Combined Diphtheria and Tetanus Increase Asthma Risk - GI Link

Early-Life Infections, Immunizations Alter Childhood Asthma Risk
From Reuters Health Information CME
http://cme.medscape.com/viewarticle/719682

News Author: Megan Brooks
CME Author: Laurie Barclay, MD
CME Released: 04/02/2010; Valid for credit through 04/02/2011

April 2, 2010 — Recurrent bouts of gastroenteritis in the first two years of life increase the risk of asthma by age 6 years, a study in allergy-prone children suggests.

Combined diphtheria and tetanus (DT) immunization in the first year of life also increased the risk of childhood asthma in the prospective study.

"There are a range of possible explanations for the finding of an association between CDT in the first year and asthma," lead author Dr. Jennifer A. Thomson from the University of Melbourne, Australia told Reuters Health by email.

"CDT is only used for those children who meet specific indications such as a reaction to triple antigen (DTP)," she said. "The requirement for combined DT may reflect (or) be a marker for those children with delayed or altered development of their immune systems and consequent inherent allergic tendency."

The role of early childhood infections and immunizations in the development of allergic diseases "remains controversial," Dr. Thomson and colleagues noted in a March 23rd online paper in Pediatric Allergy and Immunology.

To investigate associations between gastroenteritis, otitis media, and lower respiratory tract infections before age 2, immunizations, and asthma, the researchers enrolled 620 infants who had first-degree relatives with allergies. The children all belonged to the Melbourne Atopy Cohort Study. By age 6, 488 (79%) were still in the study.

Each of the three types of infection was associated with a modest increase in risk of asthma by age 6, the investigators report. The average increased risk per infection episode ranged from 7% to 58%. The relative risks (RR) with gastroenteritis, otitis media, and lower respiratory tract infection (including bronchitis) were 1.07, 1.30, and 1.58, respectively.

Children with at least three bouts of gastroenteritis in the first two years of life had a greater than twofold increased relative risk of having asthma by age 6 (crude RR, 2.36; adjusted RR, 2.03).

"Children with recurrent gastroenteritis in infancy/early childhood may be at increased risk of asthma in later childhood and therefore a higher level of clinical suspicion and monitoring for asthma is appropriate," Dr. Thomson told Reuters Health.

By age 1, approximately 98% of the children had received at least one immunization with diphtheria/tetanus/pertussis (DTP) and 99% received at least one Sabin oral polio immunization. Less than 5% received at least one combined DT immunization in each of the first or second years.

According to the researchers, combined DT immunization in the first year yielded crude and adjusted relative risks of asthma at age 6 years of 1.76 and 1.88, respectively.

Dr. Thomson said she was not aware of other studies that reported an association between combined DT vaccination and asthma. She emphasized, however, that the study does not suggest a "causal link." Rather, it shows a statistical association "for which a range of explanations (some noted above) may apply."

"While chance is an unlikely explanation for the finding, it can not be eliminated completely; nor can unknown or recognized confounders for which we lacked data be definitively excluded," Dr. Thomson said.

Importantly, she added, the association between combined DT and the later development of asthma "should not deter parents from immunizing their children when weighted against the benefits."

The study also found that oral polio immunization in the second year of life was associated with a decreased risk of asthma at 6 years (crude RR, 0.60; adjusted RR, 0.63).

"Early childhood immunizations that are administered orally such as Sabin and/or more recently introduced immunizations such as the rotavirus vaccine may offer benefit in preventing the development of childhood asthma and other allergic diseases," Dr. Thomson said.

Pediatr Allergy Immunol. Published online March 23, 2010. Abstract
Reuters Health Information 2010. © 2010 Reuters Ltd.

Clinical Context
The impact of early childhood infections and immunization on subsequently developing allergic diseases is still unclear. Results have been inconsistent from epidemiologic studies assessing immunization and allergic disease, with different findings based on which vaccines were given and in which settings.

One theory suggests that immunization may contribute to the development of allergic diseases by preventing natural infection, by providing a different microbial exposure, or by affecting the natural microbial flora. On the other hand, an alternate theory proposes that by providing some microbial exposure, immunization may help prevent the development of allergic disease.

Study Highlights
• This prospective study examined the association between early childhood infections and immunization and the development of allergic disease, particularly asthma, in a high-risk cohort of allergy-prone children from birth to age 6 years.
• The study cohort consisted of 620 infants who had first-degree relatives with allergic diseases and who were recruited into the Melbourne Atopy Cohort Study.
• A questionnaire administered by an interviewer gathered data on risk factors and outcomes, which were based on parental report and/or clinician diagnosis.
• Potential risk factors were gastroenteritis; otitis media; lower respiratory tract infections; and other early childhood infections, as well as immunizations from birth to age 2 years.
• Outcomes were current asthma, allergic rhinitis, and eczema reported at age 6 years.
• RR and confounding were determined with univariate and multivariate regression analysis.
• Study retention was 79% of the original cohort at 6 years.
• All of the early childhood infections studied, including otitis media and lower respiratory tract infections, were associated with an increased risk for asthma at age 6 years, but the most consistent increased risk was with multiple episodes of gastroenteritis.
• Participants with at least 3 episodes of gastroenteritis were at increased risk for the development of asthma at age 6 years (crude RR, 2.36; 95% CI, 1.41 - 3.95; adjusted RR, 2.03; 95% CI, 1.50 - 2.75).
• For scheduled immunizations, Sabin immunization in the second year was associated with a lower risk for asthma at age 6 years (crude RR, 0.60; 95% CI, 0.37 - 0.98; adjusted RR, 0.63; 95% CI, 0.39 - 1.02).
• Combined DT immunization in the first year was associated with a greater risk for asthma at age 6 years (RR, 1.76; 95% CI, 1.11 - 2.78; adjusted RR, 1.88; 95% CI, 1.28 - 2.77).
• A similar pattern was not seen with combined DT immunization in the second year.
• The investigators concluded that recurrent gastroenteritis in early childhood is associated with a later risk for asthma, which could reflect a cause-and-effect relationship or exposure to common risk factors.
• They also noted that Sabin immunization in the second year is associated with a lower risk for asthma in later childhood.
• Although combined DT immunization in the first year may be a risk factor for asthma, the need for combined DT immunization could also be a marker of greater risk for asthma in later childhood.
• The investigators recommend that clinicians have a higher level of clinical suspicion and monitoring for asthma among those children with recurrent gastroenteritis.
• Limitations of this study include possible overestimation of risk for the general population of children, possible unknown confounders, limited statistical power, lack of data on perinatal risk factors or child care, reliance on parental or clinician reporting, and some loss to follow-up.
Clinical Implications
• In the prospective Melbourne Atopy Cohort Study, recurrent gastroenteritis in early childhood was associated with a later risk for asthma, which could reflect a cause-and-effect relationship or exposure to common risk factors.
• In this cohort, Sabin immunization in the second year was associated with a lower risk for asthma in later childhood. Although combined DT immunization in the first year may be a risk factor for asthma, the need for combined DT immunization could also be a marker of greater risk for asthma in later childhood.

Authors and Disclosures
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Author(s)
Megan Brooks
Megan Brooks is a freelance writer for Reuters Health Information.

Disclosure: Megan Brooks has disclosed no relevant financial relationships.
Editor(s)
Brande Nicole Martin
CME Clinical Editor, Medscape, LLC

Disclosure: Brande Nicole Martin has disclosed no relevant financial relationships.
CME Author(s)
Laurie Barclay, MD
Freelance writer and reviewer, Medscape, LLC

Disclosure: Laurie Barclay, MD, has disclosed no relevant financial relationships.