**8. Quality of life studies**

treatment invery young children is of agreat importance, but several issues have tobe answered [70–72]. Immunotherapy can overcome problems related to the long-term pharmacotherapy [73], adherence and compliance to the standard treatment. Low-adherence and bad compliance to a long-term pharmacotherapy, both drug (problems with the usage of inhaled drugs) and non/drug-related factors can be overcome with the introduction of immunotherapy. All chronic diseases have an impact on quality of life due to high score of school absenteeism, impaired school performance, frequent emergency unit visits. Children with allergic diseases especially those with asthma showed low physical activity performance [74, 75]. High level of anxiety as well as higher incidence of depression and other physiological disorders can be seen in children and adolescents with asthma, allergic rhinitis and atopic dermatitis. A certain number of studies confirmed the impact of SLIT on all previous mentioned aspects of

Over the last 20 years, sublingual allergen immunotherapy has gained popularity based on controlled trails that have demonstrated a favorable safety profile [78, 79]. Although a great number of DB-PC-RCT showed clinical efficacy of SCIT since the British Committee on Safety of Medicines in the UK reported 26 SCIT-related anaphylactic deaths between 1957 and 1986, the interest for alternative routes constantly grows. The risk of subcutaneous immunotherapy (SCIT)-related systemic adverse events (SAEs) still represent a major concern that may, sometimes limit the use of this effective treatment, especially in the pediatric population. On the other side the overall safety of SLIT has been widely proven and accepted [80]. Moreover, Nichani study showed that SLIT can be safely administered to patients who previously experienced systemic reactions in response to subcutaneous allergen immunotherapy.

According to double-blind placebo-controlled-randomized clinical trials (DB-PC-RCTs) for allergic asthma, allergic rhinitis or allergic rhinoconjunctivitis [80–84] and real-life studies only several life-threatening and nonlife-threatening severe systemic reaction related to SLIT are reported [50, 85–87]. Overall prevalence of systemic adverse events was lower than 20% in DB-PC-RCT, whereas the prevalence of severe systemic reactions was between 1 and 2% of total recorded events [88–93]. Most commonly postmarketing surveys reported mild to moderate usually self-resolved systemic reactions [94, 95]. A very important issue concerning SLIT particularly in the pediatric population is to define risk factors for developing systemic reactions. Up to now several potential risk factors are defined: inadequate administration conditions (use of non-standardized extracts, administration of products containing a mixture of many allergens, overdosing [92]), and/or patient-related nonspecific risk factors (include cardiovascular diseases and long-term therapy with noncardioselective betablockers) that are very uncommon in children [96]. Those conditions are considered as special precaution, but not contraindication for SLIT introduction. On the other side uncontrolled asthma or severe asthma, oral lesion, or acute infections can represent temporary contraindication for SLIT. Although previous systemic reaction due to SCIT were considered as absolute

**7. Safety and tolerability of SLIT in allergic children**

quality of life [76, 77].

108 Allergen

According to many DB-PC-RCT, real-life studies and meta-analysis quality of life (QOL) is a very important issue for children and adults with allergic diseases. As it has been already mentioned, their quality of life is not so often satisfied particularly in school-aged period [101]. Standard pharmacotherapy treats only symptoms but not the disease itself, nor the quality of life. Although lots of studies proved clinical efficacy of SLIT, only a small part of them take QOL in consideration. One of them is Ciprandi et al. study [102] that has showed the improvement of QOL in polysensitized patients with AR and/or asthma treated with SLIT. Bousquet et al. study of DB-PC-RCT proved that patients on SLIT had a better QOL compared with the group of patients on placebo [103]. However, the results from the studies are controversial. While Bousquet et al. and Ciprandi et al. showed the improvement of the QOL in SLIT groups, Khinchi et al. found no statistical significant difference in QOL scores among three groups, that is, SLIT, SCIT, and placebo, using a 36-item short-form health survey (SF-36) questionnaire [104].
