Mechanisms of allergy and adult asthmaThe early-life origins of asthmaSaglani, Sejal; Bush, Andrew Author Information aImperial School of Medicine at National Heart and Lung Institute, London, UK bRoyal Brompton Hospital, London, UK Correspondence to Andrew Bush, MB, BSc (Hons), MA, MD, FRCP, FRCPCH, Professor of Paediatric Respirology, Department of Paediatric Respiratory Medicine, Royal Brompton Hospital, Sydney Street, London SW3 6NP, UK Tel: +44 20 7351 8232; fax: +44 20 7351 8763; e-mail: [email protected] Current Opinion in Allergy and Clinical Immunology: February 2007 - Volume 7 - Issue 1 - p 83-90 doi: 10.1097/ACI.0b013e32801297e6 Buy Metrics Abstract Purpose of review 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. Recent findings 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. Summary 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. Copyright © 2007 Wolters Kluwer Health, Inc. All rights reserved.