Challenges in severe asthma: Do we need new drugs or new biomarkers?

Abstract

Severe asthma is a complex, heterogenous airway condition. There have been significant advances in severe asthma management in the past decade using monoclonal antibody therapies that target the inflammatory component of the disease. Patient selection has been paramount for the success of these biologicals, leading to significant interest in biomarkers to guide treatment. Some severe asthmatics remain suboptimally controlled despite trials of biologicals and many of these patients still require chronic systemic corticosteroids. New therapeutics are currently in development to address this unmet need. However, whether these patients could be better treated by using novel biomarkers that inform selection among currently available biologics, and that objectively measure disease control is unclear. In this review, we examine the currently used biomarkers that guide severe asthma management and emerging biomarkers that may improve asthma therapy in the future.

Upper Airway Alarmin Cytokine Expression in Asthma of Different Severities

“…However, severe asthma phenotypes are highly heterogeneous due to inherent differences in etiopathological mechanisms, and thus it may be valuable to measure the expression of inflammatory mediators prospectively in severe asthma patients to determine which patients are most likely to benefit from this drug. While bronchial brushings and induced sputum may be used for measuring cytokine levels, harvesting cells through these methods is technically challenging, invasive, and not always feasible, particularly in patients with reduced lung function or scant sputum production [5]. Therefore, the upper airways may be an attractive target for study as potential surrogates of the lung.…”

“…Approximately half of severe asthma is poorly controlled, with a significant health burden and impact on quality of life despite adherence to standard inhaled therapies, including inhaled corticosteroids (ICSs) and long-acting β 2 agonists (LABAs) [3]. The majority of these patients have evidence of type 2 (T2) inflammation and are candidates for biologic therapies directed against T2 inflammatory mediators (e.g., immunoglobulin E (IgE), interleukin (IL-4)/IL-13, IL-5, and thymic stromal lymphopoietin, (TSLP)); however, it remains a challenge to determine which therapeutic is likely to work for an individual patient [4,5].…”

Optimization and Characterization of Novel ALCAM-Targeting Antibody Fragments for Transepithelial Delivery

“…The fact that the cortisone (budesonide) control performed so well ( Figure S4 ) is not surprising, since cortisone is known to be highly efficacious in this mouse model [ 63 ]. However, since a considerable number of patients are insensitive to cortisone treatment [ 64 , 65 ], and corticosteroids alone typically do not suffice for the management of severe asthma [ 66 , 67 ], there remains a strong need for the development of further drugs targeting other pathways, such as cytokines, cytokine receptors, or cell adhesion molecules such as CD6 or ALCAM [ 68 , 69 ].…”

Eosinophilic Airway Diseases: From Pathophysiological Mechanisms to Clinical Practice

“…In recent years, a wide range of mAbs targeting IgE or type 2 cytokines have been proved to be highly effective and safe in reducing symptoms and exacerbation in patients with severe allergic and eosinophilic asthma [ 156 ]. However, these therapies are not suitable for about half of patients with severe asthma who often present with non-allergic, non-eosinophilic type 2-low asthma [ 60 , 157 , 158 ]. For this reason, in the era of precision medicine, investigating the different pathways involved in the different endotypes of asthma can help identify new targeted therapies ( Table 2 ).…”