Smoke affects lung growth, gene expression

By: Apurva Yeluru

Posted: 4/17/08

Doctors and scientists have known for years that cigarette smoke has a range of damaging effects on the human body. In adults, excessive smoking can cause emphysema, a condition in which the lungs become rigid and brittle.

Babies and young children are particularly susceptible to the effects of second-hand smoke.

A team of Hopkins researchers led by Sharon McGrath-Morrow, a lung specialist from Hopkins Hospital, observed the effects of cigarette smoke in newborn mice to quantify its effects.

In the study, two groups of mice were exposed to cigarette smoke: newborn mice and their mothers, and six-week old mice. Some subjects in both groups were comprised the control group, but the rest were exposed to cigarette smoke for two weeks.

During the first week of the study, the mice were exposed to one hour of cigarette smoke per day. This time increased to two hours per day during the second week of the study.

Two weeks in mice is comparable to about two years in humans, so the study's results would be relevant to newborn babies and infants.

At the end of the two weeks, all the eight-week old mice and half the two-week old mice were sacrificed for observation. The other half of the two-week old mice were sacrificed when they turned eight-weeks old to look at the long-term effects of early exposure.

Lung growth was obviously impaired in mice exposed to smoke. Lungs mostly grow after birth, especially in the first two years of life for humans, but continue growing through adolescence.

Alveoli, little sacs inside the lung where the exchange of gas into the bloodstream occurs, are the most crucial part of the lung; these are the most susceptible to damage caused by cigarette smoke.

In the study, it was observed that the number of alveoli in the eight-week old mice was modestly lower than in a healthy mouse. Alveoli are the site of oxygen absorption in the lungs, so a decreased number of alveoli can cause hypoxia, or low oxygen levels in the blood.

The lung cells were subjected to oxidative stress, a negative effect of reactive oxygen introduced by toxic materials in the environment.

Cell death was also noticed by the researchers, at a much higher frequency than ever noticed in adult mice, suggesting that neonatal lungs are much more sensitive to cigarette smoke than adult lungs.

The study also led to another surprising observation: Cigarette smoke affects gene expression in the lung cells. It was found that 754 genes were repressed, or expressed at lower levels than normal, due to smoke.

Ten percent of these are genes involved in the immune system of the lung. These genes code for proteins called interferons, which are produced in response to pathogens in the body.

Thus, lungs become more susceptible to foreign agents like viruses and bacteria, and more prone to infection.

The researchers concluded that exposure to cigarette smoke in the early years of life significantly damages lungs more than exposure in the later years of life, affecting the growth, function and immunity of the lungs.

The effects of early exposure to cigarette smoke are more lasting, and, in humans, much more detrimental than later exposure.