Primary Prevention: The Challenge of the Future

In an attempt to reverse the observed epidemiological trend, primary prevention strategies for decades aimed at avoiding risk factors and inhibiting their mechanism of action. More recently, attempts were initiated to promote protecting factors and stimulate their mechanisms of action.

Alimentary Ways to Protect
For numerous reasons, breast-feeding is the preferred method of infant nutrition; however, there is still controversy as to whether breast-feeding protects against the
development of allergic diseases.

On the basis of the available data, an “Expert Group” of the “European Academy of Allergology and Clinical Immunology” recommends exclusively breast-feeding for 4 to 6 month irrespective of family history of atopy.

For a long time, primary prevention strategies for asthma were almost exclusively focused on allergen avoidance measures early in life, which were supposed to prevent primary sensitization to both food and inhalant allergens.

For several years, the use of hydrolyzed formula was recommended as an alternative for infants, for whom breast milk was not available and who were genetically predisposed to atopic diseases. Indeed, the German Infant Nutritional Intervention (GINI) Study demonstrated that extensively as well as certain partially hydrolyzed formulas compared to unhydrolyzed infant formulas resulted in a lower incidence of atopic eczema during the first 3 years of life. This study still represents the only large and well-designed trial when comparing different formulas in relation to primary prevention of atopic dermatitis and sensitization to food proteins.

More recently, new alimentary strategies to prevent allergic manifestations are being studied. These include supplementation with probiotics (e.g., lactobacilli) or prebiotics (oligosaccharides influencing the intestinal microflora). So far, the information from the initial studies on supplementation with probiotics is inconclusive.
It will be interesting to see the outcomes of well-designed intervention studies focused on the efficacy of this approach.

Endotoxin

Microbial exposures are abundant in these environments and microbial studies investigating stables report a large variety of gram-negative and gram-positive germs as well as a diversity of molds and fungi.
In addition, nonviable parts of microbes, such as endotoxin from the outer wall
of gram-negative bacteria, are found in abundance in stables and also in elevated
concentrations in indoor environments of adjacent farmhouses.
Endotoxins are a family of molecules called lipopolysaccharides (LPS) and are intrinsic parts of the outer membranes of gram-negative bacteria. LPS and other bacterial wall components are found in high concentrations in stables, where pigs, cattle, and poultry are kept engaged with antigen-presenting cells via CD14 ligation to induce strong interleukin (IL)-12 responses. IL-12, in turn, is regarded as an obligatory signal for the maturation of naive T cells into Th1-type cells. Endotoxin concentrations were recently found to be highest in stables of farming families and
also in dust samples from kitchen floors and mattresses in rural areas in southern Germany and Switzerland.

These findings support the hypothesis that environmental exposure to endotoxins and other bacterial wall components is an important protective determinant related to the development of atopic diseases. Indeed, endotoxin levels in samples of dust from children’s mattresses were found to be inversely related to the rate of occurrence of hay fever, atopic asthma, and atopic sensitization.
On the other hand, high exposure to endotoxins may only be a surrogate marker for other bacterial products such as nonmethylated cytidine-guanosine, dinucleotides specific for prokaryotic DNA (CpG motifs). Cell wall components from atypical mycobacteria or gram-positive bacteria, such as lipoteichoic acid, are known to affect immune responses in ways similar to endotoxin.