Abstract
Airway hyperresponsiveness (AHR) represents a central pathophysiological hallmark of asthma, with airway smooth muscle (ASM) being the effector tissue implicated in the onset of AHR. ASM also exerts pro-inflammatory and immunomodulatory actions, by secreting a wide range of cytokines and chemokines. In asthma pathogenesis, the overexpression of several type 2 inflammatory mediators including IgE, IL-4, IL-5, IL-13, and TSLP has been associated with ASM hyperreactivity, all of which can be targeted by humanized monoclonal antibodies (mAbs). Therefore, the aim of this review was to systematically assess evidence across the literature on mAbs for the treatment of asthma with respect to their impact on the ASM contractile tone. Omalizumab, mepolizumab, benralizumab, dupilumab, and tezepelumab were found to be effective in modulating the contractility of the ASM and preventing the AHR, but no available studies concerning the impact of reslizumab on the ASM were identified from the literature search. Omalizumab, dupilumab, and tezepelumab can directly modulate the ASM in asthma, by specifically blocking the interaction between IgE, IL-4, and TSLP, and their receptors are located on the surface of ASM cells. Conversely, mepolizumab and benralizumab have prevalently indirect impacts against AHR by targeting eosinophils and other immunomodulatory effector cells promoting inflammatory processes. AHR has been suggested as the main treatable trait towards precision medicine in patients suffering from eosinophilic asthma, therefore, well-designed head-to-head trials are needed to compare the efficacy of those mAbs that directly target ASM contractility specifically against the AHR in severe asthma, namely omalizumab, dupilumab, and tezepelumab.
Highlights
Asthma is a chronic, heterogeneous, inflammatory airway disorder consisting of a generally variable airflow limitation and several clinical symptoms including chest tightness, cough, wheezing, and shortness of breath [1]
The question of this systematic review was to assess if current monoclonal antibodies (mAbs) for the treatment of asthma may have an impact on airway smooth muscle (ASM) contractility and Airway hyperresponsiveness (AHR)
The administered mAb was clone R35–92, a purified rat antimouse immunoglobulin E (IgE) mAb showing efficacy in murine asthma models that parallels the results reported for omalizumab in allergic asthmatic patients [50]
Summary
Heterogeneous, inflammatory airway disorder consisting of a generally variable airflow limitation and several clinical symptoms including chest tightness, cough, wheezing, and shortness of breath [1]. Airway hyperresponsiveness (AHR) represents a central pathophysiological hallmark of asthma, underpinned by predominant inflammatory traits involving different phenotypes and endotypes [2,3]. Since airway smooth muscle (ASM) is the effector tissue that strives to shorten and constricts the bronchial lumen in response to stimuli, it is mainly implicated in the onset of AHR [4]. Traditionally ASM has been considered as the main effector of AHR exclusively for its contractile properties [5]. Type 2 (T2)-high asthma is a complex endotype associated with high type 2 inflammatory markers including immunoglobulin E (IgE), interleukins (IL)-4, IL-5, Biomedicines 2021, 9, 1281. It is established that ASM may have proinflammatory and immunomodulatory functions, by secreting a wide range of cytokines and chemokines [6], contributing to structural alterations associated with the disease [7].
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