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Lung function in developing lambs: is it affected by preterm birth?

¹Anatomy and Developmental Biology, Monash University, Melbourne; ; ²Veterinary Science, University of Melbourne, Melbourne; and ; ³Allergy, Immunology, and Respiratory Medicine, Alfred Hospital, Melbourne, Victoria, Australia

Submitted 8 February 2009 ; accepted in final form 11 August 2009

Children born before term often have reduced lung function, but the effects of preterm birth alone are difficult to determine owing to iatrogenic factors such as mechanical ventilation. Our objective was to determine the effects of preterm birth alone on airway resistance, airway reactivity, and ventilatory heterogeneity as an index of intrapulmonary gas mixing. Preterm birth was induced in sheep 12 days before term; controls were born at term (147 days). Lung function was assessed at 8 wk postterm. To assess medium-large airway function we measured airway resistance and reactivity to carbachol. Multiple breath N₂ washout (MBW) was used to assess ventilatory heterogeneity in conducting (S_cond) and acinar (S_acin) airways. Baseline airway resistance and responsiveness to carbachol were similar in preterm and term lambs. Airway responsiveness to carbachol was greater in females than males (P < 0.05), and baseline airway resistance tended to be higher in females than males (P = 0.06). There were no significant differences in ventilatory heterogeneity between preterm and term lambs; for all animals combined, mean S_acin was 0.29 ± 0.05 liter^–1 and S_cond was 0.26 ± 0.03 liter^–1. Males had significantly higher S_cond than females, indicating poorer gas mixing in small conducting airways; there was no sex difference in S_acin. We conclude that preterm birth per se in lambs does not affect baseline airway resistance, airway responsiveness, or ventilatory heterogeneity as measured by MBW. The observed sex-related differences in airway responsiveness and ventilatory heterogeneity in the conducting airways could help explain sex differences in lung function observed in humans.

prematurity; multiple breath nitrogen washout; airway responsiveness; sex differences