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When Does Asthma Begin? In Utero Sensitization to Indoor Allergens
From: Columbia University
| By:
Rachel Miller |
EDITOR'S INTRODUCTION |
High exposure to indoor allergens--cockroaches, dust mites, cats, dogs, molds--has been implicated as contributing to the development of asthma, especially in the poor, urban communities most adversely affected by this disease.  Recent evidence raises the possibility that exposure in utero may lead to sensitization to certain allergens. In fact, preliminary research by Rachel Miller, M.D., Irving Assistant Professor of Clinical Medicine at Columbia University, may demonstrate the possibility of infants born with sensitizations to allergens that their mothers do not have. |
 ndoor allergens are very important in inner-city asthma, in part because they represent a very large exposure. In fact, other studies have shown that American children who live in cities spend at least 93 percent of their time indoors. Recently, a lot of discussion has taken place about certain indoor allergens as being particularly important in urban asthma. |
Sensitization and asthma may occur from exposure to allergens at a very young age. Asthma really is an allergy in many senses of the word. "Sensitization" is the medical or immunological term for T-cell reactivity that in some cases may lead to developing an asthma allergy. |
In 1997, the National Cooperative Inner City Asthma Study published a very important study that looked at more than 600 children with asthma across eight cities in the United States. They looked at risk factors for the development of asthma, and, interestingly, they found that a high exposure and allergy to cockroaches specifically, and not other indoor allergens, was associated with worse asthma and more missed school days. |
A lot of this allergen research was done by Fernando Martinez's group at the Respiratory Science Center, University of Arizona, and published in a 1995 study entitled "Asthma and Wheezing in the First Six Years of Life." The group looked at 9-month-old babies and measured Immunoglobulin E (IgE) antibodies, which are produced when you have an allergic reaction. They found that children who had a high IgE level at 9 months were more likely to develop asthma by age 6, suggesting that allergies can start quite early in a child's life. |
At this point, we are left with the problem that we really do not know the timing or the intensity of an exposure that is critical to the development of asthma or allergies. We are interested in whether T-cell reactivity to allergens--sometimes a precursor to allergies or asthma--may in fact develop prenatally, at an extremely young age. Measuring an allergy antibody in cord blood has not been shown to be a helpful biomarker. However, we have been able to perform cord blood proliferation assays, or tests. We measure the T-cell reactivity to specific allergens in cultures. Cells multiply or proliferate only if they've been previously exposed to an allergen and have developed an immune response. (White blood cells made in the thymus gland--T-lymphocytes, or T-cells--coordinate the immune system.) |
A few groups have performed cord blood proliferation assays in very small studies. They have shown that cord blood cells may sometimes proliferate or multiply following stimulation in culture with several allergens--food, dust mites, cat dander and some pollens. |
We have developed the following hypothesis: High exposure to indoor allergens during the prenatal period occurs in populations at a high-risk for asthma--namely the South Bronx and northern Manhattan. This exposure may lead to the development of sensitization in newborns. We are also currently trying to address some possible mechanisms for in utero sensitization. |
Exposures to allergens in the home
Our protocol starts with pregnant women we have recruited as part of a cohort study for the Columbia Center for Children's Environmental Health (CCCEH). These women are African-American and Dominican from the South Bronx and northern Manhattan. We interview the women during pregnancy and focus specific attention on their environment, their medical and personal histories and some demographic information. Research workers go to their homes and collect dust, measuring that dust for the allergen content in microscopic particles. |
Right after a baby is born, we collect cord blood from the umbilical cord, representing fetal blood. We measure the IgE allergy antibody, and isolate the white blood cells and perform several assays, including allergen-induced proliferation assays. Within one day postpartum we collect the mother's blood and perform the exact same assays and look at allergen-specific IgE levels. |
We follow this young cohort of babies through at least 2 years of age. A lot of follow-up occurs, including a more thorough evaluation by age 2 in a follow-up questionnaire, another visit to the home with examination of dust allergen levels, and an immunological evaluation. |
We found that in the overwhelming majority of cases, a measurable cockroach allergen existed in the dust in these women's kitchens. The levels were actually quite high. Our examination of microscopic particles in the dust in the pregnant women's beds also showed a measurable cockroach allergen in the overwhelming majority of cases. When we looked at mouse allergen, we found a very similar pattern. In the overwhelming majority of cases, mouse allergen was actually measurable in the kitchen dust and in the pregnant mother's bed. |
The situation for dust mites and other important indoor allergens was quite different and opposite. In the majority of cases, dust mite allergen was not really measurable or elevated in these pregnant women's homes. |
Impact of allergen exposure
Our results showed a lot of proliferation. In possibly 55 percent of the cases, the cord blood proliferated in response to cockroach allergen. This suggests that these cells may have received some degree of exposure to cockroach allergen and may have developed an immune response to cockroach protein. There was also a lot of proliferation going on to dust mite, mouse and tree allergens. It's far less common for tetanus, as one might predict, since most mothers do not receive a tetanus immunization during pregnancy. In summary, in utero sensitization to multiple allergens may be occurring and may be quite frequent. |
When we examined the mothers, we found some similarities and some differences. Again, we looked at the stimulation index--how much these cells multiply, or how reactive these mothers are to the same allergens. In the case of mothers, dust mites may be the most important allergen. While sensitization to multiple allergens occurs in the mothers as well, in some cases it occurs to a different degree than among the babies. |
That led us to ask the questions, "Are the babies and mothers different? Does the mother have to be sensitized for the baby to be sensitized?" One way we examined the data was through samples of mother-and-baby pairs. We found examples of the baby being sensitized to cockroaches when the mother was not. We also found examples of neither one of them being sensitized and examples of both of them being sensitized. A baby who is born sensitized to cockroaches when the mother doesn't have that sensitization--the case in many pairs we've tested so far--suggests that the immune response may have happened in the placenta. |
Dust mites showed some similar patterns. We have mothers who are sensitized to dust mite allergens, when the baby really is not. We also have cases where both of them are sensitized. Again, we found some examples of the baby being born with a sensitization and the mother not having it, suggesting that maternal T-cell reactivity, or sensitization, is not required for the baby to develop an immune reaction. |
In conclusion, I want to emphasize our three main preliminary findings to date. First, exposure to indoor allergens may be really quite prevalent. Second, in utero sensitization to multiple indoor allergens may be relatively common--in preliminary studies, possibly over 55 percent in the case of cockroach allergens. Third, in utero sensitization may occur even if the mother doesn't have the same T-cell reactivity. This suggests that perhaps this process of development of in utero sensitization may in fact be occurring in the placenta. Our research may be suggesting that children at a very young age may already be on the road to the development of asthma or allergies. |
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