Viruses, Bacteria and Microbes May Play a Role in Causing–and Preventing–Asthma in Children
By Carrie L. Adkins
When Nietzsche said, “That which does not kill us makes us stronger,” he was referring to threats more grandiose than viruses. But his maxim holds true even with these humble beasts, especially when it comes to childhood asthma.
Researchers have long known that certain viral infections, such as RSV and rhinovirus, exacerbate asthma, but evidence now suggests that severe infections can actually prevent children from developing the disease.
While the link is still under investigation, it’s titillating the scientific community. Several studies have shown that severe viral infections in early life may be associated with persistent lower levels of IgE and less allergic sensitizations in later life, says Fernando Martinez, MD, professor of pediatrics and director of the respiratory sciences center at the University of Arizona, Tucson, Ariz.
The ironic twist is that the most dangerous and severe viruses are actually the most beneficial. The severity of a virus is not based on its class, such as RSV vs. rhinovirus, but on the strength of the individual strain. And now that modern medicine has enabled us to lessen the severity of many viruses, we have a potential explanation for the rise of asthma.
“We’re seeing increasingly that in societies where families are smaller, where hygiene is better and there is less infection, that characteristic allergies and asthma seem to be increasing,” Dr Martinez notes. “It’s a plausible idea that these increases may be associated with less severe infections. Biology is not politically correct. By saving all those children … we may be keeping alive people who are more likely to develop allergies and asthma.”
STRONG VS. WEAK
So how can a severe infection be more beneficial than a mild one? The answer lies in how infections in early life guide the development of the immune system, Dr. Martinez explains. One of the most important mechanisms in the immune system is the T-helper cell, a type of lymphocyte. These cells modulate the type of reaction to environmental threats. Th-1 cells are associated with the body’s defense against infection and trigger the release of immunoglobulin type G. Th-2 cells are associated with allergies and asthma, and trigger IgE release, Dr. Martinez explains. It’s this Th-2 response that causes the inflammation associated with asthma.
Because an infant’s highly malleable immune system is not fully developed at birth, it matures through a process of repeated infections, he says. When a child is exposed to an immunological threat, his body must decide whether to react with Th-1 or Th-2 cells. These early decisions may determine how a child will react to all future threats.
When a child is exposed to a weak virus, his immune system activates an antiviral pathway, which causes the body to fight with Th-2 cells. This, in turn, causes higher IgE production, according to Farhad Imani, PhD, instructor of medicine at Johns Hopkins School of Medicine, Baltimore, Md.
Stronger viruses, however, have adapted and developed a mechanism to inhibit human or animal intracellular antiviral pathways. Because viruses avoid these pathways, the body attacks them with Th-1 cells instead. When one type of T-cell is active, it works to suppress the other, so if a severe infection causes the body to produce Th-1 cells, those cells will further fight the properties of a Th-2 reaction, Dr. Imani says. As a consequence of the chain reaction caused by Th-1 cell activation, a child has a much lower chance of developing asthma and atopic diseases because the immune system will now respond to future threats with a Th-1 response.
Early infections are particularly important in children because their immune systems are still developing until about age three, Dr. Imani continues. If a child is exposed to more mild viruses or allergens, his immune system may learn to react to threats in an allergic, inflammatory way, Dr. Martinez says. If, however, that same child is exposed to a severe virus, his body will learn to react with Th-1 cells instead. Researchers have proposed that many factors may affect this early immune decision, including exposure to tobacco smoke, diet, genetics and breast feeding, he adds.
A group of researchers in Japan studied 867 school children who were tested and vaccinated against TB at 3 months, 6 years and 12 years.1 The children who had the strongest reaction to the TB vaccine were the least likely to develop asthma and related conditions. In other words, their bodies learned to react to asthma triggers in non-asthmatic ways.
This idea of early exposure preventing later disease is further demonstrated in large families, Dr. Martinez tells ADVANCE. The youngest children from large families have fewer allergies than their older siblings do. This may be because the younger children are exposed to more infections via the older children, enabling them to turn on their Th-1 systems first. Researchers are also looking at the possibility that as women grow older they transmit less of their own allergies to their babies.
Viruses aren’t the only organisms that play a role in asthma–parasites and bacteria have their places too. Within the last 50 years we have simultaneously witnessed a dramatic reduction in parasitic infections and an explosion in asthma in developed countries, Dr. Martinez says. Up to 80 to 90 percent of children in poor areas of Venezuela or Latin America are parisitized, for example, yet their asthma and allergy rates are significantly lower than in developed, parasite-free countries, he says.
While parasites protect against asthma, mycoplasma may play a role in exacerbating it. About five years ago Richard J. Martin, MD, head of the pulmonary division and vice chairman of the department of medicine at National Jewish Medical and Research Center, Denver, began treating a severely asthmatic, steroid-dependent woman. When he analyzed her airway lining tissue for cilia dysfunction, he found something else entirely–mycoplasma invaded the submucosal tissue.
Dr. Martin followed this lead and studied an additional 19 asthmatics and 10 controls.2 He found that over 50 percent of the asthmatics did, indeed, have mycoplasma in their airways.
“It looks promising that mycoplasma may play a role in at least a subset of asthmatics,” he tells ADVANCE. “If this is true, then it’s a whole new way of looking at the pathogenesis and treatment of asthma.”
For one thing, it introduces the possibility of treating asthma with antibiotics. In the same study, Martin et al. administered clarithromycin to the study group and found a positive response in lung function and airway inflammation. Anecdotally, Dr. Martin has seen several patients who have been treating their asthma successfully with clarithromycin for several years. But while the antibiotic can control the asthma when patients take it, as soon as they stop, their symptoms return. The drug isn’t strong enough to kill the mycoplasma, Dr. Martin explains, it can only suppress it. One possible solution may be to use multiple antibiotics simultaneously, he suggests.
While infections may be associated with less allergies and asthma, it’s not reasonable to begin infecting children with potentially life-threatening viruses to prevent them from future asthma and allergies. Instead, Dr. Martinez suggests, the most successful strategy is to further investigate the immune system and find harmless ways to imitate nature.
“We’re keeping children from infections we don’t want them to have anymore, so we have to find a vaccination that will enhance immune response without jeopardizing children’s lives,” he says.
The potential problem with a vaccination is that many vaccines are attenuated viruses and may actually serve to set the immune system on the wrong path, Dr. Imani warns.
While researchers don’t yet think that the immune system of a patient with developed asthma will be able to un-learn its asthmatic response, they do they believe that asthma may be prevented some day.
“The hope of a cure,” Dr. Martinez says, “is centered on understanding what determines what develops later in life.”
1. TB May Protect Against Asthma. Chemistry & Industry News. Http://ci. mond.org/9702/970209.html.
2. Kraft M, Cassell GH, Bettinger CM, Duffy LB, Pak J, Martin RJ. Mycoplasma pneumoniae as a cofactor in chronic asthma. Abstract presented at ALA/ATS, San Francisco, 1997.
Carrie Adkins is assistant editor of ADVANCE.