and one monoclonal antibody directed against the alpha-subunit of the IL-5 receptor (benralizumab) have been developed. All these IL-5 target drugs have been shown to reduce the number of exacerbation in patients with severe asthma selected on the basis of peripheral blood eosinophil count. There are still a number of unresolved issues related to the anti-IL5 strategy in eosinophilic asthma, which are here reviewed. These issues include the effects of such therapy on airway obstruction and asthmatic symptoms, the level of baseline eosinophils that predicts a response to treatment, the relationship between blood and airway eosinophilia, and, perhaps most importantly, how to elucidate the pathogenetic role played by eosinophils in the individual patient with severe eosinophilic asthma.

2018 ◽  
Vol 39 (01) ◽  
pp. 091-099 ◽  
Author(s):  
Kian Fan Chung

AbstractSevere therapy-resistant asthma has been defined as “asthma which requires treatment with high dose inhaled corticosteroids (ICSs) plus a second controller (and/or systemic corticosteroids) to prevent it from becoming ‘uncontrolled’ or which remains ‘uncontrolled’ despite this therapy”. Patients who usually present with ‘difficult-to-treat asthma’ should first be assessed to determine whether he/she has asthma with the exclusion of other diagnoses and if so, whether the asthma can be classified as severe therapy-resistant. This necessitates an assessment of adherence to medications, confounding factors, and comorbidities. Increasingly, management of severe therapy-resistant asthma will be helped by the determination of phenotypes to optimize responses to existing and new therapies. Severe asthma patients are usually on a combination of high dose ICS and long-acting β-agonist (LABA) and, in addition, are often on a maintenance dose of oral corticosteroids. Phenotyping can be informed by measuring blood eosinophil counts and the level of nitric oxide in exhaled breath, and the use of sputum granulocytic counts. Severe allergic asthma and severe eosinophilic asthma are two defined phenotypes for which there are efficacious targeted biologic therapies currently available, namely anti-immunoglobulin E (IgE) and anti-interleukin (IL)-5 antibodies, respectively. Further progress will be realized with the definition of noneosinophilic or non-T2 phenotypes. It will be important for patients with severe asthma to be ultimately investigated and managed in specialized severe asthma centers.


2020 ◽  
pp. 1-9
Author(s):  
Nightingale Syabbalo ◽  

Asthma is a chronic inflammatory airway disease with several distinct phenotypes, characterized by different immunopathological pathways, clinical presentation, severity of the disease, and response to treatment. The phenotypes of asthma include eosinophilic, neutrophilic, mixed granulocytic, and paucigranulocytic asthma. Approximately 3.6-10% of patients with asthma have severe refractory disease, which is unresponsive to high dose inhaled corticosteroids (ICS), and long-acting β2-agonists (LABA). Most patients with eosinophilic asthma are responsive to corticosteroids, and interleukintargeted biologics, whereas, patients from other phenotypes, such as neutrophillic and paucigranullocytic asthma are resistant to treatment with ICS and biotherapeutics. The hallmark of severe refractory asthma is airway hyperresponsiveness, and remodeling. Histopathologically, patients with severe asthma have airway smooth muscle (ASM) hyperplasia and hypertrophy; subepithelial basement membrane thickening and fibrosis; all which contribute to fixed airflow limitation. Severe refractory asthma is very difficult to treat pharmacologically. It requires innovative therapies, such as bronchial thermoplasty which reduces the hypertrophied ASM mass and relieves the AHR, and broncoconstriction. Bronchial thermoplasty has been shown to improve asthma control, reduce severe exacerbations, hospitalizations, emergency room visits, and improve the quality of life, which persist up to 5 years following the procedure


Author(s):  
Juçara Noeli Silva ◽  
Alcides Rocha ◽  
Ivani Aparecida de Souza ◽  
Rodrigo Athanazio ◽  
Eduardo Vieira Ponte

2017 ◽  
Vol 119 (1) ◽  
pp. 16-20 ◽  
Author(s):  
Enrico Heffler ◽  
Giovanni Terranova ◽  
Carlo Chessari ◽  
Valentina Frazzetto ◽  
Claudia Crimi ◽  
...  

2021 ◽  
Vol 42 (3) ◽  
pp. 228-234
Author(s):  
Bo Zhao ◽  
Haiming Zheng ◽  
Xiaopan Li ◽  
Rui Zheng

Objective: This study aimed to explore the usefulness of the peripheral blood eosinophil count (PBEC) in assessing the level of fractional exhaled nitric oxide (FeNO) and predicting bronchodilation test results. Methods: We retrospectively analyzed the data of 384 outpatients who underwent FeNO measurement at our Department of Respiratory and Critical Care Medicine from March to June 2019. The FeNO level was compared among different PBECs to explore the association among them. Furthermore, the sensitivity and specificity of PBECs in predicting bronchodilation test results were assessed by using receiver operating characteristic (ROC) curve analysis. Results: There was a moderate correlation between PBECs and FeNO levels (r = 0.414; p < 0.05). In the subjects with PBECs ≥ 0.3 × 109/L, the median FeNO level was 39 ppb (interquartile range, 22.5‐65.5 ppb), significantly higher than in the subjects with PBECs < 0.3 × 109/L. The area under the ROC curve was 0.707 (p < 0.05). The maximum Youden index (0.348) was at PBECs = 0.205 × 109/L, which achieved sensitivity and specificity of 63% and 71.8%, respectively. Conclusion: PBECs ≥ 0.3 × 109/L can predict a positive bronchodilation test result and a high FeNO level, with a probability of 50% in the subjects with chronic cough and shortness of breath; in the absence of corresponding symptoms and a low PBEC, the predictive value was small. For hospitals not able to conduct FeNO measurements, for outpatients with poor economic conditions, and for patients with confirmed or suspected novel coronavirus disease 2019, the PBEC, in conjunction with a patient's clinical symptoms, can improve the diagnostic accuracy of allergic asthma and assessment of airway inflammation while reducing the risk of infection.


2021 ◽  
pp. 1-12
Author(s):  
Hirofumi Watanabe ◽  
Toshihiro Shirai ◽  
Keita Hirai ◽  
Taisuke Akamatsu ◽  
Hiromasa Nakayasu ◽  
...  

2020 ◽  
Vol 125 (2) ◽  
pp. 171-176
Author(s):  
Njira L. Lugogo ◽  
James L. Kreindler ◽  
Ubaldo J. Martin ◽  
Bill Cook ◽  
Ian Hirsch ◽  
...  

2019 ◽  
Vol 159 ◽  
pp. 105806 ◽  
Author(s):  
Frank C. Albers ◽  
Christopher Licskai ◽  
Pascal Chanez ◽  
Daniel J. Bratton ◽  
Eric S. Bradford ◽  
...  

Lung Cancer ◽  
2010 ◽  
Vol 67 ◽  
pp. S40-S41 ◽  
Author(s):  
A. Shelton ◽  
R.H. Green ◽  
P. Bradding ◽  
C.M. Free

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