What Causes Allergy? What Causes Asthma? A short review of two recent articles
During my training in Allergy/Clinical Immunology the estimates for allergy in the population was about 20%. Over the past 20 years there has been an alarming increase. The reason for this is unknown. There are plenty of theories including exposure to allergens, pollutants, and endotoxins (Hygiene Hypothesis). Other suspected factors include immunizations, diet, viral infection, and parasitic infection. One common well proven factor is the genetic predisposition or tendency inherited from mom or dad. The best bet is that there are many factors that lead to sensitization and subsequent development of allergic conditions. In the most recent Journal of Allergy Clinical Immunology (JACI 2009 June) there are two articles on risk factors for developing allergy. One of the articles was reviewed by a good friend of mine, Dr. Dennis Ownby who is the director of Allergy-Immunology at the Medical College of Georgia. One article looks at associations with folic acid levels and the second article looks at the intrauterine bacterial environment.
In 2008 there was report of increased allergic sensitization in mice fed diets enriched with folic acid. Folic acid then was suspected as a risk factor for developing allergy, but that was in mice. A Norwegian study from 2009 found that high levels of folate were associated with a higher prevalence of respiratory illness in children. One study in mice and one published in humans. So why implicate folate?
Almost 20 years ago it was shown that taking folic acid before and during pregnancy significantly decreased the occurrence of neural tube defects (spina bifida). The impact of this was so great that by 1998 it was mandated by the FDA that cereal grain products be fortified with folic acid. The population has seen an increase in exposure to folic acid somewhat coincidental with the increase in allergic conditions. Is there an association?
The study ‘Higher serum folate levels are associated with a lower risk of atopy and wheeze’ by E.C. Matsui and W. Matsui (JACI 2009;123:1253-9) used the National Health and Nutrition Examination Survey (NHANES) 2005-2006. There were over 8,000 individuals (all greater than 2 years of age) who answered questions about allergy, had allergy tests performed, and had serum folate levels determined. The study found that high levels of folate were actually protective against atopy and wheeze. More folate = less atopy and less wheeze.
The editorial by Dr. Ownby (JACI 2009;123:1260-1) eloquently looked at the background studies and critiques the current study. As with many studies such as this, more needs to be looked at in the quest to find factors associated with developing allergy.
The second article looks at infection as a reason for developing asthma and allergy. The timing of the infection and the organisms involved was of great interest.
There have been a few studies that looked at the effect of infection in the mother and the use of antibiotics during pregnancy and at delivery as an allergic risk factor for the newborn. The antibiotic decreases normal bacterial immune stimulation and altered maturation of the immune system allowing allergic sensitization to occur. In the article entitled ‘ Intrauterine bacterial growth at birth and risk of asthma and allergic sensitization among offspring at the age of 15-17 years’ by L. Kesk-Nisula et al (JACI 2009;123:1305-11) children born to a group of Finish women who delivered infants by cesarean section in 1990-1992 were evaluated for asthma and allergic sensitization. Intrauterine bacterial cultures were done on 460 children. Years later (at age 15-17 years) these children filled out a questionnaire about asthma and allergy (self-report) and underwent skin testing. The presence of a pathologic anaerobic bacteria or a Streptococcus species cultured at birth was associated with a tremendous risk (odds ratio = OR) of ever having asthma (OR = 4.51 for anaerobes/2.53 for Streptococcus) or of currently having asthma (OR =7.34 for the anaerobes/3.37 for Streptococcus). This study concluded that specific types of bacteria cultured from the mother at the time of birth may have a role in the development of asthma. The authors suggest that the study of maternal microflora to which the infant is exposed to may be a future target for prevention of asthma in children.
In the development of allergy/asthma genetics is a major factor. Many other exposures work upon the genetic predisposition. When epidemiologic studies show increases in condition prevalence investigators look for associations and risk factors that may prove to be causative by performing more extensive investigation. Folic acid usage increased concurrent with an increase in the prevalence of allergy. The large epidemiologic did not find an association. The study of intrauterine microflora is unique. The authors note that it is the first study of its kind. I would guess that more studies like this will be done and in different populations to verify the findings. So for now, do not worry about the folic acid and keep posted about the intrauterine bacterial environment.
Fred Leickly
June 24, 2009
· 
fleickly · 
3 Comments
Posted in: Allergies, Asthma
3 Responses
Thank you very much for your blog. I check it every few days. My wife was treated twice with antibiotics for group b strep, once early in the pregnancy and again during delivery. When our son was diagnosed with atopic dermatitis and later multiple food allergies this was one of the things we wondered about. Both my wife and I have asthma and allergies so we know that is probably the main reason, but this adds another factor into the mix. If the same scenario comes up if we have more children I wonder what we will do? According to the CDC the risk of GBS without antibiotics is 1 in 200. With antibiotics it is 1 in 4,000. With our genetics and my sons’ current situation this could possibly be an important decision! I hope more research will be done before then.Thanks again!!
Mr. Clark,
Thank you for checking the site. I hope you have found it useful.
I think you are a clairvoyant. The questions you asked were the topic of my next posting. After a few more edits and proof-readings today, I should have this one ready. It is a review of an article in the May 2009 issue of the JACI. This was is an update on allergy during pregnancy, lactation, and early infancy. The issue of antibiotic exposure is listed as a risk factor (not a bonafide cause) for developing allergy. In the circumstance you described, the numbers quoted, and what we know about the devastating effects of that infection on an infant there would be no hesitation to use the antibiotics.
The family history of allergy is certainly a major issue. How all the other factors play out may depend on the individual circumstance. Take a look at the posting and let me know if it covers things for you.
Keep the questions coming.
Warmest regards,
Fred Leickly
Great post, It does shed light on things. Your site is a huge help to my family and hopefully others as well! Definately will have future questions, Much Thanks
Leave a Reply