Photo Credit: by Mars Hartdegen, Flickr.com
A diagnosis of asthma is not normally cause for celebration. But according to the latest research, it seems that the root cause of this disease may actually offer some protective measures against a deadly condition known as sepsis. The key to this odd association may be certain elements of the immune system that in asthma patients are active at abnormal levels, causing the asthma symptoms but maybe also protecting against the aggressive bacterial infections that cause sepsis.
Sepsis is a condition that develops in response to a bacterial infection. It occurs most often in people who are in the hospital or have just left. While any bacterial infection can lead to sepsis, the most common causes are bloodstream infections, pneumonia, abdominal, and kidney infections. When the body faces a large-scale infection the immune system kicks in to fight this off; however; this response can inadvertently go into overdrive and release into the bloodstream the immune factors that cause inflammation, causing a body-wide inflammation response. If this occurs, the body can go into “septic shock” and begin to shut down. According to many doctors, the key to sepsis treatment is prevention — treating the infection before it becomes so severe that sepsis occurs — and this is where individuals with asthma may have a step up on the rest of us.
Asthma is a complex condition that causes shortness of breath because of inflammation in the airways, often requiring chronic-use medication. Researchers and doctors are still trying to unravel the exact mechanisms behind this inflammation. It appears as though there is a mix of environmental and genetic factors that will cause someone to suffer from asthma symptoms. At the moment, three specific immune system components are believed to be involved: the type-2 helper (Th2) cells, a cytokine named interleukin 17, and toll-like receptor proteins (TLRs). The immune system is an incredibly complex mess of many interacting proteins and cells – but in short, these three components all act to cause inflammation in response to a pathogen; or in the case of asthma, even in the absence of a pathogen.
Herein lays the key to why those with asthma are less likely to suffer sepsis and septic shock: the inflammation response is already active in their bodies – on the one hand causing asthma and on the other, ready to pounce when an infection does occur. This could prevent the infection from progressing to the septic shock stage.
At present this proposed mechanism of protection against sepsis is still only a hypothesis. What is known, however, is a much lower incidence of sepsis and sepsis-related mortality occurs in patients with asthma when compared with similar patients (with the same age, ethnicity, gender, income, etc.). This is by no means the only circumstance where a pathogen or disease that is harmful under most conditions has a beneficial outcome under different conditions. One well-known example is the fact that having the genetic disease, sickle-cell anemia, protects against malaria infection. In sickle cell anemia, a single mutation in the DNA coding for red blood cells causes them to have a sickle-shape and not transport oxygen as efficiently. As a result though, these sickle cells are harder for deadly malaria parasites to invade and destroy. Evolutionary biologists have long thought such a mutation should have died off in the population because the effects are so severe. This is not the case, however, and it could be due to its protective function against malaria, evidenced by the fact that rates of sickle-cell are much higher in areas where malaria is still a major problem.
Another example, more closely related to the asthma-sepsis data, is the now well-studied phenomenon that parasitic worms can help to regulate various auto-immune conditions such as irritable bowel syndrome (IBS) and even asthma. The way in which they seem to do so again has to do with the interactions between pathogens and the immune system. Auto-immune disorders occur when an overactive immune system begins to attack its own body tissues. Having a parasitic worm, however, gives the immune system another target to focus on and can thus relieve the symptoms of auto-immune disease in some cases. Researchers discovered this phenomenon when they realized that incidences of disorders like IBS and asthma occur more often in countries that eliminated most parasite infections. This is consistent with what we now call the “hygiene hypothesis”: essentially, because we evolved for millennia with parasite infections our bodies developed the immune system responses to tolerate them, and when the parasites are removed the immune response is left with nothing to do and attacks the body. Under this theory the overly clean and parasite-free environment of developed nations is the cause of a number of auto-immune conditions and allergies.
It’s an ongoing struggle to understand the complex relationship between our bodies, the organisms that inhabit them, and the mechanisms we evolved to fight them off – it seems the difference between friend and foe is not always black and white. However, better treatments could result from understanding these interactions and viewing pathogens as existing on a spectrum of good and bad, depending on the situation, while taking environment and even genetics into account. Advances in the study of microbiomes are starting to shed light on these relationships—and future study of exactly why asthma patients suffer lower rates of sepsis will inform doctors on how to better prevent sepsis in the rest of us.
Dr. Bradley van Paridon is a writer and science communicator who holds a PhD in Parasitology.
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