Examination of allergic disease trends around the globe demands an in-depth study on possible risk factors that can lead to this group of diseases. These risk factors could help understand the varying prevalence rates of allergic disorders between countries that have been observed so far.
A risk factor is defined as;
“An aspect of personal behavior or lifestyle, an environmental exposure, or a hereditary characteristic that is associated with an increase in the occurrence of a particular disease, injury, or health condition” (Dicker, Coronado, Koo, & Parrish, 2006).
For allergies, the risk factors can be divided into two broad categories, host and environmental factors.
The interaction of different host and environmental factors is responsible for the phenotypic expression of allergies. Environmental risk factors are modifiable either through lifestyle or behavioral changes. However, the host factors, which are inherent individual physiological factors, cannot be changed. In case of environmental factors, they typically play a role in sensitization, which leads to the development of allergic disease. Sensitization refers to the human body’s reaction to an allergen in the form of an allergic reaction (Yoo & Perzanowski, 2014). For example, exposures to environmental risk factors like air pollution particulate matter, pollen, certain foods and irritants leads to allergic reactions.
Amongst all the host factors, genetic factors have been found to have the highest influence in developing allergy (Ober & Yao, 2012). Mutant genes and their abnormal byproducts along with epigenetic changes have been found to be associated with allergic manifestations in numerous studies (Holloway, Yang, Rosenwasser, & Holgate, 2011).
These are crucial to develop an understanding of the disease susceptibility. For example, young adults are highly susceptible to sensitization to inhalant allergens. However, with age, this susceptibility has been found to diminish (Halken, 2003). Such genetic factors lead to atopy, where individuals have inherent hyperallergic tendencies.
Genetic host factors
The interplay of multiple genetic factors with the environmental factors impacts the pathophysiology of allergic diseases. The mutant genes inherited by individuals from parents influence the disease susceptibility. The genetically susceptible individuals upon coming in contact with environmental allergens develop the disease. For example, the mutations resulting in loss of function of the gene encoding for filaggrin find the association with atopic diseases (McLean, 2011). Moreover, two independent variants, R510X and 2282del4, have shown a significant association with atopic asthma (Palmer et al., 2006). Scientists have undertaken the comprehensive review of molecular pathways and the genes responsible for pathogenesis. However, specific cellular defects responsible for allergies are yet to be known.
Influence of gender as a factor
The gender-based differences also influence susceptibility to allergies. These differences include the genetic and physio-biological aspects that differ between men and women. These may also involve the difference in environmental exposure to allergens, depending upon socioeconomic status, family roles, the pattern of employment and culture. Thus the gender-based risk factors are divisible into inherent and extrinsic factors.
The biological factors which make the basis for gender difference include hormonal metabolism, immunologic functions, anatomical structure and genetic influences (Setlow, Lawson, & Woods, 1998). For example, It has been stated that females develop stronger immune responses than men, which protects them from infectious diseases. The heightened immunity, however, increases susceptibility to autoimmunity and allergy. Sex difference has also been found to impact the prevalence, severity and incidence of asthma (Laffont, Blanquart, & Guéry, 2017).
Influence of age as a factor
Age factor assumes a significant position with respect to the risk of allergic sensitization and acquiring the atopic disease. The process of aging impacts the bodily functions at both the cellular and systemic level. Also, a range of phenotypic changes in organs and organ system accompanies aging. This causes loss of homeostasis, higher susceptibility to diseases and reduction in the ability to respond to challenges. This remodeling of the immune system and physiological changes increases the prevalence of allergies in aging people (De Martinis, Sirufo, & Ginaldi, 2017).
Environmental risk factors
While genetic factors influence the predisposition of an individual to allergic diseases, they also govern the sensitivity to environmental triggers. With prevalent changes in the environment, changing climate, increased air pollution and exposure to new allergens have led to increased cases of allergy (Jenerowicz et al., 2012). These environmental factors explain the sudden rise in allergies, especially atopic diseases around the globe.
The ‘hygiene hypothesis’ mainly form a part of the reasoning for environmental exposure resulting in atopic diseases in predisposed individuals (Bloomfield, Stanwell-Smith, Crevel, & Pickup, 2006). These environmental factors are also responsible for differential prevalence and incidence of allergies in rural and urban areas. Some of the most common environmental factors are discussed below.
An allergen is any substance capable of triggering an immune response (Blumenthal & Fine, 2014). Common allergens include pollen, dust mites, mold, insect venom, animal dander, medication and various foods. The exposure resulting in sensitization against the proteins found in allergens result in allergic condition. These are divisible into inhaled and non-inhaled allergens, depending upon route of exposure. The genetically disposed of individuals upon exposure, experience IgE and IgG response which result in allergic reactions (Pawankar, Canonica, Lockey, & Holgate, 2011). The tables below show the different type of allergens.
Primary site of exposure
|Pollens||Nose, eyes||Windborne||Up to 30% worldwide|
|Mold spores||Nose, eyes||Windborne||Up to 30% worldwide|
|Dust and storage mite||Nose, lungs||Transient after disturbance||Temperate zones and farming|
|Insects||Nose, lungs||Transient after disturbance||Widespread and common|
|Animal dander||Nose, lungs||Airborne for hours||Common and dependant on exposure|
Table 1: Inhaled allergens as risk factors for allergies (Source: Platts-Mills et al. 2011)
The number of particles that are airborne, time spent outdoors, and efficiency of the indoor environment determines the level of exposure to the outdoor allergens. Also, the sensitization reactions are proposed to occur at certain threshold levels.
Table 2: Non-Inhaled allergens as risk factors for allergies (Source: Platts-Mills et al. 2011)
Non inhaled allergens
|Primary site of exposure||Sensitization|
|Peanuts, tree nuts, egg, chicken, soy, wheat etc||Oral and skin||Variable sensitization, up to 4%. No clear relation with exposure|
|Insect bites, stings, etc.|
|Hymenoptera||Skin and blood circulation|
Air pollution tends to act as an adjuvant for the sensitization reactions. The allergic diseases show a high prevalence in industrialized nations and urban areas, where exposure to air pollutants is higher. The pollutants such as ozone, sulfur dioxide, nitrogen dioxide and diesel exhaust particles are major constituents of air pollution. These particles exaggerate the adverse impact of allergens in allergic individuals (Takizawa, 2011). The studies have also shown a relationship between high pollution levels and mortality rates due to the reduction in lung function (Bayer-Oglesby et al., 2005; Schindler et al., 2009).
Infection as a risk factor
The ‘hygiene hypothesis’ put forward by Strachan in 1989 concerns infections and allergies (Strachan, 1989). As per the theory, exposure to viral and bacterial infections in early childhood, from unhygienic contact with siblings, may confer protection from the development of allergies. However, infections are also found to be responsible for causing allergic diseases. The study by Holt, Strickland, & Sly, (2012) provides evidence for a synergistic effect of mucosal immune response due to infection and allergen sensitization in causing allergic asthma. Atopic dermatitis has also shown a positive correlation with infectious diseases (Wang, 2015).
The discussion of major host and environmental factors has shown the potential of different risk factors contributing to allergy. However, these factors do not operate in isolation, rather interact with each other in stimulating allergic responses. An individual develops susceptibility towards specific allergic disorders pertaining to as the host factors interact with environmental factors.
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