Reducing Exercise-induced Bronchoconstriction in Children With Asthma and Obesity

Asthma and Childhood Obesity: Understanding Potential Mechanisms and Identifying Strategies to Improve Respiratory Symptoms

Guidelines from the American Thoracic Society strongly recommend interval warm-up exercise before planned exercise to reduce exercise-induced bronchoconstriction severity. However, no empirical data on the effects of interval warm-up exercise on exercise-induced bronchoconstriction severity are available in obese asthmatic children, where excess fat exerts such an unfavorable burden on the respiratory system, particularly during exercise. The objective of this study is to investigate the effects of interval warm-up exercise on exercise-induced bronchoconstriction severity in obese and nonobese asthmatic children. Our approach will be to investigate exercise tolerance, respiratory function, and exercise-induced bronchoconstriction severity and the effects of (1) 8x30sec interval warm-up & (2) pretreatment with a bronchodilator compared with a no-treatment control on exercise-induced bronchoconstriction severity in 8-12 yr, prepubescent, obese and nonobese asthmatic children.

[Aim]: To investigate the effects of interval warm-up exercise on exercise-induced bronchoconstriction severity. [Hypothesis]: Interval warm-up exercise will reduce exercise-induced bronchoconstriction severity after an exercise challenge test to a similar extent as bronchodilator and better than control.

Note related to early termination: Although the intent of the study was to compare obese and nonobese children, early termination precluded us from completing this analysis and thus the pooled results are included in the results. The brief summary has been updated to reflect the presented results.

The investigators will enroll prepubescent, 8 - 12 yr old, obese (body mass index > 95th percentile; N=25) and nonobese (body mass between 16th and 84th percentile; N=25) children with mild asthma. The investigators will investigate the severity of exercise-induced bronchoconstriction during planned exercise performed 15 minutes after the following three conditions performed on separate days in a random order: (1) 8x30sec interval warm-up, (2) short-acting beta agonist or albuterol, & (3) control, in prepubescent, 8 - 12 yr old, obese and nonobese children with mild asthma.

The investigators will measure the following in all participants:

1. Pulmonary function: spirometry, lung volumes, diffusing capacity of lung for carbon monoxide, maximum voluntary ventilation, maximal inspiratory and expiratory pressures, airway resistance, and expired nitric oxide
2. Exercise tolerance during graded cycle ergometry: Gas exchange, ventilation, heart rate, blood pressure, pulse oximetry, electrocardiogram
3. Ratings of perceived breathlessness and exercise induced bronchoconstriction in response to a 6 minute high-intensity exercise challenge after three conditions performed on three separate days:

Three conditions that will precede the exercise challenge include:

1. 8x30sec of interval warm-up 15min prior to exercise challenge: This includes eight 30sec bouts of high-intensity interval exercise at 85-95% of HRmax, with 45sec of recovery between.
2. Two puffs of albuterol 15 min prior to exercise challenge
3. Control: seated rest for 15min prior to exercise challenge

Control visit was always completed first. The order of the albuterol and interval warm-up exercise visits was randomized.

Inclusion Criteria:

• no history of smoking, no history or evidence of heart disease, no history of uncontrolled hypertension, no documented and/or diagnosed sleep disorders, no diagnosed diabetes, no metabolic disorders, no history of significant mental illness, no dietary restrictions, no serious health conditions, or no musculoskeletal abnormality that would preclude exercise.
• Normal weight children with a body mass index between the 16th and 84th percentile
• Obese children with a body mass index > 95th percentile but less than 170% above the 95th percentile and less than an absolute body mass index of 40 kg·m2
• Pulmonary function criteria 1) forced vital capacity ≥ 80% predicted, 2) forced expiratory volume in the first second (FEV1) ≥ 75% predicted, and total lung capacity ≥ 80% predicted

Exclusion Criteria:

• Children with significant diseases other than obesity and mild asthma will be excluded. A significant disease is defined as either a disease that in the opinion of the PI or medical consultant Dr. Craig Nakamura may put the participant at risk because of participation in the study or a disease that may influence the results of the study or the patient's ability to participate in the study.
• Children who cannot follow directions (e.g., eating before testing), adequately perform procedures (e.g., pulmonary function tests), or keep appointments (e.g., no shows for testing), will be excluded from study participation.
• Because the risk of severe exercise induced bronchoconstriction increases in children with moderate or severe obstructive airway disease, children with FEV1 < 75% predicted will be excluded from the study. Diagnosis of asthma (i.e., airway responsiveness with reversible obstruction) will be established by spirometry (i.e., improvement of FEV1 of ≥8% after administration of bronchodilator).
• Children without reversible airway obstruction will also be excluded from the study.
• Children who have been hospitalized for an asthma exacerbation or who have taken oral glucocorticoids for asthma in the past year, and children who have been admitted to an intensive care unit or been intubated because of their asthma in the past five years, will be excluded to reduce the risk of exacerbation during the study.