Characterization of pharyngeal resistance during sleep in a spectrum of sleep-disordered breathing.

Aims of the study were 1) to compare Hudgel's hyperbolic with Rohrer's polynomial model in describing the pressure-flow relationship, 2) to use this pressure-flow relationship to describe these resistances and to evaluate the effects of sleep stages on pharyngeal resistances, and 3) to compare these resistances to the pressure-to-flow ratio (DeltaP/V). We studied 12 patients: three with upper airway resistance syndrome (UARS), four with obstructive sleep hypopnea syndrome (OSHS), three with obstructive sleep apnea syndrome (OSAS), and two with simple snoring (SS). Transpharyngeal pressures were calculated between choanae and epiglottis. Flow was measured by use of a pneumotachometer. The pressure-flow relationship was established by using nonlinear regression and was appreciated by the Pearson's square (r(2)). Mean resistance at peak pressure (Rmax) was calculated according to the hyperbolic model during stable respiration. In 78% of the cases, the value of r(2) was greater when the hyperbolic model was used. We demonstrated that Rmax was in excellent agreement with P/V. UARS patients exhibited higher awake mean Rmax than normal subjects and other subgroups and a larger increase from wakefulness to slow-wave sleep than subjects with OSAS, OSHS, and SS. Analysis of breath-by-breath changes in Rmax was also a sensitive method to detect episodes of high resistance during sleep.     

Variable site of airway narrowing among obstructive sleep apnea patients

The purpose of this was to determine whether the site of physiological narrowing within the upper airway was uniform or differed among patients with obstructive sleep apnea. Inspiratory pressures were measured with an esophageal balloon catheter and three catheters located at different sites along the upper airway: supralaryngeal airway, oropharynx, and nasopharynx. Peak inspiratory pressure differences between catheters allowed assessment of pressure gradients across three airway segments: lungs-larynx-retroepiglottal airway (esophageal-supralaryngeal pressure), hypopharynx (supralaryngeal-oropharynx pressure), and transpalatal airway (oropharynx-nasopharynx pressure). In five patients, hypopharyngeal obstruction was present, and in four patients no hypopharyngeal obstruction existed. In these four patients the site of obstruction was located at the level of the palate. In a given subject, the site of obstruction was the same during repeated measurements. The presence or absence of hypopharyngeal narrowing during sleep was not predictable from gradients measured across different segments of the upper airway during wakefulness. We conclude that the site of physiological upper airway obstruction varies among patients with obstructive sleep apnea and is not predictable from pressure measured during wakefulness. We speculate that uvulopalatopharyngoplasty may not relieve obstructive apneas in patients with hypopharyngeal obstruction.     

Upper airway dilating forces during wakefulness and sleep in dogs

We measured the pressure within an isolated segment of the upper airway in three dogs during wakefulness (W), slow-wave sleep (SWS) and rapid-eye-movement (REM) sleep. Measurements were taken from a segment of the upper airway between the nares and midtrachea while the dog breathed through a tracheostoma. These pressure changes represented the sum of respiratory-related forces generated by all muscles of the upper airway. The mean base-line level of upper airway pressure (Pua) was -0.5 +/- 0.03 cmH2O during W, increased by a mean of 2.1 +/- 0.2 cmH2O during SWS, and was variable during REM sleep. The mean inspiratory-related phasic change in Pua was -1.2 +/- 0.1 cmH2O during wakefulness. During SWS, this phasic change in Pua decreased significantly to a mean of -0.9 +/- 0.1 cmH2O (P less than 0.05). During REM sleep, the phasic activity was extremely variable with periods in which there were no fluctuations in Pua and others with high swings in Pua. These data indicate that in dogs the sum of forces which dilate the upper airway during W decreases during SWS and REM sleep. The consistent coupling between inspiratory drive and upper airway dilatation during wakefulness persists in SWS, but is frequently uncoupled during REM sleep.     

Neuromuscular and mechanical responses to inspiratory resistive loading during sleep

The purposes of this study were 1) to characterize the immediate inspiratory muscle and ventilation responses to inspiratory resistive loading during sleep in humans and 2) to determine whether upper airway caliber was compromised in the presence of a resistive load. Ventilation variables, chest wall, and upper airway inspiratory muscle electromyograms (EMG), and upper airway resistance were measured for two breaths immediately preceding and immediately following six applications of an inspiratory resistive load of 15 cmH2O.l-1 X s during wakefulness and stage 2 sleep. During wakefulness, chest wall inspiratory peak EMG activity increased 40 +/- 15% (SE), and inspiratory time increased 20 +/- 5%. Therefore, the rate of rise of chest wall EMG increased 14 +/- 10.9% (NS). Upper airway inspiratory muscle activity changed in an inconsistent fashion with application of the load. Tidal volume decreased 16 +/- 6%, and upper airway resistance increased 141 +/- 23% above pre-load levels. During sleep, there was no significant chest wall or upper airway inspiratory muscle or timing responses to loading. Tidal volume decreased 40 +/- 7% and upper airway resistance increased 188 +/- 52%, changes greater than those observed during wakefulness. We conclude that 1) the immediate inspiratory muscle and timing responses observed during inspiratory resistive loading in wakefulness were absent during sleep, 2) there was inadequate activation of upper airway inspiratory muscle activity to compensate for the increased upper airway inspiratory subatmospheric pressure present during loading, and 3) the alteration in upper airway mechanics during resistive loading was greater during sleep than wakefulness.     

Noninvasive determination of upper airway resistance and flow limitation.

We have shown that a polynomial equation, FP = AP3 + BP2 + CP + D, where F is flow and P is pressure, can accurately determine the presence of inspiratory flow limitation (IFL). This equation requires the invasive measurement of supraglottic pressure. We hypothesized that a modification of the equation that substitutes time for pressure would be accurate for the detection of IFL and allow for the noninvasive measurement of upper airway resistance. The modified equation is Ft = At3 + Bt2 + Ct + D, where F is flow and t is time from the onset of inspiration. To test our hypotheses, data analysis was performed as follows on 440 randomly chosen breaths from 18 subjects. First, we performed linear regression and determined that there is a linear relationship between pressure and time in the upper airway (R2 0.96 +/- 0.05, slope 0.96 +/- 0.06), indicating that time can be a surrogate for pressure. Second, we performed curve fitting and found that polynomial equation accurately predicts the relationship between flow and time in the upper airway (R2 0.93 +/- 0.12, error fit 0.02 +/- 0.08). Third, we performed a sensitivity-specificity analysis comparing the mathematical determination of IFL to manual determination using a pressure-flow loop. Mathematical determination had both high sensitivity (96%) and specificity (99%). Fourth, we calculated the upper airway resistance using the polynomial equation and compared the measurement to the manually determined upper airway resistance (also from a pressure-flow loop) using Bland-Altman analysis. Mean difference between calculated and measured upper airway resistance was 0.0 cmH2O x l(-1) x s(-1) (95% confidence interval -0.2, 0.2) with upper and lower limits of agreement of 2.8 cmH2O x l(-1) x s(-1) and -2.8 cmH2O x l(-1) x s(-1). We conclude that a polynomial equation can be used to model the flow-time relationship, allowing for the objective and accurate determination of upper airway resistance and the presence of IFL.     

Upper airway resistance and geniohyoid muscle activity in normal men during wakefulness and sleep

Sleep-related reduction in geniohyoid muscular support may lead to increased airway resistance in normal subjects. To test this hypothesis, we studied seven normal men throughout a single night of sleep. We recorded inspiratory supraglottic airway resistance, geniohyoid muscle electromyographic (EMGgh) activity, sleep staging, and ventilatory parameters in these subjects during supine nasal breathing. Mean inspiratory upper airway resistance was significantly (P less than 0.01) increased in these subjects during all stages of sleep compared with wakefulness, reaching highest levels during non-rapid-eye-movement (NREM) sleep [awake 2.5 +/- 0.6 (SE) cmH2O.l-1.s, stage 2 NREM sleep 24.1 +/- 11.1, stage 3/4 NREM sleep 30.2 +/- 12.3, rapid-eye-movement (REM) sleep 13.0 +/- 6.7]. Breath-by-breath linear correlation analyses of upper airway resistance and time-averaged EMGgh amplitude demonstrated a significant (P less than 0.05) negative correlation (r = -0.44 to -0.55) between these parameters in five of seven subjects when data from all states (wakefulness and sleep) were combined. However, we found no clear relationship between normalized upper airway resistance and EMGgh activity during individual states (wakefulness, stage 2 NREM sleep, stage 3/4 NREM sleep, and REM sleep) when data from all subjects were combined. The timing of EMGgh onset relative to the onset of inspiratory airflow did not change significantly during wakefulness, NREM sleep, and REM sleep. Inspiratory augmentation of geniohyoid activity generally preceded the start of inspiratory airflow. The time from onset of inspiratory airflow to peak inspiratory EMGgh activity was significantly increased during sleep compared with wakefulness (awake 0.81 +/- 0.04 s, NREM sleep 1.01 +/- 0.04, REM sleep 1.04 +/- 0.05; P less than 0.05). These data indicate that sleep-related changes in geniohyoid muscle activity may influence upper airway resistance in some subjects. However, the relationship between geniohyoid muscle activity and upper airway resistance was complex and varied among subjects, suggesting that other factors must also be considered to explain sleep influences on upper airway patency.     

Upper airway pressure-flow relationships in obstructive sleep apnea

We examined the pressure-flow relationships in patients with obstructive sleep apnea utilizing the concepts of a Starling resistor. In six patients with obstructive sleep apnea, we applied incremental levels of positive pressure through a nasal mask during non-rapid-eye-movement sleep. A positive critical opening pressure (Pcrit) of 3.3 +/- 3.3 (SD) cmH2O was demonstrated. As nasal pressure was raised above Pcrit, inspiratory airflow increased in proportion to the level of positive pressure applied until apneas were abolished (P less than 0.01). However, at pressures greater than Pcrit, esophageal pressures either did not correlate or correlated inversely with inspiratory airflow provided that esophageal pressure was less than Pcrit. When pressure was applied to a full face mask, inspiratory airflow did not occur and Pcrit could not be obtained at pressures well above Pcrit demonstrated with the nasal mask. These results are consistent with the view that the upper airway functions as a Starling resistor with a collapsible segment in the oropharynx. These findings offer a unifying construct for the association of sleep apnea, periodic hypopnea, and snoring.     

Collapsibility of the human upper airway during normal sleep

Upper airway resistance (UAR) increases in normal subjects during the transition from wakefulness to sleep. To examine the influence of sleep on upper airway collapsibility, inspiratory UAR (epiglottis to nares) and genioglossus electromyogram (EMG) were measured in six healthy men before and during inspiratory resistive loading. UAR increased significantly (P less than 0.05) from wakefulness to non-rapid-eye-movement (NREM) sleep [3.1 +/- 0.4 to 11.7 +/- 3.5 (SE) cmH2O.1-1.s]. Resistive load application during wakefulness produced small increments in UAR. However, during NREM sleep, UAR increased dramatically with loading in four subjects although two subjects demonstrated little change. This increment in UAR from wakefulness to sleep correlated closely with the rise in UAR during loading while asleep (e.g., load 12: r = 0.90, P less than 0.05), indicating consistent upper airway behavior during sleep. On the other hand, no measurement of upper airway behavior during wakefulness was predictive of events during sleep. Although the influence of sleep on the EMG was difficult to assess, peak inspiratory genioglossus EMG clearly increased (P less than 0.05) after load application during NREM sleep. Finally, minute ventilation fell significantly from wakefulness values during NREM sleep, with the largest decrement in sleeping minute ventilation occurring in those subjects having the greatest awake-to-sleep increment in UAR (r = -0.88, P less than 0.05). We conclude that there is marked variability among normal men in upper airway collapsibility during sleep.     

Effect of inspiratory nasal loading on pharyngeal resistance

Nasal obstruction has been shown to increase the number of apneas during sleep in normal subjects and in some may actually cause the sleep apnea syndrome. We postulated that the pharynx may act as a Starling resistor, where increases in negative inspiratory pressure result in elevated resistance across a collapsible pharyngeal segment. To test this theory in normal subjects we studied 10 men and 10 women during wakefulness. Pharyngeal resistance (the resistance across the airway segment between the choanae and the epiglottis) was determined in the normal state and with three inspiratory loads added externally. Flow was measured using a pneumotachometer and a sealed face mask; epiglottic pressure by a latex balloon placed just above the epiglottis and choanal pressure by anterior rhinometry. Pharyngeal resistance (measured at 300 ml/s) could thus be determined. Base-line inspiratory pharnygeal resistance was 1.6 +/- 0.2 cmH2O . l-1 . s. This increased to 2.3 +/- 0.3, 2.8 +/- 0.4, and 2.9 +/- 0.4 cmH2O . l-1 . s, respectively, with the addition of 1.3, 2.7, and 6.7 cmH2O . l-1 . s inspiratory load. The resistance at each level of load was significantly different from the base-line resistance determination (P less than 0.05) but not different from each other. We conclude that added nasal resistive loads during inspiration cause an increase in pharyngeal resistance during wakefulness but that this resistance does not increase further with additional increments of load.     

A mathematical model to detect inspiratory flow limitation during sleep.

The physiological significance of inspiratory flow limitation (IFL) has recently been recognized, but methods of detecting IFL can be subjective. We sought to develop a mathematical model of the upper airway pressure-flow relationship that would objectively detect flow limitation. We present a theoretical discussion that predicts that a polynomial function [F(P) = AP(3) + BP(2) + CP + D, where F(P) is flow and P is supraglottic pressure] best characterizes the pressure-flow relationship and allows for the objective detection of IFL. In protocol 1, step 1, we performed curve-fitting of the pressure-flow relationship of 20 breaths to 5 mathematical functions and found that highest correlation coefficients (R(2)) for quadratic (0.88 +/- 0.10) and polynomial (0.91 +/- 0.05; P < 0.05 for both compared with the other functions) functions. In step 2, we performed error-fit calculations on 50 breaths by comparing the quadratic and polynomial functions and found that the error fit was lowest for the polynomial function (3.3 +/- 0.06 vs. 21.1 +/- 19.0%; P < 0.001). In protocol 2, we performed sensitivity/specificity analysis on two sets of breaths (50 and 544 breaths) by comparing the mathematical determination of IFL to manual determination. Mathematical determination of IFL had high sensitivity and specificity and a positive predictive value (>99% for each). We conclude that a polynomial function can be used to predict the relationship between pressure and flow in the upper airway and objectively determine the presence of IFL.     

Effects of upper airway anesthesia on pharyngeal patency during sleep

Pharyngeal patency depends, in part, on the tone and inspiratory activation of pharyngeal dilator muscles. To evaluate the influence of upper airway sensory feedback on pharyngeal muscle tone and thus pharyngeal patency, we measured pharyngeal airflow resistance and breathing pattern in 15 normal, supine subjects before and after topical lidocaine anesthesia of the pharynx and glottis. Studies were conducted during sleep and during quiet, relaxed wakefulness before sleep onset. Maximal flow-volume loops were also measured before and after anesthesia. During sleep, pharyngeal resistance at peak inspiratory flow increased by 63% after topical anesthesia (P less than 0.01). Resistance during expiration increased by 40% (P less than 0.01). Similar changes were observed during quiet wakefulness. However, upper airway anesthesia did not affect breathing pattern during sleep and did not alter awake flow-volume loops. These results indicate that pharyngeal patency during sleep is compromised when the upper airway is anesthetized and suggest that upper airway reflexes, which promote pharyngeal patency, exist in humans.     

Geniohyoid muscle activity in normal men during wakefulness and sleep

Reduction in the activity of upper airway "dilator" muscles during sleep may allow the pharyngeal airway to collapse in some individuals. However, quantitative studies concerning the effect of sleep on specific upper airway muscles that may influence pharyngeal patency are sparse and inconclusive. We studied seven normal men (mean age 27, range 22-37 yr) during a single nocturnal sleep study and recorded sleep staging parameters, ventilation, and geniohyoid muscle electromyogram (EMGgh) during nasal breathing throughout the night. Anatomic landmarks for placement of intramuscular geniohyoid recording electrodes were determined from a cadaver study. These landmarks were used in percutaneous placement of wire electrodes, and raw and moving-time-averaged EMGgh activities were recorded. Sleep stage was determined using standard criteria. Stable periods of wakefulness and non-rapid-eye-movement (NREM) and rapid-eye-movement (REM) sleep were selected for analysis. The EMGgh exhibited phasic inspiratory activity during wakefulness and sleep in all subjects. In six of seven subjects, mean and peak inspiratory EMGgh activities were significant (P less than 0.05) reduced during stages 2 and 3/4 NREM sleep and REM sleep compared with wakefulness. This reduction of EMGgh activity was shown to result from a sleep-related decline in the level of tonic muscle activity. Phasic inspiratory EMGgh activity during all stages of sleep was not significantly different from that during wakefulness. Of interest, tonic, phasic, and peak EMGgh activities were not significantly reduced during REM sleep compared with any other sleep stage in any subject. In addition, the slope of onset of phasic EMGgh activity was not different during stage 2 NREM and REM sleep compared with wakefulness in these subjects.(ABSTRACT TRUNCATED AT 250 WORDS)     

Induction of upper airway occlusion in sleeping individuals with subatmospheric nasal pressure

In collapsible biologic conduits, occlusion and cessation of flow occur when upstream pressure falls below a critical pressure (Pcrit). To examine the relationship between Pcrit and the development of upper airway occlusion, we examined the relationship between maximal inspiratory airflow and nasal pressure in seven normal subjects during sleep. At varying levels of subatmospheric pressure applied to a nasal mask during non-rapid-eye-movement (NREM) sleep, maximal inspiratory airflow decreased in proportion to the level of nasal pressure. When nasal pressure fell below a Pcrit, subjects demonstrated upper airway occlusions terminated by arousals. In these normal subjects, the upper airway Pcrit was found to be -13.3 +/- 3.2 (SD) cmH2O. In four subjects who sustained sleep while nasal pressure remained below the Pcrit, recurrent occlusive apneas were demonstrated. The relationship between maximal inspiratory airflow and nasal pressure in each subject was fit by linear regression and demonstrated upper airway Pcrit at the zero-flow intercept that were not significantly different from those observed experimentally. These data demonstrate that the normal human upper airway during sleep is characterized by a negative Pcrit and that occlusion may be induced when nasal pressure is decreased below this Pcrit.     

Developmental changes in response to subatmospheric pressure loading of the upper airway.

Children snore less than adults and have fewer obstructive apneas, suggesting a less collapsible upper airway. We therefore hypothesized that the compensatory upper airway responses to subatmospheric pressure loading decrease with age because of changes in upper airway structure and ventilatory drive. We measured upper airway upstream pressure-flow relationships during sleep in 20 nonsnoring, nonobese children and adults. Measurements were made by correlating maximal inspiratory airflow with the level of nasal pressure applied via a mask. The slope of the upstream pressure-flow curve (S(PF)) was used to characterize upper airway function. We found that S(PF) was flatter in children than in adults (8 +/- 5 vs. 30 +/- 18 ml x s(-1). cmH(2)O(-1), P < 0.002) and that S(PF) correlated with age (r = 0.62, P < 0.01) and body mass index (r = 0. 63, P < 0.01). The occlusion pressure in 100 ms during sleep was measured in six children and two adults; it correlated inversely with S(PF) (r = -0.80, P < 0.02). We conclude that the upper airway compensatory responses to subatmospheric pressure loading decrease with age. This is associated with increased body mass index, even in nonsnoring, nonobese subjects. Ventilatory drive during sleep plays a role in modulating upper airway responses.     

Upper airway and respiratory muscle responses to continuous negative airway pressure

To determine upper airway and respiratory muscle responses to nasal continuous negative airway pressure (CNAP), we quantitated the changes in diaphragmatic and genioglossal electromyographic activity, inspiratory duration, tidal volume, minute ventilation, and end-expiratory lung volume (EEL) during CNAP in six normal subjects during wakefulness and five during sleep. During wakefulness, CNAP resulted in immediate increases in electromyographic diaphragmatic and genioglossal muscle activity, and inspiratory duration, preserved or increased tidal volume and minute ventilation, and decreased EEL. During non-rapid-eye-movement and rapid-eye-movement sleep, CNAP was associated with no immediate muscle or timing responses, incomplete or complete upper airway occlusion, and decreased EEL. Progressive diaphragmatic and genioglossal responses were observed during non-rapid-eye-movement sleep in association with arterial O2 desaturation, but airway patency was not reestablished until further increases occurred with arousal. These results indicate that normal subjects, while awake, can fully compensate for CNAP by increasing respiratory and upper airway muscle activities but are unable to do so during sleep in the absence of arousal. This sleep-induced failure of load compensation predisposes the airways to collapse under conditions which threaten airway patency during sleep. The abrupt electromyogram responses seen during wakefulness and arousal are indicative of the importance of state effects, whereas the gradual increases seen during sleep probably reflect responses to changing blood gas composition.     

Control of respiratory activity of the genioglossus muscle in micrognathic infants

The genioglossus (GG) muscle activity of four infants with micrognathia and obstructive sleep apnea was recorded to assess the role of this tongue muscle in upper airway maintenance. Respiratory air flow, esophageal pressure, and intramuscular GG electromyograms (EMG) were recorded during wakefulness and sleep. Both tonic and phasic inspiratory GG-EMG activity was recorded in each of the infants. On occasion, no phasic GG activity could be recorded; these silent periods were unassociated with respiratory embarrassment. GG activity increased during sigh breaths. GG activity also increased when the infants spontaneously changed from oral to nasal breathing and, in two infants, with neck flexion associated with complete upper airway obstruction, suggesting that GG-EMG activity is influenced by sudden changes in upper airway resistance. During sleep, the GG-EMG activity significantly increased with 5% CO2 breathing (P less than or equal to 0.001). With nasal airway occlusion during sleep, the GG-EMG activity increased with the first occluded breath and progressively increased during the subsequent occluded breaths, indicating mechanoreceptor and suggesting chemoreceptor modulation. During nasal occlusion trials, there was a progressive increase in phasic inspiratory activity of the GG-EMG that was greater than that of the diaphragm activity (as reflected by esophageal pressure excursions). When pharyngeal airway closure occurred during a nasal occlusion trial, the negative pressure at which the pharyngeal airway closed (upper airway closing pressure) correlated with the GG-EMG activity at the time of closure, suggesting that the GG muscle contributes to maintaining pharyngeal airway patency in the micrognathic infant.     

Nasal and oral airway pressure-flow relationships.

We examined the inspiratory and expiratory pressure-flow relationships of both the oral and nasal airways before and after exercise in normal upright subjects. With the use of a partitioned facemask, nasal resistance was measured using posterior rhinomanometry, and oral resistance was measured by recording transoral pressure during oral breathing. Both the nasal and oral pressure-flow relationships for inspiration and expiration were curvilinear and were well described by a power function of the form delta P = aVb (where P is pressure, V is flow, a and b are constants) (r2 = 0.96 +/- 0.01). The exponent b describes the curvilinearity of the pressure-flow curve and can be used to infer the flow regimen. At rest, the inspiratory nasal and oral curves suggested a similar degree of turbulence (b = 1.77 +/- 0.06 and 1.83 +/- 0.04, respectively). However, inspiratory flow regimens were inferred to be more turbulent than those during expiration both before and after exercise. After exercise, decreases in inspiratory nasal resistance at low flows were associated with a change in flow regimen from fully turbulent to orifice flow over the entire flow range. Thus the application of a power function to nasal and oral pressure-flow data permits representation of the whole relationship and allows insight into the nature of the flow regimens.     

Modulation of upper airway collapsibility during sleep: influence of respiratory phase and flow regimen.

We hypothesized that upper airway collapsibility is modulated dynamically throughout the respiratory cycle in sleeping humans by alterations in respiratory phase and/or airflow regimen. To test this hypothesis, critical pressures were derived from upper airway pressure-flow relationships in six tracheostomized patients with obstructive sleep apnea. Pressure-flow relationships were generated by varying the pressure at the trachea and nose during tracheostomy (inspiration and expiration) (comparison A) and nasal (inspiration only) breathing (comparison B), respectively. When a constant airflow regimen was maintained throughout the respiratory cycle (tracheostomy breathing), a small yet significant decrease in critical pressure was found at the inspiratory vs. end- and peak-expiratory time point [7.1 +/- 1.6 (SE) to 6.6 +/- 1.9 to 6.1 +/- 1.9 cmH(2)O, respectively; P < 0.05], indicating that phasic factors exerted only a modest influence on upper airway collapsibility. In contrast, we found that the inspiratory critical pressure fell markedly during nasal vs. tracheostomy breathing [1.1 +/- 1.5 (SE) vs. 6.1 +/- 1.9 cmH(2)O; P < 0.01], indicating that upper airway collapsibility is markedly influenced by differences in airflow regimen. Tracheostomy breathing was also associated with a reduction in both phasic and tonic genioglossal muscle activity during sleep. Our findings indicate that both phasic factors and airflow regimen modulate upper airway collapsibility dynamically and suggest that neuromuscular responses to alterations in airflow regimen can markedly lower upper airway collapsibility during inspiration.     

Activation of upper airway muscles before onset of inspiration in normal humans

Animal studies have shown activation of upper airway muscles prior to inspiratory efforts of the diaphragm. To investigate this sequence of activation in humans, we measured the electromyogram (EMG) of the alae nasi (AN) and compared the time of onset of EMG to the onset of inspiratory airflow, during wakefulness, stage II or III sleep (3 subj), and CO2-induced hyperpnea (6 subj). During wakefulness, the interval between AN EMG and airflow was 92 +/- 34 ms (mean +/- SE). At a CO2 level of greater than or equal to 43 Torr, the AN EMG to airflow was 316 +/- 38 ms (P < 0.001). During CO2-induced hyperpnea, the AN EMG to airflow interval and AN EMG magnitude increased in direct proportion to CO2 levels and minute ventilation. During stages II and III of sleep, the interval between AN EMG and airflow increased when compared to wakefulness (P < 0.005). We conclude that a sequence of inspiratory muscle activation is present in humans and is more apparent during sleep and during CO2-induced hyperpnea than during wakefulness.     

Posterior cricoarytenoid muscle activity during wakefulness and sleep in normal adults

Six normal adults were studied 1) to compare respiratory-related posterior cricoarytenoid (PCA) muscle activity during wakefulness and sleep and 2) to determine the effect of upper airway occlusions during non-rapid-eye-movement (NREM) sleep on PCA activity. A new electromyographic technique was developed to implant hooked-wire electrodes into the PCA by using a nasopharyngoscope. A previously described technique was used to induce upper airway occlusions during NREM sleep (Kuna and Smickley, J. Appl. Physiol. 64: 347-353, 1988). The PCA exhibited phasic inspiratory activity during quiet breathing in wakefulness and sleep in all subjects. Discounting changes in tonic activity, peak amplitude of PCA inspiratory activity during stage 3-4 NREM sleep decreased to 77% of its value in wakefulness. Tonic activity throughout the respiratory cycle was present in all subjects during wakefulness but was absent during state 3-4 NREM sleep. In this sleep stage, PCA phasic activity abruptly terminated near the end of inspiration. During nasal airway occlusions in NREM sleep, PCA phasic activity did not increase significantly during the first or second occluded effort. The results, in combination with recent findings for vocal cord adductors in awake and sleeping adults, suggest that vocal cord position during quiet breathing in wakefulness is actively controlled by simultaneously acting antagonistic intrinsic laryngeal muscles. In contrast, the return of the vocal cords toward the midline during expiration in stage 3-4 NREM sleep appears to be a passive phenomenon.