Epidemiology of allergic disorders – risk factors and the allergic march
Over the years, we have seen the rise of allergies. More people have been affected by this and is now dubbed as the most common chronic disorders affecting adults and children alike. Among the risk factors of allergies is exposure to the allergen. But one of the most prevalent concepts in allergy development remains to be the hygiene theory, wherein it was made evident that exposure to allergens may not be as harmful as we think but may help with the tolerance of our immune response and later lessens risk of allergy development.
Key messages:
• In developed countries, one in three children suffers from at least one allergic disorder.
• Although exposure to allergens has been considered to be an important factor in the past, it is now clear that early exposure may not be harmful.
• Living on a farm and exposure to farm animals is associated with protection against allergies. Such protection has been linked to the exposure to environmental microbes which may have the potential to modulate the early immune system so as to prevent the subsequent development of allergic disorders.
Allergic disorders have become the most common chronic disorders affecting both children and adults. In developed countries, one in three children suffers from at least one allergic disorder.1 Food allergy and infantile eczema are frequently the first manifestations of a life-long problem of allergies. Allergic rhinitis and asthma usually manifest at 3 to 5 years of age.
Such sequence of manifestations of allergic disorders has been described as the allergic march. Over the past 3 decades, major advances have been made in terms of the treatment of established allergic disorders. These advances include the development of different preparations of steroid delivered typically onto the skin or locally into the nostrils or the lower airways so as to minimize the systemic side effects.
Many preparations of biologics are now available for severe and refractory asthma or atopic dermatitis. Recent attention has shifted to the development of potential primary preventive treatments, such as the use of infant formula which may facilitate protection against allergic diseases.2
However, the exact causes of these allergic disorders remain unclear. It is now widely accepted that the manifestations are due to complex interactions of genetic and environmental factors (Figure 1). Although exposure to allergens has been considered to be an important factor in the past, it is now clear that early exposure may not be harmful. In the case of peanut allergy, evidence revealed that early exposure was found to be beneficial in preventing subsequent manifestations of peanut allergy in high risk infants.3
Figure 1: The complex interplay between genetic, epigenetic and environmental factors in development of allergic disorders. Convergence of these factors leads to the clinical phenotypes and molecular endotypes of allergic disorders. The measures combating the COVID-19 pandemic will have potential long term consequences affecting the early microbial exposure of infants. The public health measures are likely to affect the subsequent development of allergic diseases.
Furthermore, early exposure to a wide variety of respiratory viral or bacterial infections through attendance of day care, contacts with older siblings, or living on a farm may alter the airway immunological response and reduce the potential to develop allergic conditions such as asthma.
Early studies in the rural environment across the world consistently documented that living on a farm and exposure to farm animals were associated with protection against allergies. Such protection has been linked to the exposure to environmental microbes which may have the potential to modulate the early immune system so as to prevent the subsequent development of allergic disorders.4
This concept, termed as the hygiene hypothesis, has led to several clinical trials testing the possibility of primary preventive treatment, such as the MARTHA Trial, evaluating whether minimally processed farm milk may prevent allergies.5
The use of various metabolites such as short-chain fatty acids is also being tested as a potential factor facilitating immunological tolerance.
The Covid-19 pandemic has drastically changed the behaviour of social interactions. Along with hygiene measures and school closures, it is highly likely that microbial exposure of infants born in the past 2 years have been exposed to unusually sterile environments. It is too early to tell how such changes may affect this cohort of children given the relatively limited microbial exposure in early life. Clear understanding of how the microbes and their metabolites interact with the immune system will be crucial for the development of primary preventive treatments for allergies in the near future.
References
1. Wong GW, Leung TF, Ko FW. Changing prevalence of allergic diseases in the Asia-pacific region. Allergy Asthma Immunol Res 2013;5:251-7.
2. von Berg A, Filipiak-Pittroff B, Schulz H, Hoffmann U, Link E, Sußmann M, Schnappinger M, Brüske I, Standl M, Krämer U, Hoffmann B, Heinrich J, Bauer CP, Koletzko S, Berdel D; GINI plus study group Allergic manifestation 15 years after early intervention with hydrolyzed formulas--the GINI Study. Allergy 2016;71:210-9.
3. Du Toit G, Roberts G, Sayre PH, Bahnson HT, Radulovic S, Santos AF, Brough HA, Phippard D, Basting M, Feeney M, Turcanu V, Sever ML, Gomez Lorenzo M, Plaut M, Lack G. Randomized trial of peanut consumption in infants at risk for peanut allergy. N Engl J Med. 2015 Feb 26;372(9):803-13.
4. Deckers J, Marsland BJ, von Mutius E. Protection against allergies: Microbes, immunity, and the farming effect. Eur J Immunol 2021;51:23872398.
5. MARTHA Trial. Accessed 5 May 2022. https:// www.martha-studie.de/english-version/
