Abstract
Allergic diseases such as asthma are influenced by a combination of genetic and environmental factors. In genetically susceptible individuals, contact with an allergen triggers a chain of reactions that involve a number of blood and some tissue cells. These reactions are accompanied by secretion of chemicals that initiate symptoms of allergic diseases. Hygiene hypothesis is an attempt to explain the high number of allergic diseases noted in developed countries compared to poor, less developed countries. It claims improved environmental and domestic hygiene in these regions has resulted in weaker immunity in children. This predisposes them to allergic diseases later in life. An increasing number of researches continue to reinforce this theory. However, most are inconclusive in their findings. The developments in the hygiene theory present various challenges to public health professionals. One is that it can cause change in public attitude about hygiene culminating in undesirable effects. Nevertheless, the theory can be a helpful instrument for developing selective hygiene interventions such as vaccine therapies with the ‘right’ immune-boosting microbes.
Introduction
Allergic diseases are one of the most common diseases in developed western countries (Kumawat & Jha, 2011; Marra, et al., 2009). They are complex inflammatory diseases whose development has been attributed to an interaction of genetic and environmental factors (Garn & Renz, 2007 ;Meng & Rosenwasser, 2010 ; Mutius, 2010).
Allergic asthma is a chronic inflammatory disease that results in obstruction of airways brought about by exposure to an allergen (Meng & Rosenwasser, 2010). It can be reversed with or without therapeutic intervention. Asthmatic allergy occurs when a genetically predisposed person comes in contact with an allergen. Upon contact with an allergen such as molds, pollen or animal dander, the body’s B-Lymphocyte cells produces Immunoglobulin E (IgE) that binds to its corresponding receptors located on mast cells of tissues and basophils found in blood. Studies have linked the production of IgE to the influence of Interleukin – 4 on B-cells (Lambrecht & Hammad, 2009). This binding stimulates the mast cells to release chemicals, such as histamine, serotonin, proteoglycans, serine protease, leukotriene C4 and heparin (Kumawat & Jha, 2011). These resultant chemicals in turn bind to their corresponding receptors in other cells and under a number of interleukins lead to pathologic effects such as inflammation and tissue redness. Other reactions are mucus hypersecretion and bronchial muscle contraction (Kumawat & Jha, 2011). IL-5 action on bone marrow projenitor cells is said to contribute to the inflammation of the airways which is also accompanied by infitration of helper T-cells (Lambrecht & Hammad, 2009). Mucus secretion that normally blocks the airway has been cited as the effects of IL-4 and IL-3 on the epithelia (Lambrecht & Hammad, 2009). Interleukin 13 action on bronchial smooth muscles has been associated with increased bronchial contraction (Lambrecht & Hammad, 2009). These reactions may result in difficulty in breathing and wheezing, the major symptoms of allergic asthma.
The etiology of allergic and autoimmune diseases such as asthma has been explained by a number of hypotheses. Among the prominent ones is the hygiene hypothesis. This theory was developed by Strachan in 1989 after studying the relationship between hay fever and the number of older siblings for over 17,000 British children born in 1958 (Okada, Kuhn, Feillet, & Bach, 2010). According to this theory cases of allergic and autoimmune diseases are higher in areas with high living standards compared to areas with low living standards. It asserts that high standards of hygiene observed rich nations denies infants exposure to disease causing microbes or parasitic infections confering in them high susceptibility to allergic and autoimmune disorders later in life. Hygiene practices common in developed countries such as overuse of antibacterial soap and isolation have been cited as potentially hindering the development of robust immune system and increasing the susceptibility to allergic diseases. There are a number of mechanisms that have been put forward to explain the hygiene hypothesis.
The T helper cells type 1 (Th1) –T helper cells type 2 (Th1/Th2) balance is one of immunological concepts explaining the hygiene hypothesis (Mutius, 2010; Douwes, et al., 2008). In this mechanism, infantile exposure to disease pathogens result in strong expression of anti-allergic Th1 immunity thus suppressing Th2 immunity which is present at birth. The Th1/Th2 balance is partly mediated by IgE secreting IL-4 and IL-13 that favours expression of Th2 immunity associated with allergies and asthma (Mutius, 2010). The Th1 cells are associated with the production of IL-2 and interferon ɣ that confer cell mediated immunity while Th2 cells produce allergy and asthma triggering IL-2, IL-5, IL-6 and IL13 (Okada, Kuhn, Feillet, & Bach, 2010).
Current and recent research on the hygiene hypothesis
There is a growing body of research on various aspects of the hygiene hypothesis. This section examines a few epidemiological studies conducted within the past five years.
In 2009, a large cohort study set to investigate the effect of antibiotic exposure in early age and development of asthma found a positive association between antibiotic use in early years of life and development of childhood asthma (Marra, et al., 2009). In this study exposure to antibiotics in early childhood was determined using hospital data from 1997 to 2003 (N=251 817). The incidences of asthma were determined in both exposed and unexposed members in the first 12 months of life (Marra, et al., 2009). Cox proportional hazard models were used to adjust for possible confounders and in obtaining hazard ratios. Results showed antibiotic exposure in infancy could influence development of asthma in early childhood (Marra, et al., 2009). In addition, it was determined the risk increased with the level of antibiotic administered (Marra, et al., 2009).
Prenatal microbial exposure has been associated with lower risk of childhood asthma, hay fever and eczema in farmers’ children (Douwes, et al., 2008). However, permanent exposure is necessary to maintain protection especially in allergic asthma (Douwes, et al., 2008). In a randomized cross-sectional study to assess underlying factors contributing to low cases of allergic diseases in farmers’ children, the symptoms of asthma, hay fever and eczema in addition to prenatal exposures were assessed in 1,333 farmers children and 566 reference children between 5-17yrs old (Douwes, et al., 2008). There was a strong association between prenatal exposure and asthma symptoms (OR 0.5, 95% CI 0.33-0.76). Also, the study showed that there was generally low incidence of asthmatic symptoms and eczema in farmers’ children. For asthma, it was also found that persistent exposure was necessary to maintain protection.
The association between microbial exposure in early stages of life and high sensitivity C-reactive Protein (CRP ), a major inflammation signatory biomolecule was examined in a longitudinal study using prospective data from a birth cohort in the Phillipines (N=1461) (McDade, Rutherford, Adair, & Kuzawa, 2010). The Study began prenataly in 1983 and continued after birth upto 2007. A series of logistic regression models were used to predict and evaluate the concentrations of CRP. A negative association between early childhoood microbial exposure and CRP production in late childhood was found further reinforcing the hygiene hypothesis.
Implications for public health
Studies probing the hygiene hypothesis are important in may ways. Although not conclusive , they make immense contribution to the existing body of knowledge on allergic diseases such as asthma. This knowledge base is critical in formulating appropriate intervention measures. Public health policy makers may also utilise the information in making informed decisions especially on maternal and child care. Potential application areas may include development of vaccines with ‘beneficial microbes’ in addition to developing selective hygiene interventions. Health professionals may also be required to redefine hygiene as the findings of these researches can alter public attitudes and understanding of hygiene culminating in undesirable outcomes. Findings such as that by Fawziah and others (2010) call for reexamination of hygiene measures such as frequent and thorough washing of hands with antibacterial soaps and antibiotic treatments commonly advocated by public health bodies. In light of the findings of Douwes and his team, questions remain as to whether children – animal/pet contact should be encouraged or discouraged. Although not yet elucidated, investigator also need to identify the nature of exposure favouring development of a robust immunity. This will enable the formulation of hygiene policies that wil not compromise protection against dangerous pathogens.
References
Douwes, J., Cheng, S., Travier, N., Cohet, C., Niesink, A., McKenzie, J., et al. (2008). Farm exposure in utero may protect against asthma, hay fever and eczema. European Respiratory Journal, 32(3), 603-611.
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Kumawat, M., & Jha, A. (2011). Food allergenicity and associated risk factors:an overview. Journal of Drug Delivery & Therapeutics, 1(1), 40-47.
Lambrecht, B. N., & Hammad, H. (2009). Biology of Lung Dendritic cells at the origin of Asthma. Journal of Immunology, 31, 412-424. doi 10.1016/j.immuni.2009.08.008
Marra, F., Marra, C. A., Richardson, K., Lynd, L. D., Kozyrski, A., Patrick, D. M., et al. (2009). Antibiotic use in children is associated with increased risk of Asthma. Pediatrics, 123(3), 1003-1013.
McDade, T. W., Rutherford, J., Adair, L., & Kuzawa, C. W. (2010). Early origins of inflammation : Microbial exposures in infancy predict lower levels of C-reactive protein in adulthood. Proceedings of the Royal Society Biological Sciences, 277, 1129-1137.
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Mutius, E. V. (2010). Chronic inflammatory disorders: Farm lifestyles and the hygiene hypothesis. Clinical and Experimental immunology, 160, 130-135.
Okada, H., Kuhn, C., Feillet, H., & Bach, J. (2010). The ‘hygiene hypothesis’ for autoimmune and allergic diseases: an update. Clinical and Experimental immunology, 160, 1-9.