RATIONALE:Childhood risk factors for long-term lung health often coexist and their specific patterns may affect subsequent lung function differently. OBJECTIVES:To identify childhood risk factor profiles and their influence on lung function and chronic obstructive pulmonary disease (COPD) in middle age, and potential pathways. METHODS:Profiles of 11 childhood respiratory risk factors, documented at age 7, were identified in 8,352 participants from the Tasmanian Longitudinal Health Study using latent class analysis. We investigated associations between risk profiles and post-bronchodilator lung function and COPD at age 53, mediation by childhood lung function and adult asthma, and interaction with personal smoking. RESULTS:Six risk profiles were identified: 1) unexposed or least exposed (49%); 2) parental smoking (21.5%); 3) allergy (10%); 4) frequent asthma, bronchitis (8.7%); 5) infrequent asthma, bronchitis (8.3%); and 6) frequent asthma, bronchitis, allergy (2.6%). Profile 6 was most strongly associated with lower forced expiratory volume in 1 second (FEV1) (-261; 95% confidence interval, -373 to -148 ml); lower FEV1/forced vital capacity (FVC) (-3.4; -4.8 to -1.9%) and increased COPD risk (odds ratio, 4.9; 2.1 to 11.0) at age 53. The effect of profile 6 on COPD was largely mediated by adult active asthma (62.5%) and reduced childhood lung function (26.5%). Profiles 2 and 4 had smaller adverse effects than profile 6. Notably, the effects of profiles 2 and 6 were synergistically stronger for smokers. CONCLUSIONS:Profiles of childhood respiratory risk factors predict middle-age lung function levels and COPD risk. Specifically, children with frequent asthma attacks and allergies, especially if they also become adult smokers, are the most vulnerable group. Targeting active asthma in adulthood (i.e., a dominant mediator) and smoking (i.e., an effect modifier) may block causal pathways and lessen the effect of such established early-life exposures.