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J Appl Physiol 92: 84-92, 2002;
8750-7587/02 $5.00
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Vol. 92, Issue 1, 84-92, January 2002

Effects of neck flexion and mouth opening on inspiratory flow dynamics in awake humans

Eric Verin1,3,4,5, Frédéric Sériès3,5, Chrystèle Locher1,3, Christian Straus1,2,3, Marc Zelter2,3, Jean-Philippe Derenne1,3, and Thomas Similowski1,3

1 Laboratoire de Physiopathologie Respiratoire, Service de Pneumologie, 2 Service Central d'Explorations Fonctionnelles Respiratoires, Assistance Publique-Hôpitaux de Paris, Groupe Hospitalier Pitié Salpetrière, 75651 Paris; 3 Unité Propre de Recherche de l'Enseignement Supérieur EA 2397, Université Paris VI Pierre et Marie Curie, 75005 Paris; 4 Service de Physiologie, Centre Hospitalier Universitaire de Rouen, 76031 Rouen, France; and 5 Centre de Recherche, Hôpital Laval, Institut Universitaire de Cardiologie et de Pneumologie de l'Université Laval, Quebec, Canada G1V 4G5


    ABSTRACT
TOP
ABSTRACT
INTRODUCTION
MATERIAL AND METHODS
RESULTS
DISCUSSION
REFERENCES

Phrenic nerve stimulation (PNS) can assess airflow dynamics of the upper airway (UA) during wakefulness in man. Using PNS, we aimed to assess the impact of neck flexion and mouth opening in promoting UA unstability. Measurements were made during nasal breathing in seven healthy subjects (ages = 23-39 yr; one woman). Surface diaphragm electromyogram, esophageal pressure referenced to mask pressure, and flow were recorded during diaphragm twitches with neck in neutral position and mouth closed and then with neck flexion and/or mouth opening. Twitches always exhibited a flow-limited pattern. Flow-limiting driving pressure (Pd) and peak Pd were increased by neck flexion (P < 0.01) without significant change in the corresponding flows. UA resistances at these flow values were higher with the neck flexed (P < 0.05). Mouth opening alone did not exert any significant influence. We conclude that the position of the neck has a discernible impact on the flow behavior through the nonphasically active UA faced with a negative Pd.

obstructive sleep apnea syndrome; phrenic nerve stimulation; magnetic stimulation; diaphragm; respiratory mechanics


    INTRODUCTION
TOP
ABSTRACT
INTRODUCTION
MATERIAL AND METHODS
RESULTS
DISCUSSION
REFERENCES

THE STRUCTURE AND THE FUNCTION of the upper airway (UA) are major determinants of the mechanical behavior of the respiratory system. Indeed, in humans as in several animal species, UA resistance to flow accounts for the greatest part of the total flow resistance of the respiratory system (8). It is usual to subdivide the UA into three anatomic segments: the nasopharynx, the oropharynx, and the hypopharynx. Their mechanical properties are distinct. The nasal and the hypopharyngeal segments are anatomically supported by bony and cartilaginous structures and thus are relatively stiff. Their flow resistance is roughly linear (8). The pharyngeal segment of the UA is not supported by such fixed and rigid structures and thus behaves differently. It represents the most compliant part of the UA and can be modeled as a Starling resistor (23, 30).

Experimentally, UA collapsibility can be studied through the flow response to the application of changing pressure at the nose [subatmospheric in normals, positive in OSAS patients with the obstructive sleep apnea syndrome (OSAS)] (6, 20, 23). In this situation, UA tends to narrow and close when the pharyngeal transmural pressure gradient decreases to 0, which is largely determined by intrinsic UA characteristics (namely their shape, dimension, and compliance) (16). The only force available to maintain the patency of UA faced with the negative pressure related to inspiratory efforts is provided by the adapted contraction of UA dilator muscle. They stabilize the UA by decreasing their resistance and collapsibility, thus reducing the work of breathing (31). In addition to their strength and action, the timing of UA dilator muscle activation plays a crucial role in the maintenance of UA patency. Indeed, a precise coordination is needed for the activation of UA muscles to precede that of inspiratory muscles (9).

During sleep, several phenomena can compromise this finely tuned equilibrium, thus increasing UA unstability and promoting airflow obstruction (15, 19, 21, 23). These include an increase in UA resistance and the development of more negative inspiratory pressure swings (1), impaired UA muscle function (3, 4), and a defective preactivation of UA dilator muscle respective to inspiratory muscle (9). Neck flexion (12, 13) and mouth opening (14), both of which commonly occur during sleep, induce anatomic and mechanical changes that increase UA resistance, which is likely to promote UA instability and obstruction. The position of the head seems to be of major importance in this regard. The present study was therefore designed to experimentally evaluate the effects of neck flexion and mouth opening (without oral flow) on inspiratory flow dynamics during nasal breathing in awake normal subjects.

To address this issue, we took advantage of the unique ability of phrenic nerve stimulation (PNS) to provoke, when applied at the end of expiration, a diaphragm contraction dissociated from the activity of UA muscles (24, 26). Thus PNS innovatively gives access to flow dynamics through the passive UA, meaning that, contrary to what happens during normal breathing, the diaphragm twitch-related inspiration occurs independently of the preinspiratory phasic activity of the UA dilator muscle. This technique should thus be particularly suitable to identify the influence of changes such as neck flexion or mouth opening on factors that determine inspiratory flow dynamics, including the mechanical efficiency of UA muscles and the mechanics of the passive pharynx.


    MATERIAL AND METHODS
TOP
ABSTRACT
INTRODUCTION
MATERIAL AND METHODS
RESULTS
DISCUSSION
REFERENCES

Subjects

Seven healthy volunteers were studied (ages = 23-39 yr; one woman; body mass index = 20 ± 9 kg/m2). None of them suffered from respiratory or other diseases, nor did they have clinical symptoms suggestive of sleep-related respiratory abnormalities. They were all known as nonsnorers. The study received ethical and legal clearance from the appropriate French authorities. Subjects were duly informed of the purpose of the study and of the methods used and gave written consent to participate.

Measurements

Pressures and flow. Throughout the study, subjects breathed exclusively through the nose via an airtight nasal mask opened to the air through a pneumotachograph (Hans Rudolph, Kansas City, MO) connected to a linear pressure transducer (Validyne MP45, ±2 cmH2O; Validyne, Northridge, CA). Esophageal pressure (Pes) was measured (Validyne MP45, ±100 cmH2O) with a balloon catheter (80-cm length, 1.4-mm internal diameter; Marquat, Boissy-Saint-Léger, France) passed through one nostril after topical anesthesia and positioned in the esophagus as to reflect pleural pressure according to the occlusion test (2). Mask pressure was measured by using a similar pressure transducer. Driving pressure (Pd) was obtained by on-line electronic subtraction of mask pressure from Pes.

Electromyograms. Surface recordings of the left and right costal diaphragmatic electromyographic activity were obtained by using skin-taped silver cup electrodes placed between the midclavicular line and the lateral border of the sternum in the 7th to 8th left and right intercostal spaces and connected to a Nihon Kohden (Neuropack Sigma) electromyograph (Nihon Kohden, Tokyo, Japan).

Abdominal wall displacements. Abdominal displacements were assessed by using a mechanical strain gauge (piezo-electric sensor encased in a molded box; Nihon Kohden) attached to an elastic belt placed around the abdomen at the level of the umbilicus.

All signals were recorded on a Performa Apple computer and stored after digitization at 10 kHz for subsequent analysis.

Stimulations

Cervical magnetic stimulation (CMS) was performed with a Magstim 200 stimulator (Magstim, Whitland, Dyfed, UK) equipped with a 90-mm coil (2.5 T), as previously described (27, 28).

All stimulations were delivered at the end of a relaxed expiration, according to the monitoring of Pes and abdominal displacement traces, to control as precisely as possible for the confounding effects of lung volume and abdominal configuration on the results of phrenic stimulation (5).

Procedures

Reference values. Subjects were seated in a comfortable armchair, first with their necks in a neutral position and their mouths closed (Nn-Mc). The consistency of the neck neutral position throughout the experiments was ascertained by tightly fitting the head of subjects in headrests. Five stimulations were first obtained by using the maximal output of the stimulator. In six subjects, the intensity was then decreased in a stepwise manner (10% decrement) until the flow and pressure responses disappeared. At least three stimulations were performed at each stimulation intensity.

Neck flexion and mouth opening. Neck flexion was obtained by asking subjects to realize a maximal anteflection of the neck so that the chin rested on the sternum. Mouth opening was obtained by asking subjects to wear a mouthpiece that determined a 20-mm aperture between incisors and was occluded to prevent any oral flow. PNS was performed in the following conditions that were applied in random order: 1) neck in neutral position, mouth opened (Nn-Mo); 2) neck flexed, mouth closed (Nf-Mc); and 3) neck flexed, mouth opened (Nf-Mo). For each condition, the same sequence of PNS as for Nn-Mc was performed (5 stimulations at maximal intensity followed by a stepwise decrease in intensity).

Effects of posture. In five subjects (nos. 2, 4, 5, 6, 7), the same experimental procedure (with the exception of the recruitment curve) was carried out in the supine position.

Data Analysis

Phrenic stimulation-induced inspirations were considered flow-limited when flow plateaued or decreased despite a Pes continuing to become more negative (Fig. 1). We henceforth termed limiting Pd (Pdlim) the Pd value corresponding to the point where the inspiratory flow reached its maximal value (VImax). UA resistance at this point (RuaVImax) was computed as the ratio of Pdlim to VImax. Before the point of flow limitation, the pressure-flow relationship was roughly linear. It was thus appropriately fitted by a linear regression of order 0 (Pd = aV), providing another approach to UA resistance until flow had reached a flow-limitation regimen (Rua = 1/a). Beyond that value, flow dropped down to a minimal value (VImin) despite the continuing rise of Pd to a maximum Pd (Pdpeak) (Fig. 1). Pdpeak always corresponded to VImin. The difference between VImax and VImin is henceforth termed Delta VI. UA resistance at VImin (RuaVImin) was thus calculated as the ratio of Pdpeak to VImin. The difference between RuaVImin and RuaVImax is henceforth termed Delta Rua.


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  		Fig. 1.   Representative tracings of flow-limited twitches obtained in one subject in response to cervical magnetic stimulation (CMS) at maximal intensity with neck in neutral position and the mouth closed (Nn-Mc; A); neck in neutral position and the mouth open (Nn-Mo; B); neck anteflexed and the mouth closed (Nf-Mc; C); and neck anteflexed and the mouth open (Nf-Mo; D). In each panel, the upper trace represents inspiratory flow (V), whereas the lower trace represents driving pressure (Pd). V first linearly increases with Pd, until a maximal value (VImax; 1) corresponding to the limiting Pd (Pdlim; 2). Beyond this point, V decreases to a minimal value (VImin; 3), corresponding to the peak Pd (Pdpeak; 4).

Statistical Analysis

Statistical analysis was performed by using the SuperAnova 4.5 software (Abacus Concept, Berkeley, CA) running on an Apple Macintosh computer. Linear regressions were calculated by using the least-square method (with 95% confidence intervals) from all the data points obtained without intrasubject averaging. Effects of neck flexion and mouth opening were studied using an ANOVA for repeated measures with a post hoc protected Fisher's test. This analysis was run by using all data points without intrasubject averaging and with the subject number intervening as an external factor in addition to the condition tested. (This procedure was chosen to minimize the loss of information while taking interindividual variations into account.) Effects of posture were studied similarly. Data are reported as means ± SE. Differences were considered significant when the P value of a type I error was <0.05.


    RESULTS
TOP
ABSTRACT
INTRODUCTION
MATERIAL AND METHODS
RESULTS
DISCUSSION
REFERENCES

Flow Limitation in Neutral Position of the Head

During spontaneous breathing, there were no signs of flow limitation whatever the condition considered. Conversely, CMS consistently induced a typical flow-limitation pattern in every subject (Fig. 1) and at all stimulation intensities. Increasing stimulation intensity from submaximal values to the maximal output of the stimulator resulted in more negative Pdlim values and higher VImax values, with a linear relationship linking the increase in VImax to Pdlim (P < 0.0001; Fig. 2). There was also a significant linear relationship between stimulation intensity and Pdpeak, Delta VI, difference in Pd (Delta P), and RuaVImax. Conversely, VImin and RuaVImin were not significantly influenced by stimulation intensity, but VImin increased as Pdpeak became more negative (P < 0.0001; Fig. 2). Delta VI increased with the amplitude of the corresponding Delta P (P < 0.0001; Fig. 2).


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  		Fig. 2.   Relationships between VImax and Pdlim (A); VImin and Pdpeak (B); and drop in V (Delta V) and the drop in Pd (Delta P) during the flow-limited period of the twitch (C). These relationships were obtained by varying the intensity of CMS with Nn-Mc. Data shown represent all points obtained in all subjects. Curvilinear dashed lines indicate the 95% confidence interval of the linear regression.

Effects of Neck Flexion and Mouth Opening

Recruitment curves. Neck flexion and mouth opening did not alter the linear nature of the relationship between VImax and Pdlim that was established by varying stimulation intensity, nor did they modify its slope. In the four study conditions, varying stimulation intensity also resulted in a significant relationship between VImin and Pdpeak on one hand and between Delta P and VI on the other hand. Slopes of these relationships were similar in all cases (Table 1).

                              
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  		Table 1.   Linear relationships of order 0 

Neck flexion. At maximal stimulation intensity, neck flexion resulted in higher (more negative) values of both Pdlim and Pdpeak (Fig. 3). Because changes in these respective pressure values were proportionate, Delta P was unaffected by neck flexion (Fig. 3). VImax tended to increase with neck flexion, but the difference did not reach statistical significance (Fig. 3). VImin was not significantly affected by neck flexion but exhibited a tendency to be lower when the neck was flexed and the mouth was open (Fig. 3). As a result of the trends for VImax and VImin, there was a significant influence of neck flexion on Delta VI. Delta VI in the Nf-Mc position was significantly higher than in the Nn-Mc position (P = 0.0295); this was also the case for the Nn-Mo position vs. the Nf-Mo position (P = 0.0294) and Nn-Mc vs. Nf-Mo (P = 0.0410; Fig. 3). In terms of resistance, neck flexion was associated with a significant increase in Rua (Table 2) and in RuaVImax in Nf-Mo (Fig. 4). RuaVImin was significantly higher with the neck flexed than with the neck in neutral position. Delta R was also higher with the neck flexed but not significantly so (Fig. 4).


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  		Fig. 3.   Effect of neck flexion and mouth opening on Pd (A) and V (B). Delta P, difference between Pdlim and Pdpeak. Values are means ± SE for data obtained in a given condition in the 7 subjects studied, without intrasubject averaging. *Significant difference with the Nn-Mc condition (P < 0.05).


                              
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  		Table 2.   Values of upper airway resistance



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  		Fig. 4.   Mean values ± SE of UA resistance measured at VImax (RuaVImax) and at VImin (RuaVImin) and of the changes in the resistance (Delta Rua) under the four conditions tested (Nn-Mc, Nn-Mo, Nf-Mc, and Nf-Mo). *Significant difference with the Nn-Mc condition (P < 0.05). ns, Not significant.

Mouth opening. Opening the mouth (without oral flow) did not significantly affect inspiratory flows (Fig. 3). It tended to increase Pd, with the neck in both positions, but the rise did not reach statistical significance (Fig. 3). As a result, there was no discernible influence of mouth opening on the different resistances calculated or on Delta R (Table 2 and Fig. 4) except for the increase in RuaVImax due to neck flexion, which became statistically significant only when the mouth was open (Fig. 4). Nevertheless, with the neck in neutral position, there was a trend for resistances to be higher with the mouth open than with the mouth closed.

Effect of posture. In any given condition, shifting from the seated to the supine posture did not result in significant changes in twitch-related flows (VImax, VImin, Delta VI), pressures (Pdlim, Pdpeak, Delta P), or resistances (RuaVImax, RuaVImin, Delta R). Effects of mouth opening or neck flexion were similar in the subjects studied supine and seated; namely, VImax and VImin were unaffected by neck flexion and mouth opening; Pdlim and Pdpeak were significantly more negative when the neck was flexed than when the neck was in neutral position (P < 0.01 between Nn-Mc and Nf-Mc for Pdlim; P < 0.05 for Pdpeak), without any effects of mouth opening; Delta VI was higher when the neck was flexed, but the difference did not reach significance; Delta P did not change when the head and mouth positions were modified; RuaVImax and RuaVImin (Fig. 5) were higher when the neck was flexed (P < 0.05) as was Delta R (for which the difference, however, did not reach statistical significance).


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  		Fig. 5.   Mean values ± SE of RuaVImax under the four conditions tested (Nn-Mc, Nn-Mo, Nf-Mc, and Nf-Mo) in 5 subjects seated (left) and supine (right). *Significant difference with the Nn-Mc condition (P < 0.05). Shifting to the supine posture did not have any visible influence on the absolute values of resistance; effects of neck flexion and mouth opening were similar in both postures.


    DISCUSSION
TOP
ABSTRACT
INTRODUCTION
MATERIAL AND METHODS
RESULTS
DISCUSSION
REFERENCES

The salient finding of this study is that, in normal awake subjects breathing through the nose, neck flexion modifies the mechanical behavior of the passive UA, as studied with PNS, in both seated and supine postures. Conversely, mouth opening has no discernible effect with this technique.

Definition of UA Resistance

Because we used Pes to compute Pd rather than the supralaryngeal pressure, what we term UA resistance in this paper represents in fact the total resistance of the respiratory system. This must be kept in mind when interpreting the results but is probably not a major issue. Indeed, UA resistance accounts for most of the total respiratory resistance as we measured it (29), particularly during nasal breathing (8). Because of our study design (exclusive nose breathing, emphasizing the contribution of UA resistance to the respiratory system resistance; careful control of the lung volume and abdominal configuration at which stimulations were performed, minimizing the risks of respiratory mechanic alterations from one condition to the other), it is likely that changes in UA mechanics induced by neck flexion and mouth opening that we observed predominantly pertained to changes in the mechanical properties of the UA. Finally on this point, we used two separate approaches to estimate UA resistance during the initial part of the twitch-related rise in flow before the occurrence of flow limitation. On one hand, we computed the slope of the relationship of flow to Pd by using a linear regression of order 0 (Table 2); on the other hand, we divided the pressure value at the point of flow limitation (Pdlim) with the corresponding flow (VImax). When Table 2 and Fig. 4 are analyzed, it can be seen that the first approach provided resistance values that were systematically lower than those provided by the second approach. This difference between the two resistance values is explained by the shape of the V-Pd relationship, with a steep increase after an inflexion point in its last portion. The only situation where the difference between the two values reached statistical significance was the reference condition (Nn-Mc). It is interesting to note that this difference was minimal when the neck was flexed with the mouth opened or closed. This provides another illustration of the consistency of a mechanical effect of neck flexion on UA.

PNS-Induced Flow Limitation

UA includes a collapsible locus at the pharyngeal level (8) that is placed between two noncollapsible segments, one upstream (the nose) and one downstream (the larynx) (30). In such a configuration, the flow regimen will depend on the transmural pharyngeal pressure resulting from the balance between the intraluminal pressure and the intrinsic tissue (dilating) pressure; in this instance, flow through the pharynx will increase with Pd until it will be no more counterbalanced by an equivalent dilating pressure (transmural pressure = 0). At this intraluminal pressure value, the flow will cease to increase (flow limitation) (23). During spontaneous breathing, and particularily in OSAS patients whose inspiratory flow regimen is flow limited, UA dilator muscles are active. The resulting dilating force decreases intrinsic pressure tissue and therefore counteracts the pharyngeal collapsing force by maintaining a positive transmural pressure gradient. With PNS, the absence of active UA dilation before the buildup of Pd implies that flow limitation and UA closure are likely to occur even during wakefulness in normal subjects. This explains why, as in a previous study (24), we were able to observe a twitch-induced flow limitation in subjects who never were flow limited during spontaneous breathing. In our study, Pdlim became more negative and VImax increased with increasing stimulation intensity and Pdlim became more negative with neck flexion and mouth opening.

Other than the level of Pd inducing flow limitation, the pattern of flow observed in normal awake subjects in response to phrenic stimulation is markedly different from that observed, for instance, during spontaneous breathing in obstructive sleep apnea syndrome patients during sleep. In the latter situation, flow limitation typically takes the form of a plateau. In other words, once inspiratory flow has been reached, it stays roughly constant during the rest of the inspiratory effort. During diaphragm twitches in normal awake subjects, inspiratory flow rises in response to Pd up to a maximal value (VImax; Fig. 1) (24) but then decreases to a minimal value (VImin) corresponding to Pdpeak and later increases again (Fig. 1). This is consistent with the UA being much more collapsible than normal during the initial part of the pressure twitch and then reopening because of the reflex activation of UA dilators triggered by the negative intrathoracic pressure following the diaphragm contraction (24, 32).

Critical to the understanding of our data is how closely PNS is capable of mimicking the dissociation between the preinspiratory phasic activity of UA dilator muscle and diaphragm contraction that is characteristic of obstructive sleep apnea. The inconsistency of the genioglossus phasic activity in normal subjects breathing spontaneously while awake and sitting and the fact that PNS was not precisely clocked during expiration make the accidental coupling of a spontaneous phasic-UA contraction and of a diaphragm twitch highly unlikely. Our first report on the technique (24) included the illustration of the absence of genioglossus phasic activation before PNS-induced diaphragm contraction. Recent data from our team (25) show that the closing pressure assessed with PNS is less negative when stimulations are delivered at end expiration than at the beginning of expiration. This is in line with the expiratory decrease in UA caliber and goes against UA dilator activity consistently preceding end-expiratory stimulations. In this study involving nine healthy subjects, genioglossus activity was monitored systematically, and no consistent pattern of genioglossus EMG activity before PNS was observed. In the same perspective, a coactivation of UA dilators and of the diaphragm by CMS would jeopardize our data. The positioning of the magnetic coil in our setup (centered over the 7th cervical vertebra and slightly inclined forward) makes direct neuromuscular activation of UA dilator muscle by the magnetic field unlikely. Had such an activation occurred, the contraction of the UA dilators would necessarily have started before that of the diaphragm (shorter nervous conduction time, for obvious anatomical reasons) and probably would have overlapped it. According to the known effect of UA dilator activation on UA patency, this should decrease UA resistance and improve UA stability. All results obtained with PNS up to now demonstrate an opposite pattern. Furthermore, there is no difference between focal electrical PNS and CMS in terms of UA behavior (24), which suggests that CMS does not directly activate UA dilators. Of note, CMS does not evoke any genioglossus motor potential (Sériès, unpublished observations). All in all, we are confident that PNS does indeed provide an adequate model of UA dilators-diaphragm dissociation. Nevertheless, the information that it gives on UA behavior does not pertain to the passive UA, because the tonic component of UA dilators is not eliminated from the equation. Variations in this tonus can therefore modify the response to PNS and have to be taken into account when interpreting our results. Of note, if anything, the sleep-related suppression of UA dilator tonic activity should worsen the influence of neck flexion and mouth opening that is observed in its presence.

Lack of Influence of Mouth Opening

The influence of mouth opening on the flow and pressure response to phrenic stimulation was found to be marginal. Figures 3 and 4 show that the combination of mouth opening with neck flexion increased Delta V, RuaVImax, and Delta Rua, but there was no effect of mouth opening alone. Pdlim and Pdpeak were always more negative with the mouth opened than with the mouth closed, but these changes did not reach statistical significance. This was the case both in sitting and supine postures (Fig. 5). These results vary from those reported by Meurice et al. (14), who showed that mouth opening during sleep in healthy subjects was associated with an increase in UA resistance and collapsibility. These authors concluded that mouth opening during sleep, a frequent event that does not necessarily imply a change in breathing route, could promote sleep-related breathing abnormalities. The apparent discrepancy between these results and ours may be due to the mechanisms of UA changes associated with mouth opening. The downward movement of the mandible, inevitably coupled with a posterior displacement and associated with a decrease in pharyngeal diameter (11), can enhance the propensity for UA to collapse. These anatomic changes shorten UA dilator muscle (7), the corresponding mechanical disadvantage (length-tension relationship) reducing their ability to develop a force effective enough to counteract the negative inspiratory transmural pressure gradient. This can account for the less negative critical pressure (Pcrit) with the mouth open vs. closed found by Meurice et al. (14) in normal subjects during sleep. In that study, Pcrit was determined from the pressure-flow relationship of spontaneous flow-limited breaths by using continuous negative airway pressure to induce flow limitation. The phasic activity of UA dilators was thus present and important to UA stability. The decrease in its mechanical counterpart due to mouth opening can probably be called on to explain the detrimental effect on Pcrit. Putting this interpretation together with the lack of change in UA behavior after mouth opening when the phasic contraction of UA dilators is out of the picture (our study) strongly supports that the main determinant of the changes in UA stability following mouth opening is a reduction in the dilating efficiency of the phasic contraction of UA dilators rather than a change in the geometry of the passive UA [but of note, in the study by Meurice et al. (14), as opposed to ours, UA dilator tone was decreased by sleep]. By contrast, the very fact that neck flexion increased UA resistance as determined from PNS suggests a more important role for UA geometrical changes.

Effects of Neck Flexion on UA Characteristics

In our study, Pdlim decreased with neck flexion. VImax tended to increase, although not significantly, whereas VImin remained constant. As a result, Delta VI was significantly higher in conditions in which the neck was flexed. This was also the case for RuaVImax and RuaVImin. To explain a disproportionate change in Pd and flow leading to increased resistance, one has to consider the three segment model described above, with simultaneous modifications in the resistances placed upstream and downstream the collapsible locus (17, 20). According to the Starling resistance model, VImax is equal to the ratio of Pcrit minus Pdlim to downstream resistance (22) and the slope of the VImax-Pdlim relationship is proportional to the reciprocal of downstream resistance (17). Therefore, the effects of the rise in stimulation intensity on Pdlim and VImax can be accounted for by an increase in downstream resistance (laryngeal and/or intrathoracic resistance) with or without a decrease in upstream resistance. But this also implies that increasing stimulation intensity decreases the pressure at which UA closes (Pcrit). This could be accounted for by the effects of increasing Pd on tracheal traction, which is known to improve UA stability (33). A direct stimulation of UA muscles by CMS is unlikely, as discussed above. Finally, because nasal resistance has been shown to decrease with neck flexion (17), our results suggest that neck flexion induced an increase in downstream resistance equivalent to or slightly larger than the decrease in upstream resistance. We did not measure Pcrit (corresponds to the luminal pressure at which flow is 0) in the different conditions studied. Nevertheless, it is possible from our results to speculate about changes in Pcrit with neck flexion and mouth opening. According to the Starling resistance model, VImax is equal to the ratio of Pcrit minus Pdlim to downstream resistance (22). Therefore, the lack of major change of VImax that we observed, taken together with the increase in downstream resistance that must have occurred (see above), suggests an increase in the Pcrit-Pdlim difference proportionate to that of the increase in downstream resistance. As Pdlim became more negative with neck flexion in our subjects, it follows that parallel changes in Pcrit must have occurred to keep the difference with Pdlim proportional to downstream resistance.

Changes in UA behavior with neck flexion (12, 13) may have several explanations, including modifications in pharyngeal dimensions and compliance. Neck flexion displaces the tongue backward, thereby reducing the pharyngeal caliber (18) and modifying the oropharyngeal shape (10). This probably explains why neck flexion has been reported to make Pcrit less negative, whereas neck extension has the opposite effect (34). Data from a cat model of isolated passive UA demonstrate that neck flexion considerably alters UA flow behavior (17, 33). Although the extreme degree of neck flexion chosen in our protocol with the purpose of standardizing experimental conditions may represent a limitation to our study because such a flexion seldom occurs naturally, our results provide new information about the determinants of the increase in UA resistance that is associated with neck flexion. Indeed, following a reasoning pattern mirrorring that used to discuss the effects of mouth opening on UA behavior, we are led to conclude that neck flexion is deleterious for UA stability through changes in the geometry of the airway rather than through changes in the efficiency of the UA dilators phasic activity, the effects of which are not taken into account with PNS. The respective role of the two factors could not be discerned from previous studies having evidenced the impact of neck flexion on UA (12, 13). Table 2 indicates a wide inter-individual variability of the effects of neck flexion. This could be accounted for by morphological factors or inter-individual variations in the importance of the UA dilators tonic activity.

Effects of Body Posture

Sleep, compared with breathing awake while sitting, is characterized by the supine posture, which can modify UA characteristics (1) and cause a decrease in UA muscle tone. Both can result in an increased UA unstability promoting obstructive events. In the five subjects so studied, the supine position did not appear to influence either the baseline values of UA resistance as determined with PNS or the variations in the twitch-related flow dynamics induced by mouth opening or neck flexion. This finding differs from that of Anch et al. (1), who evidenced an increase in UA resistance in the supine posture in awake individuals that they attributed to a structural encroachement on the pharyngeal airway. The nose is a major determinant of the UA flow dynamics in response to diaphragm twitches (24), possibly because of the absence of preinspiratory activation of the alae nasi muscles. In the present study, which was performed in natural conditions, namely without a nasal dilator (24), it is possible that a very high level of nasal resistance obscured the effect of posture on pharyngeal properties.

In conclusion, we have shown that neck flexion in awake normal subjects has a deleterious effect on the stability of the UA. The very technique we used, i.e., PNS, which by design eliminates the contribution of the phasic preinspiratory activation of UA dilator muscle to UA flow behavior, suggests that the mechanical changes observed with neck flexion are a direct consequence of anatomic changes of the UA related to the position of the neck. Conversely, the deleterious influence of mouth opening on UA stability (14) may depend more on changes in the mechanical efficiency of UA dilator muscle. Whether controlling for the position of the neck during sleep in patients with sleep-disordered breathing would be useful and how PNS could be used for this aspect of patient care remain to be determined.


    ACKNOWLEDGEMENTS

This study was supported in part by the Association pour le Développement et l'Organisation de la Recherche en Pneumologie, Paris, France.


    FOOTNOTES

Address for reprint requests and other correspondence: T. Similowski, Service de Pneumologie et de Réanimation, Groupe Hospitalier Pitié-Salpêtrière, 47-83, Bd de l'Hôpital, 75651 Paris Cedex 13, France (E-mail: thomas.similowski{at}psl.ap-hop-paris.fr).

The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received 7 February 2001; accepted in final form 24 August 2001.


    REFERENCES
TOP
ABSTRACT
INTRODUCTION
MATERIAL AND METHODS
RESULTS
DISCUSSION
REFERENCES

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J APPL PHYSIOL 92(1):84-92
8750-7587/02 $5.00 Copyright © 2002 the American Physiological Society


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