Asthma is a chronic heterogeneous disease affecting more than 330 million people worldwide [1,2]. It constitutes a significant socioeconomic burden, especially in its severe uncontrolled form [3]. Over the next 20 years, asthma management in the United States is predicted to cost more than $960 billion [4]. Asthma is usually characterized by chronic airway inflammation and variable symptoms including cough, chest tightness, shortness of breath and wheezing, along with variable expiratory airflow limitation, which can become persistent due to airway remodeling [5]. Based on age of onset, atopy status, preservation of airflow, comorbidities, exacerbations, response to treatment and prognosis, as well as the underlying airway inflammation, different phenotypes and endotypes are embraced by the definition of asthma [6]. Hence, “asthma” has been proposed as an umbrella term under which all these phenotypes and endotypes, frequently overlapping, lie, with allergic asthma holding a key position [7]. It is estimated that allergic mechanisms are present in about 80% of child asthmatics and 40–50% of adult asthmatics [8]. Thus, the allergic phenotype is the most common asthma phenotype in the general asthma population [9,10] and the most commonly reviewed allergic disease in the literature [11]. The frequency of allergic asthma and the difficulty in precisely recognizing and differentiating it from other type 2 (T2) overlapping endotypes in clinical practice constitute a great challenge in the era of the pursuit of therapeutic strategies made to measure for every patient; that is, the era of precision medicine and tailor-made interventions.

Since the nature of asthma is complex and heterogeneous, framing the definition of allergic asthma is a great challenge. An “allergy”—and, therefore, “allergic”—is currently defined as an immune-mediated hypersensitivity reaction [8]. Recently, however, a more provocative—albeit refreshing—definition has been proposed [12]. Allergic asthma is usually defined as asthma associated with sensitization to aeroallergens. This definition consists of two criteria: (A) identification of allergic sensitization (in vivo and/or in vitro) and (B) association between aeroallergen exposure and asthma symptoms [9]. However, allergic asthma is often defined in the literature only with regard to the presence of sensitizations independently of their correlation with symptoms, thus further blurring the picture of this phenotype. Moreover, severe asthma represents one of the main goals of precision medicine, with monoclonal antibodies being at the forefront. Hence, when choosing a biologic agent, a stricter definition of allergic asthma is required. As derived from the populations of the randomized controlled trials (RCTs) that informed the regulatory approval in current published guidelines regarding biologics for severe asthma, the allergic subtype is clearly distinguished from the eosinophilic one. It is defined as the asthma phenotype characterized by symptoms resulting from exposure to a perennial aeroallergen and serum total IgE levels of 30–1300 IU/mL that are not adequately controlled with high doses of inhaled corticosteroids/long-acting beta2-agonists (ICSs/LABAs) and/or other background controllers [13]. This definition seems to be of particular use in the selection of omalizumab-eligible patients within the context of personalized medicine for severe allergic asthma. However, to complicate the puzzle even more, despite the clear distinction between allergic and eosinophilic asthma stated in current guidelines, different treatment options are currently proposed that ignore or misconceive the overlapping natures of these subtypes in clinical practice [13,14].