Asthma and Allergic Disease

Biological Basis of Asthma and Allergic Disease

Asthma and allergic disease are multifaceted genetic traits triggered by environmental factors in genetically susceptible individuals who are genetically susceptible. The prevalence of asthma in the United States has been on the rise for over 20years such that one out of six people are diagnosed with asthma and most of them are children (Umetsu, Meyer, & DeKruyff, 2007). Thus, this increase seen in children in developed countries has been contributed to the decline in infection during childhood, not attributed in the polymorphic genes, which regulate allergic diseases (Umetsu, Meyer, & DeKruyff, 2007; Maria Yazdanbakhsh, Peter G. Kremsner, Ronald van Ree, 2002). the inappropriate immunological reactions to harmless antigens driven by a TH2-mediated immune reaction is the of allergic disease. Thus, This immunological reaction explains the functional TH1 and TH2 cells, which displays a polarized cytokine profiles (Maria Yazdanbakhsh, Peter G. Kremsner, Ronald van Ree, 2002). Several bacteria and viruses extract a TH1-mediated immune reaction that down-regulates the TH2 reaction. However, the environment and genetic factors in combination results in the production of a Th2-biased immune reaction, and the overproduction of Th2 cytokines (such as IL-4, IL-5, IL-9, and IL-13). Which in turn synchronize the inflammation in allergy and asthma by augmenting isotype switch to IgE, thus, boosting “the growth of eosinophils, basophils, and mast cells, and causing airway hyperreactivity (AHR), a cardinal feature of asthma” (Umetsu, Meyer, & DeKruyff, 2007).

“Hygiene Hypothesis”

The ‘hygiene hypothesis' was first proposed by Strachan in 1989 which suggests that lack of exposure to infections and unhygienic contact with older siblings leads to the development of allergic diseases (Mutius, 2007). Further, with the improvement in hygiene in developed countries, coupled with the improved public health measures and the introduction of vaccines and antibiotics, that helped in the reduction in the occurrence of infections that normally would have stimulated the immune system in some unclearly understood way that alleviates against asthma and allergies (Umetsu and DeKruyff, 2006). The first proposed mechanism of action, which was first proposed about “hygiene hypothesis” argued that deficiency in the stimulation of TH1 reaction of the immune system lead to the overactive TH2 reaction that in turn led to allergic illnesses. However, there are still some lacking concepts for the actual cause of the allergic disease different pieces of a multifaceted interaction between a host's immune system, characteristics of the attacking microorganism, different environmental exposure, and the relationships between a genetic background and a range of exposures become apparent leading to asthma and allergic disease ( Mutius, 2007).

Recent research

A case-control study was conducted in Norfolk, UK on the effects of hygiene hypothesis on asthma and allergic disease. The study included 602 children ages 1 to 5 years old. Both cases and controlled subjects were identified using UK Diagnostic Criteria for allergic dermatitis (AD) and a variety of direct and indirect methods to measure any exposure to infection during infancy. The result revealed that reduced odds of AD was related with rising birth order ( thus, the OR for one older sibling was 0.59, with a 95% Confidence Interval of = 0.42, to 0.84 and for more that 2 older siblings OR = 0.49, 95% Confidence Interval = 0.31to 0.77). however, there was no significant reduction in AD found. The study concluded that the increased exposure to infection could not elucidate the reduction of risk of AD in second and subsequent siblings. These finding cast uncertainty on the hygiene hypothesis as an underlying explanation for AD in children (Gibbs et al, 2004).

Another cross-sectional questionnaire study that included 1,595 subjects was conducted among rural adults aged 18 to44years old. During the first 3 years of life 37 percent of them lived on the farm, these groups were referred to as "farm subjects". A randomize sample was used to measure the bronchial hyper-responsiveness (BHR) to methacholine and sensitization, and lung function. The purpose of the study was to examine the differences between farm and nonfarm subjects. The result of the study revealed among the farm groups, sensitization against allergens inhalant (odds ratio (OR) 0.7 with a 95% confidence interval (CI) of 0.6 to0.9), and asthma diagnosis (OR = 0.7 confidence interval = 0.4 to 1.1) had lesser allergens compared to nonfarm groups. Stratifying for sensitization, farm groups exhibited a lesser OR of asthma diagnosis (0.5 CI = 0.3 to 1.0) and a non significantly decreased OR of BHR with sensitization (0.8 CI = 0.5to1.1). the researchers concluded that there was lower prevalence of respiratory allergies and report of asthma symptoms and diagnosis exhibited among subjects who grew on the farm. Although no difference in the prevalence of bronchial hyper-responsiveness could be found between the farm and nonfarm groups (A. Schulze et al, 2007).

Public Health Application

Both of the studies above concluded that childhood exposure to infections could aid in protecting against asthma and allergic disease, which suggest that reduction in infections exposure could have played a part in recent rise in the occurrences of asthma and allergies diseases in the US. Thus, both studies are consistent with the hygiene hypothesis theory, which argued that the improvements in public health and hygiene reduced stimulus by microrganisms in the environment, could have influenced the immune reaction in childhood as aconsequence increased the predisposition to asthma and allergic disease (Maria Regina Alves Cardos et al,2004). As a public health official and policy maker understanding the immunological basis of the hygiene theory, which explains a shift from the Th2 to a Th1 type pattern, of the immune response during childhood that results in reduced frequent allergic responses. It explains that the immune response during childhood is based on a predominance of cytokines of the TH2, which is likely to augment IgE, and hyper-reactivity of the respiratory tract (Umetsu, D. T., Meyer, E. H., & DeKruyff, R. H. (2007).

I would recommend the development of asthma vaccine for all ages. These vaccinations can be used to selectively stimulate allergen-specific Th1 reaction. and development of novel stimulation therapy for children that can stimulate the creation of IL-12, IL-18, and IL-2 in triggering the Th1 immune reaction in the lung. in so doing could prevent “children from developing allergen-specific Th2 type cells during the first months and years of life, which are believed to be the most critical for the development of asthma later in life” ( Wohlleben and Erb, 2006).

CONCLUSION

Asthma continues to be a major health concerns in the US, in despite of the widespread use of inhaled corticosteroids and bronchodilators. Currently no successful preventive measure exists. Though, several recent researches revealed that by using different immune stimulatory strategies may help protects animals from developing asthma. I believe that a well-balanced immune stimulation therapy, which could trigger Th1 reaction, might be the most effective method (Wohlleben and Erb, 2006). If the Th1 reacts successfully and inhibit the development of Th2 cells then asthma and allergen-specific cells would in turn play a part in the inhibition of allergen-specific Th2 reactions. in addition reduces the anti-allergic Th1 reaction, thus making sure that no pathological Th1 reactions would develop in the lung. However, we have to be cautious in over emphasizing the safety aspect of any vaccine or stimulation therapy because younger children would be the most promising group for an effective immune stimulation therapy that could prevent or cure asthma (Wohlleben and Erb, 2006).

Finally, these methods have some possible serious side effects. A particular concern may be the stimulation of allergen-specific Th1 cells, because the Th1 response could lead to airway inflammation and subsequent damages to tissue cell leading to an encounter to inhaled allergen therapy. At present it is unknown if allergen-specific Th1 reaction can cause chronic inflammatory syndrome following the repeated exposure to allergen in people. Conversely, the main danger related with Th1 reaction can make it impractical to treat healthy children with stimulation therapy that can stimulate allergen- specific Th1 reactions (Wohlleben and Erb, 2006).

References:

1. Mutius, E.V. (2007). Allergies, infections and the hygiene hypothesis – The epidemiological evidence doi:10.1016/j.imbio.2007.03.002 . retrieved January 26, 2010 from http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B7GW1-4NM5S14-1&_user=10&_coverDate=06%2F27%2F2007&_rdoc=1&_fmt=high&_orig=search&_sort=d&_docanchor=&view=c&_searchStrId=1181970857&_rerunOrigin=scholar.google&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=824635ed1e9fe810bce8bad51f411f8a

2. Umetsu, D. T., & DeKruyff, R. H. (2006). The regulation of allergy and asthma. Immunological Reviews, 212(1), 238–255. DOI: 10.1111/j.0105-2896.2006.00413.x; Retrieved from the Walden Library Academic Search Premier database.(AN 21667826) http://web.ebscohost.com.ezp.waldenulibrary.org/ehost/pdf?vid=3&hid=4&sid=8bc497c2-d1f6-46b3-b4e4-d1d08aecccd2%40sessionmgr13

3. Yazdanbakhsh, M., Kremsner, P. G., Ree, R.V. (2002). Allergy, Parasites, and the Hygiene Hypothesis. Science; Vol. 296. no. 5567, pp. 490 - 494
DOI: 10.1126/science.296.5567.490. retrieved January 26, 2010 fromhttp://www.sciencemag.org/cgi/content/abstract/296/5567/490

Umetsu, D. T., Meyer, E. H., & DeKruyff, R. H. (2007). Natural killer T cells regulate the development of asthma. International Reviews of Immunology, 26(1/2), 121–140. DOI: 10.1080/08830180601070237; Retrieved from the Walden Library Academic Search Premier database.(AN 24515668) http://web.ebscohost.com.ezp.waldenulibrary.org/ehost/pdf?vid=7&hid=9&sid=53f6a867-f8a1-491a-a2e6-bdeeeb678621%40sessionmgr14

5. Gibbs, S., Heidi Surridge, Ruth Adamson, Bernard Cohen , Graham Bentham and Richard Reading (2004). Atopic dermatitis and the hygiene hypothesis: a case-control study. International Journal of Epidemiology, Volume 33, Number 1, pp. 199-207. Retrieved January 28, 2010 from http://ije.oxfordjournals.org/cgi/content/full/33/1/199

6. Ran D. Balicer, Itamar Grotto, Marc Mimouni, and Daniel Mimouni (2007).
Is Childhood Vaccination Associated With Asthma? A Meta-analysis of Observational Studies Pediatrics, 120: e1269 - e1277 http://pediatrics.aappublications.org/cgi/content/full/120/5/e1269

7. A. Schulze, R. T. van Strien, G. Praml, D. Nowak, and K. Radon(2007).
Characterisation of asthma among adults with and without childhood farm contact European Respiratory Journal; 29: 1169 - 1173. http://www.erj.ersjournals.com/cgi/content/full/29/6/1169

8. Crowding: risk factor or protective factor for lower respiratory disease in young children? Maria Regina Alves Cardoso*1, Simon Nicholas Cousens2, Luiz Fernando de Góes Siqueira1, Fátima Maria Alves1,3 and Luiz Antônio V D'Angelo (2004). http://www.ncbi.nlm.nih.gov/pmc/articles/PMC434510/pdf/1471-2458-4-19.pdf

9. Wohlleben, G., & Erb, K. J. (2006). Immune stimulatory strategies for the prevention and treatment of asthma. Current Pharmaceutical Design, 12(25), 3281–3292. DOI: 10.2174/138161206778194114. Retrieved from the Walden Library Academic Search Premier database. (AN 22139036) http://web.ebscohost.com.ezp.waldenulibrary.org/ehost/pdf?vid=8&hid=9&sid=53f6a867-f8a1-491a-a2e6-bdeeeb678621%40sessionmgr14

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