The introduction of biologics for the treatment of patients with refractory asthma represented a marked therapeutic advance. For more than 10 y, the only biologic available has been the monoclonal anti-IgE antibody omalizumab, reserved for patients with asthma caused by perennial allergen. In recent years, other biologics have been licensed for the treatment of severe eosinophilic asthma. They include monoclonal antibodies that target the Th2-pathway cytokines, such as IL-5 (mepolizumab and reslizumab) or its receptor (benralizumab) and the IL-4 and IL-13 receptor (dupilumab). The effectiveness of these biologics was demonstrated in several placebo controlled trials, the main outcomes being the significant reduction of the rate of asthma exacerbation and the improvement of respiratory function in actively treated patients. Based on the further understanding of the pathogenesis of asthma, new cytokines network and new targets are emerging, such as thymic stromal lymphopoietin, which can activate Th2 cells, innate lymphoid cells, or both, or prostaglandin D2 (PGD2), to develop additional biologics.

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Specific immunotherapy is the only treatment acting on the causes and not only on symptoms of respiratory allergy. It was first introduced as subcutaneous immunotherapy (SCIT) with the aim to induce immunological tolerance to the administered allergen(s). In the 1980s, sublingual immunotherapy (SLIT) was developed, mainly to improve the safety, which was a critical issue at that time. This article reviewed the available literature, including a large number of randomized controlled trials, meta-analyses, and real-life studies as well, on the outcomes of SCIT and SLIT concerning the treatment critical issues of the two routes, that are efficacy, safety, cost-effectiveness, and compliance to treatment. The efficacy of SCIT and SLIT is similar in respiratory allergy, providing, based on the induction of typical changes in the immunologic response, an early control of symptoms that steadily increases during the treatment and its efficacy lasts after the recommended duration of three years. Such results are the reason why SCIT and SLIT have economic advantage over symptomatic drugs. ated more than a century ago as a merely empirical treatment of hay fever (6), while SLIT was introduced only in the 1980s, when the knowledge on pathophysiology of allergy and mechanisms of AIT became clear (7). In this review, meta-analyses were preferred to evaluate the effectiveness and safety of SCIT and SLIT, while large-scale trials performed for registration from the regulatory agencies were used for the latest generation of SLIT products. Also real-life studies on very large patients population were considered. The milestones in the development of allergen immunotherapy The injective route was introduced in 1911 although the pathogenesis of allergic disease was not fully elucidated until the discovery of IgE antibodies in the 1960s (8), which clarified the mechanisms of allergy and the immunologic modifications achieved with AIT (9,10). Despite this, safety issues emerged in the 1980s, when fatal reactions to SCIT from the UK (11) and USA (12) were described. Nowadays it has been clarified that

In conclusion, respiratory system resistance improved after 4 weeks, whereas FEV1 improved after 24 weeks of treatment with benralizumab in patients with severe asthma. Oscillometry and spirometry can be used as a monitoring tool to detect early and late effect of benralizumab.