Shortness of Breath During Exertion in Obesity
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 [Less Than] %body fat [Less Than] 50) younger (20-45 yr) men and women with (n [?] 25) and without exertional dyspnea (n [?] 25). We will also make the same measurements in non-obese (15 [Less Than] % body fat [Less Than] 25) younger men and women who will serve as a control group (n[?]25). in addition, we will make the same measurements in physically trained 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. We will measure body composition by underwater weighing and fat distribution by MRi. 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 as in Study 1. We will include blood draw for lactates and assess physical activity, health disposition and subjective perception of breathlessness ( described in Study 3) 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 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 younger men and women 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. in addition, we will also test older (65-75 yr), mild-to-moderately obese men (n [?] 12) and women (n [?] 12), who will engage only in the combined exercise training and weight loss program. non-obese men and women (65-75 yr) will be recruited to serve as a control group (continue with their normal living routine for 12 weeks; n [?] 24). We estimate that 214 subjects will be screening failures; therefore a total of 406 subjects will enroll in the study.
To address the hypothesis in study 3, we will make the same pre intervention measurments as Study 2. in addition, we will assess how subjective ratings of breathlessness change when challenging the respiratory system during submaximal constant load cycling. Three different randomized challenges may be used: 1) small resistive or mechanical load placed on the breathing valve (i.e., increased work of breathing); 2) carbon dioxide loading (by either inhaling a gas mixture consisting of 3-4% carbon dioxide in balance of oxygen or breathing room air through a long piece of tubing (i.e., increased ventilatory demand) 3) inhaling of a gas mixture consisting of 79% helium and 21% oxygen (i.e., decreased work of breathing). We will enroll mild-to-moderately obese (30[Less Than]%body fat[Less Than]50) adults (20-45yr) with (n[?]12) and without exertional dyspnea (n[?]12) as well as non-obese (15[Less Than]% body fat[Less Than]25) adults who will serve as a control group (n[?]12). 72 subjects are needed to complete study 3. We estimate that 48 participants will be screening failures. a total of 120 subjects will enroll in this study.
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. Additionally, we will study the effects of mild-to-moderate obesity in older (65-75 yr), otherwise healthy and symptom free, adults for the same reasons mentioned above. 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.