Allergic and eosinophilic asthma in the era of biomarkers and biologics: similarities, differences and misconceptions

Oppenheimer, John; Hoyte, Flavia; Phipatanakul, Wanda; Silver, Jared; Howarth, Peter H.; Lugogo, Njira L

doi:10.1016/j.anai.2022.02.021

Cited by 61 publications

(45 citation statements)

References 112 publications

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“…Secretion of IL-5 and IL-13 from ILC2s leads to eosinophilic inflammation but not IgE class switching, which is primarily driven by IL-4. Hence, IgE-driven mechanisms are associated with allergic asthma, while ILC2s-driven mechanisms are associated with eosinophilic asthma, with eosinophils per se contributing to both types of T2 asthma [ 59 , 60 , 61 ].…”

Section: Pathogenic Mechanisms In Allergic Asthmamentioning

confidence: 99%

Allergic Asthma in the Era of Personalized Medicine

Papapostolou

Makris

2022

JPM

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Allergic asthma is the most common asthma phenotype and is characterized by IgE sensitization to airborne allergens and subsequent typical asthmatic symptoms after exposure. A form of type 2 (T2) airway inflammation underlies allergic asthma. It usually arises in childhood and is accompanied by multimorbidity presenting with the occurrence of other atopic diseases, such as atopic dermatitis and allergic rhinitis. Diagnosis of the allergic endotype is based on in vivo (skin prick tests) and/or in vitro (allergen-specific IgE levels, component-resolved diagnosis (CRD)) documentation of allergic sensitization. Biomarkers identifying patients with allergic asthma include total immunoglobulin E (IgE) levels, fractional exhaled nitric oxide (FeNO) and serum eosinophil counts. The treatment of allergic asthma is a complex procedure and requires a patient-tailored approach. Besides environmental control involving allergen avoidance measurements and cornerstone pharmacological interventions based on inhaled drugs, allergen-specific immunotherapy (AIT) and biologics are now at the forefront when it comes to personalized management of asthma. The current review aims to shed light on the distinct phenotype of allergic asthma, ranging over its current definition, clinical characteristics, pathophysiology and biomarkers, as well as its treatment options in the era of precision medicine.

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Section: Pathogenic Mechanisms In Allergic Asthmamentioning

confidence: 99%

Allergic Asthma in the Era of Personalized Medicine

Papapostolou

Makris

2022

JPM

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“…14 Finally, a concept that is being challenged is the mutually exclusive approach to allergic or eosinophilic asthma in these clusters, particularly given the influence of this arbitrary distinction on biologic selection in severe asthma. 23 Guidelines rely on this separation of phenotypes to make treatment recommendations in severe asthma despite the presence of significant overlap. This needs to be taken into consideration in future iterations of our current guidelines.…”

Section: Other Considerationsmentioning

confidence: 99%

“…It can result from allergic sensitization via mast cell degranulation and production of IL-5 with resultant eosinophilia. 23 In addition, elevated IL-5 can result from type 2 innate lymphoid cells (ILC2) and Th2 cell differentiation that is driven by thymic stromal lymphopoietin (TSLP), IL-33, and IL-4. 37 These overlapping causes of eosinophilia begin to highlight the inherent challenges in specifically identifying the underlying cause of elevation in EOS in a specific patient with asthma.…”

Section: Sputum and Blood Eosinophilsmentioning

confidence: 99%

Phenotyping, Precision Medicine, and Asthma

Mohan

Lugogo

2022

Semin Respir Crit Care Med

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The traditional one-size-fits all approach based on asthma severity is archaic. Asthma is a heterogenous syndrome rather than a single disease entity. Studies evaluating observable characteristics called phenotypes have elucidated this heterogeneity. Asthma clusters demonstrate overlapping features, are generally stable over time and are reproducible. What the identification of clusters may have failed to do, is move the needle of precision medicine meaningfully in asthma. This may be related to the lack of a straightforward and clinically meaningful way to apply what we have learned about asthma clusters. Clusters are based on both clinical factors and biomarkers. The use of biomarkers is slowly gaining popularity, but phenotyping based on biomarkers is generally greatly underutilized even in subspecialty care. Biomarkers are more often used to evaluate type 2 (T2) inflammatory signatures and eosinophils (sputum and blood), fractional exhaled nitric oxide (FeNO) and serum total and specific immunoglobulin (Ig) E reliably characterize the underlying inflammatory pathways. Biomarkers perform variably and clinicians must be familiar with their advantages and disadvantages to accurately apply them in clinical care. In addition, it is increasingly clear that clinical features are critical in understanding not only phenotypic characterization but in predicting response to therapy and future risk of poor outcomes. Strategies for asthma management will need to leverage our knowledge of biomarkers and clinical features to create composite scores and risk prediction tools that are clinically applicable. Despite significant progress, many questions remain, and more work is required to accurately identify non-T2 biomarkers. Adoption of phenotyping and more consistent use of biomarkers is needed, and we should continue to encourage this incorporation into practice.

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“…Mepolizumab is a subcutaneously (SC), monthly-administered humanized IL-5 antagonist mAB, approved in Spain in 2016 for the treatment of patients with severe refractory asthma inadequately controlled with standard high-dose inhaled corticosteroids (ICS) and other long-term controller agents [ 17 , 18 ]. Although the efficacy and safety of mepolizumab has been widely demonstrated in severe eosinophilic asthma in previous randomized controlled trials (RCT) and real-world studies (RWE), the role of mepolizumab has not been fully assessed in populations with co-existing severe eosinophilic and allergic asthma [ 19 , 20 ]. In the Canary Islands, a geographical area leading in the national prevalence of asthma and number of prescribed biologics for SA in Spain [ 21 , 22 ], the coexistence of overlapping type-2 inflammation subtypes—eosinophilic and allergic—in moderate and SA have been formerly described [ 23 , 24 ].…”

Section: Introductionmentioning

confidence: 99%

Real-Life Performance of Mepolizumab in T2-High Severe Refractory Asthma with the Overlapping Eosinophilic-Allergic Phenotype

et al. 2022

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Severe asthma (SA) is categorized into multiple overlapping phenotypes and clinical characteristics driven by complex mechanistic inflammatory pathways. Mepolizumab is a human monoclonal antibody effectively targeting interleukin-5 in severe eosinophilic asthma. However, the eligibility of biologics in coincident SA phenotypes is still unclear. We assessed the efficacy and safety of mepolizumab in real-life patients with the overlapping T2-high SA endotype. This was a phase IV, single-centre observational cohort study including patients with severe refractory T2-high asthma in treatment with mepolizumab. After 12 months of treatment with mepolizumab, significant improvements (p < 0.0001) in asthma control and lung function were recorded. Rates of clinically significant annual asthma exacerbation were also decreased by 71.22% after 52-week therapy with mepolizumab (p < 0.001) associated with a reduction in the mean daily dose of oral corticosteroids. Two patients (3.27%) had to discontinue mepolizumab due to musculoskeletal disorders with no severe safety issues reported. The use of mepolizumab as an add-on therapy in routine clinical practice was safely associated with significant clinical and functional in the overlapping eosinophilic-and-allergic SA phenotype. The current data should support clinical and therapeutic decision-making in this T2-high SA endotype.

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Allergic and eosinophilic asthma in the era of biomarkers and biologics: similarities, differences and misconceptions

Cited by 61 publications

References 112 publications

Allergic Asthma in the Era of Personalized Medicine

Allergic Asthma in the Era of Personalized Medicine

Phenotyping, Precision Medicine, and Asthma

Real-Life Performance of Mepolizumab in T2-High Severe Refractory Asthma with the Overlapping Eosinophilic-Allergic Phenotype

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