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To the Editor: While the prevalence of asthma and allergic disease is increasing worldwide,¹ both diseases appear to be less common in rural settings in developing countries and farming communities in industrialized countries.² Indeed, some locales seem to be almost free of asthma.³ To explain the low prevalence of asthma in these settings, the "hygiene hypothesis" suggests that early childhood exposure to high levels of bacterial and viral pathogens leads to a lower risk of asthma and atopy.^4-5 The immune response to these infections would presumably inhibit helper T cell type 2 (T_H2)–type allergic responses.

We recently reported on the potential of environmental endotoxin—a cell-wall component from gram-negative bacteria that is ubiquitous in the environment—to provide an atopy-protective effect.⁶ Infants sensitized to common allergens had significantly lower levels of house-dust endotoxin in their homes. Furthermore, higher house-dust endotoxin levels correlated with increased proportions of interferon-–producing CD4 T_H1 lymphocytes in peripheral blood, suggesting that household endotoxin exposure may have an atopy-protective effect by augmenting T_Hl-type immune development. Therefore, we sought to determine if people in locales with a lower prevalence of asthma and atopy have greater exposure to environmental endotoxin.

Methods
We measured levels of house-dust endotoxin obtained from homes in 3 different settings: urban homes in Denver; farm homes and associated barns (with animals such as cows, horses, goats, chickens, cats, and dogs) located in Colorado except for 1 pair each in New Hamphire, Wyoming, and Missouri, respectively; and homes in rural India and Peru that are inhabited by similar animals. Methods for house dust collection, preparation, and endotoxin measurement were described previously.⁵

Results
Urban homes had significantly lower house-dust endotoxin levels than farm homes and rural homes in developing countries (P<.001, Wilcoxon rank sum test) (Figure 1). Farm barns had significantly higher endotoxin levels compared with both farm homes (P<.001, t test) and rural homes in developing countries (P = .03, t test). Farm home and associated barn endotoxin levels were significantly correlated (Spearman r = 0.67, P = .02).

View larger version (14K): [in this window] [in a new window] Figure. House-Dust Endotoxin Concentrations From Homes in Denver, US Farms, and Rural Areas of Peru and India House-dust endotoxin levels are reported in endotoxin units (EU)/mL, using reference standard endotoxin provided by the US Food and Drug Administration. Log transformation of endotoxin values normalized the distribution of the data. Data points with error bars and associated numbers indicate the geometric mean values and SEM for each location subgroup. Wilcoxon rank sum test, P<.001. Farm barns outnumber farm homes because some homes had more than 1 associated barn and also because some barns were sampled with permission from workers when farm homeowners were not home.

Comment
Greater levels of exposure to environmental endotoxin from early childhood, especially in rural areas of developing countries and in farming communities, may help explain the low prevalence of asthma and allergies observed in children raised in these environments. If environmental endotoxin exposure in early life has an atopy-protective effect, then T_H1-type activity may be induced separately from exposure to serious infections, thus suggesting a possible strategy for allergy and asthma prevention.

Jose E. Gereda, MD; Donald Y. M. Leung, MD, PhD; Andrew H. Liu, MD
National Jewish Medical and Research Center and
University of Colorado Health Sciences Center
Denver

1. Beasley R, Crane J, Lai CK, Pearce N. Prevalence and etiology of asthma. J Allergy Clin Immunol. 2000;105:466-472. 2. von Mutius E. The environmental predictors of allergic disease. J Allergy Clin Immunol. 2000;105:9-19. FULL TEXT | ISI | PUBMED 3. Weinberg EG. Urbanization and childhood asthma: an African perspective. J Allergy Clin Immunol. 2000;105:224-231. FULL TEXT | ISI | PUBMED 4. Martinez FD, Holt PG. Role of microbial burden in aetiology of allergy and asthma. Lancet. 1999;354(suppl 2):SII12-SII15. 5. Ball TM, Castro-Rodriguez JA, Griffth KA, Holberg CJ, Martinez FD, Wright AL. Siblings, day-care attendance, and risk of asthma and wheezing during childhood. N Engl J Med. 2000;343:538-543. FREE FULL TEXT 6. Gereda JE, Leung DY, Thatayatikom A, et al. Relation between house-dust endotoxin exposure, type 1 T-cell development, and allergen sensitisation in infants at high risk of asthma. Lancet. 2000;355:1680-1683. FULL TEXT | ISI | PUBMED

Letters Section Editors: Stephen J. Lurie, MD, PhD, Senior Editor; Phil B. Fontanarosa, MD, Executive Deputy Editor.

JAMA. 2000;284:1652-1653.

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