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

Am J Respir Crit Care Med. 2020 Dec 15;202(12):1646-1655. doi: 10.1164/rccm.202001-0194OC.

Abstract

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 (V̇maxFRC)-have been linked to increased risk for childhood asthma.Objectives: To examine the individual and combined effects of tptef/te and V̇maxFRC 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 ± SD: 2.0 ± 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 V̇maxFRC 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 V̇maxFRC 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 V̇maxFRC developed active asthma by mid-adult life. Infant V̇maxFRC 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 V̇maxFRC to development of asthma, and link deficits at birth in tptef/te with HRCT-assessed structural airway abnormalities in adult life.

Keywords: HRCT imaging; airflow limitation; asthma; infant lung function.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Age of Onset*
  • Asthma / diagnosis*
  • Asthma / physiopathology*
  • Child
  • Child, Preschool
  • Cohort Studies
  • Exhalation / physiology*
  • Female
  • Fetal Diseases / diagnosis*
  • Fetal Diseases / physiopathology*
  • Follow-Up Studies
  • Humans
  • Infant
  • Infant, Newborn
  • Longitudinal Studies
  • Male
  • Signal Processing, Computer-Assisted
  • Spirometry
  • Tidal Volume
  • Young Adult