Interaction between Asthma and Lung Function Growth in Early Life

Rationale: The causal direction between asthma and lung function deficit is unknown, but important for the focus of preventive measures and research into the origins of asthma. Objectives: To analyze the interaction between lung function development and asthma from birth to 7 years of age. Methods: The Copenhagen Prospective Studies on Asthma in Childhood is a prospective clinical study of a birth cohort of 411 at-risk children. Spirometry was completed in 403 (98%) neonates and again by age 7 in 317 children (77%). Measurements and Main Results: Neonatal spirometry and bronchial responsiveness to methacholine was measured during sedation by forced flow-volume measurements. Asthma was diagnosed prospectively from daily diary cards and clinic visits every 6 months. Children with asthma by age 7(14%) already had a significant airflow deficit as neonates (forced expiratory flow at 50% of vital capacity second in neonates reduced by 0.34 z score by 1 mo; P = 0.03). This deficit progressed significantly during early childhood (forced expiratory flow at 0.5 seconds in neonates at age 7 reduced by 0.82 z score by age 7; P < 0.0001), suggesting that approximately 40% of the airflow deficit associated with asthma is present at birth, whereas 60% develops with clinical disease. Environmental tobacco exposure, but not allergic sensitization, also hampered airflow growth. Bronchial responsiveness to methacholine in the neonates was associated with the development of asthma (P = 0.01). Conclusions: Children developing asthma by age 7 had a lung function deficit and increased bronchial responsiveness as neonates. This lung function deficit progressed to age 7. Therefore, research into the origins and prevention of asthma should consider early life before and after birth.