Risk factors for the development of atopic disease in infancy and early childhood

The etiology of allergic diseases, including asthma, allergic rhinitis, and atopic dermatitis, is multifactorial, involving interaction of both genetic and environmental factors [1]. The prevalence of allergic diseases has doubled in the last 3 decades. especially in Western countries [2]. This sudden rise can not be explained by genetic factors and indicates that environmental factors play a crucial role in the development and clinical expression of allergic disease [3]. Various recent immunological and epidemiological studies have provided more insight into the basic patho-physiological mechanisms and genetic- and environmental risk factors for the development of allergic disease. It is clear that most children with allergic disease started to have symptoms in early life, and that early life influences are critically important in the development of allergic disease [4, 5]. A key feature in established allergic disease is the production of allergen specific IgE and the development of allergic inflammation with influx of eosinophils, basophils, mast cells and T-cells in the tissue [3]. The aims of this thesis (chapter 3) are: (1) to evaluate the role of various environmental factors on the development of symptoms of allergic disease; (2) to provide more insight in the immunological processes that result in the development of allergic disease in early childhood. In chapter 2, the literature on the development of allergic disease is reviewed. Special emphasis is put on exposure to indoor allergens and the role of microbial stimuli during the first years of life in relation to the development of allergic disease. One of the major difficulties in immunological and epidemiological studies on the development of allergic disease is the lack of generally accepted definitions. especially for asthma. We therefore started with evaluating the prognostic value of various respiratory symptoms in early life for the development of allergic disease in later childhood. In addition, the diagnostic criteria for asthma that were used in large prospective birth cohort studies on the development of allergic disease were reviewed (chapter 4). In chapter 5, the study designs of the Prevention and Incidence of Asthma and Mite Allergy (PIAMA)- study and the Virus Mediated Allergy (VIGALL)-study are described. T -cells and other inflammatory cells communicate with each other by secreting cytokines and chemokines [6]. By quantifYing these proteins in children with various phenotypes of allergic disease, more insight can be obtained in the basic immunological pathways involved in the development of allergic disease. In chapter 6, we describe the association between a variety of serum markers at age 1 and the development of respiratory and skin- symptoms in the first 2 years oflife. Various risk factors for the development of allergic disease have been proposed, such as: male gender, formula feeding, exposure to environmental tobacco smoke during pregnancy, exposure to indoor allergens and a lack of microbial stimulation [7-12]. Primary prevention should be the ultimate goal for clinicians and researchers in the field of allergic disease. In chapter 7 we present the first results of a double blind placebo-controlled trial which aimed at reducing the exposure to HDM-allergen starting in the third trimester of pregnancy. In chapter 8 the role of viral upper- and lower respiratory tract infections on the development of the infants immune system is studied. In addition, the gene (parental allergy) by environmental (daycare, having siblings) interaction in the development of upper and lower respiratory tract infections are investigated. Finally. in chapter 9, we explore the role of ethnicity in the development of respiratory and skin symptoms.

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