Published ahead of print on July 17, 2003, doi:10.1164/rccm.200211-1304OC
© 2003 American Thoracic Society
Static and Dynamic Upper Airway Obstruction in Sleep ApneaRole of the Breathing Gas PropertiesUnitat de Biofísica i Bioenginyeria, Facultat de Medicina, Universitat de Barcelona; and Servei de Pneumologia i Al.lèrgia Respiratòria, Hospital Clinic Provincial, Institut d'Investigacions Biomèdiques August Pi Sunyer, Barcelona, Spain Correspondence and requests for reprints should be addressed to Ramon Farré, Ph.D., Unitat de Biofisica i Bioenginyeria, Facultat de Medicina, Casanova 143, E-08036 Barcelona, Spain. E-mail: rfarre{at}ub.edu
Increased upper airway collapsibility in the sleep apnea/hypopnea syndrome (SAHS) is usually interpreted by a collapsible resistor model characterized by a critical pressure (Pcrit) and an upstream resistance (Rup). To investigate the role played by the upstream segment of the upper airway, we tested the hypothesis that breathing different gases would modify Rup but not Pcrit. The study was performed on 10 patients with severe SAHS (apnea–hypopnea index: 59 ± 14 events/hour) when breathing air and helium–oxygen (He–O2) during non-REM sleep. The continuous positive airway pressure that normalized flow (CPAPopt) was measured. Rup and Pcrit were determined from the linear relationship between maximal inspiratory flow  Imax and nasal pressure (PN):Imax = (PN - Pcrit)/Rup. Changing the breathing gas selectively modified the severity of dynamic (CPAPopt, Rup) and static (Pcrit) obstructions. CPAPopt was significantly (p = 0.0013) lower when breathing He–O2 (8.44 ± 1.66 cm H2O; mean ± SD) than air (10.18 ± 2.34 cm H2O). Rup was markedly lower (p = 0.0001) when breathing He–O2 (9.21 ± 3.93 cm H2O·s/L) than air (15.92 ± 6.27 cm H2O·s/L). Pcrit was similar (p = 0.039) when breathing He–O2 (4.89 ± 2.37 cm H2O) and air (4.19 ± 2.93 cm H2O). The data demonstrate the role played by the upstream segment of the upper airway and suggest that different mechanisms determine static (Pcrit) and dynamic (Rup) upper airway obstructions in SAHS.
Key Words: obstructive sleep apnea • hypopnea • flow limitation • continuous positive airway pressure • breathing gas density
The sleep apnea/hypopnea syndrome (SAHS) is characterized by obstructive respiratory events due to increased upper airway collapsibility (1). The mechanics of the upper airway in SAHS has been interpreted by means of a collapsible resistor model (1) characterized by its critical pressure (Pcrit) and its upstream resistance (Rup). Moreover, this model has also been used to adjust the nasal continuous positive airway pressure (CPAP) applied to the patient (2, 3). Pcrit is defined as the minimal intraluminal airway pressure to keep the collapsible segment open. Therefore, for a nasal CPAP lower than Pcrit, the upper airway is collapsed during inspiration and the patient experiences apneas. As CPAP is increased, the patient exhibits hypopneas or flow limitation due to a reduced caliber of the upper airway during inspiration. In this situation, the maximum possible inspiratory flow ( Accordingly, apneas are static obstructions occurring in the absence of flow, whereas hypopneas/flow limitation are dynamic obstructions associated with inspiratory flow. The magnitude of static obstruction can be characterized by Pcrit, and the magnitude of dynamic obstruction can be assessed by the additional increase in nasal pressure required to normalize breathing flow (CPAPopt - Pcrit) or by means of Rup. Given that a patient needs different CPAP values to avoid apneas (CPAP > Pcrit) and to abolish hypopneas/flow limitation (CPAPopt), probably different mechanisms should determine the relative magnitude of static and dynamic obstructions. Although especial attention has been paid to date to study static upper airway collapsibility characterized by means of Pcrit (4–12), the dynamic obstruction in SAHS, in particular the mechanisms determining Rup, remain poorly understood. Recently reported preliminary data suggesting that Pcrit and Rup may be altered independently (13) highlight the interest in elucidating the differences between static and dynamic obstruction in SAHS. A better understanding of the mechanisms determining dynamic obstruction would be helpful to clarify the mechanics of upper airway obstruction in SAHS and, in particular, the role played by the upstream segment. The present study sought to investigate the mechanisms involved in the increased upper airway collapsibility in patients with SAHS. Specifically, we focused on the different role played by the physical properties of the breathing gas in the upstream segment and in the development of static and dynamic obstruction. The hypothesis was that breathing gases with different density would change the magnitude of dynamic obstruction (CPAPopt, Rup) in accordance with the physical properties of the gas and would not modify the magnitude of static obstruction (Pcrit). Some of the results of this study have been previously reported in the form of an abstract (14).
Ten male patients with previously diagnosed severe SAHS (age: 47 ± 13 years; body mass index: 31 ± 4 kg/m2; apnea–hypopnea index: 59 ± 14 events/hour) were studied. The protocol was approved by the Ethical Committee of the hospital, and written consent was obtained from the patients.
A conventional CPAP system was modified to apply nasal pressure during air and (helium–oxygen) He–O2 (79% He, 21% O2) breathing (Figure 1)
. The CPAP device (CP90; Taema, Antony, France) was enclosed in a small chamber with an inlet connected to a valve, allowing us to select the gas entering the CPAP device. The outlet of the CPAP device was connected to a conventional hose, an exhaust valve, and a nasal mask. A similar hose was connected in parallel to the system at the entrance of the exhaust valve. When the outlet of this hose was closed, the system behaved as a conventional CPAP system. As the outlet of the hose was progressively opened, nasal pressure was reduced down to virtually zero, whereas the gas within the circuit was continuously renewed. A humidifier was placed in the circuit to condition the breathing gas. A pneumotachograph, whose gain was set according to the air or He–O2 viscosity, and pressure transducers (DP45; Validyne, Northridge, CA) allowed the measurement of nasal pressure PN and
The study was performed during a spontaneous (not induced by sedatives) nap initiated at 2 P.M., lasting at least 2 hours. The patient was monitored by conventional polysomnography. The initial breathing gas was air or He–O2 selected at random. The CPAP level was progressively increased by steps of 0.5 to 1 cm H2O, each lasting 2 to 3 minutes until apneas, hypopneas, and flow limitation (assessed from the contour of the inspiratory waveform, Reference 15) disappeared (CPAPopt). Subsequently, the breathing gas was changed, CPAP was progressively reduced, and the process of CPAP increase was repeated. A washout period of 3 minutes was allowed each time the breathing gas was changed. All measurements were performed during non-REM sleep (Stages 2–3) with the patient in supine posture.
For each patient and breathing gas, Rup and Pcrit were computed by fitting the linear equation Differences in CPAPopt, Rup, and Pcrit between He–O2 and air were assessed by paired t tests (significance: p < 0.05).
Figure 2 illustrates the relationship between Imax and PN for He–O2 and air in two patients. When breathing room air, the patient in the bottom panel exhibited the lowest Rup and a considerably high Pcrit, whereas the patient in the top panel had the highest Rup and the lowest Pcrit. Both patients in Figure 2 exhibited lower Rup when breathing He–O2 rather than room air. Pcrit in the bottom panel was slightly lower for He–O2 than air (5.1 and 5.6 cm H2O, respectively). By contrast, Pcrit in the top panel was slightly higher for He–O2 than air (0.7 and -0.7 cm H2O, respectively).
Normalizing the breathing pattern of the patients with SAHS required significantly (p = 0.0013) lower nasal pressure when breathing He–O2 (CPAPopt = 8.44 ± 1.66 cm H2O; mean ± SD) than air (CPAPopt = 10.18 ± 2.34 cm H2O), Figure 3 . CPAPopt values for three patients are not shown in the figure because, as explained in DISCUSSION, it was not possible to apply a sufficiently high CPAP to normalize inspiration when breathing air or He–O2.
The decrease in Rup when breathing He–O2 (9.21 ± 3.93 cm H2O·s/L) when compared with air (15.92 ± 6.27 cm H2O·s/L) was systematic (p = 0.0001) and marked in all the investigated patients, as shown in Figure 3. Pcrit was similar when breathing He–O2 (4.89 ± 2.37 cm H2O) and air (4.19 ± 2.93 cm H2O), although the small difference was statistically significant (p = 0.039).
The collapsibility of the upper airway in patients with SAHS was studied by changing the physical properties of the breathing gas (He–O2 vs. air). As the measurements for both gases were performed in the same patients and under the same sleep conditions, the experimental design allowed us to exclusively modify the flow-related phenomena in a controlled way. In agreement with the hypothesis that different mechanisms determine static and dynamic obstructions in SAHS, we found that changing the physical properties of the breathing gas markedly modified the severity of hypopneas/flow limitation (CPAPopt, Rup), whereas static obstruction (Pcrit) remained almost unchanged (Figure 3). Breathing different gas mixtures is a procedure already used to study the mechanics of the upper airways in healthy subjects (16) and in patients (17) when awake and also in healthy subjects simulating snoring (18). Nevertheless, the experimental model consisting of changing the physical properties of the breathed gas has not been previously employed to study upper airway collapsibility and the role of its upstream segment in patients with SAHS during sleep. The experimental setting employed in this work (Figure 1) allowed an easy replacement of the gas breathed by the patient by simply operating a valve placed outside the patient's room and, therefore, not disturbing patient sleep. Nasal pressure within the normal range of the CPAP device was operated by means of its remote control. Nasal pressure below the normal range (0–4 cm H2O) was also applied from outside the patient's room by regulating the valve placed at the outlet of the shunt tubing (Figure 1). During the application of virtually zero nasal pressure while breathing He–O2, the fraction of gas inspired coming from room air through the exhalation valve was negligible given the high resistance of this valve when compared with that of the CPAP setting (19). The maximum CPAP that we could achieve for air (14.5 cm H2O) was lower than the value achieved when the device is conventionally used. This was due to the fact that the pressure drop generated by the blower of the CPAP device was in part devoted to overcome the resistance of the tubing and valve placed at the entrance of the CPAP device (Figure 1). The maximum CPAP that could be achieved for He–O2 (10.5 cm H2O) with the experimental setting was lower than in air. This can be explained by taking into consideration the fact that the nasal pressure applied is equal to the pressure drop across the exhalation port due to the airflow generated by the CPAP device. As the flow through the exhalation port is turbulent (19), the effective resistance depends on the gas density. Accordingly, actual nasal pressure is expected to be lower for He–O2 than air for a given flow generated by the turbine in the CPAP device. This explains why we were not able to apply a sufficiently high CPAP to normalize inspiration when breathing He–O2 or air in three patients: in two of these patients CPAPopt was neither achieved for air nor for He–O2, and in the other patient CPAPopt for air was greater than the maximum CPAP applicable with He–O2.
To determine Rup and Pcrit we used a protocol similar to those used in the literature. Namely, we increased CPAP by steps and measured the A limitation of the data analysis performed results from using a simple two-parameter model (Rup, Pcrit) to account for the complexity of upper airway mechanics in patients with SAHS. In particular, it was assumed that the collapsible upper airway is a passive system. Consequently, the model does not feature potential changes in upper airway neural activation induced by varying CPAP. Moreover, the model does not take into consideration the fact that the passive compliance (i.e., pressure–volume relationship) of the collapsible upper airway could also be CPAP dependent. Finally, in the data analysis it was assumed that the CPAP applied is equivalent to the intraluminal pressure in the collapsible segment. However, the nonlinear pressure drop due to the upper airway section from the nares to the collapsible segment (essentially the resistance of the nasal pathway) may not be negligible and is dependent on flow, and hence, on CPAP. Accordingly, these model oversimplifications may result in values of Rup and Pcrit that are influenced in part by static and dynamic phenomena, respectively. In particular, the model simplification can explain our finding that Pcrit depended slightly on the gas (Figure 3).
The reduction in the severity of dynamic obstruction that we found in patients with SAHS when breathing He–O2 is consistent with the expectations from theoretical models (21). The decrease in upstream resistance when breathing He–O2 could be due to a reduction in the nonlinear resistance of the nose when breathing a low-density gas. However, the change found in Rup (6.71 cm H2O·s/L, on average) was much greater than the expected decrease in nasal resistance when comparing air and He–O2 breathing (22). The change observed in Rup is in keeping with the explanation of inspiratory flow limitation by means of the concept of wave-speed flow. According to this concept of fluid dynamics, which is commonly used to explain expiratory flow limitation during forced spirometry (23), the maximum flow through a conduit is reached when its linear velocity is equal to the propagation speed of a pressure wave ( In accordance with the interpretation of upper airway mechanics by means of a collapsible resistor, Pcrit is the pressure for transition from a closed to an open upper airway and Rup is an index indicating how difficult it is to completely open the airway once it has been initially opened. Most of the reports on the collapsibility of the upper airway in SAHS have focused on the analysis of static obstruction. As Pcrit is directly related to the severity of apneas, which are the most representative events in SAHS, Pcrit has usually been considered as the main index characterizing upper airway collapsibility (4–12). Characterization of upper airway mechanics by means of Pcrit has proved useful in studying the changes in static upper airway collapse due to patient weight loss (25), uvulopalatopharyngoplastia (26), or sedation (27). Moreover, Pcrit has recently been measured to differentiate between the active and passive mechanisms determining apneas (28, 29). By contrast, less attention has been paid to indices associated with dynamic obstruction, which could be useful to better characterize upper airway obstruction in SAHS. The fact that Pcrit alone cannot fully describe upper airway mechanics is illustrated in Figure 4 , which includes baseline Rup and Pcrit data obtained when breathing air in this study, and data collected from published reports (8, 12, 13). This figure shows that in patients with SAHS there is no correlation between Pcrit and Rup: a given value of Pcrit is compatible with different values of Rup, and vice versa. Accordingly, the magnitude of the CPAP required to avoid apneas is independent of the supplementary CPAP increase required to normalize inspiratory flow. The lack of direct correspondence between static and dynamic obstruction explains why in some patients who require a considerably high CPAP to avoid apneas (i.e., high Pcrit), the inspiratory flow is normalized by a modest further increase in CPAP (i.e., small CPAPopt - Pcrit). Conversely, this may explain why in some patients with a low Pcrit (close to zero or even subatmospheric), the normalization of breathing flow requires a considerable level of nasal pressure (i.e., high CPAPopt - Pcrit). Recent preliminary data suggesting that upper airway caliber and collapsibility may be independently altered by long-term facilitation (13) lends further support to the characterization of upper airway mechanics by both Pcrit and Rup.
In conclusion, this study directly confirms the importance of the role played by the upper airway upstream segment in the development of obstructions during respiratory sleep disturbances (30, 31). Moreover, the data demonstrate the consistency of interpreting upper airway collapsibility by means of a simple model with two parameters (Pcrit and Rup), which selectively account for static and dynamic mechanisms, respectively. Breathing He–O2 during sleep studies is a procedure easy to implement and may help us to better understand how the static and dynamic phenomena associated with upper airway collapsibility in SAHS are mechanically and neurally modulated (13, 17, 28, 29, 32).
The authors wish to thank Dr. Ole F. Pedersen for his comments and suggestions on the manuscript.
Supported by Ministerio de Ciencia y Tecnología (SAF2002-03616) Fondo Investigaciones Sanitarias (Red Respira C03/11), Sociedad Española de Neumología y Cirugía Torácica (SEPAR-2001), and Abello Linde SA. Conflict of Interest Statement: R.F. has no declared conflict of interest; J.R. has no declared conflict of interest; J.M.M. has no declared conflict of interest; L.B. has no declared conflict of interest; E.B. has no declared conflict of interest; D.N. has no declared conflict of interest. Received in original form November 8, 2002; accepted in final form July 14, 2003
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ABSTRACT
METHODS
Caw))1/2 where A is the airway cross-sectional area, 
