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Maternal smoking during pregnancy not only poses significant immediate risks for the unborn fetus but also may have life long implications. It has broad adverse effects on fetal outcome, including increased risk of spontaneous abortion, stillbirth, low birth weight, early neonatal mortality, sudden infant death syndrome, and poor long-term pulmonary outcome. Although not widely appreciated, there is strong evidence for the deleterious effects on both prenatal and postnatal lung development following exposure to maternal smoke during pregnancy. And sadly, despite these known risks and enthusiastic antismoking campaigns, 12% of the U.S. women still smoke during pregnancy, resulting in the birth of 450,000 smoke-exposed infants in 2002. Due to the lack of molecular understanding of how smoking during pregnancy affects fetal growth, development, and function, it is not surprising that there is no effective intervention to prevent the damaging effects of smoke exposure on the developing fetus.
The mechanisms underlying the general effects of exposure to maternal smoking on fetal growth and viability are generally thought to be due to impaired oxygen supply to the fetus, however, the mechanisms underlying the harmful effects of smoking on lung are more much more complex. We are very much interested in unraveling the mechanisms of the chronic lung diseases in general, and due to nicotine, in particular. Understanding how this disease process is caused is the key to its effective prevention and treatment. Using state-of-the-art technology and innovative studies, our recent work has provided novel insights into the mechanism(s) of lung damage due to nicotine exposure on the developing lung. These studies are already showing great promise in terms of our ability to not only prevent and treat lung damage following nicotine exposure, but also normalize an already damaged lung.
These results are based on our fundamental discovery that infant’s lung has crucial fat containing cells that, under the influence of factors such as nicotine, transform into a muscle like cell, which is the hallmark of the damaged lung. Once this change has occurred, a normal functioning cell, which is essential for good lung function, is converted into a cell that has the potential to result in serious lung damage, problems with the oxygenation, and it makes infants more prone to asthma. We are in the process of teasing out the complex molecular pathways that determine the cell fate these crucial cells in the lung, i.e., what makes them to behave as “Good and Beneficial” cells and what makes them “Bad and Harmful” cells. And furthermore, we have already made unprecedented progress by showing that with appropriate manipulations we can make “Bad and Harmful” cells behave as “Good and Beneficial” cells. Based on this evidence, the work we have proposed can turn out to be pivotal in tackling the menace of damage due to nicotine exposure not only on the developing lung, but also in all other organ systems. This has an enormous potential of opening up novel interventional strategies to tackle a wide spectrum of nicotine-induced chronic diseases. |
