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Effects of environmental tobacco smoke on pulmonary allergy

Institution: University of California, Davis
Investigator(s): Laurel Gershwin, D.V.M., Ph.D.
Award Cycle: 1998 (Cycle 7) Grant #: 7RT-0107 Award: $282,568
Subject Area: Pulmonary Disease
Award Type: Research Project Awards
Abstracts

Initial Award Abstract
Epidemiologic studies show that children living in households of smokers are more likely to have allergies, particularly allergic asthma, than children who live in non-smoking environments. We are using a mouse model to study the effect of breathing second-hand or environmental tobacco smoke (ETS) on induction of allergies. Our previous work using mice has shown that ETS causes increased production of IgE antibodies (which initiate an allergic response) and specific messenger molecules called “cytokines” that are made by certain white blood cells. The effect of this is that ETS increases the IgE production to inhaled allergens, especially in mice that have already been sensitized to a particular allergen. We use a chamber into which ETS is pumped to create an environment similar to that in a smoker's home. Mice spend 6 hours per day in this environment for many weeks. Meanwhile we expose them at intervals to inhalation of antigens to mimic human allergen exposures. The lung function of exposed mice is tested to see if they show an asthmatic response to inhaled allergens after weeks of combined ETS and allergen exposure. The ETS-exposed mice are compared to control mice that breathe ambient air. To better understand the biological pathway leading up to a pulmonary allergic response, we also test for blood IgE and cytokine levels, and study the cells in their lungs. It is thought that newborn humans are more likely to produce IgE (following exposure to inhaled allergens) than older people, because the specific cytokines they make naturally are the right kind for IgE production. We think that the effect of ETS on the development of allergic sensitivity will be much greater on newborns. Therefore our next experiments will use newborn mice and determine if exposure to ETS during the critical neonatal time increases the IgE response and sets up an allergic state that persists into adulthood. We will study their responses to two classic antigens, including a fungal antigen that often causes allergic reactions in humans. Another experiment will examine the effect of exposing pregnant mice to ETS on induction of the IgE response in their newborns. In an effort to try to find a way to decrease the adverse effect of ETS inhalation on children that cannot escape the smoke in their homes, we will perform an experiment using a vaccine to modulate the IgE response. By determining if this vaccine can change the effect on ETS on IgE production, and by learning what biological pathways are involved, we hope to lay the groundwork for development of therapeutic and prophylactic drugs that can be used to protect children that are unable to reduce their exposure to ETS. Ultimately our results will demonstrate how and why ETS effects IgE production to inhaled allergens and will help to identify means with which to prevent this effect. These experiments are particularly important because now that the harmful effects of ETS are recognized and most public places are smoke-free, children within the homes of smokers are still exposed to ETS. We would hope that data showing adverse effects of ETS on childrens’ allergy and/or asthma will prompt parents to reduce or stop smoking in the home.

Final Report
There has been an increase in the incidence of asthma in the last decade. One reason proposed has been an increased exposure to a variety of air pollutants. We examined the effect of environmental tobacco smoke (ETS) on induction of an allergic response to inhaled allergen using a mouse model. In a previous TRDRP grant we showed that indeed allergic sensitization was enhanced in adult mice exposed to egg albumen by aerosol. In the present project we sought to determine if a fungal allergen would have a similar effect; and if exposure to ETS during the intrauterine and neonatal period might have an effect on enhancement of allergy in the mouse model. Results of experiments showed that exposure to the fungal allergen, Aspergillus fumigatus, caused marked decrease in pulmonary function in mice that received Aspergillus after living in an environment of ETS, as compared to mice living in ambient air. In addition, parameters of allergy such as IgE producing cells in the lungs and peripheral eosinophilia were significantly increased in the ETS-exposed mice. In another set of experiments we found that indeed ETS exposure of the mouse in utero through 6 weeks of age increased these allergic parameters. A serendipitous finding was that there was a difference in the allergic response that was gender dependent. Heretofore we had used adult female mice in the experiments. Working with litters resulted in animals of both sexes. The allergic response was greatest in the female mice. However, when data was examined separately by sex, the male ETS-exposed mice were also more allergic than males raised in ambient air. In the future we would like to examine the mechanism that causes this gender difference. The implications for human health are that exposure to ETS in utero and during the neonatal period can have a profound effect of subsequent development of allergic disease.
Publications

Gender differences in the allergic response of mice neonatally exposed to environmental tobacco smoke.
Periodical: Developmental Immunology Index Medicus:
Authors: Seymour BW, Friebertshauser KE, Peake JL, Pinkerton KE, Coffman RL, Gershwin LJ ART
Yr: 2002 Vol: 9 Nbr: 1 Abs: Pg: 47-54

Second-hand smoke is an adjuvant for T helper-2 responses in a murine model of allergy.
Periodical: Journal of Immunology Index Medicus:
Authors: Seymour BW, Pinkerton KE, Friebertshauser KE, Coffman RL, Gershwin LJ ART
Yr: 1997 Vol: 15 Nbr: 12 Abs: Pg: 6169-75