Effects of Obesity in the Aged

The overall objective of this application is to investigate the effects of obesity on lung function, exercise tolerance, and DOE in older obese adults as compared with older adults without obesity, using a novel probe for mechanically unloading the thorax at rest and during exercise. The investigators will use 1) continuous negative cuirass pressure, and 2) assisted biphasic cuirass ventilation to decrease obesity-related effects in older obese adults. Our approach will be to examine respiratory function, exercise tolerance, and DOE with and without mechanical unloading in older obese men and women (65-75 yr), including those with respiratory symptoms (defined by a score of 1 or 2 on the modified Medical Research Council Dyspnea Scale), as compared with older adults without obesity.

Specific Aims: The investigators will test the following hypotheses in older adults with and without obesity:

Aim 1) Obesity will decrease respiratory function but to a greater extent in older obese adults with respiratory symptoms, (as evidenced by altered pulmonary function and breathing mechanics at rest); Aim 2) Obesity will decrease exercise tolerance (as evidenced by peak V•O2 in ml/min/kg, i.e., physical fitness), but not cardiorespiratory fitness (as evidenced by peak V•O2 in % of predicted based on ideal body wt), except in older obese adults with respiratory symptoms where both may be reduced during graded cycle ergometry.

Aim 3) Obesity will increase DOE but to a greater extent in older obese adults with respiratory symptoms as evidenced by increased ratings of perceived breathlessness (sensory \& affective dimensions) during exercise.

Aim 4) Mechanical unloading of the thorax will improve respiratory function, submaximal exercise tolerance, and DOE in older obese adults, but to a greater extent in older obese adults with respiratory symptoms.

Over 40% of older adults (60+ yr) are obese and 30% are overweight. While regular exercise is an important component in the prevention and treatment of obesity, many older adults with obesity are unable or unwilling to exercise due to exercise intolerance and/or dyspnea on exertion (DOE). The Investigators have identified numerous obesity-related respiratory effects that could influence exercise tolerance and DOE in younger obese adults including decreased pulmonary function altered respiratory mechanics increased work of breathing and increased metabolic demands of exercise. The Investigators have also identified many age-related ventilatory constraints in older adults without obesity. However, it is unclear whether these obesity-related and aging-related effects combine to reduce exercise tolerance, impose DOE, or contribute to respiratory symptoms in older obese adults. Respiratory symptoms in older adults are often wrongly diagnosed as deconditioning and/or cardiopulmonary disease, placing older obese adults at risk of costly clinical testing, unnecessary treatment, and potentially a reluctance to exercise, which is counterproductive to weight loss (WL) and the preservation of functional capacity, thus further diminishing their quality of life. The respiratory effects of obesity are underappreciated and have not been carefully examined in older adults, especially older obese adults with "respiratory symptoms" who may experience even greater respiratory effects.

The Investigators propose that many of the obesity-related respiratory effects in older obese adults are the result of low lung volume breathing, i.e., a reduction in functional residual capacity (FRC) at rest (seated upright \& supine), and end-expiratory lung volume (EELV) during exercise. The Investigators suggest that increased fat on the chest wall (i.e., abdomen \& rib cage) produces low FRC and EELV levels, where breathing limitations like expiratory flow limitation and enhanced perception of dyspnea are more likely to occur. This is because older adults have an age-related decline in maximal expiratory flow at low lung volumes. As such, excess fat on the thorax appears to exert an unfavorable burden on the older obese adult, particularly during exercise. Our overall hypothesis is that respiratory limitations, exercise intolerance, DOE, and respiratory symptoms in older obese adults are due to mechanical loading of the thorax and low lung volume breathing coupled with the age-related decline in maximal expiratory flow. The Investigators propose to test this hypothesis with the use of an external cuirass (i.e., a plastic shell over the thorax) to mechanically unload the chest wall.

Although our laboratory has used modest WL in younger obese women to reduce the effects of obesity, the mechanisms by which WL (i.e., decreased fat over the entire body) decreases DOE remain unclear. This may be in part due to our single global assessment of DOE (i.e., sensory domain only \& pre-post WL only), and/or that changes in DOE in the time domain are not in parallel with WL. To circumvent these limitations of WL, an external cuirass will be used to mechanically unload the chest wall (includes rib cage \& abdomen) in older obese adults. This will effectively decrease the load on the chest wall thereby increasing FRC at rest and EELV during exercise (i.e., via continuous negative cuirass pressure), and potentially decreasing the work of breathing during exercise (i.e., via assisted biphasic cuirass ventilation). This novel and quantifiable probe will allow us to investigate the effects of obesity in older adults and their influence on lung function, exercise tolerance, and DOE (sensory \& affective dimensions). The proposed mechanistic studies would lead to a better understanding of the mechanical effects of obesity in older adults, which could alter testing and treatment strategies for older obese adults, especially those with exercise intolerance, DOE, and respiratory symptoms.

The overall objective of this application is to investigate the effects of obesity on lung function, exercise tolerance, and DOE in older obese adults as compared with older adults without obesity, using a novel probe for mechanically unloading the thorax at rest and during exercise. The Investigators will use 1) continuous negative cuirass pressure, and 2) assisted biphasic cuirass ventilation to decrease obesity-related effects in older obese adults. Our approach will be to examine respiratory function, exercise tolerance, and DOE with and without mechanical unloading in older obese men and women (65-75 yr), including those with respiratory symptoms (defined by a score of 1 or 2 on the modified Medical Research Council Dyspnea Scale), as compared with older adults without obesity.

Specific Aims: The Investigators will test the following hypotheses in older adults with and without obesity:

Aim 1) Obesity will decrease respiratory function but to a greater extent in older obese adults with respiratory symptoms, (as evidenced by altered pulmonary function and breathing mechanics at rest); Aim 2) Obesity will decrease exercise tolerance (as evidenced by peak V•O2 in ml/min/kg, i.e., physical fitness), but not cardiorespiratory fitness (as evidenced by peak V•O2 in % of predicted based on ideal body wt), except in older obese adults with respiratory symptoms where both may be reduced during graded cycle ergometry.

Aim 3) Obesity will increase DOE but to a greater extent in older obese adults with respiratory symptoms as evidenced by increased ratings of perceived breathlessness (sensory \& affective dimensions) during exercise.

Aim 4) Mechanical unloading of the thorax will improve respiratory function, submaximal exercise tolerance, and DOE in older obese adults, but to a greater extent in older obese adults with respiratory symptoms.

The investigators' long-term objective is to examine the effects of obesity in older obese adults and provide novel results that could clarify the mechanisms of respiratory limitations, exercise intolerance, DOE, and/or obesity-related respiratory symptoms in older obese adults. Thus, these results will have broad and immediate clinical impact on the care of older adults with obesity, especially those with exercise intolerance, DOE, and/or respiratory symptoms.

Eligibility Criteria:
Inclusion Criteria:

* Otherwise healthy older adults 65-75 years of age with normal lung function; men 30\< %body fat ≤50 and women 35\< %body fat ≤55; and ability to perform pulmonary and exercise test. Other inclusion criteria include the following:
* Nonsmokers who have no history of smoking
* No personal history of significant mental illness
* No weight loss dietary restrictions
* No current or past history of significant substance or alcohol abuse
* No history, evidence, or uncontrolled symptoms of heart disease
* No history of uncontrolled hypertension
* No current medications that may interfere with exercise capacity
* No recent history or indication of asthma
* No musculoskeletal abnormality that would preclude exercise
* No serious health conditions that would preclude study goals or participation in exercise (per PI \& medical staff \& preliminary or follow up testing; including significant other diseases, occult asthma, prior surgeries-especial lung or abdominal, or history of chemotherapy that could affect lung or heart function)
* Only postmenopausal women will be included.
* Women on hormone replacement therapy will be allowed to participate if the dosage remains similar during the entire protocol.

Exclusion Criteria:

* Volunteers with a mMRC score of 3 or 4 will be excluded due to likeliness of underlying disease.
* Individuals participating in regular vigorous conditioning exercise such as running, jogging, aerobics, cycling, or swimming more than three times per week will be excluded. However, if subjects have an exceedingly high exercise capacity (greater than 2 SD of predicted), they will be excluded.
* Maximal cycle ergometry test will be used to determine if further participation in testing is appropriate for the participant (e.g., normal exercise test, exclude presence of provokable ECG changes suggestive of heart disease, or dangerous arrhythmias or exercise induced hypertension or bronchoconstriction. If the participant develops an abnormal ECG or shows other signs of exercise intolerance or if signs of cardiovascular disease are noted during the exercise test, it will be terminated and the participant will be referred to their personal physician for further evaluation (see DMSP).
* Premenopausal women will be excluded.