Interactions between respiratory tract infections and atopy in the aetiology of asthma: Fig. 1.—

Abstract

The prevalence of asthma, in particular atopic asthma, has markedly increased in recent years. Accumulating evidence suggests that environmental factors associated with allergic sensitization and exposure to microbial stimuli during infancy and early childhood, are associated with these changes in prevalence. However, considerable controversy surrounds the role of microbial agents, as evidence has been presented for both positive and negative effects in this context.The review below focuses upon interactions between immune competence during infancy, the development of T-helper (Th)1-polarized versus Th2-polarized memory against inhalant allergens, and susceptibility to virus infection. In particular, recent finding are highlighted which suggest that delayed postnatal maturation of Th1 function is associated with increased risk for early postnatal sensitization to inhalant allergens, and also with risk for viral bronchiolitis during infancy.Variations in the kinetics of postnatal maturation of T-helper 1 function may in part be attributable to polymorphisms in the CD14 gene, which influence host responsiveness both to bacterial as well as viral stimuli. It is evident from a wide range of studies carried out in different geographical areas, that the prevalence of allergic diseases, and in particular atopic asthma, has increased markedly over the last 2-3 decades. Moreover, the increases become evident in successive birth cohorts during early childhood. It is also generally accepted that "diagnostic shift" is not a significant factor in these changes. Accordingly, given the timeframe over which the changes have occurred, the responsible factor(s) must be environmental, presumably interacting with one or more susceptibility genes.The search for the relevant genetic and environmental factors continues, and a variety of potential candidates have been identified. Prominent amongst these are factors related to respiratory infections, particularly those occurring in childhood. Paradoxically, these infections have been invoked both as potential protective factors in relation to asthma/ allergy development, and as triggers of asthma exacerbations in atopic asthmatics. The mechanisms by which these effects may be mediated are incompletely understood; however, recent findings suggest some intriguing new possibilities, which are discussed in this review. T-cell immunity to inhalant allergens: the basis of variations in responder phenotype within the adult populationThe epithelial surface of the upper and lower respiratory tract are continuously exposed to an array of pathogenic and nonpathogenic airborne antigens, and the induction and local expression of local T-cell immunity must accordingly be tightly controlled, in order to avoid the pathological consequences of chronic T-cell-driven inflammation. While it is highly plausible that resistance to airborne pathogens is a direct function of the speed of mobilization and the intensity of expression of local innate and adaptive immune mechanisms in the lung, the conve...

Induction and Inhibition of the Th2 Phenotype Spread: Implications for Childhood Asthma

“…Recent epidemiological studies have indicated that the key events essential for the development of persistent allergic asthma, such as contact with aeroallergens, occur in early childhood (1, 2, 52). There is also mounting evidence that the basis of Th2 memory against these allergens and the subsequent clinical outcome (e.g., the allergic march) are generated during these early years (53)(54)(55). Based on the results of the current study, we propose that the phenotype spread, or a similar mechanism, is responsible for the accelerated development of the allergic/asthmatic phenotype in a susceptible individual in early childhood.…”

Asthma and atopy – the price of affluence?

“…exposure to a wide spectrum of microorganisms from diverse sources). The immunological basis and the mechanisms that are thought to operate in this immunomodulation, have been discussed in detail in several recent reviews and will not be reiterated here (49)(50)(51)(52)(53)(54). In addition, a number of animal experiments have provided support for the hygiene hypothesis (55)(56)(57)(58), but these data are also beyond the scope of this review.…”

Nucleotide-Binding Oligomerization Domain-Like Receptors: Intracellular Pattern Recognition Molecules for Pathogen Detection and Host Defense

“…Several Nod1 polymorphisms have been associated with the development of atopic eczema and asthma, as well as with increased levels of serum IgE in several human populations (60,61). The link between Nod1 and asthma is intriguing in that microbial exposure in childhood is known to protect against the development of disease (62). Thus, it is possible that cytosolic recognition of bacterial products via Nod1 in the skin and mucosal surfaces regulates directly or indirectly Th2 polarization and IgE levels.…”