The early-life origins of asthma.
OBJECTIVE
Early-life events are pivotal in determining adult lung function and disease, and the prognosis of preschool wheeze is determined by gene-environment interactions, antenatally and in the first 3 years of life.


RESULTS
Birth cohort studies show that lung function tracks from the first 3 years of life into adolescence and probably beyond. Umbilical-cord-blood studies demonstrate that the immunological responses to viral infections are in part determined antenatally. The neutrophil not the eosinophil is the key effector cell in preschool wheeze. Allergic sensitization in the first 3 years of life is key to subsequent prognosis. Histological changes develop in the airway after the onset of symptoms, but by school age the full-blown airway pathology of atopic asthma is present. Although novel genes such as ADAM33 studied in isolation are of interest, unless gene expression is studied in the context of the environment, misleading conclusions will be reached. We need disease-modifying therapy; inhaled steroids do not prevent progression from intermittent to persistent wheeze.


CONCLUSIONS
The first 3 years of life are pivotal in determining lung function and prognosis of wheeze, probably throughout life. Further research requires focused hypotheses encompassing genes and the environment in which they are expressed.
Saglani
Sejal
S
Imperial School of Medicine at National Heart and Lung Institute, London, UK.
Bush
Andrew
A
D001249:Asthma / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology*; D002675:Child, Preschool; D006801:Humans; D007223:Infant; D007231:Infant, Newborn