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A6987 - Perinatal Nicotine Exposure Along with Early Life Influenza A, 2009 Pandemic H1N1 (Swine Flu) Infection, Leads to Lung Dysfunction in Adulthood
Author Block: R. McAllister1, E. Torres-Gonzalez1, J. Ritzenthaler2, G. W. Hoyle3, J. Roman1; 1Pharmacology and Toxicology, University of Louisville, Louisville, KY, United States, 2Medicine, University of Louisville, Louisville, KY, United States, 3Univ of Louisville, Louisville, KY, United States.
Rationale: Obstructive Airway Diseases (OADs) affect millions of people worldwide and are characterized by chronic inflammation and tissue remodeling in the lung. It has been proposed that the development of OAD is greatly influenced (and perhaps pre-determined) by events in early life, such as maternal smoking or an early life viral infection. Our lab previously developed a murine model of perinatal nicotine exposure, and reported that nicotine leads to airway remodeling and decreased pulmonary function in the offspring. Similarly, lower respiratory viral infections, such as Influenza A Virus (IAV), during childhood have been implicated in the development of OADs. We set out to investigate if perinatal nicotine and/or early life IAV infection could promote lung remodeling and long-term pulmonary dysfunction. Methods: C57Bl/6 mice were exposed to nicotine (drinking water at 100 µg/mL) for indicated times frames. At 14- and 30-days of age, mice were subjected to intranasal infection with a sub-lethal dose of mouse-adapted IAV pH1N1, the virus responsible for the 2009 IAV pandemic. Lung viral load was determined using TCID50/mL and Hemagglutination assays. At 4, 90 and 210 days post infection (DPI), we euthanized the animals and harvested lungs for microarray analysis (4 DPI), pathology and RT-PCR. Animals were allowed to mature until 7 months of age to be assessed for lung functional abnormalities using a flexiVent system. Results: After infection, the animals showed an increase in lung viral titers that coincided with an expected decrease in body weight gain. Both viral load and weight changes were dependent on the viral dose delivered. Histological evaluation of tissues at 4 DPI revealed increased inflammation and deposition of collagen in the lungs of infected animals. Interestingly, when tested at 7 months of age, lung functional assessments showed minor differences between mock and pH1N1 groups or nicotine-exposed groups alone. However, there were significant differences in lung function parameters between mock and animals exposed to both nicotine and IAV when challenged with methacholine. Conclusions: Perinatal exposure to nicotine along with early life IAV infection results in lung inflammation and remodeling as well as lung dysfunction that persist for extended times into adulthood. This model of nicotine exposure and IAV pH1N1 infection in young mice provides a novel tool for studying the impact of these exposures in lung.