## 3 Results
### Allergen-Specific Immunotherapy  
Classical treatments for asthma have been used to relieve the symptoms caused by the inflammatory process. Nevertheless, these do not solve the underlying problem: the disproportionate response of the immune system. In addition, classical therapies have various long-term side effects, and it is difficult to find an optimal treatment for each patient, because of asthma heterogeneity. Therefore, immunotherapy has been postulated as an effective strategy offering long-term tolerance [231]; additionally, it is less expensive than other treatments commented on previously, like biologists [96; 232; 233]. Immunotherapy involves the administration of increasing amounts of the allergen until an adequate dose to produce immunological tolerance is achieved [128]. Repeated exposure to the allergen causes the DCs to produce IL-10, IL-12, and IL-27, which are regulatory cytokines. They stimulate Th1 response, thus restoring the balance between the T1 and T2 response. In addition, IL-10, IL-12, and IL-27 also activate Treg and B cells, favoring the production of antibodies that will block future T2 responses, such as IgG\({}_{4}\)[234]. There is also a modification of the activation threshold of mast cells and basophils [202]. It has been proven that AIT has long-term benefits for asthma and AR [235; 236; 237; 238]. Its effect persists even years after ending the treatment, with a consequent reduction in medication use as well as a decrease in the risk of developing asthma [88]. Despite its more than proven efficacy, immunotherapy is mainly recommended when patients do not control their symptoms with conventional pharmacotherapy or if they do not tolerate these drugs [142; 239]. Different types of allergens can be used in immunotherapy: crude allergen extracts, purified or recombinant allergens, modified allergens (allergoids), and purified peptides [240]. Allergen administration is usually subcutaneous, but sublingual immunotherapy (SLIT) is also available, in addition to a less common route of intralymphatic immunotherapy (ILIT). The main adverse effect of immunotherapy is the development of uncontrolled allergic responses [234]. On the one hand, SCIT is based on the periodical administration of increasing amounts of the allergen until immunological tolerance is achieved. SCIT is effective against several allergens, such as HDM, birch pollen, timothy grass, and ryegrass [241; 242; 243]. However, SCIT has some drawbacks, such as the need for frequent injections; moreover, these must be administered in a hospital [239], in addition to the potential risk of anaphylaxis [244]. In several studies, AIT has been demonstrated to be more effective than conventional drugs in controlling AR symptoms. A recent randomized clinical trial compared a group of patients receiving AIT plus pharmacotherapy versus a control group receiving only drug treatment. The results showed a significant decrease in symptoms in the immunotherapy-treated group, as well as an improvement in quality of life, compared to the control group [245]. [PERSON] and collaborators developed another randomized, double-blind placebo-controlled trial with _Pileum pratense_ SCIT performed in 56 patients with moderate-severe LAR to grass pollen demonstrating that SCIT increased allergen tolerance [246]. Most patients treated with SCIT for more than 6 months showed an allergen tolerance over 50 times higher than baseline, and 56% showed a negative nasal allergen provocation test. Moreover, these authors demonstrated that SCIT was safe for patients not having serious adverse events related to the medication. On the other hand, SLIT offers multiple benefits over the subcutaneous route as it does not require injections, can be administered at home, and has a lower risk of systemic adverse effects [247]. However, it must be administered daily, which may be a problem for adherence to treatment [248]. Previous studies have demonstrated the efficacy of SLIT in asthma treatment, although it has not been officially approved [15].