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Third hand smoke and hypersensitivity

Institution: Stanford University
Investigator(s): Stephen Galli, M.D.
Award Cycle: 2012 (Cycle 21) Grant #: 21RT-0147 Award: $668,192
Subject Area: Environmental Exposure/Toxicology
Award Type: Research Project Awards

Initial Award Abstract

Asthma is one of the most prevalent chronic disorders of children and adults, with enormous impact on the health of individual patients and high annual costs in health care resources and time lost from school and work. It is well known that the children of smokers are at increased risk for developing asthma and for exacerbations of that disease if they have it, but the underlying mechanisms which contribute to these observations are not understood.

Extensive studies by others have evaluated the prevalence and adverse effects of cigarette smoking and exposure to second hand smoke (SHS) in asthmatics, and it has been concluded that cigarette smoking and exposure to SHS in asthmatics can contribute to worse patient outcomes and diminished effectiveness of steroid therapy. Other evidence supports the idea that short- and long-term effects of tobacco smoke exposure can influence the structure of the developing lung, as well as lung physiology, effects which can have lifelong consequences, and there is evidence that the most common preventable early life risk factor for asthma is exposure to tobacco smoke.

Exposure to environmental tobacco smoke remains a significant health concern and attention recently has focused on the possible role of “Third Hand Smoke” (THS) in tobacco-related disease. THS consists of residual tobacco smoke pollutants that remain on surfaces and in dust after tobacco has been smoked, are re-emitted back into the air, and/or react with other compounds in the environment to yield secondary pollutants. A recent national survey indicated that 43% of children ages 2 months to 11 years live in homes with at least one active smoker; these children are at high risk of exposure to THS.

Unfortunately, the influence on human health of exposure to THS through involuntary inhalation, digestion, or dermal uptake is unknown. However, it has been reported that exposure to cockroach allergen (CRA) might be the most important risk factor for asthma in inner-city households. The National Cooperative Inner-City Asthma Study found that asthma morbidity was highest in children with both a positive skin-test response and a high level of exposure in the bedroom to the cockroach allergens. This suggests that infants and children in low-income urban homes are more likely to be at risk of exposure to CRA, in addition to the risk of exposure to SHS and THS.

We therefore developed a new model of CRA-induced airway hypersensitivity and inflammation in infant and adult mice, and used that model to determine whether an important component of THS, namely 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), could influence the development or severity of this model of asthma in mice. We found that NNK exposure through the skin of mice markedly increased the severity of the asthma model in both infant and adult mice. In our proposed studies, we are seeking to understand how dermal exposure to components of THS, specifically NNK, can lead to the enhanced development and/or exacerbation of airway hypersensitivity and inflammation in our CRA-induced asthma model. These studies would not be ethical to perform in humans, but we can perform such studies in normal mice and in mice that have been genetically altered so that we can identify important factors contributing to the ability of NNK to exacerbate this asthma model. Such studies not only will increase our understanding of how THS might increase the development and severity of asthma in exposed children and adults, but may suggest new ways to treat such individuals to reduce this effect of THS.