Sleep, 16:S80-S84
© 1993 American Sleep Disorders Association and Sleep Research Society
6. The Upper Airway
(a) Response to Anatomy
Anatomy of the Pharyngeal Airway in Sleep Apneics:
Separating Anatomic Factors From
Neuromuscular Factors
Shiroh Isoni, Thorn R. Feroah, Eric A. Hajduk, Debra L. Morrison, Sandrine H. Launois,
Faiq G. Issa, William A. Whitelaw and John E. Remmers
Department of Medicine and Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada
Anatomical and/or neuromuscular abnormalities
may cause obstructive sleep apnea (OSA), but the contribution of each to the obstructive process is unknown
at this time. An anatomic hypothesis of pathogenesis
of OS A states that apneics have a structurally narrowed
pharynx. An alternative, but not mutually exclusive,
neural hypothesis states that apneics have a subnormal
activation of pharyngeal dilator muscles during sleep.
In fact, apneics appear to have greater activity of the
pharyngeal muscles than normals during wakefulness
(1,2), suggesting that neuromuscular factors compensate for a structurally narrowed pharynx. In other words,
neural factors and anatomic factors interact in a statedependent fashion. Undoubtedly, future research will
show that neural and anatomic factors are tightly connected, interrelated and interacting.
Because of the complexities posed by the interaction
of neural and anatomic factors in the pathogenesis of
OSA, we have chosen to separate the two in order to
investigate the intrinsic mechanical properties of the
pharynx. To this end, we depressed the pharyngeal
muscle activity and have evaluated the mechanical
properties of the hypotonic pharynx. The static mechanics of the pharyngeal airway is best expressed
graphically by static pressure/area relationships, i.e.
the "tube law" of the pharynx (Fig. 1). Cross-sectional
area of the collapsible pharynx is determined by transmural pressure (Ptm), which is defined as the difference
between luminal and tissue pressure (Ptm = PI - ptJ
This is an extension of the "balance of pressure" concept proposed by Remmers and coworkers (3) and
Brouillette and Thach (4). When P trn increases, area
increases in accordance with the "tube law" of the
pharynx. The slope of the curve is often referred to as
compliance and represents the collapsibility of the
pharynx. The curvilinear relationships mean that the
collapsibility varies with airway size. A pressure corresponding to zero area is often referred to as closing
pressure (Pelose)' When the pharyngeal dilator muscles
are active, contraction of the muscles may stiffen the
pharynx and reduce the compliance of the pharynx,
thereby increasing area for a constant Ptm (Fig. 1b).
Accordingly, activation of the pharyngeal muscles
changes the "tube law" of the pharynx depending on
the magnitude of contraction of the muscles. Comparison of characteristics of the passive pharynx between normal subjects and OSA patients should provide a conclusive test of the validity of the anatomic
hypothesis.
METHODS
Application of high nasal continuous positive airway
pressure (CPAP) during sleep depresses activity of the
pharyngeal dilator muscles, at least with regard to the
genioglossus (5). Furthermore, we have confirmed that
recruitment of the genioglossus does not occur for a
single breath after an abrupt reduction in the nasal
pressure (6,7). Accordingly, we developed a single
breath test (SBT), in which nasal pressure is abruptly
reduced at the end of inspiration from a high holding
pressure to a preselected lower test pressure for a breath,
i.e. one expiration and one inspiration. In this procedure, a variety of flow patterns, including flow limitation and cessation of flow, occurs in association with
changes in a cross-sectional area of the pharynx de-
S80
'.•
.'•.
'.
"
ANATOMY OF PHARYNGEAL AIRWAY IN APNEICS
Area
"tube law"
S81
Area
active
(
AA
Ptm = PI - Pti
Pclose
Compliance
=
~
dPtm
(a)
active
passive
Pclose
Pclose
(b)
FIG. 1. Schematic explanation of "tube law" of the pharynx. (a) Size of the cross-sectional area is determined by transmural pressure
(P,m), which is defined as luminal pressure (P,) minus surrounding tissue pressure (PIi). Closing pressure (Polo.,) is a pressure when the area
is just obliterated. Compliance of the pharynx is defined as the slope of the "tube law". (b) Contraction of the pharyngeal dilator muscles
change the "tube law" of the pharynx so that the area increases for a constant P,m'
pending on the level of the test pressure. When a series
of SBTs is performed at different test pressures with
pharyngeal endoscopic examination, the area oflumen
of the passive pharyngeal airway can be related to airway pressure. Analysis at the end of expiration in the
SBT, when pressure along the airway is identical, reveals static mechanics of the passive pharynx while its
dynamic behavior can be studied during inspiration in
the SBT.
RESULTS AND DISCUSSION
Distribution of sites of narrowing
Using single breath tests, 64 patients were endoscopically examined and the distribution of collapsible
segments was determined in the passive pharynx during sleep (8). We examined three pharyngeal segments:
the nasopharynx (from the end of nasal septum to the
margin of the soft palate), the oropharynx (from the
margin of the soft palate to the tip of the epiglottis)
and the hypopharynx (from the tip of the epiglottis to
the vocal cords). According to the extent of narrowing
at Pelose under static condition, each segment was defined as the primary site (>75% reduction of the area
from the control value obtained at the holding pressure) or secondary site (25-75% reduction). Four categories of pharyngeal narrowing were determined (Fig.
2). The primary nasopharyngeal narrowing was most
commonly observed (80%). Half of these patients had
a primary site of narrowing only at the nasopharynx
(right semicircle), whereas the other half of the patients
had primary sites of narrowing more caudally (left semicircle). It is noteworthy that only 22% of the patients
had a primary site of narrowing exclusively at the nasopharynx without any secondary sites of narrowing.
Prediction of UPPP outcome
Because our methods reveal intrinsic anatomical
properties, we anticipated that the results of our endoscopic examination should predict outcome ofuvulopalatopharyngoplasty (UPPP). Specifically, we hypothesized that OSA patients with exclusively
nasopharyngeal narrowing would respond favorably to
the surgery and that those with other patterns of pharyngeal narrowing do not respond to the surgery. This
hypothesis has been tested in 31 apneics; 18 in the
perspective study reported by Launois et al. (6) plus
13 additional apneics (8). Eleven patients were identified as having exclusively nasopharyngeal narrowing,
and 20 were classified as having the other patterns.
Eighty-one percent of the former group improved respiratory status during sleep, whereas 90% of the latter
did not. These results demonstrate that patients witli
primary narrowing only at the nasopharynx respond
favorably to UPPP, but do not indicate whether a secondary narrowing of oropharyngeal or hypo pharyngeal
Sleep. Vol. 16. No.8. 1993
S82
S. ISONI ET AL.
1.5
Primary narrowing
at NP ... Primary
site(s) at OP or HP
Primary narrowing
at NP ... Secondary
site(s) at OP or HP
(64 OSA patients)
-
1.2
C\I
E 0.9
..8a..
~ 0.6
.
..
...
FIG. 2. Distribution of the sites of pharyngeal narrowing in 64
OSA patients.
0.3
segments predicts an unfavorable surgical response in
patients with primary nasopharyngeal narrowing.
o
•
N-IFL
IFL
04-~~~r-r-~~~~~-r-r~~
Static pharyngeal mechanics
Measurements of cross-sectional area of the pharynx
and airway pressure at the end of test expiration in a
series of single breath tests allowed construction of
pressure/area curve for the passive pharynx under static conditions. Figure 3 illustrates an example of velopharyngeal pressure/area relationships of a patient
who had a primary site of narrowing only at the velopharynx, the subsegment of the nasopharynx. The
maximum area was obtained at 14 cm H 2 0 of the
holding pressure and the velopharynx closed at 3 cm
H 2 0. The dependence of area on pressure was quite
steep near the Pelose and was virtually flat near holding
pressure, demonstrating the very collapsible characteristics of the velopharynx near Pelose' The distinct
curvilinear relationships were satisfactorily fitted by
an exponentialfunction [Avp = 1.32 - 3.11 exp( -0.307
PAW)] with high R2 values (R2 = 0.988). We have obtained the static pressure/area relationships for the velopharynx in nine patients with primary narrowing only
at the nasopharynx (7). Although the absolute values
of Pelose and maximum area differed from patient to
patient, a common exponential function described the
data for all examined patients when the difference between airway pressure and closing pressure in the normalized area/maximum area was plotted. This suggests
that the passive velopharynx behaves mechanically
similarly in all of these apneics. Unfortunately, these
pressure/area relationships cannot be considered to
represent the "tube law" of the pharynx because changes
in lung volume with changing airway pressure may
alter the mechanical properties of the pharynx (9,10).
Dynamic pharyngeal mechanics
When inspiration occurs through such a collapsible
pharynx, the size of the pharynx may be reduced with
Sleep. Vol. 16. No.8. 1993
o
3
6
9
12
15
Airway Pressure (cmH20)
FIG. 3. Static velopharyngeal pressure/area relationships in an OSA
patient who had a primary narrowing only at the velopharynx. Note
the distinct curvilinear relationship that was satisfactorily fitted by
an exponential function. Inspiratory flow limitation (IFL) occurred
when inspiration started at the steeper portion of the curve as shown
by the closed circles.
a decrease in PI at the segment, and inspiratory flow
limitation (IFL), a condition in which flow (VI) is independent of the magnitude of driving pressure (LlP) ,
will tend to occur. In fact, in the patient presented in
Fig. 3, such IFL was observed when test pressure exceeded Pelose by 0 - 5.5 cm H 2 0, the pressure range
associated with the highly compliant velopharynx as
shown by filled symbols. By contrast, no IFL occurred
when test pressure was set at the higher pressure range
associated with the less compliant velopharynx as
shown by open symbols.
Figure 4 demonstrates typical changes in VI' velopharyngeal area (Avp) and resistance across the velopharynx (Rvp) as a function of the pressure drop across
the velopharynx, LlP = P NP - POP (nasopharyngeal
pressure minus oropharyngeal pressure), during inspiration at various test pressures. At the highest test
pressure, VI increased during inspiration with very small
changes in Avp and Rvp. At the lower test pressures,
VI increased initially and then remained constant during IFL, even though LlP continued to increase. Concomitantly, Rvp progressively increased and Avp progressively decreased throughout inspiration.
Because VI is mathematically independent of LlP during IFL (Fig. 4), IFL appears to be a situation in which
the water fall model of the upper airway can be used
to interpret the mechanical event (11-13). In this analogy, the height of the water fall does not influence the
..
t·
..
S83
ANATOMY OF PHARYNGEAL AIRWAY IN APNEICS
0.5
80
0.4
V, (L·s·')
70
, , _ - -..... (5)
0.3
t---::7'"''-::::::::-==':l::==+=::::l:l==Ilo<:=::---o ( 4 )
0.2
(3 )
..-
(2)
0.1
.
U)
60
~
1.5
0.5
2.5
2
1.4
5
-- 30
0.6
0.2
0
(5 )
Q.
L-=:::~=~~::;:::::=:~=~(4)
~
>
2 (3)
0
0.5
1.5
15
2.5
2
(2 )
12
Rvp (emH20·L·'·s)
a: 20
•
•
10
(3 )
9
O~TTrrrMnn~TT~~~~~~
(4 )
o
6
3
0.5
FIG. 4.
50
:I: 40
1
0.8
0.4
6
N
1.2
Avp (em2)
-J
1
1.5
6,P= PNP-POP (emH2 0)
2.5
Dynamic changes in flow (V,), the velopharyngeal area
(Ayp) and velopharyngeal resistance (Ryp) as a function of pressure
drop across the velopharynx, ll.P = P NP - Pop (nasopharyngeal pressure minus oropharyngeal pressure) at different mask pressures.
Numbers in the parentheses represent mask pressure that was held
constant during inspiration. During IFL, Rvp progressively increased
with progressive narrowing of the velopharynx.
flow, which suggests that it is inappropriate to calculate
the resistance across the water fall (14). However, the
behavior of the pharynx appears not to resemble that
of a water fall. Rather, the aperture of the flow-limiting
segment appears to vary directly with upstream pressure and inversely with ~P. Resistance, by contrast, is
independent of upstream pressure and increases with
increases in ~P. In other words, resistance appears to
increase during inspiration, mainly due to reduction
in cross-sectional area, although many factors, such as
airway geometry and characteristics of the airflow, may
contribute to changes in resistance. Figure 5 demonstrates a dependence ofRvp on Avp in a patient having
a primary site of narrowing only at the velopharynx.
The data in the figure include inspirations with IFL
and no IFL. Regardless of flow regimes, a unique relationship was obtained between Rvp and Avp. Changes
in Rvp were inversely related to those in Avp. This
suggests that calculation ofRvp during inspiration, even
during IFL, may allow an approximation of Avp in the
passive pharynx.
According to a fundamental principle in fluid dynamics (i.e. VI = ~P/R), VI varies with ~P and Rvp.
When Rvp and ~P increase proportionally, VI will remain constant. The water fall model ignores the above
principle in fluid dynamics during IFL. Alternatively,
taking geometrical changes into consideration, IFL can
0.2
0.4
0.6
0.8
1
Avp (cm2)
1.2
1.4
FIG. 5. Dependence of the velopharyngeal resistance (Ryp) on the
velopharyngeal area (Ave) in an OSA patient. Data include both IFL
inspiration and non-IFL inspiration. Changes in Ryp are inversely
related to those in Ayp.
be interpreted as a unique situation where VI remains
constant or decreases owing to simultaneous increases
in ~P and Rvp as a result of progressive narrowing of
the pharynx during the period.
CONCLUSIONS
We have developed a novel method to separate anatomic factors from neuromuscular factors influencing
pharyngeal mechanics. This technique involves manipulating nasal airway pressure during medicated sleep
and, when combined with endoscopic visualization of
the pharynx, allows identification of location of collapsing segments and evaluation of their mechanical
properties in patients with OSA. Collapsing sites are
commonly located at more than one pharyngeal segment, and the nasopharynx was the most common site
of narrowing. Patients having a primary narrowing exclusively at the nasopharynx favorably responded to
uvulopalatopharyngoplasty. Under static conditions,
cross-sectional area of the passive velopharynx varied
exponentially with airway pressure, becoming progressively more compliant as it narrowed. Inspiratory
flow limitation (IFL) occurred in the airway pressure
range associated with the highly collapsible velopharynx. During IFL, the velopharynx progressively narrowed as the driving pressure increased, and velopharyngeal resistance varied inversely with
velopharyngeal area. We speculate that flow does not
increase during IFL due to simultaneous increases in
Sleep, Vol. 16, No.8, 1993
S84
S. ISONI ET AL.
resistance and driving pressure in the passive velopharynx.
A future goal in this approach is to evaluate the
importance of anatomic factors in the pathogenesis of
OSA by comparing mechanical characteristics of the
passive pharynx between normal subjects and patients
with OSA. In addition, we believe our method will
elucidate the interdependence among the pharyngeal
segments during inspiration as well as the dynamic
behavior of one segment.
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