Conclusion
Natural infection with influenza can contribute to asthma exacerbation. Thus, influenza vaccine prevents asthma exacerbation by protecting against natural infection. Influenza vaccines do not cause asthma or asthma exacerbation. Other vaccines currently routinely recommended to the general population in the U.S.* have not been shown to cause asthma or asthma exacerbation. Aluminum adjuvants in vaccines have not been shown to cause asthma in children.
Epidemiological Evidence
The 2012 report on adverse effects of vaccines by the Institute of Medicine (IOM) [1], now called the National Academy of Medicine (NAM), described a number of studies with sufficient validity and precision that all found no association between inactivated influenza vaccination and asthma exacerbation [2-10]. The report described several studies with sufficient validity and precision that generally reported no association between live attenuated influenza vaccination (LAIV) and asthma exacerbation as well [11-17]. However, a 2015 white paper on the safety of influenza vaccines concluded that LAIV was associated with an increase in wheezing in children ages 18 to 35 months who had a history of wheezing; in the U.S. LAIV is not approved for children under 2 years of age and “should not be used” in children 2-4 years of age with a history of wheezing or asthma in the previous year [18]. Two studies of the 2013-2014 and 2014-2015 flu seasons in the United Kingdom study found that LAIV was well tolerated among those with well-controlled asthma or recurrent wheezing [19, 20]. A prospective observational cohort study found an increased risk of wheezing among California children 2-4 years of age during the 42-day risk interval after receiving quadrivalent LAIV during the 2013–2014 influenza season [21].
One study published in 2015 suggests a possible protective effect of MMR vaccination against asthma [22]. A 2002 Vaccine Safety Datalink (VSD) study did not find an association between asthma and diphtheria, tetanus and whole cell pertussis vaccine (relative risk: 0.92; 95% confidence interval: 0.83-1.02), oral polio vaccine (RR: 1.09; 95% CI: 0.90-1.23), or measles mumps and rubella (MMR) vaccine (RR: 0.97; 95% CI: 0.91-1.04); weak associations were found with Haemophilus influenzae type b (Hib) vaccine (RR: 1.18; 95% CI: 1.02-1.36) and hepatitis B vaccine (RR:1.20; 95% CI: 1.13-1.27). A 2022 VSD study found an association between aluminum adjuvanted vaccines and persistent asthma among both children with eczema (adjusted hazard ratio: 1.26 per 1 mg increase in aluminum; 95% CI: 1.07-1.49) and children without eczema (aHR 1.19; 95% CI: 1.14-1.25). However, these limited observational data are insufficient to draw clear causal conclusions.
Proposed Biological Mechanism
Influenza, along with other natural viral respiratory infections, can contribute to asthma exacerbation, as these viruses enter and replicate within airway epithelial cells, causing damage and initiating an immune response. Natural influenza infection also causes greater morbidity in asthmatic subjects than in the general population, perhaps due to a difference in the antiviral response of asthmatics [23].
The 2012 IOM report described cases of asthma exacerbation after both inactivated and live attenuated influenza vaccination [24]; however, even after considering knowledge about the aforementioned natural infection, the IOM concluded that this mechanistic evidence was weak [1].
Animal studies suggest that aluminum adjuvants could impact allergy risk through inducing a T helper 2 cell (Th2) immune response [25, 26]. In allergic asthma, Th2 lymphocytes mediate airway inflammation and hyper-responsiveness [27]. Exposure to aluminum through vaccination could bias the immune profile toward Th2 immune responses, thus theoretically increasing risk of allergic diseases such as asthma [28].
* These conclusions do not necessarily consider vaccines recommended only for special populations in the United States such as Yellow Fever vaccine (international travelers) or Smallpox vaccine (military personnel).
References
1. Institute of Medicine, in Adverse Effects of Vaccines: Evidence and Causality, K. Stratton, et al., Editors. 2012, National Academies Press (US): Washington (DC).
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