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
As an organization accredited by the ACCME, Medscape, LLC, requires everyone who is in a position to control the content of an education activity to disclose all relevant financial relationships with any commercial interest. The ACCME defines "relevant financial relationships" as financial relationships in any amount, occurring within the past 12 months, including financial relationships of a spouse or life partner, that could create a conflict of interest.
Medscape, LLC, encourages Authors to identify investigational products or off-label uses of products regulated by the US Food and Drug Administration, at first mention and where appropriate in the content.
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.

Children Vaccinated for Flu at Three Times the Risk for Hospitalization than Unvaccinated Peers

...and those with asthma at a higher risk of hospitalization if they get the flu vaccine.

The American Thoracic Society: Flu Shot Not Effective in Preventing Flu-Related Hospitalizations in Asthmatic Children
News Release
FOR RELEASE MAY 19, 2009 at 1:30 p.m. PDT

FOR MORE INFORMATION, CONTACT:
Keely Savoie or Brian Kell
ksavoie@thoracic.org or bkell@thoracic.org
ATS Office: 212-315-8620 or 212-315-6442 (until May 13)
Cell phones: 917-860-5814 (KS) or 516-305-9251 (BK)
ATS Press Room: 619-525-6323, 619-525-6324 or 619-525-6325 (May 15 to 20)
Mini-Symposium time: May 19: 1:30 p.m. to 4 p.m.
Presentation time: May 19: 3:20 p.m.
Location: San Diego Convention Center, Room 3 (Upper Level)

Flu Shot Not Effective in Preventing Flu-Related Hospitalizations in Asthmatic Children

ATS 2009, SAN DIEGO— The inactivated flu vaccine does not appear to be effective in preventing influenza-related hospitalizations in children, especially the ones with asthma. In fact, children who get the flu vaccine are more at risk for hospitalization than their peers who do not get the vaccine, according to new research that will be presented on Tuesday, May 19, at the 105th International Conference of the American Thoracic Society in San Diego.

Flu vaccine (trivalent inactivated flu vaccine—TIV) has unknown effects on asthmatics.

“The concerns that vaccination maybe associated with asthma exacerbations have been disproved with multiple studies in the past, but the vaccine’s effectiveness has not been well-established,” said Avni Joshi, M.D., of the Mayo Clinic in Rochester, MN. “This study was aimed at evaluating the effectiveness of the TIV in children overall, as well as the children with asthma, to prevent influenza-related hospitalization.”

The CDC’s Advisory Committee on Immunization Practices (ACIP) and the American Academy of Pediatrics (AAP) recommend annual influenza vaccination for all children aged six months to 18 years. The National Asthma Education and Prevention Program (3rd revision) also recommends annual flu vaccination of asthmatic children older than six months.

In order to determine whether the vaccine was effective in reducing the number of
hospitalizations that all children, and especially the ones with asthma, faced over eight consecutive flu seasons, the researchers conducted a cohort study of 263 children who were evaluated at the Mayo Clinic in Minnesota from six months to 18 years of age, each of whom had had laboratory-confirmed influenza between 1996 to 2006. The investigators determined who had and had not received the flu vaccine, their asthma status and who did and did not require hospitalization. Records were reviewed for each subject with influenza-related illness for flu vaccination preceding the illness and hospitalization during that illness.

They found that children who had received the flu vaccine had three times the risk of hospitalization, as compared to children who had not received the vaccine. In asthmatic children, there was a significantly higher risk of hospitalization in subjects who received the TIV, as compared to those who did not (p= 0.006). But no other measured factors—such as insurance plans or severity of asthma—appeared to affect risk of hospitalization.

“While these findings do raise questions about the efficacy of the vaccine, they do not in fact implicate it as a cause of hospitalizations,” said Dr. Joshi. “More studies are needed to assess not only the immunogenicity, but also the efficacy of different influenza vaccines in asthmatic subjects.”

###

Session # C94: “Viral Infections in Childhood Respiratory Disease”
Abstract # 561: “Flu Vaccination in Asthmatics: Does It Work?”
http://www.call4abstracts.com/ats/society_admin/abs_preview.php?absnum=561
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ATS 2009 · San Diego
International Conference
Abstract Number: 561
Contact/Presenting Author: Avni Y. Joshi
Department/Institution: Internal Medicine, Mayo Clinic
Address: 200, First St. SW
City/State/Zip/Country: Rochester, MN, 55905
Phone: 01-507-284-2511 Fax: 01-507-284-0902 E-mail: joshi.avni@mayo.edu
ATS member: No Student or in training: Yes
Funding Source: None.
Abstract Category: 14.03 - Pediatric Asthma
Presentation format: Either Poster or Oral
Preview Disclosure
Travel Award: Yes
Publication of email address: Yes, joshi.avni@mayo.edu
I confirm that all authors listed on this abstract have knowledge of the abstract submission:
Yes
Title: Flu Vaccination in Asthmatics: Does It Work?
A. Y. Joshi, MD1, V. N. Iyer, MD,MPH1, M. F. Hartz, MD1, G. W. Volcheck, MD,Ph.D1, A. M. Patel,
MD1 and J. T. Li, MD,Ph.D1. 1Mayo Clinic College of Medicine, Rochester, MN.
INTRODUCTION: Influenza is known to be associated with asthma exacerbation but the
effectiveness of the trivalent inactivated flu vaccine (TIV) in asthmatics is unknown.

METHODS: We conducted a cohort study of all pediatric subjects( 6 months to 18 years age) who were evaluated at Mayo Clinic, Rochester, MN, USA who had laboratory confirmed influenza during each flu season from 1999-2006 to evaluate the efficacy of TIV. A case control analysis was performed with the cases and the controls being the subjects with asthma who did and did not required hospitalization with the influenza illness respectively.

RESULTS:
There were 236 subjects with laboratory confirmed influenza from 1996-2006.

In assessing the effectiveness of the TIV for preventing hospitalization with influenza in all subjects, there was an overall trend towards higher rates of hospitalization in subjects who got the TIV as compared to the ones who did not get the TIV( OR:2.97, CI: 1.3,6.7).Using Cochran-Mantel-Haenszel (CMH) test for Asthma status stratification, there was a significant association between hospitalization in asthmatic subjects and TIV (P=0.006).

http://www.call4abstracts.com/ats/society_admin/abs_preview.php?absnum=561 (1 of 2) [5/11/2009 1:43:56 PM]
http://www.call4abstracts.com/ats/society_admin/abs_preview.php?absnum=561
In the asthmatic subset:
There was no association between ER visit and receiving the TIV ,severity of asthma and the risk of hospitalization or the hospital length of stay and receiving the TIV.

In assessing access to medical care, there was no association between hospitalizations and health care insurance plans (Odds ratio:0.3, P= 0.13)

CONCLUSION:
1) TIV did not provide any protection against hospitalization in pediatric subjects' esp. children with asthma. On the contrary, we found a 3- fold increased risk of hospitalization in subjects who did get the TIV vaccine.This may be a reflection not only of the vaccine effectiveness but also the population of children who are more likely to get the vaccine.

2) More studies are needed to assess not only the immunogenicity but also efficacy of different influenza vaccines in asthmatic subjects.
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