Postnatal growth rate, but not mild preterm birth, influences airway structure in adult sheep challenged with house dust mite.

The authors recently showed that preterm birth per se, in the absence of assisted ventilation or elevated inhaled oxygen levels, alters the structure of the airway walls in young lambs. The initial aim of the present study was to determine whether these changes persist into adulthood. Preterm (P; n = 7) lambs were delivered 14 days before term and compared with control lambs (C; n = 8) born at term ( approximately 147 days). After weaning, the sheep were kept as a flock with daily exposure to pasture until approximately 1.2 years old. All sheep were sensitized to house dust mite extract and then given aerosol challenges with house dust mite 10 to 12 weeks before autopsy. At autopsy, the right lung was fixed in neutral-buffered formalin at an inflation pressure of 20 cm H(2)O. The architecture of the walls of airway generations 4, 6, and 8 and the bronchioles was assessed by computer-aided image analysis of histological sections of airway walls cut in cross-section. Morphometric analysis showed that preterm birth per se had no significant effect on airway wall structure. Within both groups (preterm and term), we identified animals that grew at different growth rates after birth; a second aim, therefore, was to determine the influence of postnatal growth rates on airway structure at maturity. The 15 sheep were divided into 2 groups based on nonoverlapping growth rates between birth and 200 days of age: slower growing sheep (SG; n = 7) gained 102 +/- 5 g/day and faster growing sheep (FG; n = 8) gained 197 +/- 14 g/day (P < .01). In SG sheep, the pulmonary airways had thinner walls and less smooth muscle in relation to basement membrane perimeter. The airway epithelium was also thinner in the SG sheep. In the bronchiolar epithelium, there were fewer goblet cells and Clara cells in SG compared to FG sheep. We conclude that the early effects of preterm birth on the airway epithelium do not persist to maturity. However, slow growth after birth results in altered airway development, with effects persisting to maturity.