Feature Article: Aluminum and Asthma?

When it’s time to decide about vaccines for their children, parents are often wrought with angst. They want to protect their children and do “the right thing,” but they worry that vaccination could inadvertently harm the child. These fears are often made worse if a parent seeks out information on the internet or social media. Indeed, even in casual conversations with other parents, vaccine safety concerns may be magnified.

Often the most concerning ideas are those that are vague; for example, the notion that vaccines are replacing infectious diseases with chronic diseases. This idea is validated in parents’ minds by the fact that they have never seen or experienced the infectious disease that the vaccine is aimed at, but they have seen or experienced the chronic condition being put forth as an example.

Asthma is one such example. Asthma is a chronic condition in which airways in the lungs suffer prolonged, low-level inflammation, causing the individual to have periodic episodes of breathing difficulties and wheezing when the inflammation is aggravated.

• Find out more about changes in the lungs due to asthma in this video from the American Lung Association.

While the causes of asthma continue to be studied, several factors are known to contribute to the likelihood of developing this condition. These include family history, other allergies, infections during childhood that are caused by certain respiratory viruses, exposure to particular environmental conditions (e.g., dust, mites, smoke, chemicals, molds and smog), and obesity.

Recently, a paper was published that suggested a potential association between the amount of aluminum children were exposed to in vaccines during the first two years of life and their likelihood of being diagnosed with asthma between 2 and 5 years of age. Like concerns about vaccines causing chronic conditions, concerns about aluminum in vaccines have been around for some time, which is why these researchers completed the study. Because of this interest, we wanted to work through these findings together with our readers.

Study

Daley MF, Reifler LM, Glanz JM, et al. Association between aluminum exposure from vaccines before age 24 months and persistent asthma at age 24-59 months. Acad Peds. 2022, Article in press.

Brief summary

This study analyzed data from the Vaccine Safety Datalink (VSD), a U.S.-based research network designed to monitor vaccinations for the purposes of vaccine safety. Three aspects of this study are worth looking at more closely to understand what it does and does not tell us about aluminum and asthma: study population, aluminum processing, and disease caused by aluminum.

Study population

The study population included 326,991 children born between January 2008 and December 2014 who received care from one of seven VSD sites. Of these, 7,546 were identified as having asthma based on the study definition. For each child, immunization records were used to determine their aluminum exposure from vaccines during the first two years of life with the goal of comparing that exposure with the likelihood of developing asthma between 3 and 5 years of age. Two population-based choices made by the researchers are important given the goals of this study:

• First, children were not included if they were diagnosed with asthma before 24 months of age. The authors indicated that they wanted to ensure that the exposure to aluminum in vaccines was distinct in time from the development of asthma.
• Second, the data were subdivided based on whether a child had been diagnosed with eczema prior to 12 months of age. This choice was made because children with eczema are at increased risk for developing asthma.

As a result of these two choices, more than 6% of children (n = 25,188) were excluded from the study sample (because they were diagnosed with asthma before 24 months of age) and more than 4% (n = 14,337) were separated and compared with the remaining cohort (because they were diagnosed with eczema before 12 months of age). Given the number of children excluded because they developed asthma prior to “completing” their exposure to aluminum, we need to be cautious about our interpretation of these data, particularly as related to causality. It is notable that more children were excluded because they had the condition being studied than children in the subgroup considered to be at increased risk for developing the condition.

Aluminum processing

The goal of this study was to evaluate exposure to aluminum and development of asthma. However, this aspect of the study also has important considerations to keep in mind when considering the findings:

• First, the authors chose to measure total aluminum exposure from vaccines in the first two years of life and compare that with development of asthma in the next three years of life. This is like saying that the ice cream you consumed in elementary school is associated with your weight gain in middle school. It’s problematic because so many other things, including ice cream you ate while in middle school, would also affect your weight. And, like ice cream, aluminum does not simply accumulate in the body. Once aluminum reaches the bloodstream, most of it (90%) is bound to a protein, called transferrin, and removed through our kidneys. About half is eliminated within 24 hours and about three-fourths, within two weeks. As such, aluminum exposure in the first two years of life would be difficult to associate with the development of a disease in the third to fifth year of life — a time when most of the aluminum from the vaccines is long gone.
• Related to this, and equally important, vaccines are not the only source of aluminum exposure in the first five years of life. Indeed, aluminum is introduced daily through the environment, food and water. And, while most aluminum that is consumed does not enter our bloodstream, some does, so only looking at one source of aluminum does not present a complete picture of aluminum exposure.
• Further, studies of aluminum processing have demonstrated that the amount of aluminum from food and water that enters our bloodstream varies based not only on the quantities in each food, but also on the chemical environment at the time. For example, if you eat an orange at lunch with your turkey and cheese sandwich, you are likely to absorb more aluminum from the cheese and bread in your sandwich than if you eat a banana with your sandwich. Does this mean you should not have that orange? Of course, not. We consume milligrams of aluminum every day and only a small portion of that aluminum makes it out of our digestive tract and into our body. But this example demonstrates the larger point that understanding what happens following aluminum exposure is more complex than simply comparing a quantity of aluminum and a particular disease outcome.

By opting to evaluate exposure to aluminum based solely on vaccine content in the first two years of life, the study established an arbitrary assumption. And, while one could argue that this was a low threshold to which all children were exposed, we have no information about the other quantities to which children were exposed. The authors tried to evaluate breastfeeding during the first two years of life, but the data were limited, and there was no information related to which formulas the non-breastfed infants were fed (aluminum concentrations vary by product and preparation), daily volumes they consumed, etc. The authors also failed to control for exposure to environmental pollutants or a family history of asthma or allergies. This critical lack of controls severely limited the authors’ ability to isolate the effect of the one variable they were interested in studying — aluminum intake. Additionally, all participants continued to consume food and water during years three to five, when they were diagnosed, and here too, there were no data to evaluate their exposures. In short, while it is difficult to assess the effects of exposure in a situation like this, applying arbitrary assumptions that exclude ongoing exposures and biological processing variability does not really help us understand anything about the association between these two variables.

Disease caused by aluminum

Aluminum-containing ingredients are included in some vaccines because they serve as adjuvants, which are ingredients that increase the immune response to a vaccine. The authors theorized that the aluminum content in vaccines could change the type of immune response generated by the vaccine (T helper 1 (Th1) vs T helper 2 (Th2)). Because the latter (Th2) induces chemicals that cause low levels of inflammation, they hypothesized that a disease based on long-term inflammation, like asthma, was theoretically possible. While understanding the mechanism by which an adjuvant increases the immune response is an important undertaking, the type of study the authors undertook will not answer that question. Further, if we evaluate the larger context, some observations are important:

• The aluminum in vaccines is processed and removed, so even if the type of immune response shifts when aluminum is present, it would not induce long-term generation of the chemicals that cause inflammation — especially one to three years later.
• When people become ill from exposure to high levels of aluminum, they most often experience conditions related to bone density because when remaining aluminum accumulates in our bodies, most of it accumulates in our bones.
• And, while the lungs have been found to contain aluminum, it is typically in a different form because it is inhaled when we breathe, rather than deposited from our bloodstream.

For these reasons, an analysis to understand the hypothesis that an adjuvant changes the way the vaccine is processed would be better answered using alternative research approaches.

What this study did and did not show

The primary conclusion these authors presented was that “a positive association was found between vaccine-related aluminum exposure and persistent asthma.”

Unfortunately, this primary conclusion fails to provide additional context:

1. Of the more than 300,000 children included in this study, just over 7,500 were diagnosed with asthma (2.3%). On the other hand, about 70% of the children were exposed to the highest quantities of aluminum in vaccines (4 mg or more).
2. The average age when the children in both the eczema and non-eczema groups were diagnosed was between 44 and 45 months of age — almost two years after the aluminum exposure period being measured, which if you recall from the earlier section, aluminum breaks down over time. Likewise, if aluminum exposure from vaccines was associated with the development of asthma and a subgroup of the children were predisposed to developing asthma, one might expect that the children with eczema would develop the disease sooner.
3. In both groups, other measures were also positively associated with the diagnosis of asthma, including male sex, non-Hispanic Black race/ethnicity, having food allergies, and two measures of healthcare utilization (outpatient and emergency department visits). In some categories, early-life severe bronchiolitis and being born prematurely were also associated with development of asthma. Indeed, many of these measures were more positively associated with development of asthma than cumulative aluminum exposure.

Likewise, as described earlier, choices made in designing this study can’t be dismissed because the real world does not operate in closed systems. Deciding to only look at aluminum delivered by vaccines while ignoring the everyday exposures from other sources is not representative of what happens. Further, using cumulative measures of aluminum introduced by vaccines as if they are static over a four- to five-year period ignores everything we know about aluminum chemistry and processing.

Takeaway

This study did not prove a causal relationship between aluminum exposure in vaccines and the development of asthma. Like the Indian folktale about the blind men and the elephant, this study provides one bit of information that needs to be considered in the context of a much larger and more complex system. While more studies will be done to further explore the hypothesis that this study has generated, parents should continue to follow the recommended immunization schedule to protect their children from very real, potentially life-threatening, diseases.

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