2003 October 01 Wednesday
Antibiotic Use In Babies Increases Risk Of Asthma, Allergies

A Henry Ford Hospital study shows use of antibiotics in babies dramatically increases the risk of allergies and asthma by age 7.

For the Henry Ford study, researchers followed 448 children from birth to seven years. The children were evenly divided by gender.

Data was collected prenatally and at the first four birthdays until the children were 6 and 7 years old, when they underwent a clinical evaluation by a board-certified allergist. The data included information about all prescribed oral antibiotics; blood tests that measure the antibody (immunoglobulin E) that causes allergies; and skin reaction tests that show whether a person is hypersensitive to an allergen. Researchers also collected data on all clinical visits and made home visits to collect environmental samples.

Of the 448 children, 49 percent had received antibiotics in the first six months of life. The most common antibiotic category prescribed was penicillin.

Among the findings:

  • By age 7, children given at least one antibiotic in the first six months were 1.5 times more likely to develop allergies than those who did not receive antibiotics. They were 2.5 times more likely to develop asthma.
  • By age 7, children given at least one antibiotic in the first six months and who lived with fewer than two pets were 1.7 times more likely to develop allergies, and three times more likely to develop asthma.
  • By age 7, children given at least one antibiotic in the first six months and whose mother had a history of allergies were nearly twice as likely to develop allergies.
  • By age 7, children given at least one antibiotic in the first six months and who were breast-fed for more than four months were three times more likely to develop allergies. However, breast-feeding did not influence the risk between antibiotics and asthma.

Note that between the second and third bullet items above the only difference was the reduction in pet exposure and the result was a higher incidence of allergies and asthma.

The oddest result that I see is the fourth item where breast-feeding increased the risk of allergies but not of asthma. One potential explanation: the breast milk might cause the immune system of babies to develop more rapidly and hence to be more likely to react to allergens. Given that breast milk probably has other benefits that makes its use a tough call.

Broader spectrum antibiotics increase the risk.

Overall, children given antibiotics in their first half-year were 2.6 times more likely to develop allergic asthma, the team told a meeting of the European Respiratory Society on Tuesday. With broad-spectrum antibiotics, which kill a wide range of bacteria, the risk was far higher: children were 8.9 times more likely to suffer from asthma.

Selection of an antibiotic more narrowly tailored for the target bacteria therefore would reduce risk of allergy and asthma among babies.

This is evidence for the "hygiene hypothesis" to explain the increased incidence of asthma and allergy in modern society.

The new study also backs the growing belief that antibiotics disrupt the normal development of a child's immune system through a phenomenon known as the "hygiene hypothesis."

This "hygiene hypothesis" has been gathering strength in recent years. The latest result certainly strengthens the argument considerably. The idea is basically remiscent of the saying "idle hands are the devil's workshop". Remove the normal antigens that the immune system is exposed to and it starts reacting to things it ought not react to. Our ancestors lived in dirt floor dwellings and had much more exposure to animals, dirt, and nature in general. We live lives which bring us in much less exposure to the antigens we evolved to deal with. Exposure to those antigens appear to be necessary to instruct the immune system on what it should identify as a threat.

From a signal processing perspective you can think of the immune system as a sensor system that will incorrectly react to weaker signals in the absence of stronger signals to react to. The immune system never experienced enough evolutionary pressure to not react to weaker signals because there were so many stronger signals around for it to pay attention to.

Surely antibiotics are overused and this latest report is yet another reason to reduce the use of antibiotics in situations where they are not necessary. But some children will inevitably get bacterial infections in their early months of life that require antibiotic treatment. So what to do about this problem? One potential solution is to develop vaccines that will retrain the immune system to not react to allergens. It may some day be standard practice to give babies anti-allergy vaccines.

In the shorter term having dogs licking babies faces may be a good thing. Also, it might be possible to come up with formulations of beneficial bacteria to give to babies to replace normal harmless bacteria that are wiped out by antibiotic therapy.

The argument that cleaner environments cause problems in the immune system is especially interesting because it demonstrates how moving humans out of the environments they evolved in creates problems that can be quite subtle and that can go unrecognized for many years. This is not the only such problem of this sort. To take another but rather more obvious example, the higher incidence of obesity in affluent nations is a problem that has arisen because of the lifestyles that are the result of living in industrial societies. Obesity is even more interesting than the allergy/asthma problem because obesity is a behavioral problem. Obese people are driven by strong urges to eat more than what is good for them in modern circumstances.

There are other behavioral problems that arise from growing up in industrial society as well. To take another example, humans are obviously not evolved to handle recreational drugs. Recreational drugs interfere with mechanism of pleasure that evolved to guide learning and other activities. Drugs hijack pleasure systems. Many minds become too easily trained to crave the pleasures that the drugs give them and so the pursuit of pleasure becomes far more harmful than it was in our evolutionary past. Humans are going to have to develop methods of adapting themselves to the changes they are creating in their environment.

Update: In another example of the importance of the sensitivity of the immune system to the timing of exposures to various antigens researchers in the United States and Germany have just discovered that the date of first introduction of babies to cereals affects their odds of developing diabetes.

Babies with a family history of diabetes who were introduced to cereals before or after the recommended age of four to six months had a higher risk of developing a precursor to the disease, researchers said Tuesday.

US team lead researcher Dr. Jill Norris says early exposure to cereal proteins may cause an immature immune system to react inappropriately.

She hypothesizes that the youngest babies have extremely vulnerable immune systems. Older babies, denied solids for so long, simply ate more and overwhelmed still developing systems with foreign cereal proteins. The hypothesis has yet to be proved and Norris stressed the scenarios refer to at-risk babies.

Another theory is that children who don't start eating cereals by 6 months of age are more likely to be deficient in vitamins and that this causes their immune systems to malfunction and start making auto-antibodies (i.e. antibodies to ones's own proteins).

By Randall Parker    2003 October 01 01:59 PM   Entry Permalink | Comments (5)
2003 May 21 Wednesday
New Pill Camera Can Be Maneuvered In Gut

Dr. Annette Fritscher-Ravens and colleagues at the University College London have successfully tested in humans a small swallowable gut camera that can be steered around in the gut.

Fritscher-Ravens and her colleagues say they have patented just such a method. Using technology very similar to that found in TV remotes or electronic car-keys, they attached tiny electrodes to the front and rear portions of the video capsule, along with a tiny antenna. Using a drive/reverse switch, they have been able to steer and propel the capsule through the gut, lingering wherever a lesion or other suspicious formation occurs

Passive camera pills known as capsule endoscopes are already available and in clinical and research use. But this new design allows doctors to tell the camera pill to move itself to areas of interest.

An existing passive capsule endoscope was recently used to discover greater side-effects from NSAIDs on the small intestine than had previously been reported.

The capsule endoscope, developed by Given Imaging, allows medical professionals to view the entire small intestine. The system uses a disposable miniature video camera contained in a capsule, which the patient swallows. The capsule passes through the digestive tract, transmitting color images, without interfering with the patient's normal activities. Capsule endoscopy diagnoses a range of diseases of the small intestine including Crohn's Disease, Celiac disease, benign and malignant tumors of the small intestine, vascular disorders, medication related small bowel injury and pediatric small bowel disorders.

The study enrolled 40 patients, with a mean age of 49.5, who had arthritis including osteoarthritis, rheumatoid arthritis and gout. Twenty patients took NSAIDS daily for three months. Twenty patients took acetaminophen alone or nothing at all. All patients fasted overnight and underwent capsule endoscopy. The pylorus, the sphincter muscle that controls the lower opening of the stomach where it empties into the upper part of the small intestine, was marked on each video. Two investigators who were not told which therapy the participants received, reviewed each video beginning after the pylorus, where the small intestine starts.

Severe injury to the small bowel was seen in 23 percent of NSAID users compared to no severe injury in the controls. Severe damage was associated with high doses of indomethacin, naproxen, oxyprozocin and ibuprofen.

Given the widespread long term use of NSAIDs this is an important result. A repeat of this study with a larger variety of NSAIDs and more test subjects could provide useful guidance in NSAID selection.

Update: this latest finding using a camera capsule to see the effects of NSAIDs on the intestines should not be surprising in retrospect. A 1999 study on mice found NSAIDs might be contributing to the development of inflammatory bowel disease.

A question raised by these experiments is the possible role of nonsteroidal anti-inflammatory drugs (NSAIDs) in promoting inflammatory bowel disease. In the researchers' mice, COX-2 inhibition by NSAIDs produced histologic changes reminiscent of human celiac disease. In view of the megaquantities of NSAIDs consumed worldwide, we'll need to delve more deeply into the full effects of COX-2 inhibition on immune homeostasis

By Randall Parker    2003 May 21 12:43 PM   Entry Permalink | Comments (10)
2003 May 04 Sunday
The Future Of Nutritional Genomics

Writing in the New York Times Bruce Grierson explores the potential use of individual genetic profiles to choose the ideal personalized diet.

A trip to the diet doc, circa 2013. You prick your finger, draw a little blood and send it, along with a $100 fee, to a consumer genomics lab in California. There, it's passed through a mass spectrometer, where its proteins are analyzed. It is cross-referenced with your DNA profile. A few days later, you get an e-mail message with your recommended diet for the next four weeks. It doesn't look too bad: lots of salmon, spinach, selenium supplements, bread with olive oil.

Once DNA sequencing costs fall far enough and more DNA sequence variations are tied to health risks and to interactions with dietary and other health habits personal dietary advisories will become possible to create. However, the most powerful use of personal genetic profiles will likely to develop therapies that reduce individual genetic risks and problems.

Suppose someone has a greater risk of getting heart disease on a high saturated fat diet. Well, people still want to eat fat. When the genetic variations that increase heart disease risk are all identified and the mechanisms by which they increase risk become better understood it is very likely that therapies will be developed to change the expression of the genes of high risk people. In the extreme one can imagine genetic therapies to fix the causes of genetic risks.

Gene therapy will even be utilized to make food consumption easier to do. For instance, one can easily imagine those with lactose intolerance getting a gene therapy via a swallowed pill to program intestinal cells to make more lactase enzyme to break down lactose.

By the time that nutritional genomics becomes possible it is likely that complete genetic variation mapping for each person will become possible. Therefore a person won't send a DNA sample off to be tested just for nutritional advice. Rather, someone will submit their genetic map to an advice service and the advice service will then respond with specific dietary and lifestyle recommendations. Also, the service will probably include a suggested list of preventative treatments including drugs to take regularly and preemptive gene therapies to undergo.

By Randall Parker    2003 May 04 03:58 PM   Entry Permalink | Comments (0)
2002 September 25 Wednesday
Personalized Medicine Research Project

The intent of the Personalized Medicine Research Project is to collect enough genetic and health record information about a large enough number of people that it will become possible to discover more genetic variations that contribute to disease.

Marshfield Clinic's publicly funded Personalized Medicine Research Project will collect DNA from 80,000 people and match the genetic profiles with medical histories and other information in a statistical database.

Researchers at the clinic, a not-for-profit health care provider southwest of Wausau, Wis., with 400,000 patients, and a pioneer in genetic research, said they hope to discover the genetic components of common disorders such as heart disease, cancer and diabetes and to tailor the health care of individuals based on their genetic profiles.

The medical records that the project staff will enter into databases will become more useful with time as the genetic assay technologies become cheaper and more powerful. As the number of people enrolled in this project increases and as the assay methods become more powerful an increasing number of medically important genetic variations will be discovered.

By Randall Parker    2002 September 25 06:13 PM   Entry Permalink | Comments (1)
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