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• Influenza vaccine effectiveness for preventing asthma exacerbations
  Robert L. Davis
  Published on: 9 January 2022

• Published on: 9 January 2022

  Influenza vaccine effectiveness for preventing asthma exacerbations

  • Robert L. Davis, Epidemiologist
  • Other Contributors:
    • Paul Gargiullo, Frank DeStefano, Robert Chen

  Dear Editor,

  We are concerned that the conclusions of the recent article by Christy et al [1] are not supported by their data, and that their article might be misinterpreted by some as casting doubt on the usefulness of influenza vaccine among asthmatics.

  In observational studies such as the one by Christy, a crucial issue in interpreting the results is understanding how the authors went about...

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  Dear Editor,

  We are concerned that the conclusions of the recent article by Christy et al [1] are not supported by their data, and that their article might be misinterpreted by some as casting doubt on the usefulness of influenza vaccine among asthmatics.

  In observational studies such as the one by Christy, a crucial issue in interpreting the results is understanding how the authors went about controlling for the underlying reasons that would determine, among asthmatics, why certain of them received influenza vaccine and why others did not. As one example, patients with severe asthma could have been more regular patients of the clinic and were thus more likely to be vaccinated and have exacerbations detected there. Sporadic users of clinic services would have been less likely to have been vaccinated there (if at all) and may not have had their exacerbations treated there. Dichotomizing utilization, as Christy did, or classifying asthma as mild, moderate or severe, may not have completely controlled for this behavior in the analysis.

  In a prior study done by us, we found that controlling extensively for identifiable ‘characteristics’ of severity among the asthmatic subjects, such as number of prior emergency department visits or utilization of asthma medication provided only incomplete control of the extent of the severity of the level of asthma. [2] In that past study, we used unconditional Poisson regression models that simultaneously adjusted for severity of asthma and for sex, age, HMO, preventive care practices, and seasonal fluctuations in asthma exacerbations. To control for severity of asthma, we used the number of inhaled beta-agonist dispensings, the number of hospitalizations and ED visits for asthma during the 6 months before the influenza season, and we also adjusted for preventive care practices with frequency of cromolyn dispensings during the 6 months before the influenza season. Even so, in this analysis, the relative risk for asthma exacerbations among those vaccinated ranged from 1.4 to 2.2, similar to that found by Christy et al.

  It was only when we analyzed our data using a self-control method of adjustment that influenza vaccine was shown to be efficacious in reducing asthma exacerbations. Using the self-control method, incidence rate ratios of asthma exacerbations after vaccination ranged from 0.59 to 0.78 during 3 influenza seasons, and the protective effect was statistically significant in each season. Christy et al. state that ‘the adverse effect of vaccination disappeared only after the authors eliminated the unvaccinated group from the analysis, but this is a questionable methodology for assessing vaccine effectiveness’. The self control methodology is one that is well accepted, has been used for many studies - including ones of adverse events following immunization, myocardial infarction following strenuous physical activity, and motor vehicle accidents associated with cell phone usage - and allows for more exact adjustment of individual characteristics that would otherwise confound observational studies. [3-6] Our self-control analysis had not simply eliminated the unvaccinated group from the analysis, instead it focused on comparing rates of acute asthma attack before versus after influenza vaccination. The self-control method used each subject’s pre-vaccination rate as a baseline rate unique to that subject, thereby avoiding confounding by differences in asthma severity between subjects. Although most commonly used for events that occur very closely linked in time to some proposed trigger, this method can also be applied to events more distant in time, as we did in our study. [7]

  In conclusion, we disagree with the authors’ claim that self-control analyses are not valid. Our previous study suggests that influenza vaccination may protect against asthma exacerbation.

  References

  (1). Christy C, Aligne CA, Auinger P,et al. Effectiveness of influenza vaccine for the prevention of asthma exacerbations. Arch Dis Child 2004:89:734-735

  (2). Kramarz P, Destefano F, Gargiullo PM et al. Does influenza vaccination prevent asthma exacerbations in children. J Pediatr 2001; 138:306-10.

  (3). Albert CM, Mittleman MA, Chae CU, et al. Triggering of sudden death from cardiac causes by vigorous exertion. N Engl J Med 2000;343:1355-61.

  (4). Farrington CP, Nash J, Miller E. Case series analysis of adverse reactions to vaccines: a comparative evaluation. Am J Epidemiol 1996;143:1165-73.

  (5). Mittleman MA, Mintzer D, Maclure M et al. Triggering of myocardial infarction by cocaine Circulation. 1999;99:2737-41

  (6). Riddlemeier DA, Tibshirani RJ. Association between cellular- telephone calls and motor vehicle collisions. N Engl J Med. 1997;336:453- 8.

  (7). Maclure M, Mittleman MA. Should we use a case-crossover design? Annu Rev Public Health 2000: 21:193-221.

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  Conflict of Interest:
  None declared.

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