We determined the effects of exercise on active expiration and end-expiratory lung volume (EELV) during steady-state exercise in 13 healthy subjects. We also addressed the questions of what affects active expiration during exercise. Exercise effects on EELV were determined by a He-dilution technique and verified by changes in end-expiratory esophageal pressure. We also used abdominal pressure-volume loops to determine active expiration. EELV was reduced with increasing exercise intensity. EELV was reduced significantly during even mild steady-state exercise and during heavy exercise decreased an average of 0.71 +/- 0.3 liter. Dynamic lung compliance was reduced 30-50%; EELV remained greater than closing volume. Changing the resistance to airflow (via SF6-O2 or He-O2 breathing) during steady-state exercise changed the peak gastric and esophageal pressure generation during expiration but did not alter EELV; breathing through the mouthpiece produced similar effects during exercise. EELV was significantly reduced in the supine position. With supine exercise active expiration was not elicited, and EELV remained the same as in supine rest. With CO2-driven hyperpnea (7-70 l/min), EELV remained unchanged from resting levels, whereas during exercise, at similar minute ventilation (VE) values EELV was consistently decreased. At the same VE, treadmill running caused an increase in tonic gastric pressure and greater reductions in EELV than either walking or cycling. We conclude that both the exercise stimulus and the resultant hyperpnea stimulate active expiration and a reduced FRC. This new EELV is preserved in the face of moderate changes in mechanical time constants of the lung. This reduced EELV during exercise aids inspiration by optimizing diaphragmatic length and permitting elastic recoil of the chest wall.

A placebo-controlled, partial cross-over, double-blind, randomized study was performed with 46 adults with sleep apnea-hypopnea syndrome (SAHS) to determine the effect of therapeutic and subtherapeutic (0-1 cm H(2)O) nasal continuous positive airway pressure (CPAP) treatment on polysomnographic and neuropsychological testing. The following neuropsychological tests were administered: Geriatric Depression Scale, Trail Making A and B, Digit Span Test Forward and Backward, Epworth Sleepiness Scale, SteerClear, Digit Symbol, Controlled Oral Word Association, and Complex Figure Recall. Compared with results without CPAP, subtherapeutic CPAP did not affect any measured polysomnographic parameter. Comparison of neuropsychological test results obtained between the initial periods of effective treatment (Group 1, 16.1 d; Group 2, 19.6 d; p = NS) in all subjects showed significant improvements in Digit Symbol, Digit Span Backward, and Complex Figure tests. However, there were no group differences in changes in test results during the period when one group was on effective CPAP and the other on ineffective CPAP (Group 1, 16.1 d; Group 2, 13.9 d; p = NS). The results indicate the feasibility and importance of using ineffective CPAP as a placebo treatment and the importance of including a placebo control in studies evaluating the effect of treatment on neuropsychological function in SAHS.

Oral mandibular advancement devices are becoming an increasingly important treatment alternative for obstructive sleep apnea (OSA). The first aim of the study was to determine whether a new oral elastic mandibular advancement device (EMA) prevents pharyngeal airway closure during sleep in patients with OSA. The second aim of the study was to determine if the polysomnographic response to the oral mandibular advancement device was dependent on the site of airway closure. Overnight polysomnograms were performed in 28 untreated OSA subjects with and without EMA. A third polysomnogram was performed in 12 of the subjects to determine the site of airway closure without the device. Site of airway closure above or below the oropharynx was determined by measuring the respective presence or absence of respiratory fluctuations in oropharyngeal pressure during induced occlusions in non-rapid eye movement (NREM) sleep. Mean apnea-hypopnea index (AHI) was 52.6 +/- 28.2 (SD) events/h without the device and 21.2 +/- 19.3 events/h with the device. Nineteen subjects (68%) had at least a 50% reduction in AHI with the device. The change in AHI with the device (AHI without device - AHI with device) was directly related to the AHI without the device. All three subjects with airway closure in the lower pharyngeal airway had a greater than 80% reduction in AHI with the device. Two of the nine subjects with airway closure in the velopharynx had a similar therapeutic response. The results show the effectiveness of EMA in the treatment of OSA. The results also indicate that polysomnographic severity of OSA and the site of airway closure should not be used to exclude patients from this oral device treatment.

The sleeping state places unique demands on the ventilatory control system. The sleep-induced increase in airway resistance, the loss of consciousness, and the need to maintain the sleeping state without frequent arousals require the presence of complex compensatory mechanisms. The increase in upper airway resistance during sleep represents the major effect of sleep on ventilatory control. This occurs because of a loss of muscle activity, which narrows the airway and also makes it more susceptible to collapse in response to the intraluminal pressure generated by other inspiratory muscles. The magnitude and timing of the drive to upper airway vs. other inspiratory pump muscles determine the level of resistance and can lead to inspiratory flow limitation and complete upper airway occlusion. The fall in ventilation with this mechanical load is not prevented, as it is in the awake state, because of the absence of immediate compensatory responses during sleep. However, during sleep, compensatory mechanisms are activated that tend to return ventilation toward control levels if the load is maintained. Upper airway protective reflexes, intrinsic properties of the chest wall, muscle length-compensating reflexes, and most importantly chemoresponsiveness of both upper airway and inspiratory pump muscles are all present during sleep to minimize the adverse effect of loading on ventilation. In non-rapid-eye-movement sleep, the high mechanical impedance combined with incomplete load compensation causes an increase in arterial PCO2 and augmented respiratory muscle activity. Phasic rapid-eye-movement sleep, however, interferes further with effective load compensation, primarily by its selective inhibitory effects on the phasic activation of postural muscles of the chest wall. The level and pattern of ventilation during sleep in health and disease states represent a compromise toward the ideal goal, which is to achieve maximum load compensation and meet the demand for chemical homeostasis while maintaining sleep state.

The purpose of this study was twofold, namely, to determine (1) if phasic respiratory muscle activity can be inhibited during nocturnal mechanical ventilation, and (2) the mechanism by which this inhibition occurs. Twelve normal subjects were studied during non-rapid eye movement (NREM) sleep (Stages 2 to 4) while receiving negative (NPV, 8 subjects) or positive (PPV, 4 subjects) pressure ventilation and during spontaneous breathing. EMGdia (surface), end-tidal CO2 pressure (PETCO2), esophageal pressure (Pe), and ventilation were measured with a flow-through hood (NPV) or a mask (PPV). The following results were obtained during steady-state (3 to 22 min) mechanical ventilation. (1) A decrease in PETCO2 of 2 to 6 mm Hg resulted in elimination of phasic EMGdia in all subjects. Inhibition of respiratory muscle EMG (and a positive shift in Pe) occurred coincident with the breath-by-breath reduction in PETCO2, so that EMGdia was usually eliminated after the initial 4 to 6 breaths while using the ventilator. (2) Returning PETCO2 to the spontaneous sleeping level by adding CO2 to the inspired air (isocapnic mechanical ventilation) caused significant increases in EMGdia. During this isocapnic mechanical ventilation, however, EMGdia usually remained less than during eucapnic control. (3) Stopping the ventilator during hypocapnic ventilation caused a prolongation of expiratory time (TE) that was proportional to the degree of hypocapnia during the mechanical ventilation (100 to 1,200% increase over control). During isocapnic ventilation, cessation of mechanical ventilation caused no change in TE.(ABSTRACT TRUNCATED AT 250 WORDS)

Cystic fibrosis (CF) is often associated with low hemoglobin oxygen saturation and with limited exercise tolerance, yet published reports do not agree on the effect of exercise on oxygenation in CF. We studied oxygen saturation (SaO2) by ear oximetry in 91 patients with CF during progressive exercise to exhaustion. Only 13 of 91 patients changed SaO2 by 5% or more; of these, 4 patients increased SaO2 by 5% or more, whereas 9 decreased by 5% or more. Small changes in SaO2 did not relate to resting pulmonary function, but large decreases in SaO2 were much more likely to be found in patients with forced expiratory volume in one second (FEV1) less than 50% of VC than in those with better pulmonary function (desaturation of 5% or greater was found in only 1 of 62 patients with FEV1 greater than 50% of VC, but in 8 of 29 patients with FEV1 less than or equal to 50% VC). However, even in severely affected patients, modest increases or no change in saturation were more common than large decreases, and 17 of 29 patients with FEV1 less than 50% VC ended exercise with SaO2 greater than 90%, including 3 patients with initial SaO2 below 90%. No single resting pulmonary function test or combination of tests could predict oxygen changes with exercise. Most patients with CF tolerate even maximal exercise without significant desaturation, but patients with FEV1 less than 50% of VC should have supervised exercise testing with ear oximetry before undertaking an exercise program.

We examined the effects of high-frequency- (30-Hz) low-pressure oscillations (< 1 cmH2O) applied to the upper airway, via a nose mask, on genioglossus (EMGgg), sternomastoid (EMGsm), and diaphragm electromyogram (EMGdia) activity in sleeping humans. Ten patients with sleep apnea and six normal subjects were studied. The pressure oscillations were applied through the mask for a single breath. The subjects were studied in non-rapid-eye-movement (NREM) and rapid-eye-movement (REM) sleep. In the normal subjects, during NREM sleep, peak EMGgg, EMGsm, and EMGdia activity increased significantly in response to the oscillations in 63, 51, and 46%, respectively, of all trials. During REM sleep, significant increases occurred in 73, 88, and 13%, respectively, of all trials. Similar responses were observed in the patients with obstructive sleep apnea. Peak EMGgg, EMGsm, and EMGdia activity increased significantly in 74, 50, and 67%, respectively, of all NREM sleep trials and in 55, 81, and 76%, respectively, of all REM sleep trials. An important finding was that in 46% of the trials in the patients with sleep apnea the oscillation-induced increase in EMGgg activity was associated with a partial or complete reversal of the upper airway obstruction with an increase in tidal volume. This was observed in NREM and REM sleep. We conclude that there are upper airway receptors that respond to low-pressure-high-frequency oscillations applied to the upper airway that have input to the genioglossus and other muscles of respiration. These responses may be utilized in future treatment for sleep apnea.

To investigate the response of inspiratory and expiratory muscles to naturally occurring inspiratory resistive loads in the absence of conscious control, five male "snorers" were studied during non-rapid-eye-movement (NREM) sleep with and without continuous positive airway pressure (CPAP). Diaphragm (EMGdi) and scalene (EMGsc) electromyographic activity were monitored with surface electrodes and abdominal EMG activity (EMGab) with wire electrodes. Subjects were studied in the following conditions: 1) awake, 2) stage 2 sleep, 3) stage 3/4 sleep, 4) CPAP during stage 3/4 sleep, 5) CPAP plus end-tidal CO2 pressure (PETCO2) isocapnic to stage 2 sleep, and 6) CPAP plus PETCO2 isocapnic to stage 3/4 sleep. Inspired pulmonary resistance (RL) at peak flow rate and PETCO2 increased in all stages of sleep. Activity of EMGdi, EMGsc, and EMGab increased significantly in stage 3/4 sleep. CPAP reduced RL at peak flow, increased tidal volume and expired ventilation, and reduced PETCO2. EMGdi and EMGsc were reduced, and EMGab was silenced. During CPAP, with CO2 added to make PETCO2 isocapnic to stage 3/4 sleep, EMGsc and EMGab increased, but EMGdi was augmented in only one-half of the trials. EMG activity in this condition, however, was only 75% (EMGsc) and 43% (EMGab) of the activity observed during eupneic breathing in stage 3/4 sleep when PETCO2 was equal but RL was much higher. We conclude that during NREM sleep 1) inspiratory and expiratory muscles respond to internal inspiratory resistive loads and the associated dynamic airway narrowing and turbulent flow developed throughout inspiration, 2) some of the augmentation of respiratory muscle activity is also due to the hypercapnia that accompanies loading, and 3) the abdominal muscles are the most sensitive to load and CO2 and the diaphragm is the least sensitive.