Breathing abnormalities during sleep, apnea and hypopnea, are common events in older men and postmenopausal women. Although the etiology of these remains obscure, a number of observations have been made. First, a reduction in normal chemosensitivity during sleep is suggested by the frequent hypoxia and hypercapnia seen during sleep disordered breathing and has been demonstrated by ourselves and others. Although the explanation for this alteration in ventilatory control is unknown, recent investigation during wakefulness suggests that respiratory rhythm, resting ventilation, and ventilatory chemosensitivity tend to correlate closely with measures of metabolic rate, i.e. oxygen consumption (VO2) and carbon dioxide production (VCO2). As VO2-VCO2 is reported to be decreased during sleep, we hypothesize that the reduced metabolic rate observed in sleeping man may be the mediator of not only the previously described decrement in chemosensitivity seen during sleep, but also the dysrhythmic breathing. As also men are particularly prone to these disorders, age and gender related variation in sleeping metabolic rate may determine susceptibility to sleep disordered breathing. To solidify an association between VO2-VCO2, chemosensitivity, and breathing during sleep the following studies are planned. Normal men and women between the ages of 20 and 75 years will be studies to determine: a) If disordered breathing occurs in subjects with large decrements in VO2-VCO2 and not in those maintaining waking levels. b) If episodes of breathing dysrhythmias occur when VO2-VCO2 is at its lowest level. c) If increasing age is associated with larger sleep induced decrements in VO2-VCO2 and more breathing abnormalities. d) The effects of testosterone, estrogen, and progesterone on metabolism and breathing during sleep. e) The effects of artificially increasing and decreasing sleeping metabolic rate on breathing pattern. Ventilatory chemosensitivity will also be measured in both groups during sleep to confirm its correlation with metabolic rate. Second, it has been reported that upper airway resistance increases during sleep, probably secondary to decreased airway patency at the level of the hypopharynx. Although some increase in resistance is likely to occur in everyone due to reduced muscle tone, those people with the smallest airway (hypopharynx) seem prone to develop apnea. We plan to measure upper airway patency and resistance during wakefulness in normal men and women, and patients with obstructive sleep apnea to determine: a) If males differ from females; b) If age affects upper airway patency; c) The influence of testosterone on the upper airway; and d) If people with apnea differ from age, sex, and weight-matched controls. By investigation of metabolism, chemosensitivity, and upper airway patency we hope to gain insight into the mechanism of apnea and hyponea during sleep.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Clinical Investigator Award (CIA) (K08)
Project #
Application #
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Colorado Denver
Schools of Medicine
United States
Zip Code
Stauffer, J L; White, D P; Zwillich, C W (1990) Pulmonary function in obstructive sleep apnea. Relationships to pharyngeal resistance and cross-sectional area. Chest 97:302-7
Gleeson, K; Zwillich, C W; White, D P (1990) The influence of increasing ventilatory effort on arousal from sleep. Am Rev Respir Dis 142:295-300
Ballard, R D; Irvin, C G; Martin, R J et al. (1990) Influence of sleep on lung volume in asthmatic patients and normal subjects. J Appl Physiol 68:2034-41
Stauffer, J L; Buick, M K; Bixler, E O et al. (1989) Morphology of the uvula in obstructive sleep apnea. Am Rev Respir Dis 140:724-8
Wiegand, L; Zwillich, C W; White, D P (1989) Collapsibility of the human upper airway during normal sleep. J Appl Physiol 66:1800-8
Wiegand, L; Zwillich, C W; White, D P (1988) Sleep and the ventilatory response to resistive loading in normal men. J Appl Physiol 64:1186-95
White, D P; Gleeson, K; Pickett, C K et al. (1987) Altitude acclimatization: influence on periodic breathing and chemoresponsiveness during sleep. J Appl Physiol 63:401-12
Robinson, R W; White, D P; Zwillich, C W (1987) Relationship of respiratory drives to dyspnea and exercise performance in chronic obstructive pulmonary disease. Am Rev Respir Dis 136:1084-90
Robinson, R W; Zwillich, C W; Bixler, E O et al. (1987) Effects of oral narcotics on sleep-disordered breathing in healthy adults. Chest 91:197-203
Stauffer, J L; Zwillich, C W; Cadieux, R J et al. (1987) Pharyngeal size and resistance in obstructive sleep apnea. Am Rev Respir Dis 136:623-7

Showing the most recent 10 out of 19 publications