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BACKGROUND Sex influences the risk of wheezing illnesses and the prevalence of asthma throughout childhood. OBJECTIVE To better understand mechanisms of these effects, we analyzed longitudinal relationships between sex, lung physiology and asthma in the Childhood Origins of ASThma (COAST) birth cohort study. METHODS COAST children were followed prospectively from birth and assessed annually. Results of spirometry, fractional exhaled nitric oxide (FeNO), mannitol provocation testing (MPT), and 3He gas MRI were assessed by sex using multivariate models including age, asthma diagnosis, and wheezing histories. RESULTS Girls had higher pre-bronchodilator FEV0.5/FVC values than boys (mean difference 0.017, 95% CI 0.000-0.034; p=0.05) of equivalent age. Post- bronchodilator findings were more pronounced, with boys demonstrating reduced FEV0.5/FVC values compared to girls of equivalent age (mean difference 0.032, 95%CI 0.014-0.049; p=0.0005). Conversely, girls were noted to have higher ventilation defects on 3He MRI than boys (p=0.01). No differences were noted in the rate of positive responses to mannitol provocation or FeNO measurements. CONCLUSIONS Lower airflow values are present by spirometry for prepubertal males when compared to age matched females; however, greater 3He ventilation defects were noted in girls. This could represent a greater degree of subclinical air trapping in prepubertal girls, as residual volumes are not detected on standard spirometric readings. No differences were noted between the two sexes with airway hyper-responsiveness (MPT) or inflammation (FeNO). Prospective peripubertal follow up will determine if these differences persist or change with the de novo expression and remission of asthma based on sex and age.

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