Is Atopy Per Se a Risk Factor for Having Atopic Diseases?

Taking the former proposal to consider longitudinal studies, to elucidate the attributable risk of different exposures, a cohort of more than 1,000 children was evaluated by their atopic status, and related to asthma, rhinitis, and eczema. Sensitization to dust mites was the strongest independent risk factor for having asthma  to grass pollen for having rhinitis  and to peanut for having eczema. Even though less than half of the original cohort was skin tested at the age of 4, some relevant tendencies were evident: the prevalence and severity of asthma correlated with allergen sensitization, the risk of all allergic diseases increased with the number of positive prick tests, there was a predominance of male sex at this age, but they conclude that only 30–40% of allergic diseases is attributable to atopy, and the rest to the affected organ or other factors. A recent report suggests that asthma attributable to atopy could vary depending on allergen exposure and its modifications because of the environment such as climate.

But atopy alone does not explain much of the real life, where multiple factors could influence the development of atopic diseases, such as respiratory viral infections and the development of asthma. In a cohort of more than 2,000 children, where the presence of current asthma at 6 years of life was correlated with atopy and respiratory tract infections in first year, concluded that both conditions were independently associated with a significant risk of having asthma by the age of 6. Also, maternal feeding evidences a protective behavior.

Another longitudinal study demonstrated the association of infantile chest infections with wheezing and asthma, and the importance of early life atopic status for the presence of wheezing, asthma, and bronchial hyper-responsiveness at 10 years of life. Other conditions such as familiar asthma, early passive smoking, and having eczema at the age of 4 were also significantly associated with asthma and wheezing but not with bronchial sensitivity.
We must preliminary conclude that atopy per se is not enough, neither to express atopic diseases nor to justify the increased incidence of them.

What About Infections and the Hygiene Hypothesis?

In 1989, Strachan  proposed that allergic diseases could be prevented by infections in early childhood, and the transmission of them by unhygienic contact with older siblings. Smaller family size, higher standard of living, and personal cleaning reduced the chances of spreading “protective” infections, originating the hygiene
hypothesis.
A recent comparison of two genetically related but cultural and socio-economic different populations (Russian and Finnish) evidenced higher specific IgE levels in Finnish but more total IgE and specific microbial antibodies in Russians.
Enterovirus infection represented the strongest protective factor against allergen
sensitization.
In this direction, farmers’ children from a rural environment were evaluated for atopic symptoms (by questionnaire) and atopy (by skin test), as well as endotoxin measurement. Compared to non-farmers’ children, they presented significantly fewer symptoms of current asthma (adjusted OR 0.67; 95% CI 0.49–0.91; P = 0.01) and rhinitis (OR 0.50; 95% CI 0.33–0.77; P = 0.002). If having unpasteurized milk
also, a significant reduction of atopy (OR 0.24; 95% CI 0.10–0.53; P = 0.001) and current eczema symptoms were added (OR 0.59; 95% CI 0.40–0.87; P = 0.008), while reducing IgE (P < 0.001) and increasing IFNg (P = 0.02). Pasteurized milk, vaccinations, early use of antibiotics, and the westernized lifestyle with less exposure to infectious agents could contribute to this lack of stimulation, essential in the first years of life to change the initial Th2 profile toward a Th1 just not to favor atopy development.
Ten years ago the hygiene hypothesis was suggested, an extensive analysis was done to determine its current relevance, and the conclusions were:
 (a) atopic diseases, but not necessarily asthma, are highly prevalent in smaller and more affluent families;
(b) the postulate of protective infections against atopy is immunologically plausible; the reversal is inconclusive;
(c) the modulating effects of antibiotic therapy and diet influencing intestinal flora need to be evaluated extensively;
(d) The inverse association of family size and allergic sensitization could potentially help to discern underlying causes of the increasing prevalence of atopic diseases.
However, the Th1/Th2 paradigm and how it fits in the hygiene hypothesis must be analyzed. Table 1 considers how all these factors affect both Th2 and Th1 illnesses, and its scheme outlines factors influencing immune system development at different time points.
In this context, genetically inheritance should be the beginning, while the attributable genetic risk ranges from 30% to 80% depending on the disease considered.
Then, susceptibility to multiple exposures will determine if “western and industrialized world” affects the development of atopic diseases in these individuals.
There, developing countries with the objective of reaching a better quality of life increase their risk as shown by the increased atopic prevalence in people who migrated to developed regions and in urban cities when compared to rural.
As a conclusion, we do not need to go back in evolution, we must maintain the control over infections, but need to clarify the role of each microbial stimulus (especially at the gastrointestinal tract), in parallel with genetic background and every co-factor. Large longitudinal birth cohort studies, getting representative
biological and environmental samples, will help us in the future.

Work Exposure

With an obvious gap in concentration, some same outdoor pollutants could be found at working places. But time and dose exposure could promote the starting of irritant asthma, like sulfite mill workers in whom sulfur dioxide established a risk of four to six times greater for new-onset medical-diagnosed asthma. Not only
pollutants are capable of inducing asthma, instruments and surface cleaners, adhesives and latex particles have been implicated in that process within healthcare workers. The list of demonstrated provoking agents, as well as mechanism involved, goes beyond the present analysis.

What About Environmental Pollution and Work Exposure?

The effects of air pollution have been described some years ago as significantly harmful in children with elevated IgE and bronchial hyper-responsiveness. Airborne particulate of a size of less than 10 μm (PM10), sulfur dioxide, black smoke, and nitrogen dioxide provoked lower airways symptoms in these patients (wheezing
and dyspnea), as well as a decrease in peak expiratory flow greater than 10% while
particulate amounts increased.
PM10, nitrogen dioxide, and carbon monoxide showed a considerable correlation with emergency assistance in children, but not in adults. In children under 5 years, peak carbon monoxide level was predictive of hospitalization because of asthma attack.
Going from an epidemiological to a bio-immunological approach, one of the risk factors that could explain the increasing prevalence of atopic diseases in industrialized countries has been the exposure to diesel exhaust particles, recognized as enhancer of IgE-dependent allergic inflammation, and the consequent
symptoms of asthma and rhinitis. Once again, a recent revision cannot be conclusive in considering these particles as a significant risk factor for having atopic diseases.
About indoor pollution, there is no doubt that tobacco smoke constitutes the key factor to be considered, since it has been implicated in the development of asthma in children and non-smoking adults exposed. About those smoking actively, the RR for incidental asthma was reported as high as 3.9 (95% CI 1.7–8.5).