Lessons from the Developing World: There is more to asthma than atopy

Abstract

Atopic asthma is the most common chronic disease in childhood with high prevalence in many industrialized countries. Recent studies have shown that, in contrast, among non-affluent populations the association between asthma and markers of atopy are not as significant as those observed in most Western countries. However, overall asthma prevalence in Latin America has been shown to be higher than expected. This finding may be in line with the concept of the ‘hygiene hypothesis’, in which a lower risk of asthma and allergy development may be associated with early life exposures to a high burden of infections (bacteria, viruses and parasites). On the basis of this hypothesis, a strong Th1-immune stimulation by microbial exposition and its products in early childhood may inhibit skewing towards Th2 immunity in atopic predisposed children. Consequently, other asthma phenotypes may emerge in different environmental settings, especially among nonaffluent populations. A fact that has been noticed is that the impact of hygiene seems to be mostly associated with markers of atopy instead of asthma-like symptoms. There is no consensus on why there is a greater prevalence for non-atopic asthma in non-affluent countries, but one possible explanation is that the role of crowding in poor urban environments as well as the early introduction of nursery care for children in the first years of life may facilitate an early and aggressive milieu mediated by respiratory viruses and environmental pollutants. A series of prospective longitudinal studies suggest that there is a significant association between early life bronchiolitis and persistent respiratory symptoms/asthma. These studies and other recent data, mostly experimental, suggest that some viruses, especially RSV and RV, may affect the airways, initiating a cascade of events (inflammatory or not) that seem to facilitate the persistence of symptoms. The evaluation of post-viral or even premorbid/predisposing effects associated with airway hyper-responsiveness or with lung function development seem to in part explain the persistence of respiratory symptoms in a complex model aiming to detect mechanisms associated with asthma, independent of atopy. It is well known that atopy is a main driving force in this explanatory model that leads to asthma, and these children are at greater risk of developing childhood asthma than non-atopic subjects who wheeze. Yet the morbidity associated with non-atopic/non-eosinophilic asthma and the size of the population possibly affected by this phenotype is beginning to be recognized as very important for understanding mechanisms of disease. Possible future asthma preventing strategies for affluent or nonaffluent populations depend on a better understanding of these phenotypes, that are far from exclusive, since they express a balancing act of environmental impact on the airways, and how the response is affected by predisposing genetic factors.