**3. Biomarkers and prediction**

exclusively by a well-trained staff at the allergy departments. They are very important for distinguishing allergic and nonallergic rhinitis as well as for the diagnosis of local allergic rhinitis (LAR)—typical clinical history of allergic rhinitis with positive nasal provocation test, usually with elevated eosinophils in nasal smear, but with negative skin prick or/and *in vitro* allergy tests [16]. *In vitro* allergy tests are cornerstone of allergy diagnostic especially in the pediatric population. All children with positive clinical history of allergic diseases (atopic dermatitis, allergic rhinitis, and/or asthma) should be evaluated, particularly those with positive uni- or bilateral family history of atopic diseases. Determinations of total IgE, followed with evaluation of the allergen-specific antibody levels are precede the introduction of allergen-specific immunotherapy. It is also a very important to be mentioned that the interpretation of the allergy tests should be strictly done in the light of clinical history of a certain patients. Novel diagnostic tools are also capable to determine sensitization to a specific pure or recombinant allergens that is of a great importance for individualized treatment approach. Sometimes this kind of tests are the most relevant to confirm the diagnosis of allergy sensitization. To data, the most commonly used system to determine allergen-specific IgE is the ImmunoCAP system that are considered as a goal standard for *in vitro* diagnosis of allergen condition. Despite great technological improvements in *in vitro* diagnostics of allergies, several problems still remain. Although elevated IgE is a marker of IgE-mediated allergy, this is not sufficient for the induction of symptoms. According to the data, more than 20% of patients with elevated IgE are in fact asymptomatic. Elevated serum IgE level is irrelevant as long as it does not bind to Fcέ receptors on effectors cells (mastocytes, eosinophils, and basophils). Positive allergen-specific IgE in serum is not sufficient to confirm allergy in all cases [17–19]. At the current state of art it is a very important to be a little bit septic about allergy diagnostic test results only based on determination of allergen-specific serum IgE levels and to consider clinical history, accompanied by adequate skin prick tests or provocation tests, which drive the diagnosis before considering allergen-specific immunotherapy inclusion. During the last decades, there has been a huge improvement in *in vitro* allergy diagnosis due to novel approaches that include molecular components. It has been already mentioned that allergen-specific tests are not enough sensitive and specific for allergy diagnosis, through the advent of molecular technology, some weaknesses, and shortcomings of classical approach that used only natural extracts could be solved. Component resolved diagnosis (CRD) of the specific IgE response provides more individual approach in diagnosis of allergic patients and better selection of patients for allergen-specific immunotherapy. It is also of a great value for monitoring of the efficacy, immunogenicity and safety of allergenspecific immunotherapy [20, 21]. Cellular allergy testing represents one more *in vitro* allergy diagnostic tool. It expands the tools of allergist to diagnose and monitor allergic diseases. The basophil activation test (BAT) is the most common used cellular allergy tests in routine clinical practice and in research. That test is able to document type I sensitization to a specific allergen, as fraction of blood basophils activated by soluble allergen. Basophil sensitivity can be used for identification the main sensitizer among cross-reacting allergens or allergen preparation as well as for monitoring progress of allergen-specific immunotherapy and anti-

IgE therapy [22–24].

104 Allergen

Determination of a certain biomarkers that are known to be important in pathophysiology of allergic diseases can be a very useful in primary prevention, early intervention and disease course modification [25]. Currently reliable tools that can adequately predict which children will develop asthma are still lacking [26]. Nowadays identification and determination of biomarkers in diagnosis of allergic diseases represent an important step toward better understanding of a great number of different endotypes. Biomarkers are also very important for increasing drug effectiveness through a more individualized therapeutic approach. Discovering novel biomarkers or combining them with the existing one and better understanding of different asthma endo- and phenotypes are important goals in allergy research improving both allergy diagnosis and treatment [27–29]. Fractional exhaled nitric oxide FeNO is considered a very good biomarker of eosinophilic inflammation of lower airways. Many data showed that FeNO is a reliable predictor of corticosteroids responsiveness [30]. The results form the most recent studies indicated that allergen-specific immunotherapy has also an impact on the decrease of eosinophilic airway inflammation [31]. Periostin is a downstream molecule of interleukin (IL)-4 and/or IL-13 has been recently marked as a surrogate biomarker of type 2 inflammation and tissue remodeling in bronchial asthma. It has been shown that serum periostin can predict the efficacy of anti-IL-13 antibody (lebrikizumab) and anti-IgE antibody (omalizumab). Sputum eosinophils are useful for estimating the efficacy of anti-IL-5 antibody (mepolizumab) [32, 33].
