COMMENTARY

More Hay, Less Hay Fever?

William T. Basco, Jr., MD

Disclosures

April 25, 2011

Exposure to Environmental Microorganisms and Childhood Asthma

Ege MJ, Mayer M, Normand AC, et al
N Engl J Med. 2011;364:701-709

Study Summary

Previous research shows that children exposed to microbes early in life are less likely to develop asthma as they age. Ege and colleagues went beyond existing studies and evaluated the degree of children's microbial exposure and its correlation with development of symptoms of asthma and atopy. Their analysis included children from 2 studies. The Prevention of Allergy -- Risk Factors for Sensitization Related to Farming and Anthroposophic Lifestyle (PARSIFAL) study included 6843 children recruited in 2000-2002 in southern Germany. The Multidisciplinary Study to Identify the Genetic and Environmental Causes of Asthma in the European Community (GABRIELA) cohort included 9668 children recruited in 2006-2007 in Austria, Germany, and Switzerland. Dust samples from the households of some of the children in each cohort were obtained for analysis (489 samples were collected from the first cohort and 444 were collected from the other). Collection methodology differed between studies, with one collecting dust from the children's mattresses while the other collected airborne dust samples.

Farm exposure was 52% in the PARSIFAL cohort and 16% in the GABRIELA cohort. Demographic, historical, and symptom ascertainment was by questionnaire, and surveys assessed farm exposures. For the analysis, children were divided into those who lived on a family-run farm and those who did not. In both cohorts, the prevalence of asthma was approximately 10%. Children were labeled as having asthma if they had either a physician diagnosis of asthma or had at least 2 documented episodes of wheezing. In both studies, children with microbial exposure above predetermined levels were considered exposed.

The primary outcome of interest was the diagnosis of either asthma or atopy, adjusting for farm exposure. Overall, children living on farms were less likely to have asthma in both of the study cohorts. In the PARSIFAL cohort, the odds ratio (OR) for having asthma was 0.49 (95% confidence interval [CI] 0.35-0.69); and in the GABRIELA cohort, the OR was 0.76 (95% CI 0.65-0.89). With respect to atopy, farm exposure appeared to be even more protective, with adjusted ORs of 0.24 in one cohort and 0.51 in the other. More children in farm households had exposure to the bacteria or fungi measured by the investigators, and these children had an increased diversity of exposure as measured in part by the number of different bacteria or fungi recovered in the dust samples. For example, the percentages exposed to gram-positive cocci, gram-positive rods, Aspergillus versicolor, and other yeast were all higher among farm children, in some cases by a factor of 2 (exposure frequencies twice as high among farm children compared with non-farm children).

The investigators calculated a diversity score for each child on the basis of the number of microbes to which each child was exposed. In both study cohorts, the percentages of children who had asthma declined in an almost linear fashion with increasing numbers of bacteria or fungi recovered from dust samples. The investigators did not observe a dose-response association between microbial diversity exposure and atopy. The investigators also demonstrated, through factor analysis, that certain species were the predominant drivers of the associations with developing asthma. They concluded that children of these cohorts who live on farms were protected from developing asthma and atopic disease. The investigators mentioned that even though the samples for exposure were obtained from inside the children's houses, these samples consistently demonstrated higher overall levels of microbial exposure and a greater variety of exposure of children living on farms, suggesting introduction of microbes from the external environment to the home.

Viewpoint

These data add to growing evidence that early exposure to nonpathologic microbes may actually be protective against developing the spectrum of atopic disease. In an editorial commentary,[1] James Gern, MD reviewed other data that demonstrated similar associations and potential mechanisms by which early exposure to microbes may produce the protective effect. This study adds strength to this body of evidence by demonstrating a dose-response effect, an important finding given that the data are nonexperimental and show only association. It is more challenging to think about how these findings might apply to daily practice, considering that increased farm microbe exposure is not the same thing as reducing household cleanliness in an urban environment in attempting to increase a child's microbial exposure. In fact, current studies suggest that certain microbes actually drive the effect, and if those microbes are not present in urban settings, then altering urban families' household cleanliness may not provide the same benefit as exposure to the actual farm microorganisms. In any case, it is fascinating to see how our understanding of asthma and atopic disease triggers has evolved from trying to limit early exposures to potential antigens to a consideration of whether we should actually be more permissive in early exposure, hoping to avoid later sensitization.

Abstract

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