**1. Introduction**

#### **1.1. Epidemiology of asthma and rhinitis**

With a global prevalence of 6.9% (ranging from 3.8 in Asia-Pacific and Northern and Eastern Europe to 11.3% in North America), asthma is one of the most common chronic diseases in children, adolescent, and adults [1]. The prevalence rate of allergic rhinitis, asthma, and eczema in Serbia has been investigated as a part of the International Study of Asthma

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and Allergies Phase Three. The study included around 14,000 from 5 regional centers different geographical and urban characteristics (children both from urban and rural areas participated). Investigators analyzed the prevalence of allergic diseases in two age groups (the first one preschool children aged 6–7 years old and the second one children between the age of 13–14 years old. The prevalence of asthma was 6.59% in younger age group, whereas the prevalence in older age group was around 5.36%. Note that 7.17% of preschool children and 14.89% of school children were diagnosed allergic rhinitis. Overall, asthma prevalence was 5.91%, rhinitis 11.46%, and eczema 14.27% [2]. The growing worldwide burden of allergic diseases is properly defined as the "allergy epidemic." The German epidemiological Multicenter Allergy Study (MAS) suggested an age-related evolution of atopic and allergic diseases, usually named "atopic march." In fact, on epidemiological bases, infantile eczema and food allergy usually precede the onset of allergic airway disease (rhinitis and asthma). It is also interesting to point out that unlike other common chronic diseases such as diabetes mellitus or hypertension, it is well established that the development of allergic diseases start just after birth or according to some authors maybe earlier in prenatal period [3]. The incidence of asthma is the highest in preschool and early school age with an improvement in symptoms and a decrease in prevalence afterwards, but with one more pic in incidence in adolescents' period especially in female teenagers mainly due to hormone disturbance. It is well known that allergic diseases are multi factorial which means that in their pathophysiology both genetic and environmental factors are included. Atopic family history is one of the most important risk factors for the development of asthma. MAS cohort study analyzed the main risk factors for persistent asthma/wheeze in an early adolescent's period. According to the results from this huge study wheezing before the age of 3 as well as wheezing after the age of 6, accompanied with early atopic dermatitis, positive family history of atopic diseases and positive allergy tests, particular to perennial allergens represent the main risk factors [4, 5].

Although according to birth cohort studies data we are aware that genetic burden has an important influence in allergies development and despite lots of efforts, we have still failed to identify responsible genes. Many factors in the environment contribute to the development of allergies (e.g., diet, immunizations, antibiotics, pets, and tobacco smoke), but we do not know how to modify the environment to reduce the risks [6]. According to several epidemiological studies, a decline in microbial diversity was proposed to have an important role in allergic epidemic, best summarized in hygiene hypothesis, and nowadays defined as "biodiversity hypothesis." Identification of prenatal and early postnatal risk factors is of a great importance for early prevention and successful intervention. Two recent studies showed that reduce food diversity in early childhood can be associated with atopic sensitization andallergic diseases later on. It is also suggested that high "antigen burden" in early life can be a protective factor necessary to "educate" the immune system and to prevent childhood allergic diseases. Early allergy prevention that includes: administrations of probiotics to pregnant mothers and to high-risk children, oral or intranasal extracts, and earlier introduction of foods is still matter of a debate due to conflicting results [7, 8]. Despite many different options are currently available for the diagnostic workup and management, the burden of allergic airway diseases still represents a major health problem in childhood. It is a very well known that allergic diseases are multifactorial in terms that both genetic and environmental and risk factors are involved in its pathogenesis. Taking about different endo- or phenotype is very common when we analyze these diseases. Looking for a better quality of life (QOL) and disease of overall morbidity and mortality rate seek further investigation on every single individual risk factor that can have even the smallest impact on the disease development. Searching for a new and more individualized treatment for allergic diseases most of current research is focusing on the identification of biological and clinical predictive markers of allergy and asthma onset [9].
