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The Proceedings of the American Thoracic Society 4:277-282 (2007)
© 2007 The American Thoracic Society
doi: 10.1513/pats.200702-033AW

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Microbial Manipulation of Immune Function for Asthma Prevention

Inferences from Clinical Trials

Jennifer Yoo1, Haig Tcheurekdjian1, Susan V. Lynch2, Michael Cabana3 and Homer A. Boushey1

1 Division of Allergy and Immunology, Department of Medcine, 2 Department of Anesthesia and Perioperative Care, and 3 Department of Pediatrics, University of California, San Francisco, San Francisco, California

Correspondence and requests for reprints should be addressed to Homer A. Boushey, M.D., Box 0130, 1292-M, University of California, San Francisco, 505 Parnassus Avenue, San Francisco, CA 94143-0130. E-mail: homer.boushey{at}ucsf.edu

ABSTRACT

The "hygiene hypothesis" proposes that the increase in allergic diseases in developing countries reflects a decrease in infections during childhood. Cohort studies suggest, however, that the risks of asthma are increased in children who suffer severe illness from a viral respiratory infection in infancy. This apparent inconsistency can be reconciled through consideration of epidemiologic, clinical, and animal studies. The elements of this line of reasoning are that viral infections can predispose to organ-specific expression of allergic sensitization, and that the severity of illness is shaped by the maturity of immune function, which in turn is influenced by previous contact with bacteria and viruses, whether pathogenic or not. Clinical studies of children and interventional studies of animals indeed suggest that the exposure to microbes through the gastrointestinal tract powerfully shapes immune function. Intestinal microbiota differ in infants who later develop allergic diseases, and feeding Lactobacillus casei to infants at risk has been shown to reduce their rate of developing eczema. This has prompted studies of feeding probiotics as a primary prevention strategy for asthma. We propose that the efficacy of this approach depends on its success in inducing maturation of immune function important in defense against viral infection, rather than on its effectiveness in preventing allergic sensitization. It follows that the endpoints of studies of feeding probiotics to infants at risk for asthma should include not simply tests of responsiveness to allergens, but also assessment of intestinal flora, immune function, and the clinical response to respiratory viral infection.

Key Words: asthma • gastrointestinal • lactobacilli • microbes • prevention







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