Another One Bites the Dust: Kicking Asthma to the Curb

Background

In 2016, the CDC reported that 8.3% of children have asthma. Asthma is a chronic lung disease in which airways become inflamed and narrowed. The cause of asthma is unknown, but scientists suspect that genetics, infections as a child, and exposure to certain allergens or viruses may have an impact on one’s development of asthma. There is no cure for this disease, although there are medicines that can help reduce an asthmatic person’s symptoms. (NIH National Heart, Lung, and Blood Institute)

Previous research has shown that children who grow up on traditional dairy farms have an apparent protection from asthma due to high levels of microbial exposure (Ege et al 2011). The problem is that researchers have been unable to define the exact effect that these microbes have on the immune systems of dairy farm children. Stein et al (2016) developed a protocol that would hopefully bridge the gap of the causes and effects of the dairy farm lifestyle and immunity against asthma.

What Did They Look For?

In their study, Stein et al (2016) examined two very similar populations, the Amish of Indiana and the Hutterites of South Dakota, to try to explain the different proportions of asthma between these two groups. What specific environmental characteristics affect the immune responses in these two populations, and how are those immune responses different? The researchers wanted to determine if there are significant differences in the immune systems of children from each group. They also aimed to find a direct effect of environmental exposure from dust in each population on the immune system in regards to asthma.

What Did They Find?

Because there is an apparent protection against asthma in children living on dairy farms (Ege et al 2011), Stein et al (2016) chose the Amish and Hutterites as their populations of interest. These two populations practice similar lifestyles as far as factors that are known to affect the risk of asthma except for their farming methods (Stein et al 2016). The Amish run single family, traditional dairy farms, while the Hutterites run industrialized, communal farms. Because the lifestyle habits of these two populations are very similar, the researchers were able to rule out any of those habits having differing effects on the children in each population with respect to their risk of asthma. Stein et al (2016) analyzed the mechanisms of the immune system affected by dairy farm microbial exposure to produce protection from asthma in comparison to that of industrial farm microbial exposure.

As part of their study, Stein et al (2016) performed a genetic analysis on the two populations to determine the genetic similarity of the two groups. They found that the Amish and Hutterites are strikingly similar, genetically speaking. These findings are based on the two populations sharing very similar single nucleotide polymorphisms (SNPs), which are a single letter change in one’s genetic code in which that specific change is common among members of a population. This similarity ruled out any differences in the study due to genetics (Stein et al 2016).

Additionally, the researchers looked at white blood cell and allergy-specific antibody levels, as well as specific markers on some white blood cells that are important to the body’s immune response in relation to asthma. Using mouse models, they also examined the effect that dust specific to each type of farm has on the airway. Stein et al (2016) found that the Amish children had lower concentrations of cells and cell markers that are associated with asthmatic reactions compared to the Hutterite children. These findings further support the hypothesis that dairy farms, like those run by Amish people, influence the body’s immune system to protect it from developing asthma.

When the researchers studied the types of cells circulating the body, they found that the Amish children had a lower concentration of cells that are important in fighting off allergens, which often play a big role in triggering asthma. They also found in the Amish evidence that other cells that fight off invaders of the body were likely recently formed, which would indicate a more active and efficient immune system (Stein et al 2016). If the body is making and replacing a lot of special fighting cells, this indicates that the body is capable of fighting off invaders efficiently. Since the Amish showed evidence of rapidly making and replacing their fighter cells, we are provided with some insight into the ways in which the Amish population is able to avoid asthma.

A great medium for microbes to get into one’s body is in the form of dust. Stein et al (2016) looked directly at the effects of the dust found in the homes of both populations  on the airways of mouse models. The researchers administered dust samples retrieved from the homes of each population into the airways of mouse models. Dust from Amish homes induced a smaller immune response in the airways of healthy mice than the dust from Hutterite homes, suggesting some amount of protection against asthmatic symptoms by Amish dust extracts. However, there was limited protection by Amish dust extracts in mice with deficiencies of the innate immune system, which is the non-specific response of the body to fight off invaders. This suggests that the Amish have protection against asthma due to their innate immune system, which is primed by microbes in the environment (Stein et al 2016).

Questions for Future Studies

The next step for this study would most likely be looking into differences between in the microbial composition of the two populations’ environments. What microbes are present or absent in the Amish environment in comparison to the Hutterite environment? Are there any significant differences at all? Then, based off of those differences, researchers could look into the direct effects that the differing microbes have on the body. They can analyze the metabolic pathways that the different microbes engage in and how the body reacts to those processes and the products made by them. Although this study provided evidence that the innate immune system is a key player in Amish protection against asthma, they were unable to provide a clear view on what exact microbes in the environment influence how the innate immune system changes and protects against asthma. An analysis of the microbial composition of the dust extracts from each population may give a clearer view on this.

Although this study provided a stepping stone toward explaining protection against asthma in certain populations, it had a number of limitations. For example, the researchers did not have a lot of samples. This can be an issue in studies that aim to generalize a finding, because they only tested a small group of people that are very specific and cannot be applied to a broader population. The findings in this study can be applied specifically to Amish in Indiana and Hutterites in South Dakota, because those are the populations that Stein et al (2016) examined. However, because this information cannot be generalized to other populations, further studies are required to gain more information on environmental factors and their influence on asthma in general.

Further Reading

  • An article by Bach (2002) provides information on how exposure to infectious agents can influence the risk of autoimmune disorders and allergies. It is a great review article that compiles information from various studies on the effects of environmental exposure in relation to autoimmunity and allergies.
  • For more information on the genetic and mechanistic background of dairy farm microbial exposure on the risk of asthma, Schuijs et al (2015) gives a detailed description that relates to this post’s original paper.
  • Braun-Fahrländer et al (2002) relates how exposure to environmental endotoxins can influence tolerance to allergens. This may provide more information on understanding why Stein et al chose to take dust samples from the Amish and Hutterite populations and examine those effects on mice.

References

Bach, JF. 2002. The Effect of Infections on Susceptibility to Autoimmune and Allergic Diseases. The New England Journal of Medicine, 347, 911-920. DOI: 10.1056/NEJMra020100

Braun-Fahrländer et al. 2002. Environmental exposure to endotoxin and its relation to asthma in school-age children. The New England Journal of Medicine, 347, 869-877. DOI: 10.1056/NEJMoa020057

Centers for Disease Control and Prevention. 2016. Asthma: Data, Statistics, and Surveillance.

Ege et al. 2011. Exposure to Environmental Microorganisms and Childhood Asthma. The New England Journal of Medicine, 364, 701-709. DOI: 10.1056/NEJMoa1007302

NIH National Heart, Lung, and Blood Institute. Asthma. https://www.nhlbi.nih.gov/health-topics/asthma

Schuijs et al. 2015.  Farm dust and endotoxin protect against allergy through A20 induction in lung epithelial cells. Science, 349, 1106-1110. DOI: 10.1126/science.aac6623

Stein et al. 2016. Innate Immunity and Asthma Risk in Amish and Hutterite Farm Children. The New England Journal of Medicine, 375, 411-421. DOI: 10.1056/NEJMoa1508749