Contemporaneous maturation of immunologic and respiratory functions during early childhood: implications for development of asthma prevention strategies

Patrick Holt, John Upham, Peter Sly

Research output: Contribution to journalArticle

170 Citations (Scopus)

Abstract

The term asthma refers to a spectrum of wheezing syndromes resulting from airways inflammation triggered by a range of environmental stimuli, the most important of which are aeroallergens and viruses. We describe below a model for the cause of atopic asthma in which discrete sets of developmental factors governing the postnatal maturation of the immune and respiratory systems play central and complementary roles in disease causality. Within the immune system, the relevant developmental processes involve maturation of T(H)1 and associated innate immune functions that combat infection and concomitantly antagonize the early programming of T(H)2-polarized immunologic memory against inhalant allergens. Within the respiratory system, the relevant developmental processes involve intensive lung growth and airway remodeling during infancy. We hypothesize that delayed maturation of T(H)1-associated functions during early postnatal life increases the risk for sensitization to aeroallergens and for severe respiratory infection, resulting in airway inflammation at a crucial stage in lung development and precipitating changes in lung growth that are the harbingers of susceptibility to persistent asthma. We further hypothesize that protection of the growing lung against the effects of inflammation during infancy and early childhood has unique potential as a generic strategy for asthma prophylaxis.
Original languageEnglish
Pages (from-to)16-24; quiz 25
JournalJournal of Allergy and Clinical Immunology
Volume116
Issue number1
DOIs
Publication statusPublished - 2005

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