Fetal origins of asthma: A longitudinal study from birth to age 36 years

Rationale: Deficits in infant lung function—including the ratio of the time to reach peak tidal expiratory flow to the total expiratory time (tPTEF/tE) and maximal expiratory flow at FRC (VmaxFRC)—have been linked to increased risk for childhood asthma. Objectives: To examine the individual and combined effects of tPTEF/tE and VmaxFRC in infancy on risk for asthma and abnormalities of airway structure into mid-adult life. Methods: One hundred eighty participants in the Tucson Children’s Respiratory Study birth cohort had lung function measured by the chest-compression technique in infancy (mean age 6 SD: 2.0 6 1.2 mo). Active asthma was assessed in up to 12 questionnaires between ages 6 and 36 years. Spirometry and chest high-resolution computed tomographic (HRCT) imaging were completed in a subset of participants at age 26. The relations of infant tPTEF/tE and VmaxFRC to active asthma and airway structural abnormalities into adult life were tested in multivariable mixed models. Measurements and Main Results: After adjustment for covariates, a 1-SD decrease in infant tPTEF/tE and VmaxFRC was associated with a 70% (P = 0.001) and 55% (P = 0.005) increased risk of active asthma, respectively. These effects were partly independent, and two out of three infants who were in the lowest tertile for both tPTEF/tE and VmaxFRC developed active asthma by mid-adult life. Infant VmaxFRC predicted reduced airflow and infant tPTEF/tE reduced HRCT airway caliber at age 26. Conclusions: These findings underscore the long-lasting effects of the fetal origins of asthma, support independent contributions by infant tPTEF/tE and VmaxFRC to development of asthma, and link deficits at birth in tPTEF/tE with HRCT-assessed structural airway abnormalities in adult life.