ABSTRACTObjectiveTo evaluate lung function patterns measured by oscillometry in children with Down syndrome and determine associations with pulmonary diagnoses that may co‐occur with Down syndrome, including evidence of dysphagia, obstructive sleep apnea, tracheomalacia, and congenital heart disease.Study Design and PatientsCross‐sectional study of children with Down syndrome who were enrolled during 2019–2022 at ages 4–18 years old.MeasurementsChildren performed oscillometry before and after albuterol administration to obtain respiratory impedance measures of resistance (R) and reactance (X). Aspiration from swallow study, obstructive sleep apnea from polysomnogram, tracheomalacia from flexible bronchoscopy, and congenital heart disease diagnoses were obtained from the electronic medical record.ResultsIn 50 children with Down syndrome, more negative X (median X5 z‐score −0.93 [IQR − 2.15, 0.17]) was observed compared to a z‐score of zero representing the mean in a pediatric reference population, but R was not increased at any frequency. Neither R nor X were related to tested pulmonary co‐occurring diagnoses. Frequency dependence of resistance (R5‐19) was elevated (median z‐score 0.50 [IQR − 0.01, 1.14]), which, in combination with the more negative X, could indicate heterogeneity in peripheral and/or central airway sizes. After bronchodilator, R5 and AX decreased −26% [IQR −32%, −12%] and −43% [IQR −58%, −28%], respectively, and X5 increased 31% [IQR 12%, 45%], indicating physiological improvement.ConclusionsIn our population, a phenotype of lower lung compliance in 50% of children with Down syndrome was not associated with the presence of co‐occurring pulmonary diagnoses. More work is needed to understand if this may be related to their diagnosis of DS.