Bioassays for Objectively Monitoring Systemic Corticosteroid Use in Severe Asthma: Ready for Precision Medicine?

CHEST Journal ◽  
2021 ◽  
Vol 160 (1) ◽  
pp. 5-6
Author(s):  
John B. Hagan ◽  
Matthew A. Rank
2019 ◽  
Vol 6 (4) ◽  
pp. 117-135
Author(s):  
Orit Gourgy Hacohen ◽  
Shai Cohen

Asthma is a heterogeneous condition in which multiple pathological pathways manifest with similar symptoms. Severe asthma (SA) is challenging to manage and comprises a significant health and economic burden. Many studies have been conducted in an attempt to define different clinical phenotypes that translate into biological endotypes, with the goal of tailoring treatment based on precision medicine. This review summarizes the current evidence for the treatments of SA, and in particular, the biologic treatments that are currently available: omalizumab, mepolizumab, reslizumab, benralizumab and dupilumab. We found only limited high-quality direct evidence regarding treatment with anti-IgE (omalizumab) in SA patients. Data regarding anti-interleukin (IL)-5 (mepolizumab, reslizumab and benralizumab) showed beneficial effects in severe eosinophilic asthma (SEA) with different levels of blood eosinophils used in clinical trials. Dupilumab, anti-IL-4/IL-13, was shown to be effective in SEA and is the only agent currently FDA-approved for the indication of oral corticosteroid dependent asthma, regardless of the blood eosinophil level. This review also summarizes the existing knowledge regarding the characteristics of the patient who may respond to the different therapies. As of today, more studies are needed to better understand the diverse mechanisms that underlie SA phenotypes. We have not yet adequately reached the goal of precision medicine. Additional studies are necessary in order to find novel surrogate markers that can predict the response to a specific biologic therapy, especially in patients who are oral corticosteroid dependent. In addition, efforts must be invested into research looking for new treatment options for patients with non-type-2 inflammation SA. Statement of novelty: we review the current evidence regarding tailored treatment therapies in SA, with a particular focus on the knowledge regarding patient selection for specific biologic treatments.


2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Takanori Numata ◽  
Katsutoshi Nakayama ◽  
Hirofumi Utsumi ◽  
Kenji Kobayashi ◽  
Haruhiko Yanagisawa ◽  
...  

Abstract Background Several major randomized control studies have demonstrated that mepolizumab, an anti-IL-5 monoclonal antibody, is effective for patients with severe eosinophilic asthma who show exacerbation or require systemic corticosteroid maintenance therapy. However, the predictive factors of the response to mepolizumab other than blood eosinophil count are unclear in clinical practice. Objective To elucidate the predictive factors of the response to mepolizumab for patients with severe eosinophilic asthma. Methods From July 2016 to December 2017, 28 patients with severe asthma received mepolizumab in our hospital. To determine the predictive factors, we retrospectively evaluated patient characteristics, comorbidities, biomarkers, pulmonary function, maintenance dose of systemic corticosteroids and number of exacerbations. Results The response rate to mepolizumab treatment was 70% (19/27; one pregnant woman was excluded from analysis). Compared with 11 patients without eosinophilic chronic rhinosinusitis (ECRS), 16 patients with ECRS showed significantly improved systemic corticosteroid-sparing effects [− 71.3 ± 37.0% vs − 10.7 ± 20.1%, P = 0.006], change from baseline FeNO [− 19 ± 57 (%) vs 30 ± 77 (%), P = 0.023] and symptoms [14 patients (88%) vs five patients (45%), P = 0.033]. ECRS was identified as a predictive factor of the response to mepolizumab in a multivariate logistic regression analysis [odds ratio = 22.5, 95% CI (1.5–336), P = 0.024]. Of the eight patients previously administered omalizumab, five responded to mepolizumab. Staphylococcus aureus enterotoxin B IgE results were negative in 80% of responders (P = 0.14). Conclusion Both groups showed improved symptom scores and a decreased number of exacerbations. Mepolizumab substantially improved the clinical variables of patients with eosinophilic asthma complicated with ECRS.


2019 ◽  
Vol 199 (7) ◽  
pp. 823-829 ◽  
Author(s):  
Salman Siddiqui ◽  
Loren C. Denlinger ◽  
Stephen J. Fowler ◽  
Praveen Akuthota ◽  
Dominick E. Shaw ◽  
...  

2019 ◽  
Vol 28 (152) ◽  
pp. 190054 ◽  
Author(s):  
Ian Pavord ◽  
Thomas Bahmer ◽  
Fulvio Braido ◽  
Borja G. Cosío ◽  
Marc Humbert ◽  
...  

The European Respiratory Biologics Forum gathered participants from 21 countries in Madrid, Spain, to discuss the management and treatment of severe asthma in the era of biologics. The current insights on the pathophysiology of severe asthma were discussed, as well as the role of respiratory biologics in clinical practice and strategies for eliminating chronic use of oral corticosteroids. The participants also highlighted the key challenges in identifying patients with severe asthma based on phenotypes, biomarkers and treatable traits, and the existing problems in patient referral to specialist care. The monitoring of treatment was debated and the need for a change towards precision medicine and personalised care was emphasised throughout the meeting. This review provides a summary of the discussions and highlights important concerns identified by the participants regarding the current management of severe asthma.


2020 ◽  
Vol 15 (3) ◽  
pp. 187-194
Author(s):  
Amelia Licari ◽  
Riccardo Castagnoli ◽  
Enrica Manca ◽  
Martina Votto ◽  
Alexander Michev ◽  
...  

Pediatric severe asthma is actually considered a rare disease with a heterogeneous nature. Recent cohort studies focusing on children with severe asthma identified different clinical presentations (phenotypes) and underlying pathophysiological mechanisms (endotypes). Phenotyping and endotyping asthma represent the current approach to patients with severe asthma and consist in characterizing objectively measurable and non-invasive indicators (biomarkers) capable of orienting diagnosis, management and personalized treatment, as advocated by the Precision Medicine approach. The aim of this review is to provide a practical overview of current and emerging biomarkers in pediatric severe asthma.


2021 ◽  
Vol Volume 14 ◽  
pp. 525-538
Author(s):  
Manisha Ramphul ◽  
David KH Lo ◽  
Erol A Gaillard

2016 ◽  
Vol 22 (7) ◽  
pp. 833-847 ◽  
Author(s):  
Anand A. Dalal ◽  
Mei Sheng Duh ◽  
Laurence Gozalo ◽  
Marie-Noëlle Robitaille ◽  
Frank Albers ◽  
...  

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