Background: Spirometry is the gold standard for assessing airway function for clinical studies; however, obtaining high quality data in young children remains challenging. Since the forced oscillation technique (FOT) requires less subject cooperations, there has been increasing interest in FOT, particularly in young children. We evaluated whether spirometry and FOT in young children provides comparable ability to detect a treatment effect. Methods: We recently reported in a randomized controlled trial that vitamin C compared to placebo treatment of mothers who smoked during pregnancy (MSDP) results in the offspring having significantly higher forced expiratory flows at 5-years of age, as well as significantly less wheeze at 4-6 years of age. In these same offspring, we also measured FOT at 8-Hz impedance at 3, 4, and 5 years of age. Results: Although spirometry demonstrated significantly increased forced expiratory flows (FEFs) in the vitamin C compared to placebo treatment group at 5-years of age (p < 0.001), we were not able to detect a similar treatment effect using FOT impedance. Conclusions: It may be challenging to obtain technically successful spirometry in pre-school children; however, forced expiratory flows may provide a better outcome than single frequency FOT impedance to assess improvements in airway function in these young subjects.

Rationale: Animal models suggest pre-eclampsia (Pre-E) affects alveolar development, but data from humans are lacking. Objective: Assess the impact of Pre-E on airway function, diffusion capacity, and respiratory morbidity in preterm and term infants born from mothers with Pre-E. Methods: Infants born from mothers with and without Pre-E were recruited for this study; term and preterm infants were included in both cohorts. Respiratory morbidity in the first 12 months of life was assessed through monthly phone surveys. Raised volume rapid thoracoabdominal compression and measurement of diffusion capacity of the lung to carbon monoxide (DLCO)) were performed at 6 months corrected age. Results: There were 146 infants in the Pre-E cohort and 143 in the control cohort. The Pre-E cohort was further divided into non-severe (N=41) and severe (N=105) groups. There was no significant difference in DCLO and DLCO/aveolar volume amongst the three groups. Forced vital capacity was similar amongst the three groups, but the non-severe Pre-E group had significantly higher forced expiratory flows that the other two. After adjusting for multiple covariates including prematurity, the severe Pre-E group had a lower risk for wheezing in the first year of life compared to the other two. Conclusions: Pre-E is not associated with reduced DLCO, lower forced expiratory flows, or increased wheezing in the first year of life. These results differ from animal models and highlight the the complex relationships between Pre-E and lung function and respiratory morbidity in human infants.

Background: The pathogenesis of atopic dermatitis (AD) results from complex interactions between environmental factors, barrier defects, and immune dysregulation resulting in systemic inflammation. Therefore, we sought to characterize circulating inflammatory profiles in pediatric AD patients and identify potential signaling nodes which drive disease heterogeneity and progression. Methods: We analyzed a population of 87 infants that were at high risk for atopic disease based on dermatitis diagnoses. Clinical parameters, serum, and peripheral blood mononuclear cells (PBMCs) were collected upon entry, and at one and four years later. Within patient serum, 126 unique analytes were measured using a combination of multiplex platforms and ultrasensitive immunoassays. Results: We assessed the correlation of inflammatory analytes with AD severity (SCORAD). Key biomarkers, such as IL-13 (corr=0.47) and TARC (corr=0.37), among other inflammatory signals, significantly correlated with SCORAD across all timepoints in the study. Flow cytometry and pathway analysis of these analytes implies that CD4 T cell involvement in type 2 immune responses were enhanced at the earliest time point (year 1) relative to the end of study collection (year 5). Importantly, forward selection modeling identified 18 analytes in infant serum at study entry which could be used to predict change in SCORAD four years later. Conclusions: We have identified a pediatric AD biomarker signature linked to disease severity which will have predictive value in determining AD persistence in youth and provide utility in defining core systemic inflammatory signals linked to pathogenesis of atopic disease.