A controlled trial of immunotherapy for asthma in allergic children

Authors: Adkinson N, Eggleston P, Eney D, Goldstein E, Schuberth K, Bacon J, et al.
Source: New England Journal of Medicine. 336:324-31; January 30, 1997.
Institution: Johns Hopkins Universtiy School of Medicine, Baltimore.
Financial support: National Institute of Allergy and Infectious Diseases.



Injections of allergens have been shown to be effective in the treatment of allergic rhinitis. Efficacy has also been shown in some studies of single-allergen models of asthma. This study was designed to look at the use of multiple-allergen injections for the treatment of children with severe, perennial asthma. Children were randomized to multiple-allergen injections vs. placebo, in addition to standard, modern medical therapy.


Results Authors' Discussion

This study showed no significant benefit for allergen injections in the treatment of perennial asthma in children, over a period of 30 months. The others discuss several possible explanations. They rebut the possibilities that these patients did not have severe enough asthma to show an effect, that they were over-medicated or that the allergens used were not potent enough.

They note that this population was selected for compliance and received presumably optimal therapy for asthma; the results might be different in a less compliant or under-medicated group. They also note that immunotherapy might be beneficial earlier in the course of asthma, which is supported by the subgroup analysis that found an effect in younger patients with milder asthma. Further studies in this subgroup should be undertaken.


(By Elizabeth Leef Jacobson, MD; Allergy/Immunology, The New York Hospital, Cornell University Medical Center).

The subject of whether immunotherapy is effective in asthma has been visited frequently in the medical literature. In February 1996, a similar study by Creticos et. al. (1) was published in the NEJM. It evaluated adult asthmatics with ragweed sensitive asthma (single allergen therapy). It too showed no benefit (save a minimal improvement in peak flow). In an accompanying editorial (2), Peter Barnes stated that immunotherapy is no longer used for asthma in the United Kingdom, and that the treatment should be re-evaluated in the United States. In these days of managed medicine, with the clinical impression of allergists being that immunotherapy is still a useful adjunct in asthma therapy and criticisms that single allergen therapy is not as realistic as multiple allergen therapy, this study was undertaken.

This is a well designed trial. The choice of placebo ensures good blinding. Because allergen extracts are not strictly standardized and the children were on different combinations of extracts, they did not all receive the same microgram amounts of antigen. This cannot be avoided in a study involving multiple extract allergen immunotherapy.

As stated in the discussion, the authors selected for an extremely compliant population of children. This was accomplished by having a long run in time and a requirement to rid the home of furred pets (which would have eliminated at least half of my patients and may explain part of the decrease from 350 to 121 subjects). The subjects were seen every two weeks, and both groups saw an improvement in medication use and a significant improvement in bronchial hyperreactivity as measured by methacholine sensitivity. A significantly larger group of children on treatment had systemic reactions than those who received placebo.

This level of compliance is unrealistic in a standard allergy practice. When a person comes in for "allergy shots" on a weekly basis, he is likely to say, "hey, doc, I ran out of my medicine." or, "I have sinusitis". Often, he gets a peak flow measurement prior to his injection, and early intervention is possible before a flare. The routine of regular visits imprints the routine of asthma medication compliance. This, in large part, may be why the clinical impression of many allergists is that immunotherapy is effective in asthma. In addition, the asthma patient who visits an allergist (a specialist) may receive better care than one who isn't cared for by a specialist.

All in all the advent of routine inhaled steroids has revolutionized asthma care, and added a tool which was not available to the allergists of yore who still often use immunotherapy as a treatment.

February 13, 1997

Reader comments

Mon, 17 Feb 1997
From: "Engler, RJM" <renata@erols.com>

This article has many problems with it, particularly failing to treat patients for a major allergen shown to cause asthma in inner cities - cockroach! A more balanced study is needed to address the question more fairly. Asthma, particularly early onset, can be shut off with grass pollen immunotherapy (prior study) and clinically many patients will lose out if this is not considered as one of many treatment options.


Letters to the Editor about this article, from the NEJM website.

Topics include the failure to test and treat for cockroach allergy, and whether the results can be generalized to a less compliant population.

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1. Creticos P, Reed C, Norman P, Khoury J, Adkinson N, et al. Ragweed immunotherapy in adult asthma. N Engl J Med 1996;334:501-6.

2. Barnes P. Is immunotherapy for asthma worthwhile? N Engl J Med 1996;334:531.

References related to this article from the NLM's PubMed database.

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