Shortness of Breath During Exertion in Obesity

Summary

To address the hypotheses in Study 1 we will measure respiratory function, body composition, fat distribution, breathlessness (Borg Dyspnea Index), and exercise capacity in mild-to-moderately obese (30 and amp;lt; %body fat and amp;lt; 50) younger men and women (20-45 yr) with (n = 25) and without exertional dyspnea (n = 25). We will also make the same measurements in non-obese (15 and amp;lt; % body fat and amp;lt; 25) younger men and women (20-45 yr) who will serve as a control group (n=25). In addition, we will make the same measurements in physically trained (see page 4) mild-to-moderately obese (n = 24) and non-obese individuals (n = 24). 123 subjects are needed to complete Study 1. We estimate that 135 participants will be screening failures. Therefore, a total of 258 subjects will enroll in Study 1. We will further measure respiratory mechanics, breathlessness, and the oxygen cost of breathing when the subjects are supine at rest, seated upright at rest, and during steady state cycle ergometry at ventilatory threshold (VTh). We will measure body composition by underwater weighing and fat distribution by MRI. These results will also be used to develop a computer-based mathematical model, which could potentially explain the gravitational effects of fat distribution on respiratory function in obesity, in collaboration with Dr. Behbehani, Ph.D., P.E., and Director of Biomedical Engineering at the University of Texas at Arlington. In some subjects (a maximum of 24 obese and a maximum of 24 non-obese), we will measure the oxygen cost of breathing before continuing with more detailed tests to gain further insight into the magnitude of differences in the oxygen cost breathing between subjects with and without exertional dyspnea.

To address the hypotheses in Study 2, we will make the same measurements of respiratory function, body composition, fat distribution, breathlessness (Borg Dyspnea Index), exercise capacity, the oxygen cost of breathing, and we will include blood draw for lactates and assess physical activity and health disposition before and after three different intervention programs: 1) an endurance exercise training program without weight loss; 2) a weight loss program without aerobic exercise training; and 3) a combined program of weight loss with aerobic exercise training. These measurements may be repeated halfway through the intervention programs. We will make these measurements in mild-to-moderately obese (30 and amp;lt; %body fat and amp;lt; 50) younger men and women (20-45 yr) with (n = 72) and without exertional dyspnea (n = 72); subjects will either be assigned to the exercise training, weight loss, or combined program such that each intervention is undertaken by 48 subjects. We estimate that 162 subjects will be screening failures; therefore a total of 306 subjects will enroll in the study.

Participant Eligibility

Mild-to-moderate obesity. We have elected to study the effects of mild-to-moderate obesity in younger (20-45 yr), otherwise healthy and symptom free, adults for six reasons. One, mild-to-moderate obesity is very prevalent. Two, they are able to perform heavy exercise testing without difficulty, as well as the detailed lung measurements and underwater weighing procedures. Three, their pulmonary function is not greatly affected except for EELV. Four, they present a less complicated model of obesity than extreme obesity. Five, many are usually free of coexisting comorbidities unlike that of more obese subjects. And six, these subjects may benefit the most from early intervention to prevent the development of further obesity and/or cardiovascular comorbidities. Obese subjects will be included on the basis of having a percent body fat between 30 and 50, as determined by underwater weighing. As a guide, BMI will be used as an inclusion criterion in initial telephone screening (BMI 30-45).

Patients with exertional dyspnea. These patients will be recruited from local physician groups, fitness centers, and local advertisements. To confirm dyspnea, the patients must have a rating of perceived breathlessness (RPB, 0-10 Borg scale) > 4 at VTh, which is greater than the value observed in preliminary testing for healthy lean and obese men and women (2 + 1).

Patients without exertional dyspnea. These patients will be recruited by the same methods used for patients with exertional dyspnea. Patients must have a rating of perceived breathlessness (RPB, 0-10 Borg scale) < 2 at VTh .

Non-obese control subjects. These subjects will be included on the basis of having a percent body fat between 15 and 25, as determined by underwater weighing. As a guide, BMI will be used as an inclusion criterion in initial telephone screening (BMI < 28).

Physically trained subjects (mild-to-moderately obese and non-obese control). These subjects will be included on the basis of participating in daily organized exercise with specific training goals (i.e. marathon, iron man, endurance races, cycling, etc.).

General subject criteria include nonsmokers or ex-smokers with normal pulmonary function or pulmonary function consistent with obesity, no history or evidence of heart disease, no history of uncontrolled hypertension, no current medications that could interfere with exercise capacity, no significant 12-lead ECG abnormalities, no history of asthma, or no musculoskeletal abnormality that would preclude exercise.