Long-term studies of the natural history of asthma in childhood

Segmentation of children with asthma and other wheezy disorders remains the main research challenge today, as it was when described 2 centuries ago. Early childhood wheezy disorders follow different temporal trajectories, probably representing different underlying mechanisms (endophenotypes). Prospective identification of endophenotypes allowing accurate prediction of the clinical course is currently not possible. The variability of the clinical course remains an enigma and difficult to predict. Three of 4 school-aged children with asthma have outgrown disease by midadulthood. The risk of persistence increases with severity, sensitization, smoking, and female sex. Genetic risk variants might help disentangle the heterogeneity of asthma and other wheezy disorders. At early school age, children with asthma have reduced lung function. It is an important and unresolved question whether the airflow limitation associated with asthma already existed at birth or developed along with symptoms. Likewise, the association between the infant's bronchial responsiveness and development of asthma and other wheezy disorders is unclear. Neither primary prevention through manipulation of environmental factors nor secondary prevention through the use of inhaled corticosteroids can effectively halt the long-term disease progression in childhood. In conclusion, the natural history of asthma and the associated airway changes is still poorly understood, and we have not managed to translate findings from long-term studies into a deeper understanding of the underlying endophenotypes or improved disease management. We propose the need for a translational research approach based on long-term clinical studies of birth cohorts with comprehensive and objective assessments of intermediate phenotypes and environmental exposures combined with interdisciplinary basic research and a systems biology approach. (J Allergy Clin Immunol 2010;126:187-97.)