Fetal Origins of Asthma: A Longitudinal Study From Birth to Age 36 Years

Abstract

To determine the relationship between the low percentage of expiratory time necessary to reach tidal expiratory flow (tPTEF/tE) and flow at the end tidal point (VmaxFRC) in early infancy to the development of asthma, airflow limitation, and airway structural abnormalities in this 36-year birth cohort of the Tucson Children’s Respiratory Study.This is a birth cohort consisting of 1246 healthy infants born between 1980 to 1984 enrolled in the TCRS. Only 180 infants <6 months of age were tested by using the chest compression technique for pulmonary function testing because this technique was not developed until the end of the enrollment period.Demographic information was obtained via parent completed questionnaires. Infant lung function testing included tidal breathing indices, functional residual capacity via a helium-dilutions-gas-equilibration method, and partial expiratory-flow curves, from which the tPTEF/tE was determined. VmaxFRC was determined via partial expiratory flow-volume curves by using the chest compression technique. Active asthma was defined as a physician diagnosis of asthma at any age, with active symptoms within the previous year based on questionnaires obtained every 2 to 4 years between the ages of 6 and 36 years. Survey information, spirometry (prebronchodilator and postbronchodilator and full lung volumes), and high-resolution computed tomography of the chest was completed at the age of 26 years. Data were analyzed via multivariate linear regression models and generalized estimating equations.A total of 180 infants, who underwent pulmonary function testing, were compared with 1066 participants who did not undergo testing. The tested cohort revealed 8% with active asthma at the age of 6 years and 18% at the age of 36 years. Levels of infant tPTEF/tE and VmaxFRC were lower for participants who developed active asthma. tPTEF/tE and VmaxFRC were associated with a significant risk for active asthma (P = .003 and P =.007, respectively) and those in the lowest tertile of both indices were at highest risk (P = .009 and P = .01, respectively). Both tPTEF/tE and VmaxFRC were associated with an increased odds of developing active asthma between the ages of 6 and 36 years (70% [P = .001] and 55% [P = .005], respectively). At the age of 26 years, low infant tPTEF/tE was associated with reductions in airway diameter, total area, and luminal and wall areas, whereas VmaxFRC was associated with reduced forced expiratory volume in 1 second to forced vital capacity, forced expiratory volume in 1 second, and forced expiratory flow 25% to 75% levels.Reduced tPTEF/tE and VmaxFRC levels in infancy may indicate an increased risk for active asthma by the age of 36 years on the basis of pulmonary function testing and airway imaging in adulthood.Recognizing risk factors for asthma may extend beyond family history and personal history of atopy and respiratory infections. This study reveals that airflow limitation early in infancy may help predict asthma later in life and warrants further studies to standardize methods for clinical use and application. Understanding the time course of asthma development is essential in prevention and treatment.