Serum Levels of Epithelial-Derived Cytokines as Interleukin-25 and Thymic Stromal Lymphopoietin after a Single Dose of Mepolizumab in Patients with Severe Non-Allergic Eosinophilic Asthma: A Short Report

The bronchial epithelium has continuous contact with environmental agents initiating and maintaining airway type 2 inflammation in asthma. However, there is a lack of data on whether reduced airway eosinophilic inflammation can affect the production of epithelial-derived mediators, such as interleukin-25 (IL-25) and thymic stromal lymphopoietin (TSLP). The aim of this study was to investigate the changes in serum levels of IL-25 and TSLP after a single dose of mepolizumab, a humanized monoclonal antibody to interleukin-5 (IL-5), in patients with severe non-allergic eosinophilic asthma (SNEA). We examined 9 SNEA patients before and four weeks after administration of 100 mg mepolizumab subcutaneously. The fractional exhaled nitric oxide (FeNO) level was analysed using an electrochemical assay (NIOX VERO®, Circassia, UK). Serum IL-25 and TSLP levels were measured by ELISA. Four weeks after the single dose of mepolizumab, blood eosinophil count significantly decreased from 0.55 ± 0.20 × 109/l to 0.14 ± 0.04 × 109/l (p=0.01) and FEV1 increased from 2.1 ± 0.5 l (65.4 ± 8.8% of predicted) to 2.6 ± 0.4 l (76.4 ± 9.1% of predicted) (p=0.04), while FeNO level has not changed (32.3 ± 8.4 vs 42.9 ± 12.6 ppb). Serum IL-25 level significantly decreased from 48.0 ± 17.2 pg/mL to 34.8 ± 17.1 pg/mL (p=0.02) with same tendency in TSLP level: from 359.8 ± 71.3 pg/mL to 275.6 ± 47.8 pg/mL (p=0.02). It has also been noticed a significant relation between changes in the blood eosinophil count and serum IL-25 level (r = 0.81, p=0.008), as well as between changes in serum IL-25 and TSLP levels (r = 0.93, p=0.004) after a single dose of mepolizumab. Thus, anti-IL-5 treatment with mepolizumab might diminish the production of bronchial epithelial-derived cytokines IL-25 and TSLP in patients with SNEA which is potentially related to reduced eosinophilic inflammation. This trial is registered in ClinicalTrial.gov with identifier NCT03388359.

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Blood eosinophil count to predict bronchial eosinophilic inflammation in COPD

European Respiratory Journal ◽

10.1183/13993003.01659-2015 ◽

2016 ◽

Vol 47 (5) ◽

pp. 1562-1564 ◽

Cited By ~ 27

Author(s):

Florence Schleich ◽

Jean-Louis Corhay ◽

Renaud Louis

Keyword(s):

Eosinophil Count ◽

Blood Eosinophil ◽

Eosinophilic Inflammation ◽

Blood Eosinophil Count

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Evaluation of the peripheral blood eosinophil count as a predictor for fractional exhaled nitric oxide or bronchodilator reversibility test outcome

Allergy and Asthma Proceedings ◽

10.2500/aap.2021.42.210016 ◽

2021 ◽

Vol 42 (3) ◽

pp. 228-234

Author(s):

Bo Zhao ◽

Haiming Zheng ◽

Xiaopan Li ◽

Rui Zheng

Keyword(s):

Nitric Oxide ◽

Roc Curve ◽

Peripheral Blood ◽

Eosinophil Count ◽

Blood Eosinophil ◽

Test Results ◽

Fractional Exhaled Nitric Oxide ◽

Peripheral Blood Eosinophil ◽

Blood Eosinophil Count ◽

Feno Level

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.

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Blood eosinophil count group shifts and kinetics in severe eosinophilic asthma

Annals of Allergy Asthma & Immunology ◽

10.1016/j.anai.2020.04.011 ◽

2020 ◽

Vol 125 (2) ◽

pp. 171-176

Author(s):

Njira L. Lugogo ◽

James L. Kreindler ◽

Ubaldo J. Martin ◽

Bill Cook ◽

Ian Hirsch ◽

...

Keyword(s):

Eosinophil Count ◽

Blood Eosinophil ◽

Eosinophilic Asthma ◽

Blood Eosinophil Count ◽

Severe Eosinophilic Asthma

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Baseline blood eosinophil count as a predictor of treatment response to the licensed dose of mepolizumab in severe eosinophilic asthma

Respiratory Medicine ◽

10.1016/j.rmed.2019.105806 ◽

2019 ◽

Vol 159 ◽

pp. 105806 ◽

Cited By ~ 9

Author(s):

Frank C. Albers ◽

Christopher Licskai ◽

Pascal Chanez ◽

Daniel J. Bratton ◽

Eric S. Bradford ◽

...

Keyword(s):

Treatment Response ◽

Eosinophil Count ◽

Blood Eosinophil ◽

Eosinophilic Asthma ◽

Blood Eosinophil Count ◽

Severe Eosinophilic Asthma

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Eosinophils Target Therapy for Severe Asthma: Critical Points

BioMed Research International ◽

10.1155/2018/7582057 ◽

2018 ◽

Vol 2018 ◽

pp. 1-6 ◽

Cited By ~ 13

Author(s):

L. Brussino ◽

E. Heffler ◽

C. Bucca ◽

S. Nicola ◽

G. Rolla

Keyword(s):

Severe Asthma ◽

Eosinophil Count ◽

Inhaled Corticosteroids ◽

Response To Treatment ◽

High Dose ◽

Blood Eosinophil ◽

Moderate Increase ◽

Eosinophilic Asthma ◽

Peripheral Blood Eosinophil ◽

Blood Eosinophil Count

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.

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