Effects of negative upper airway pressure on pattern of breathing in sleeping infants

Negative upper airway (UAW) pressure inhibits diaphragm inspiratory activity in animals, but there is no direct evidence of this reflex in humans. Also, little is known regarding reflex latency or effects of varying time of stimulation during the breathing cycle. We studied effects of UAW negative pressure on inspiratory airflow and respiratory timing in seven tracheostomized infants during quiet sleep with a face mask and syringe used to produce UAW suction without changing lower airway pressure. Suction trials lasted 2-3 s. During UAW suction, mean and peak inspiratory airflow as well as tidal volume was markedly reduced (16-68%) regardless of whether stimulation occurred in inspiration or expiration. Reflex latency was 42 +/- 3 ms. When suction was applied during inspiration or late expiration, the inspiration and the following expiration were shortened. In contrast, suction applied during midexpiration prolonged expiration and tended to prolong inspiration. The changes in flow, tidal volume, and timing indicate a marked inhibitory effect of UAW suction on thoracic inspiratory muscles. Such a reflex mechanism may function in preventing pharyngeal collapse by inspiratory suction pressure.     

Pressure-volume behavior of the upper airway

The study was performed to investigate the relationship between force generation and upper airway expansion during respiratory efforts by upper airway muscles. In 11 anesthetized dogs we isolated the upper airway (nasal, oral, pharyngeal, and laryngeal regions) by transecting the cervical trachea and sealing the nasal and oral openings. During spontaneous respiratory efforts the pressure within the sealed upper airway, used as an index of dilating force, decreased during inspiration. On alternate breaths the upper airway was opened to a pneumotachograph, and an increase in volume occurred, also during inspiration. Progressive hyperoxic hypercapnia produced by rebreathing increased the magnitude of change in pressure and volume. At any level of drive, peak pressure or volume occurred at the same point during inspiration. At any level of drive, volume and pressure changes increased with end-expiratory occlusion of the trachea. The force-volume relationship determined from measurements during rebreathing was compared with pressure-volume curves performed by passive inflation of the airway while the animal was apneic. The relationship during apnea was 1.06 +/- 0.55 (SD) ml/cmH2O, while the force-volume relationship from rebreathing trials was -1.09 +/- 0.45 ml/cmH2O. We conclude that there is a correspondence between force production and volume expansion in the upper airway during active respiratory efforts.     

Phasic respiratory modulation of pharyngeal collapsibility via neuromuscular mechanisms in rats

Obstructive sleep apnea patients experience recurrent upper airway (UA) collapse due to decreases in the UA dilator muscle activity during sleep. In contrast, activation of UA dilators reduces pharyngeal critical pressure (Pcrit, an index of pharyngeal collapsibility), suggesting an inverse relationship between pharyngeal collapsibility and dilator activity. Since most UA muscles display phasic respiratory activity, we hypothesized that pharyngeal collapsibility is modulated by respiratory drive via neuromuscular mechanisms. Adult male Sprague-Dawley rats were anesthetized, vagotomized, and ventilated (normocapnia). In one group, integrated genioglossal activity, Pcrit, and maximal airflow (V(max)) were measured at three expiration and five inspiration time points within the breathing cycle. Pcrit was closely and inversely related to phasic genioglossal activity, with the value measured at peak inspiration being the lowest. In other groups, the variables were measured during expiration and peak inspiration, before and after each of five manipulations. Pcrit was 26% more negative (-15.0 ± 1.0 cmH(2)O, -18.9 ± 1.2 cmH(2)O; n = 23), V(max) was 7% larger (31.0 ± 1.0 ml/s, 33.2 ± 1.1 ml/s), nasal resistance was 12% bigger [0.49 ± 0.05 cmH(2)O/(ml/s), 0.59 ± 0.05 cmH(2)O/(ml/s)], and latency to induced UA closure was 14% longer (55 ± 4 ms, 63 ± 5 ms) during peak inspiration vs. expiration (all P < 0.005). The expiration-inspiration difference in Pcrit was abolished with neuromuscular blockade, hypocapnic apnea, or death but was not reduced by the superior laryngeal nerve transection or altered by tracheal displacement. Collectively, these results suggest that pharyngeal collapsibility is moment-by-moment modulated by respiratory drive and this phasic modulation requires neuromuscular mechanisms, but not the UA negative pressure reflex or tracheal displacement by phasic lung inflation.     

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.     

Respiration during feeding on solid food: alterations in breathing during mastication, pharyngeal bolus aggregation, and swallowing.

During feeding, solid food is chewed and propelled to the oropharynx, where the bolus gradually aggregates while the larynx remains open and breathing continues. The aggregated bolus in the valleculae is exposed to respiratory airflow, yet aspiration is rare in healthy individuals. The mechanism for preventing aspiration during bolus aggregation is unclear. One possibility is that alterations in the pattern of respiration during feeding could help prevent inhalation of food from the pharynx. We hypothesized that respiration was inhibited during bolus aggregation in the valleculae. Videofluorography was performed on 10 healthy volunteers eating solid foods with barium. Respiration was monitored concurrently with plethysmography and nasal air pressure. The timing of events during mastication, food transport, pharyngeal bolus aggregation, and swallowing were measured in relation to respiration. Respiratory cycle duration decreased during chewing (P < 0.001) but increased with swallowing (P < 0.001). During 66 recordings of vallecular bolus aggregation, there was inspiration in 8%, expiration in 41%, a pause in breathing in 17%, and multiple phases (including inspiration) in 35%. Out of 98 swallows, 47% started in the expiratory phase and 50% started during a pause in breathing, irrespective of bolus aggregation in the valleculae. Plethysmography was better than nasal manometry for determining the end of active expiration during feeding and swallowing with solid food. The hypothesis is rejected in that respiration was not inhibited during bolus aggregation. These findings suggest that airflow through the pharynx does not have a role in preventing aspiration during bolus aggregation in the oropharynx.     

Mandible position and activation of submental and masseter muscles during sleep.

Movement of the mandible could influence pharyngeal airway caliber because the mandible is attached to the tongue and to muscles that insert on the hyoid bone. In normal subjects and patients with obstructive sleep apnea (OSA) we measured jaw position during sleep with strain gauges, as well as masseter and submental electromyograms, airflow, esophageal pressure, oximetry, electroencephalograms, and electrooculograms. Jaws of patients with OSA were open more than those of normal subjects at end expiration and opened further at end inspiration, particularly at the termination of apneas when the masseter and submental muscles contracted. Masseter activation occurred only in patients with OSA and in a pattern similar to that of submental muscles. Jaw opening at end expiration could narrow the upper airway, whereas opening at end inspiration could reflect efforts to expand the airway with tracheal tug and with submental muscle activation and efforts to open the mouth to allow mouth breathing. Masseter contraction does not close the jaw but may serve to stabilize it.     

Upper airway pressure-flow relationships and pharyngeal constrictor EMG activity during prolonged expiration in awake goats.

We undertook the present investigation to establish whether narrowing/closure of the upper airway occurs during spontaneous and provoked respiratory rhythm disturbances and whether pharyngeal constrictor muscle recruitment occurs coincident with upper airway occlusion during prolonged expiratory periods. Upper airway pressure-flow relationships and middle pharyngeal constrictor (mPC) EMG activities were recorded in 11 adult female goats during spontaneous and provoked prolongations in expiratory time (Te). A total of 213 spontaneous prolongations of expiration were recorded. Additionally, 169 prolonged expiratory events preceded by an augmented breath were included in the analyses. In separate trials on different days, Te was prolonged by systemic administration of dopamine, by raising the inspired fraction of O(2) from 0.10 to 1.00 during poikilocapnic conditions or by systemic administration of clonidine. Continuous tonic activation of the mPC EMG was observed during each prolonged Te period regardless of the duration or initiating cause. However, significant increases in subglottic tracheal pressure, with expiratory airflow braking indicative of upper airway narrowing or closure, was only observed during spontaneous events without a preceding augmented breath and during clonidine-induced events. Tonic mPC activation proved an unreliable indicator of airway occlusion. Furthermore, mPC muscle activation alone is not sufficient to induce pharyngeal occlusion during prolonged expiration. Our data suggest that airway closure is not a common occurrence during provoked respiratory disturbances in awake goats. We propose that airway closure, when present during prolonged Te, is more likely dependent on activation of laryngeal adductor muscles with glottic braking independent of pharyngeal narrowing.     

Triangularis sterni: a primary muscle of breathing in the dog

The isolated action, pattern of neural activation, and mechanical contribution to eupnea of the triangularis sterni (transversus thoracis) muscle were studied in supine anesthetized dogs. Linear displacement transducers were used to measure the axial displacements of the ribs and sternum. Tetanic stimulation of the triangularis sterni in the apneic animal caused a marked caudal displacement of the ribs, a moderate cranial displacement of the sternum, and a decrease in lung volume. During quiet breathing, there was invariably a rhythmic activation of the muscle in phase with expiration that was independent of the presence or absence of activity in the abdominal and internal interosseous intercostal muscles. This phasic expiratory activity in the triangularis sterni was of large amplitude and caused the ribs to be more caudal and the sternum to be more cranial during the spontaneous expiratory pause than during relaxation. Additional studies on awake animals showed that rhythmic activation of the triangularis sterni occurs in all body positions and is not caused by anesthesia. These findings indicate that expiration in the dog is not a passive process and that the end-expiratory volume of the rib cage is not determined by an equilibrium of static forces alone. Rather, it is actively determined and maintained below its relaxation volume by contraction of the triangularis sterni throughout expiration. The use of this muscle is likely to facilitate inspiration by increasing the length of the parasternal intercostals and taking on a portion of their work.     

Coupling between triangularis sterni and parasternals during breathing in dogs

The purpose of the present studies was to assess the functional coupling between the parasternal intercostals and the triangularis sterni (transversus thoracis) muscles during resting breathing, and we measured the electrical activity and the respiratory changes in length of these two muscles in 13 supine anesthetized dogs. The changes in muscle length were defined relative to their respective in situ relaxation length (Lr). During inspiration, the parasternal intercostals were active and shortened below Lr, causing the triangularis sterni to be passively stretched above Lr. Shortly after the cessation of parasternal contraction, the triangularis sterni became active and shortened below Lr, and in nine animals this active shortening was associated with a forcible distension of the parasternal intercostals above Lr. Deactivation of the triangularis sterni at end expiration caused both muscles to return to their respective Lr. This pattern was essentially unchanged after supplemental anesthesia and bilateral phrenicotomy. We conclude that in dogs breathing quietly the length of the rib cage muscles during the expiratory pause is not passively determined as conventionally thought.     

Respiratory function of hyoid muscles and hyoid arch

The position of the hyoid arch suggests that it supports soft tissue surrounding the upper airway (UA) and can act to maintain UA patency. We also suspected that muscles inserting on the hyoid arch might show respiratory patterns of activity that could be affected by respiratory stimuli. To test these possibilities, we moved the hyoid arch ventrally in six anesthetized dogs either by traction on it or by stimulation of hyoid muscles. UA resistance was decreased 73 +/- (SE) 6% and 72 +/- 6% by traction and stimulation during expiration and 57 +/- 15% and 52 +/- 8% during inspiration. Moving averages of the geniohyoid (GH) and thyrohyoid (TH) obtained in six other dogs breathing 100% O2 showed phasic respiratory activity while the sternohyoid (SH) showed phasic respiratory activity in only two of these animals and no activity in four. With progressive hypercapnia, GH and TH increased as did SH when activity was already present. Airway occlusion at end expiration augmented and prolonged inspiratory activity in the hyoid muscles but did not elicit SH activity if not already present. Occlusion at end inspiration suppressed phasic activity in hyoid muscles for as long as in the diaphragm. After vagotomy activity increased and became almost exclusively inspiratory. Activity appeared in SH when not previously present. Duration and amplitude of hyoid muscle activity were increased with negative UA pressure and augmented breaths. We conclude that the hyoid arch and muscles can strongly affect UA flow resistance. Hyoid muscles show responses to chemical, vagal, and negative pressure stimuli similar to other UA muscles.     

Assessment of pharyngeal airway stability in normal and micrognathic infants

A current hypothesis for obstructive sleep apnea states that 1) negative airway pressure during inspiration can collapse the pharyngeal airway, and 2) neural control of pharyngeal airway-dilating muscles is important in preventing this collapse. To test this hypothesis we performed nasal mask occlusions to increase negative pharyngeal airway pressures during inspiration in eight normal and five micrognathic infants. Both groups developed midinspiratory pharyngeal obstruction, but obstruction was more frequent in micrognathic infants and varied in some infants with sleep state. The airway usually reopened with the subsequent expiration. The occasional failure to reopen was presumably due to pharyngeal wall adhesion. If airway obstruction occurred in sequential breaths during multiple-breath nasal mask occlusions in normal infants, there was a breath-by-breath change in the airway pressure associated with airway closure (airway closing pressure); the airway closing pressure became progressively more negative. Micrognathic infants showed less ability to improve the airway closing pressure, but this ability increased with age. These findings suggest that nasal mask occlusion can test the competence of the neuromuscular mechanisms that maintain pharyngeal airway patency in infants. Micrognathic infants had spontaneous midinspiratory pharyngeal airway obstructions during snoring. Their episodes of obstructive apnea began with midinspiratory pharyngeal obstruction similar to that seen during snoring and nasal mask occlusions. These findings imply a similar pathophysiology for snoring, spontaneous airway obstruction, and obstruction during snoring.     

Respiratory-related pharyngeal constrictor muscle activity in decerebrate cats

Kuna, Samuel T., and Christi R. Vanoye.Respiratory-related pharyngeal constrictor muscle activity indecerebrate cats. J. Appl. Physiol.83(5): 1588-1594, 1997.Respiratory-related activity of thehyopharyngeus (middle pharyngeal constrictor) and thyropharyngeus(inferior pharyngeal constrictor) muscles was determined indecerebrate, tracheotomized adult cats and compared with theelectromyographic activity of the thyroarytenoid, a vocal cordadductor. During quiet breathing, the hyopharyngeus and usually thethyroarytenoid exhibited phasic activity during expiration and tonicactivity throughout the respiratory cycle. Respiratory-related thyropharyngeus activity was absent under these conditions. Progressive hyperoxic hypercapnia and progressive isocapnic hypoxia increased phasic expiratory activity in both pharyngeal constrictor (PC) musclesbut tended to suppress thyroarytenoid activity. Passively inducedhypocapnia and the central apnea that followed the cessation of themechanical hyperventilation were associated with tonic activation ofthe hyopharyngeus and thyroarytenoid but no recruitment inthyropharyngeus activity. The expiratory phase of a sigh and progressive pneumothorax were associated with an increase in phasic thyroarytenoid activity but no change in phasic PC activity. The results indicate that a variety of stimuli modulate respiratory-related PC activity, suggesting that the PC muscles may have a role in theregulation of upper airway patency during respiration.

     

Intrinsic properties of pharyngeal and diaphragmatic respiratory motoneurons and muscles.

Breathing is a complex act requiring the coordinated activity of multiple groups of muscles. Thoracic and abdominal respiratory muscles expand and contract the lungs, whereas pharyngeal and laryngeal respiratory muscles maintain upper airway patency and regulate upper airway resistance. An appreciation of the importance of the latter muscle group in maintaining ventilatory homeostasis and in the pathophysiology of sleep apnea has led to extensive studies examining the neural regulation of pharyngeal dilator muscles. The present review examines the role of heterogeneity in motoneuron and muscle properties in determining the diversity in the electrical and mechanical behaviors of thoracic compared with pharyngeal muscle groups. Specifically, phrenic and hypoglossal motoneuron electrophysiological properties influence whether and the extent to which these neurons will fire in response to a given synaptic input arising from chemo- and mechanoreceptors and from respiratory and nonrespiratory pattern generators. Furthermore, thoracic and pharyngeal muscle properties determine the mechanical response to motoneuronal activity, including the speed of contraction, relationships between motoneuron firing frequency and force production, and whether force is maintained during repetitive activation. Heterogeneity in the functional capabilities of these motoneurons and muscles is in turn determined by diversity of their structural and biochemical properties. Thus, intrinsic properties of respiratory motoneurons and muscles act in concert with neuronal drives in defining the complex electrical and mechanical behavior of pharyngeal and thoracic respiratory motor systems.     

The interaction between breathing and swallowing in healthy individuals

In this article, we aimed at investigating the interaction between breathing and swallowing patterns in normal subjects. Ten healthy volunteers were included in the study. Diaphragm EMG activity was recorded by a needle electrode inserted into the 7th or 8th intercostal space. Swallowing was monitored by submental EMG activity, and laryngeal vertical movement was recorded by using a movement sensor. A single voluntary swallow was initiated during either the inspiration or expiration phases of respiration, and changes in EMG activity were evaluated. When a swallow coincided with either inspiration or expiration, the duration of the respiratory phase was prolonged. Normal subjects were able to voluntarily swallow during inspiration. During the inspiration phase with swallowing, diaphragmatic activity did not ceased and during the expiration phase with swallowing, there was a muscle activity in the diaphragm muscle.     

Respiratory function of pharyngeal muscles

This article reviews experimental studies of pharyngeal muscles with emphasis on m. genioglossus as a major muscle dilating pharynx and discusses neuromuscular mechanisms that maintains patency of upper airway. Mechanisms of inspiratory activation of genioglossus muscle in comparative with diaphragm are also discussed. Experimental data suggesting that upper airway muscles have a significant role in compensation of added inspiratory load are presented. It allows to regard pharyngeal dilating muscles as accessory muscles of respiration. Activation of m. genioglossus (together with others muscles dilating the pharynx) decreases airway resistance and thereby facilitates the load compensation function of "pumping" muscles. Similar to diaphragm involvement of the pharynx dilating muscles in the load compensatory response is resulted from a complex integration of several influences originating from mechano- and chemoreceptors.     

Passive movement of human soft palate during respiration: A simulation of 3D fluid/structure interaction

This study reconstructed a three dimensional fluid/structure interaction (FSI) model to investigate the compliance of human soft palate during calm respiration. Magnetic resonance imaging scans of a healthy male subject were obtained for model reconstruction of the upper airway and the soft palate. The fluid domain consists of nasal cavity, nasopharynx and oropharynx. The airflow in upper airway was assumed as laminar and incompressible. The soft palate was assumed as linear elastic. The interface between airway and soft palate was the FSI interface. Sinusoidal variation of velocity magnitude was applied at the oropharynx corresponding to ventilation rate of 7.5L/min. Simulations of fluid model in upper airway, FSI models with palatal Young's modulus of 7539Pa and 3000Pa were carried out for two cycles of respiration. The results showed that the integrated shear forces over the FSI interface were much smaller than integrated pressure forces in all the three directions (axial, coronal and sagittal). The total integrated force in sagittal direction was much smaller than that of coronal and axial directions. The soft palate was almost static during inspiration but moved towards the posterior pharyngeal wall during expiration. In conclusion, the displacement of human soft palate during respiration was mainly driven by air pressure around the surface of the soft palate with minimal contribution of shear stress of the upper airway flow. Despite inspirational negative pressure, expiratory posterior movement of soft palate could be another factor for the induction of airway collapse.     

Coordination of swallowing and respiration in unconscious subjects

We investigated the coordination of swallowing and breathing in 11 unconscious patients with an endotracheal tube in place during the recovery period from general anesthesia. Swallows occurred during both the inspiratory and expiratory phases with no preponderant occurrence during either phase. When a swallow occurred during inspiration, the inspiration was interrupted immediately and was followed by expiration, but the durations of both inspiration and expiration were progressively increased as the time from the onset of inspiration to the onset of swallowing was progressively delayed. A swallow coinciding with the expiratory phase progressively prolonged the duration of the expiration that had been interrupted as the timing of swallowing was progressively delayed. Repeated swallows invariably and in a predictable manner caused changes in the breathing pattern. Thus when the frequency of regularly repeated swallows was relatively high, the breathing pattern was characterized by regular, shallow, and rapid breaths. When the frequency of regularly repeated swallows was relatively low, the breathing pattern was characterized by regular, deep, and slow breaths. When the frequency of repeated swallows was irregular, the breathing patterns were characterized by inconsistent changes in tidal volume and respiratory frequency. Our results indicate that, in unconscious subjects, some mechanisms integrating respiration and swallowing are operative and responsible for changes in breathing patterns during swallowing.     

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.     

Role of upper airway in ventilatory control in awake and sleeping dogs

We examined the role of the upper airway in the regulation of the pattern of breathing in six adult dogs during wakefulness and sleep. The dogs breathed through a fenestrated endotracheal tube inserted through a tracheostomy. The tube was modified to allow airflow to be directed either through the nose or through the tracheostomy. When airflow was diverted from nose to tracheostomy there was an abrupt increase in the rate of expiratory airflow, resulting in prolongation of the end-expiratory pause but no change in overall expiratory duration or respiratory frequency. Furthermore, electromyogram recordings from implanted diaphragmatic and laryngeal muscle electrodes did not show any changes that could be interpreted as an attempt to delay expiratory airflow or increase end-expiratory lung volume. The effects of switching from nose to tracheostomy breathing could be reversed by adding a resistance to the endotracheal tube so as to approximate upper airway resistance. The findings indicate that under normal conditions in the adult dog upper airway receptors play little role in regulation of respiratory pattern and that the upper airway exerts little influence on the maintenance of end-expiratory lung volume.     

Application of negative expiratory pressure during expiration and activity of genioglossus in humans

The application of negative expiratory pressure(NEP) at end expiration has been shown to cause reflex-mediatedactivation of the genioglossus muscle in awake humans. To test whethera reflex contraction of pharyngeal dilator muscles also occurs in response to NEP applied in early expiration, the effect on genioglossus muscle reflex activity of NEP pulses of 500 ms, given 0.2 s after theonset of expiration and during the end-expiratory pause, was assessedin 10 normal awake subjects at rest. The raw and integrated surfaceelectromyogram of the genioglossus (EMGgg) was recorded with airflowand mouth pressure under control conditions and with NEP ranging from3 to 10 cmH₂O.Intraoral EMGgg was also recorded under the same experimentalconditions in two subjects. The application of NEP at theend-expiratory pause elicited a consistent reflex response of EMGgg inseven subjects with a mean latency of 68 ± 5 ms. In contrast, whenNEP was applied at the onset of expiration, EMGgg reflex activity wasinvariably observed in only one subject. No relationship was foundbetween steady increase or abrupt fall in expiratory flow and thepresence or the absence of a reflex activity of genioglossus duringsudden application of NEP at the beginning of expiration. Our resultsshow that a reflex activity of genioglossus is elicited much morecommonly during application of NEP at the end rather than at the onsetof expiration. These findings also suggest that when NEP is applied inearly expiration to detect intrathoracic flow limitation the absence ofupper airways narrowing does not imply the occurrence of areflex-mediated activation of genioglossus and vice versa.