Contemporaneous maturation of immunologic and respiratory functions during early childhood: implications for development of asthma prevention strategies.
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 TH1 and associated innate immune functions that combat infection and concomitantly antagonize the early programming of TH2-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 TH1-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.
Holt
Patrick G
PG
Telethon Institute for Child Health Research, Centre for Child Health Research, The University of Western Australia, Australia.
Upham
John W
JW
Sly
Peter D
PD
D001249:Asthma / Q000517:prevention & control*; D006801:Humans; D007107:Immune System / Q000254:growth & development*; D007223:Infant; D007231:Infant, Newborn; D008954:Models, Biological; D012137:Respiratory System / Q000254:growth & development*; D013601:T-Lymphocytes / Q000276:immunology