Asthma and the westernization 'package'.

Ten years ago we knew what caused asthma, and we knew how to prevent it. Asthma was an atopic disease caused by allergen exposure. The fundamental aetiological mechanism was that allergen exposure, particularly in infancy, produced atopic sensitization and continued exposure resulted in asthma through the development of eosinophilic airways inflammation, bronchial hyper-responsiveness and reversible airflow obstruction. Asthma prevalence was increasing around the world because of changes in lifestyle and domestic building design that were increasing allergen exposure. The solution was therefore clear: to prevent asthma we needed to prevent exposure to allergens. 1‐3 In recent years it has become increasingly evident that this picture is, at best, too simplistic. 4 Bronchial responsiveness is a poor surrogate measure of clinical asthma and the current evidence is that it has lower validity than standard symptom questionnaires. 5 Less than one half of asthma cases are attributable to atopy and/or eosinophilic airways inflammation, 6 and (nonallergic/non-atopic) neutrophilic airways inflammation may account for the other half. 7 Furthermore, although there are some clear cases of allergen exposure causing asthma in adults in the occupational environment, overall there is little evidence that allergen exposure is a major primary cause of asthma, 8 and even some evidence that allergen exposure early in life may have a protective effect (see below). The ‘established’ risk factors for asthma, including allergen exposure, were ‘discovered’ primarily on the basis of clinical studies and case reports of exacerbations in asthma patients. It is natural for physicians and patients to assume that the factors involved in secondary causation may also be important for primary causation. Once the theory became established it was easy to find ‘verifications’ of the allergen hypothesis, and to dismiss ‘refutations’ as chance findings or as being due to inadequate measurements of exposure and outcome. Of course, there are well-documented instances where allergen exposure does act as a primary cause of asthma, particularly in adults. However, allergen exposure does not appear to be the major primary cause of asthma that it has been assumed to be, nor to account for global patterns of asthma prevalence, or the striking increases in asthma prevalence over time. 9 Westernization and asthma As the ‘established’ asthma risk factors are increasingly being called into question, epidemiological studies are playing a major role in the search for new theoretical paradigms which are more consistent with the epidemiological evidence and which have greater explanatory power. Recent research has therefore shifted attention from allergens that may cause sensitization and/or provoke asthma attacks, to factors that may ‘programme’ the initial susceptibility to asthma, through allergic or non-allergic mechanisms. This also in part involves a shift of attention from risk factors for asthma to protective factors, and the possible role of the loss of protective factors in the global increases in asthma prevalence. Several studies have indicated that certain exposures (in particular of microbial origin) early in life may protect against atopy and asthma which has led to the ‘hygiene hypothesis’. Briefly, microbial exposure may affect T lymphocytes which have an important function in controlling immune responses including (amongst others) help for B cell production of antibodies (IgE,