6. The Upper Airway. Anatomy of the Pharyngeal Airway in Sleep Apneics: Separating Anatomic Factors From Neuromuscular Factors

Transcription

1 Sleep, 16:S80-S 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, ie 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 S80 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 P tm (Fig 1 b) 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, ie 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-

2 ANATOMY OF PHARYNGEAL AIRWAY IN APNEICS S81 Area "tube law" Area active ( AA Ptm = PI - Pti Compliance = dptm active passive (a) (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 (P Ii ) 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 commonly observed (80%) Half of these patients had of SBTs is performed at different test pressures with a primary site of narrowing only at the nasopharynx pharyngeal endoscopic examination, the area oflumen (right semicircle), whereas the other half of the patients of the passive pharyngeal airway can be related to air- had primary sites of narrowing more caudally (left semway pressure Analysis at the end of expiration in the icircle) It is noteworthy that only 22% of the patients SBT, when pressure along the airway is identical, re- had a primary site of narrowing exclusively at the naveals static mechanics of the passive pharynx while its sopharynx without any secondary sites of narrowing dynamic behavior can be studied during inspiration in the SBT Prediction of UPPP outcome ' 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 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 No8 1993

3 S82 S ISONI ET AL 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) FIG 2 Distribution of the sites of pharyngeal narrowing in 64 OSA patients segments predicts an unfavorable surgical response in patients with primary nasopharyngeal narrowing 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 = exp( PAW)] with high R2 values (R2 = 0988) 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 C\I E 8- a o N-IFL IFL 04-r-r--r-r o 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 0-55 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

4 ANATOMY OF PHARYNGEAL AIRWAY IN APNEICS S V, (L s ') ,,_-- (5) t---::7'"''-::::::::-==':l::==+=::::l:l==ilo<:=::---o ( 4 ) (3 ) Avp (em2) (5 ) L-=:::=::;:::::=:=(4) 2 (3) (2 ) 12 (3 ) Rvp (emh20 L ' s) 9 (4 ) ,P= PNP-POP (emh 20) FIG 4 Dynamic changes in flow (V,), the velopharyngeal area (Ayp) and velopharyngeal resistance (Ryp) as a function of pressure drop across the velopharynx, llp = 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 (ie 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 (2) U) 60 -J 50 6 N :I: Q 30 > a: OTTrrrMnnTT o Avp (cm2) 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, No8, 1993

5 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 REFERENCES 1 Surratt PM, Mctier RF, Wilhoit Sc Upper airway muscle activation is augmented in patients with obstructive sleep apnea compared with that in normal subjects Am Rev Respir Dis 1988; 137: Mezzanotte WS, Tangel DJ, White DP Waking genioglossal EMG in sleep apnea patients versus normal controls (a neuromuscular compensatory mechanism) J Clin Invest (in press) 3 Remmers JE, degroot WJ, Sauerland EK, Anch AM Pathogenesis of upper airway occlusion during sleep J Appl Physiol 1978;44: Brouillette RT, Thach BT A neuromuscular mechanism maintaining extrathoracic airway patency J Appl Physiol 1979;46: Strohl KP, Redline S Nasal CPAP therapy, upper airway muscle activation, and obstructive sleep apnea Am Rev Respir Dis 1986; 134: Launois SR, Feroah TR, Campbell WN, et al Site of pharyngeal narrowing predicts outcome of surgery for obstructive sleep apnea Am Rev Respir Dis 1993;147: Isono S, Morrison DL, Launois SR, Feroah TR, Whitelaw W A, Remmers JE Static mechanics of the velopharynx of patients with obstructive sleep apnea J Appl Physiol (in press) 8 Morrison DL, Launois SR, Isono S, Feroah TR, Whitelaw W A, Remmers JE Pharyngeal narrowing and closing pressure in patients with obstructive sleep apnea Am Rev Respir Dis (in press) 9 Roffstein V, Zamel N, Phillipson EA Lung volume dependence of pharyngeal cross-sectional area in patients with obstructive sleep apnea Am Rev Respir Dis 1984;130: Van de Graaff Thoracic influence on upper airway patency J Appl PhysioI1988;65: Schwartz AR, Smith PL, Wise RA, Bankman I, Permutt S Effect of positive nasal pressure on upper airway pressure-flow relationships J Appl Physiol 1989;66: Schwartz AR, Smith PL, Wise RA, Gold AR, Permutt S Induction of upper airway occlusion in sleeping individuals with subatmospheric nasal pressure J Appl PhysioI1988;64: Smith PL, Wise RA, Gold AR, Schwartz AR, Permutt S Upper airway pressure-flow relationships in obstructive sleep apnea J Appl PhysioI1988;64: Permutt S, Bromberger-Barnea B, Bane RN Alveolar pressure, pulmonary venous pressure, and the vascular waterfall Med Thorae 1962; 19: Sleep Vol 16 No8, 1993