Non-eosinophilic asthma: current perspectives

Abstract

Although non-eosinophilic asthma (NEA) is not the best known and most prevalent asthma phenotype, its importance cannot be underestimated. NEA is characterized by airway inflammation with the absence of eosinophils, subsequent to activation of non-predominant type 2 immunologic pathways. This phenotype, which possibly includes several not well-defined subphenotypes, is defined by an eosinophil count <2% in sputum. NEA has been associated with environmental and/or host factors, such as smoking cigarettes, pollution, work-related agents, infections, and obesity. These risk factors, alone or in conjunction, can activate specific cellular and molecular pathways leading to non-type 2 inflammation. The most relevant clinical trait of NEA is its poor response to standard asthma treatments, especially to inhaled corticosteroids, leading to a higher severity of disease and to difficult-to-control asthma. Indeed, NEA constitutes about 50% of severe asthma cases. Since most current and forthcoming biologic therapies specifically target type 2 asthma phenotypes, such as uncontrolled severe eosinophilic or allergic asthma, there is a dramatic lack of effective treatments for uncontrolled non-type 2 asthma. Research efforts are now focusing on elucidating the phenotypes underlying the non-type 2 asthma, and several studies are being conducted with new drugs and biologics aiming to develop effective strategies for this type of asthma, and various immunologic pathways are being scrutinized to optimize efficacy and to abolish possible adverse effects.

Adverse immunological imprinting by cytomegalovirus sensitizing for allergic airway disease

“…Interestingly, there exists a clinical correlate, namely an asthma phenotype in humans known as non-eosinophilic asthma (NEA). NEA accounts for particularly severe cases of asthma, and its most relevant clinical trait is its poor response to asthma treatment with corticosteroids [18]. Testing if non-eosinophilic AAD, reviewed here and described in greater detail in [17], qualifies as a model, or can be developed into a model, for clinical NEA is therefore of top priority.…”

Mimicking Antigen-Driven Asthma in Rodent Models—How Close Can We Get?

“…Non-Type 2 asthma, instead, is characterized by airway inflammation in the absence of eosinophils and is often associated with environmental and/or host hazards, such as cigarette smoke, pollution, work-related agents, infections, and obesity. These risk factors, alone or in conjunction, can activate specific cellular and molecular pathways leading to non-type 2 pulmonary inflammation (13). Growing evidence supports two major characteristic features of non-Type 2 asthma, namely a neutrophilic-driven inflammation and an IL-6-driven activation of the IL-17-dependent pathway (14,15).…”

Inhalations with Brine Solution from the ‘Wieliczka’ Salt Mine Diminish Airway Hyperreactivity and Inflammation in a Murine Model of Non-Atopic Asthma

“…Depending on the type of immune response, asthma can be divided into allergic (atopic) asthma, related to eosinophilia, and nonallergic (non-atopic) asthma, connected to neutrophilia [1]. Allergic asthma can be induced by allergens, contrary to the nonallergic form evoked by medications, cold, physical effort, and pollution [2,3]. The latter phenotype is more difficult in treatment, demanding higher doses of corticosteroids [4] with more pronounced exacerbations, and longer and more frequent hospitalizations [3,5].…”

“…Allergic asthma can be induced by allergens, contrary to the nonallergic form evoked by medications, cold, physical effort, and pollution [ 2 , 3 ]. The latter phenotype is more difficult in treatment, demanding higher doses of corticosteroids [ 4 ] with more pronounced exacerbations, and longer and more frequent hospitalizations [ 3 , 5 ]. According to the newest recommendations of GINA published in 2019 [ 6 ], asthma management should be based on symptom-driven (in case of mild asthma) or daily administered (in the moderate and severe form) inhaled corticosteroids.…”