New Evidence Shows Thirdhand Smoke Could Alter Your Immune System—Even Before You Are Born

A team of researchers from UC San Francisco, Lawrence Berkeley National Laboratory, the University of Southern California and UC Berkeley investigated how thirdhand smoke exposure during pregnancy and early childhood could affect the health and wellness of babies and children.

May 5, 2021

By: Leta Dickinson

Although all people are subject to the adverse health effects associated with the chemical residue left behind from burning tobacco products and e-cigarette use, called thirdhand smoke, children are among the most vulnerable. This is because they tend to spend more time indoors and are more susceptible to ingesting and touching smoke-contaminated surfaces like toys, floors, and tabletops while learning how to play and interact with their surroundings. With smaller, still developing bodies, they are exposed to more thirdhand smoke and have fewer defenses to protect themselves from the slew of toxic chemicals in thirdhand smoke.

Thus, when studying thirdhand smoke and its dangers, children are of particular interest. A group of researchers from UC San Francisco, Lawrence Berkeley National Laboratory, the University of Southern California and UC Berkeley were interested in exploring the connection between environmental exposures and the development of childhood cancers. Noting a rising number of child leukemia rates, they hypothesized that perhaps a child’s exposure to thirdhand smoke during their mother’s pregnancy and early life could be associated with a greater likelihood of leukemia development or other long-lasting health consequences. The researchers decided to model early thirdhand smoke exposure in mice to see if and how this chemical exposure would affect the health of mice later on. Their results could suggest similar effects from thirdhand smoke in human children.

Thirdhand smoke exposure is notoriously difficult to study because it often comes hand-in-hand with secondhand smoke (e.g., when a family member smokes in the presence of children, it exposes children to secondhand smoke and creates thirdhand smoke on household surfaces).  This makes it challenging to isolate the effects of third- from secondhand smoke. The controllable and monitorable nature of laboratory experiments with mice make them a good starting place to understand how thirdhand smoke might affect us.

In this experiment, pregnant mice were first separated into two groups: One group lived in enclosures containing a piece of cloth with thirdhand smoke residue, while the other, the control group, had no such exposure. These pregnant mice gave birth, and their pups inhabited the thirdhand smoke-exposed or control (no exposure) enclosures with their mothers until weaned. Then, in order to observe the relationship between leukemia, a cancer in the body’s blood-forming tissues, and thirdhand smoke, the researchers had to isolate the effect of thirdhand smoke on leukemia-susceptible, blood-forming tissues like the bone marrow. Bone marrow from five-week-old mouse pups was transplanted into a different set of healthy, unexposed mice. This way, the researchers could assume that any cancers these otherwise healthy mice developed were likely to be caused by the thirdhand smoke-exposed and unexposed bone marrow transplants. For the next year, this second set of mice was observed and monitored.

Throughout the experiment, the researchers noted four distinct differences between the mice that had early exposure to thirdhand smoke (before and just after birth) and those who did not. The exposed mice had lower birth weights (male pups only), lower cytokine levels, and altered numbers of immune cells. The mice that received the bone marrow transplants from these exposed mice pups had different tumor and leukemia patterns than the recipients of bone marrow from non-exposed mice.

The first observed effect had to do with birth weights in male mouse pups. The male pups whose mothers were exposed to thirdhand smoke had significantly lower birth weights than the pups from the control group that had mothers with no exposure. The birth weight of human babies is often used as an indicator of infant morbidity and mortality. If a similar trend of smaller babies due to thirdhand smoke exposure occurs in humans, it could lead to long-lasting health effects later in life for these individuals.  

But why only male pups? Dr. Scott Kogan, one of the study authors from UCSF, says that the current research doesn’t exactly have an answer. “We can speculate, but there isn’t a lot of information on this,” he says. “For example, we know that many cancers of blood cells are more common in men than in women; we don’t really know why that’s the case. This is an interesting observation that warrants additional follow up. It suggests that during development, for reasons we don’t understand, there appears to be—at least in mice—a greater effect of thirdhand smoke on the males than on the females.”

Another distinction between the thirdhand smoke-exposed and the unexposed mice pups was the level of cytokines. Cytokines are molecules that cells in the body use to communicate.

“[Cytokines] have many effects on health and disease,” Dr. Kogan explains, “Abnormalities of the production of cytokines can certainly influence health and disease of humans, including human children.”

The mice pups born from thirdhand smoke-exposed mothers had lower levels of 20 out of 32 cytokines that the researchers tested for. Dr. Kogan indicates that lower levels of cytokines might translate to impaired immune systems, higher rates of infection, and worse health outcomes in the development of different diseases or in disease severity.

Thirdhand smoke also affected the pups’ immune cells. When the researchers took samples from the bone marrow, spleen, and blood, they found that the numbers and types of immune cells differed between thirdhand smoke-exposed and the control mice, with thirdhand smoke suppressing the immune system to some extent. When the immune system, the body’s defense against foreign bacteria and viruses, is weakened, the body experiences more frequent and harder to treat infections.

The last finding was perhaps the most interesting. While most mice receiving bone marrow transplants, regardless of their donor’s thirdhand smoke exposure status, developed cancer at some point during observation, the types of cancer were different. The mice receiving thirdhand smoke-exposed bone marrow were diagnosed with leukemia later in life than the mice that received unexposed bone marrow. Instead, these mice with exposed bone marrow were more prone to other cancerous tumors.

Dr. Antoine Snijders, a study author from the Lawrence Berkeley National Laboratory, says this result, while perhaps confusing at first, requires careful interpretation. He points to the bone marrow transplantation as the likely explanation for this phenomenon. The thirdhand smoke-exposed mice, which had suppressed immune systems, thereby had fewer immune cells in the bone marrow sample that was transplanted, thus slowing the onset of leukemia simply because there were fewer affected cells to start with. However, the mice also underwent radiation as part of transplantation which could explain the development of other cancers, especially in the suppressed immune systems of thirdhand smoke-exposed mice. So, a weakened immune system from thirdhand smoke exposure may delay the progression of leukemia from bone marrow transplantation but also comes with a whole host of problems due to the body’s incapacitated defense mechanism that far outweigh any potential benefits from thirdhand smoke exposure.

“We don’t think that smoke is protective from childhood leukemia,” Dr. Kogan stresses. “Rather, what we thought about is that there is quite a lot of human bone marrow transplantation that is done. And it raises some questions about how the exposure of bone marrow donors to tobacco has an impact on the health of people who receive that bone marrow. That is an area that we’re interested in and that we think is important for future study.”

Of course, mice and humans have more than a few distinctions, so these findings from mice models simply serve as a starting point for further human and mouse research. Besides investigating how thirdhand smoke might affect bone marrow transplantation, the researchers are also looking to add an extra layer to the mouse study: exposing the fathers to thirdhand smoke. Previous studies have indicated that if the father is exposed to tobacco, it might increase the likelihood of leukemia development in their children. The researchers are currently exploring this possible effect of thirdhand smoke in mouse models.

The more research done on thirdhand smoke, the more we realize how potent and long-lasting its effects on the body are. This latest study adds yet another piece to this growing body of evidence. Dr. Snijders hopes for more widespread recognition of this invisible toxic residue. “I think our research and that of all of us in this field of thirdhand smoke are trying to bring [thirdhand smoke] to the forefront of general public knowledge,” he says. “Hopefully that data will then be used for framing new policies against indoor smoking or other thirdhand smoke exposure risks.”

Click here to read the research study

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