Tuesday, December 10, 2013

Can Antibiotic Exposure Influence Development of Allergic Diseases?

A recent study provides certain implications for an association between exposure to antibiotics at a young age and the development of allergic diseases, primarily asthma, in early childhood.1

            At some point, most people have gone to the doctor’s office and left with a prescription for an antibiotic. In today’s world, antibiotics have developed a connotation as a medicine that can ward off all sorts of sicknesses, which is only partially true. What many people don’t realize is that antibiotics are strictly useful for fighting bacterial infections and will have no effect on viral illnesses.* Although antibiotics have saved countless lives since the discovery of penicillin, there are some concerns about their use.

There two main negative consequences of using antibiotics more liberally than in the past: some unhealthy bacteria have increased resistance to treatment and administration of antibiotics can lead to decreased levels of healthy bacteria. The first consequence relates to overprescribing antibiotics for patients that may not be suffering from a bacterial infection. Every time a person takes antibiotics, he or she increases the likelihood that bacteria in the body will become resistant, which makes it difficult to treat later infections.#

Commensal Bacteria
The second consequence, which directly relates to the study in question, has to do with the healthy bacteria that reside in the human gastrointestinal tract. When antibiotics are introduced to the body during infancy, a critical period for the development of the immune system, disruption to gut microflora can occur.1 This could possibly predispose patients to the development of an allergic phenotype. Research shows that disruptions in the normal growth of gastrointestinal bacteria can prevent regulatory T cells from properly dampening the immune system’s response to respiratory allergens.$  For more information, click here. Reduced diversity of microbes in infant excrement has also been connected to an increased risk of allergic diseases late in childhood.2

Allergic diseases develop when a person's immune system becomes sensitized to a normally harmless antigen. Type I hypersensitivity is a category of allergic reaction in which CD4+ Th2 cells that interact with these antigens stimulate B-cells to produce Immunoglobulin E (IgE) antibodies. These antibodies will then mark the specific antigen for destruction by other immune cells.+ Once the individual has been initially exposed and developed the specific antibodies, a subsequent exposure to the allergen will result in an allergic reaction. For more information, click here.

Mechanisms of Allergic Response

The purpose of the research conducted by Hoskin-Parr et al. was to determine the relationship between antibiotic exposure in patients two years old and younger and the development of allergic diseases by the age of 7.5 years old.1 The study sought to determine if certain variables, time of exposure and number of exposures, had an effect. The research also compared the relationships for three different allergic diseases, asthma, eczema, and hay fever.

To gather data, the researchers administered questionnaires to mothers of infants. The questionnaires were given when the baby was 6 months, 15 months, and 24 months old. The mothers were asked to report if the child had taken antibiotics once, more than once, or never since the last questionnaire (or since the child was born, for the first questionnaire). Each mother was asked to report about her child’s health again once he or she reached the age of 7.5 years old.

            This study found that children who received at least one dose of antibiotics during infancy were more likely to have been diagnosed with asthma compared with those who were never treated with antibiotics by the time they were two years old.1 This effect was stronger as the number of doses received increased. Additionally, the results suggest that cumulative exposure to antibiotics may be more important than exposure during any specific time period. The same associations were found for eczema and hay fever, but effect sizes were weaker.1 Girls were less likely than boys to develop asthma or hay fever, but more likely to develop eczema. Also, children of non-white ethnicities were more likely to develop each of the allergic diseases studied compared to their white counterparts.1

            The scientists had to account for two important factors in order to fully evaluate the efficacy of their findings: reverse causation and confounding variables. The researchers included many additional variables to account for confounders. Some variables, such as sex, ethnicity, and birthweight of the child, would not seem like they would have much of an effect on the findings. Other variables, including birth mode (vaginal or Caesarian), breastfeeding, time spent outdoors, mother’s smoking, and contact with felines, are more interesting choices, because there are implications for how such factors could directly effect aspects of immune function.

To account for reverse causation, data was adjusted to exclude children who were reported to experience wheezing anytime from birth to 18 months old, and from birth to 30 months old, for which they possibly received antibiotics.1 This is because these children may not have developed asthma symptoms at an early age because they were given antibiotics, but were given antibiotics because of the appearance of the wheezing. This would be a case of reverse causation.

            After adjusting the model for confounding variables, effect sizes for the study’s findings remained relatively the same. This means that none of the factors made a significant difference in the strength of the associations between antibiotic use and the development of allergies. However, when the patients who showed signs of wheezing by the time they were 18 months old were eliminated from the analysis, the significance of the findings was decreased. When those who experienced any wheezing before they reached the 30-month mark were eliminated, the associations were even more weakened. This suggests that at least a portion of the patients whose data contributed to the relationship could be attributed to reverse causality. Therefore, inappropriate administration of antibiotics (which is known to be an issue in today’s society) to treat wheeze could result in an unauthentic association between antibiotic use in young children and later asthma.1

            This study is one of many that have had difficulty with showing the significance of its findings in the context of immunology. Many other studies have attempted to explain how antibiotics could attribute to the development of allergic diseases, but so far, none of them have had very clear results. Some of the most important suggestions for the development of allergies are the hygiene hypothesis and the important role of commensal bacteria in the GI tract. Past research has shown that children who grow up on farms (and are more likely to be exposed to a greater variety of bacterial germs) are less likely to develop asthma and other allergies as compared to children who are raised in rural areas but not on farms.3 This could be because exposure to microbial products as youth decreases Th2-biased responses characteristic of allergies.1 Overall, the immunological complexities that lead to the development of allergic diseases in individuals are not totally understood, but studies such as the one conducted by Hoskin-Parr et al. suggest that there may be a dose-dependent relationship between antibiotic use in young children and the development of allergic responses in these children later in life.

      Primary Source:

            1. Hoskin-Parr L, Teyhan A, Blocker A, & Hendeson AJW. (2013). Antibiotic exposure in the first 
            two years of life and development of asthma and other allergic diseases by 7.5 yr: A dose-
            dependent relationship. Pediatr Allergy Immunol. Accessed 9 Dec 2013. 

      Secondary Sources:

            2. Ly MP, Litonjua MA, Gold DR, & Celedon JC. (2011). Gut microbiota, probiotics, and 
            vitamin D: interrelated exposures influencing allergy, asthma, and obesity? J Allergy Clin Immunol.  
            127: 1087-1094.

      3. Genuneit J. (2012). Exposure to farming environments in childhood and asthma and wheeze
      in rural populations: a systematic review with meta-analysis. Pediatr Allergy Immunol. 23: 509-518. 

* “Antibiotics.” Medline Plus. U.S. National Library of Medicine. National Institutes of Health. Updated 27 Nov 2013. Accessed 9 Dec 2013. <http://www.nlm.nih.gov/medlineplus/antibiotics.html>.

# Nordqvist, Christian. “What Are Antibiotics? How Do Antibiotics Work?” Medical News Today. Published 30 Apr. 2009. Updated 24 Nov. 2013. Accessed 9 Dec. 2013. <http://www.medicalnewstoday.com/articles/10278.php>.

$ “Antibiotics Could Be the Cause of Many Allergies.” NewsMedical. Published 27 May 2004. Accessed 9 Dec. 2013. <http://www.news-medical.net/news/2004/05/27/1969.aspx>.

Mustafa, Syed Shahzad. “Allergy: What causes allergies?” MedicineNet. Reviewed 26 Nov. 2013. Accessed 9 December 2013. <http://www.medicinenet.com/allergy/page2.htm#what_causes_allergies>.


No comments:

Post a Comment