Respiratory disease is the most common cause of death in people with Down syndrome. Children with Down syndrome have a high risk of aspiration, and chronic aspiration can lead to respiratory diseases including pneumonitis, pneumonia, and bronchiectasis. Epidemiological studies in children without Down syndrome have shown that respiratory health in childhood is a strong predictor of respiratory health across the lifespan, with trajectories of lung health established by age 6 years. However, little is known about lung health trajectories in DS or how aspiration and lung disease in childhood leads to morbidity in Down syndrome across the lifespan. To improve respiratory health over the lifespan, this study aims to determine the effect of aspiration on lung function and inflammation in children with Down syndrome. This study is a case-control evaluation of children with Down syndrome who aspirate and those who do not aspirate. The overarching goal of this project is to identify quantifiable measures of pulmonary morbidity that can be used as outcome measures in clinical trials designed to treat and prevent aspiration in children with DS. This will be tested through AIM 1: Determine the effect of aspiration on lung function measured by oscillometry and spirometry with bronchodilator response and by six-minute walk in children with Down syndrome, and AIM 2: Determine the effect of aspiration on inflammatory blood markers in children with DS. AIM 3: Determine the effect of aspiration on caregiver-reported respiratory symptoms and quality of life. The hypothesis is that aspiration causes measurable changes in lung function, inflammatory markers, and caregiver-reported symptom and quality of life outcomes distinct from asthma in children with DS. The study will include 75 children between 3 and 18 years with DS who have had a clinical swallow study diagnosing aspiration or no aspiration. The lung function, respiratory symptom, and quality of life assessments will be repeated after 3-12 months for a subset of 40 participants. The proposed study will characterize objective lung function and airway inflammation measurements in children with DS. Establishing these measures for participant identification and clinical outcomes will enable the design of clinical trials that test treatments to diminish the effects of aspiration on lung function and inflammation and reduce respiratory disease in children with DS, which will improve respiratory health across their lifespan.