Mechanisms for Dyspnea on Exertion in Children With Obesity and Asthma: Distinct Physiological Phenotypes

The overall objective of this study is to better understand the respiratory mechanisms provoking dyspnea on exertion in obese asthmatic children.

Obesity and asthma are the most common diseases of childhood, causing activity limitation and impaired quality of life. Most obese asthmatic children report dyspnea on exertion (DOE) as their primary asthma symptom. Fear of dyspnea promotes sedentariness and reduces exercise capacity and quality of life. DOE in asthmatic children is typically attributed to bronchoconstriction but it is also possible that obesity is an equal or even major contributor to dyspnea. Excess chest and abdominal weight in obese children results in low lung volumes, which increases the risk of mechanical ventilatory constraints such as expiratory flow limitation, dynamic hyperinflation, and airway closure, all of which can provoke DOE. Unnecessary use of corticosteroids and other asthmatic medication in obese asthmatic children cannot treat obesity-specific mechanical ventilatory constraints and could have unintended deleterious effects. Therefore, there is an urgent need to better understand the mechanisms involved in DOE to provide evidence-based symptom management for obese asthmatic children that will promote regular physical activity and lessen DOE. The overall objective of this study is to better understand the respiratory mechanisms provoking DOE in obese asthmatic children. The investigators hypothesize that low lung volume breathing in obesity leads to mechanical ventilatory constraints in the presence or absence of bronchoconstriction during exercise. Whereas DOE attributable to bronchoconstriction should respond to bronchodilators, DOE attributable to obesity-specific mechanical ventilatory constraints will not respond to bronchodilators. A comprehensive physiological pulmonary function and exercise-testing based approach will be used to identify 9-17-year-old obese asthmatic children who do and do not bronchoconstrict during exercise. The presence/absence of bronchoconstriction will be determined by a comprehensive measure of exercise-induced central and peripheral airway reactivity using spirometry and impulse oscillometry (i.e., greater than or equal to 10% reduction in forced expiratory volume in 1s, FEV1, or greater than or equal to 40% increase in peripheral airway resistance, R5-20, will be indicative of bronchoconstriction). The investigators will also determine the mechanisms by which bronchodilators like albuterol affect bronchoconstriction amd mechanical ventilatory constraints in asthmatic children with obesity.