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INTRODUCTION

AUTHOR/ARTICLE INFORMATION

REFERENCES

INTRODUCTION

AUTHOR/ARTICLE INFORMATION

REFERENCES

INTRODUCTION

AUTHOR/ARTICLE INFORMATION

REFERENCES

INTRODUCTION

AUTHOR/ARTICLE INFORMATION

REFERENCES

INTRODUCTION

AUTHOR/ARTICLE INFORMATION

REFERENCES

INTRODUCTION

AUTHOR/ARTICLE INFORMATION

REFERENCES

IN THIS issue of the ARCHIVES, Dr Tsitoura and her colleagues¹ report on a remarkable international dataset of infants and young children at high risk for becoming allergic to, but not yet sensitized to, house dust mites. In a primary prevention trial, these children were randomized either to an intervention group that received a simple house dust mite–reduction strategy (mattress encasement and detailed preventive environmental recommendations, such as hot-washing of sheets and bedding) or to a control group, whose parents received information about general indoor environmental issues. After 1 year, children in the intervention group were less than half as likely as controls to have developed allergy to house dust mites (3.0% vs 6.5%). Furthermore, the frequency of asthma symptoms and asthma diagnoses was greater among the children who became sensitized to house dust mites during the study year. How potentially significant are these findings in the context of allergies and asthma? To consider this question, it is helpful to review selected issues focusing on the public health problem of asthma, which, unlike allergic rhinitis, frequently results in exacerbations that require hospitalization and other types of rescue care.

The health burden of asthma is enormous and has steadily increased during the last 3 decades in the United States, although since 1995 has shown signs of stabilizing.² Studies from England, Sweden, and Australia show a doubling of prevalence of allergic rhinitis during this time.³ These increases in respiratory allergies and asthma have been observed primarily in westernized societies. The pharmaceutical industry has developed agents for controlling asthma and allergy symptoms and exacerbations (without serious adverse effects!), and clinicians receive a plethora of reminders to use them. Health care professionals have responded with clinical management guidelines for allergic rhinitis and asthma that are based on a growing body of evidence.^{3, 4} A chronic care model now exists for responding to the specific needs of patients with chronic illness such as asthma, and methods for disseminating this model in the primary care setting have been developed and deployed (for more information, see reference 5, http://www.healthdisparities.net, http://www.nichq.org, and http://www.ihi.org).

Underlying all of this effort and activity, however, remains a fundamental questionWhere is all the asthma and allergy coming from? The atopic response is a combination of genetic predisposition and environmental exposure; since we are basically the same genetic species as our parents and grandparents, we must, therefore, look for environmental changes over this period as an explanation for these increases in prevalence. For asthma, the most likely environmental culprits are irritants (primarily environmental tobacco smoke although outdoor diesel exhaust may also play a role in some communities), respiratory infectious agents (primarily viruses), and indoor airborne allergens (primarily house dust mites, cockroaches, molds, and pet dander).

Based on the results of one longitudinal birth cohort of more than 1000 subjects, it seems that what we diagnose as asthma in childhood can be organized into 3 distinct phenotypes, which vary in their long-term health consequences and are the presumed result of different pathophysiologic processes. Although they can cause significant illness, the first 2 typestransient wheezing and nonatopic wheezing in childhoodtypically resolve in the preschool years and early adolescence, respectively.⁶

Allergy-mediated asthma, the third phenotype, usually persists into later life.⁷ This more permanent asthma presupposes that the susceptible child first becomes allergic, which occurs in 2 primary ways: by generating antigen-specific immunoglobulin E, and by generating Th2 (type 2 T helper) cells from undifferentiated T helper cells. Our current understanding is that, once changed, these Th2 cells produce mostly allergy-mediating cytokines (their Th1 differentiated counterparts produce mostly infection response-mediating cytokines).⁸ The dose, duration, and timing of the allergic exposures resulting in these changes are all fertile areas of inquiry.

Most (80%) cases of allergy-mediated asthma first manifest before age 6 years and more than half before age 3 years. The sooner in life a child develops allergy-mediated asthma, the more severe it tends to be, a clinical finding that supports the probable cumulative effect of the inflammatory component of asthma.⁶ As Martinez⁶ points out in this article, "if the adverse effects of persistent (allergy-mediated) asthma are to be prevented, diagnosis and intervention would seem to be necessary before the age of 5 or 6 years."

Allergy to house dust mites is the best known predictor of allergy-mediated asthma.¹³ Although this report focused on house dust mites only, there are additional clinically important allergens found in bedding.¹⁰ In a recent sample of inner-city children with allergy-mediated asthma from 7 US cities, 79% were sensitized to 2 or more and 51% to 3 or more indoor airborne allergens.¹¹ In the United States, the most important of these other bed-borne allergens seems to be from cockroaches.¹⁰ Thus, bed encasements and sheet washing can facilitate avoidance of other important allergens besides dust mites, which was likely an unmeasured benefit of the intervention in this trial.

Indoor sensitivity results from inhaling small quantities of an allergen repeatedly over a period of months or years.⁹ The house dust mite is arguably the best understood of these allergens, and based on literature from several different countries, there is now an established threshold of antigen-load exposure beyond which the development of allergy or asthma becomes much more likely.¹² Epidemiologic data on antigen burden in low-income vs high-income housing are mostly unavailable. However, it is reasonable to suspect that the antigen load in low-income housing stock is greater than that in larger and newer housing, which is also likely to be better equipped for cleaning. The asthma morbidity patterns from small area analyses certainly support this idea.^{13, 14} Is it possible that our urban cores have become antigen harborages in which these offending pest- and pet-derived proteins have accumulated over the last few decades and that inner city occupants, and especially children, have played the role of canaries in these man-made mines? Could a simple environmental intervention in early childhood similar to the one described by Tsitoura and colleagues not just delay the onset of allergy-mediated asthma but fundamentally alter its expression, for example, by allowing more appropriate (ie, less allergic) differentiation of the T helper cell lines?⁸

The potential impact of this provocative finding deserves further attention and understanding. We should look forward to other reports from these data and from other projects focusing on primary prevention of allergy-mediated asthma.

 
 
Author/Article Information

 
Jim Stout, MD, MPH
Department of Pediatrics
University of Washington
Box 358853
Seattle, WA 98195
(e-mail: jstout@u.washington.edu)




 
 

REFERENCES

1.
Tsitoura S, Nestoridou K, Botis P, et al.
Randomized trial to prevent sensitization to mite allergens in toddlers and preschoolers by allergen reduction and education: one-year-results.
Arch Pediatr Adolesc Med.
2002;156:1021-1027.
ABSTRACT  |  FULL TEXT  |  PDF  |  MEDLINE
 

2.
Mannino DM, Homa DM, Akibami LJ, Moorman JE, Charon G, Redd SC.
Surveillance for asthmaUnited States, 1980-1999.
MMWR Morb Mortal Wkly Rep.
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Agency Healthcare Res Quality.
Available at: http://www.ahrq.gov/clinic/epcsums/rhinsum.htm. Accessed July 12, 2002.

 

4.
National Heart Lung Blood Institute.
Expert Panel Report 2: Guidelines for the Diagnosis and Management of Asthma.
Bethesda, Md: US Dept of Health & Human Services; 1997. Publication 97-4051A.

 

5.
Wagner EH, Austin BT, Von Korff M.
Organizing care for patients with chronic illness.
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MEDLINE
 

6.
Martinez FD.
Development of wheezing disorders and asthma in preschool children.
Pediatrics.
2002;109(suppl 2):362-367.
MEDLINE
 

7.
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Peak flow variability, methacholine responsiveness and atopy as markers for detecting different wheezing phenotypes in childhood.
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MEDLINE
 

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The Th1/Th2 paradigm.
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10.
Rosenstreich DL, Eggleston P, Kattan M, et al.
The role of cockroach allergy and exposure to cockroach allergen in causing morbidity among inner-city children with asthma.
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MEDLINE
 

11.
Crain E, Walter M, O'Connor G, et al.
Home and allergic characteristics of children with asthma in seven US urban communities and design of an environmental intervention: the Inner-city Asthma Study.
Environ Health Perspect.
In press.

 

12.
Platts-Mills TA, Vervloet D, Thomas WR, Aalberse RC, Chapman MD.
Indoor allergens and asthma: report of the Third International Workshop.
J Allergy Clin Immunol.
1997;100(suppl 6 pt 1):S2-24.
MEDLINE
 

13.
Claudio L, Tulton L, Doucette J, Landrigan PJ.
Socioeconomic factors and asthma hospitalization rates in New York City.
J Asthma.
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MEDLINE
 

14.
Washington, Childhood asthma hospitalizations–King County 1987-1998.
MMWR Morb Mortal Wkly Rep.
2000;49:929-933.
MEDLINE