Journal of Manipulative and Physiological Therapeutics
Prize-winning papersEffects of diphtheria-tetanus-pertussis or tetanus vaccination on allergies and allergy-related respiratory symptoms among children and adolescents in the United States*
Introduction
The prevalence of allergic disorders has increased 50% to 100% among adults and more than doubled among children during the past 20 years. 1, 2, 3, 4 Asthma and other allergies currently affect 30 to 50 million persons in the United States. 5, 6 An estimated 17.3 million persons had symptomatic physician-diagnosed asthma in 1998.7 Asthma and allergic rhinitis, accounting for 9.1 and 8.4 million office visits, respectively, in 1996, are 2 of the 20 most common principal diagnoses given to patients of office-based physicians.8 Asthma is also one of the primary reasons for visiting a hospital outpatient department,9 with 900,000 visits. Chronic sinusitis, which is often associated with asthma and allergic rhinitis, is the most common chronic condition in the United States,10 resulting in 14.3 million office visits per year.8 Allergic rhinitis, sinusitis, and asthma are 3 of the 5 most common principal diagnoses given to children and adolescents (aged 15 years and younger) in ambulatory care, accounting for 9.4 million visits annually and 5.8% of all visits.11 The total cost of asthma care alone was estimated as $6.21 billion in 1990.12 Although there is speculation about the causes of the increased prevalence of asthma and other allergic conditions, 1, 2, 3, 4 no agent or set of agents has been shown to be responsible for the increase. In addition, the upward trend is probably not entirely a result of the increased public recognition of allergies, diagnostic coding, measurement error, or other nonclinical factors. 1, 3, 4
Studies in animals and human beings have demonstrated that components of diphtheria and tetanus toxoids and pertussis (DTP) and tetanus vaccines have adjuvant effects 13, 14, 15 and are associated with elevated levels of total and specific immunoglobulin E antibodies. 16, 17, 18 There is evidence that these components cause a Th1 to Th2 shift in CD4 cells, 19, 20 resulting in interleukin-4 (IL-4) production and greater stimulation of mast cells, subsequent release of histamine and other inflammatory mediators, and allergic symptomatology.21 Pertussis and DTP vaccines have also been shown to enhance rodents'and human beings'sensitivity to histamine. 22, 23
The biologic plausibility of a causal vaccination-allergy association is bolstered by cases of anaphylaxis immediately after immunization with the DTP and tetanus vaccines (2 cases per 100,000 injections or 6 per 100,000 children given 3 doses of DTP)24 and the high incidence of local immediate hyper-sensitivity reactions to tetanus toxoids, 25, 26, 27, 28 diphtheria,29 and the development of IgE antibodies after tetanus and diphtheria toxoids vaccinations. 30, 31 Two committees convened by the Institute of Medicine (the Committee to Review the Adverse Consequences of Pertussis and Rubella Vaccines and the Vaccine Safety Committee) concluded that there is a causal relation between the DTP vaccine and anaphylaxis24 and tetanus toxoid and anaphylaxis.32 More recently, pertussis has been shown to increase the risk of asthma in children aged less than 2½ years.33 The authors of 3 retrospective cohort studies found strong associations between pertussis or DTP immunization and the diagnosis of asthma and other atopic disorders in children aged more than 4 years. 34, 35, 36
We hypothesize that the DTP or tetanus vaccination is associated with subsequent risk of asthma and other allergies and episodes of sinusitis or sinus problems and other allergy-related respiratory symptoms among infants, children, and adolescents between the ages of 2 months and 16 years in the United States.
Section snippets
Data source and subject selection
We used data from the Third National Health and Nutrition Examination Survey (NHANES III), conducted by the National Center for Health Statistics from 1988 to 1994. 37, 38 NHANES III is based on a complex sample design with oversampling of certain groups.39 Sample weights are used to adjust for differential selection probabilities, noncoverage, and nonresponse; the weighted sample is designed to represent the civilian noninstitutionalized population of the United States.39
This analysis uses
Characteristics of subjects
Table 1 shows the number and weighted percent of the 13,944 subjects aged 2 months through 16 years by selected variables.Variable Number* Weighted%† Age (y) <5 7151 30.0 5–10 3980 35.7 11–16 2813 34.3 Race White 9048 77.9 Black 4328 16.5 Other 568 5.6 Sex Male 6894 51.2 Female 7050 48.8 Household income >$10,000 2786 12.9 $10,000–29,999 5626 37.4 $30,000–49,999 2582
Discussion
DTP or tetanus vaccination in US children is associated with lifetime history of asthma or other allergies and allergy-related symptoms in the past 12 months. This study, to our knowledge, provides the most comprehensive assessment of the effects of DTP or tetanus vaccination on allergies and allergy-related respiratory symptoms. Evidence was also presented showing that vaccination may be associated with different types of allergies at different ages. The vaccination may be associated with
Conclusion
Asthma and other allergic hypersensitivity reactions and related symptoms may be caused, in part, by the delayed effects of DTP or tetanus vaccination. One or more vaccine components may be responsible for a portion of the increased prevalence of asthma and allergies in US children. Given the consistency of the estimated effects for many types of allergies and allergic reactions, the control of confounding by known risk factors for asthma and other allergies, the observation of effects for both
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Submit reprint requests to: Eric L. Hurwitz, DC, PhD, UCLA School of Public Health, Department of Epidemiology, Box 951772, Los Angeles, CA 90095-1772; [email protected].