Tracking Respiratory Health with Oscillometry in Children with Down Syndrome - Project Summary Down syndrome (DS) is the most common chromosomal disorder, occurring in 1/700 births in the United States. People with DS have a higher rate of co-occurring cardiopulmonary conditions, and the innate differences in immune responses, muscle tone, and lung structure increase their risk of morbidity and mortality from respiratory infections. Dysphagia, or trouble swallowing with risk for aspiration of food into the lungs, occurs in ~30% of children with DS and may persist throughout childhood, further contributing to lung injury. Despite this increase in pulmonary-related morbidity and mortality compared to the general population, evidence-based practices directed at optimizing lifelong lung health specifically for people with DS are not well defined nor implemented broadly into clinical care. In people with lung diseases without DS, lung function measures, typically spirometry, are obtained to assess and monitor lung health. However, because spirometry requires coordinated forced breathing, it is often not possible to obtain acceptable measures, which can limit effective clinical evaluation and exclude people with DS from participating in lung-related research and clinical trials of pulmonary treatments that could benefit them. Advancements in cardiovascular treatments have vastly improved life expectancy in people with DS, yet respiratory infections continue to cause higher morbidity and mortality at all ages. Children with DS and aspiration have a significantly increased rate of hospitalization from respiratory illnesses and increased pulmonary inflammation and injury compared to children with DS without aspiration. Extra copies of immune receptor genes on chromosome 21 leads to abnormal immune responses in DS that may underlie more severe symptoms during respiratory infections. To evaluate the risk of respiratory complications and offer evidence-based treatments, which will ultimately improve the lives and longevity of people with DS, objective and non-invasive metrics of lung function, such as oscillometry, that can be tracked over time starting in early childhood are needed. Oscillometry only requires passive tidal breathing, with little cooperation needed from the patient. Thus, the overarching goal of this study is to understand the factors that most significantly impact lung function in children with DS. The study population will include 220 well-phenotyped children aged 5-17 years old. Respiratory impedance will be measured with oscillometry and immune profiles will be assessed from blood samples. A subset of 120 children will be tracked over two years with symptom questionnaires, respiratory pathogen panels from nasal swabs, and oscillometry. The project aims to determine the variation in oscillometry metrics and lung function profiles with respect to 1) dysphagia with aspiration and immune abnormalities and 2) severity and frequency of acute respiratory illnesses, with consideration of age, sex, and body size covariates. Collectively, the results will distinguish lung function patterns in people with DS based on pulmonary risk factors. This new knowledge will guide clinical care and inform future pulmonary-focused clinical trials to reduce the health burden attributed to pulmonary problems among people with DS.
