Ventilatory control and airway anatomy in obstructive sleep apnea

Abstract

Ventilatory instability may play an important role in the pathogenesis of obstructive sleep apnea. We hypothesized that the influence of ventilatory instability in this disorder would vary depending on the underlying collapsibility of the upper airway. To test this hypothesis, we correlated loop gain with apnea-hypopnea index during supine, nonrapid eye movement sleep in three groups of patients with obstructive sleep apnea based on pharyngeal closing pressure: negative pressure group (pharyngeal closing pressure less than -1 cm H(2)O), atmospheric pressure group (between -1 and +1 cm H(2)O), and positive pressure group (greater than +1 cm H(2)O). Loop gain was measured by sequentially increasing proportional assist ventilation until periodic breathing developed, which occurred in 24 of 25 subjects. Mean loop gain for all three groups was 0.37 +/- 0.11. A significant correlation was found between loop gain and apnea-hypopnea index in the atmospheric group only (r = 0.88, p = 0.0016). We conclude that loop gain has a substantial impact on apnea severity in certain patients with sleep apnea, particularly those with a pharyngeal closing pressure near atmospheric.

Figure 1

Example of two tidal volume (Vt) amplification measurements (VTAFs) made at the level of proportional assist ventilation (PAV) immediately preceding periodic breathing. PAV is reduced to zero for one breath, yielding a single “unassisted breath” (arrows). The three breaths preceding PAV reduction are averaged for the “assisted Vt.” VTAF, which is the amount by which PAV increases the subject's intrinsic loop gain, is calculated as the ratio of assisted Vt to unassisted Vt. When PAV is increased 10% above the existing level (at time 6,310–100 seconds after the end of this recording), periodic breathing begins, indicating that the loop gain on PAV (LG_pav) as shown is close to 1 (LG_pav = 1). The subject's intrinsic loop gain, that is, loop gain in the absence of PAV (LG_intrinsic), which is the variable of interest, is calculated as the reciprocal of VTAF based on the following relation: LG_pav = 1 = LG_intrinsic × VTAF. Here, the VTAF immediately preceding an LG_pav of 1 (periodic breathing) is 3.24 (measured from the values shown), yielding an LG_intrinsic of 0.31. Pmask = mask pressure (cm H₂O); flow (L/second); Vt = tidal volume (L); time (seconds).

Figure 2

PAV-induced periodic breathing. Sleep state remained stable during cycling in this subject. The respiratory pattern is typical crescendo–decrescendo, indicative of a high loop gain state. Cycle length is 50 seconds. EEG = electroencephalography; Pmask = mask pressure (cm H₂O); flow (L/second); Vt = tidal volume (L); time (seconds).

Figure 3

(A) Correlation between loop gain and AHI (apnea–hypopnea index) for all subjects. (B) Correlation between Pcrit (pharyngeal closing pressure) and AHI for all subjects.

Figure 4

Loop gain versus AHI for the three Pcrit groups: (A) negative Pcrit group (Pcrit less than –1 cm H₂O); (B) atmospheric Pcrit group (Pcrit between –1 and +1 cm H₂O); (C) positive Pcrit group (Pcrit greater than +1 cm H₂O).

Figure 5

Pharyngeal closing pressure was measured by dropping mask pressure (Pmask) abruptly for three breaths at a time. Negative effort dependence (peak–plateau flow pattern) is evidence that these drop-down breaths were flow limited (arrows). The pharynx is completely occluded (zero flow) at time 2,375 seconds, when mask pressure is 1 cm H₂O (zero flow breaths were excluded from the Pcrit linear regression equation). EEG = electroencephalography; Vt = tidal volume (L); flow (L/second); Pmask = mask pressure (cm H₂O); time (seconds).

Figure 6

Actual pressure–flow relationships (solid line) for each of the three Pcrit groups under hypotonic conditions. Dashed lines represent the theoretical effect of muscle activation. (A) Atmospheric Pcrit group. With sleep onset, airway closure occurs (A₁), leading to a large build-up in chemical drive that activates pharyngeal muscles. Muscle activation exerts a dilating force on the airway (A₂), which reestablishes airflow (A₃). If loop gain is low, stable breathing results. If loop gain is increased, breathing may become unstable—recurrent cycling occurs. (B) Negative Pcrit group. Here, airflow persists after sleep onset (B₁). If adequate ventilation cannot be maintained, the build-up in ventilatory drive recruits airway muscles and dilates the airway (B_2, B₃). Again, if loop gain is low, cycling with recurrent obstruction does not occur. If loop gain is high, fluctuations in breathing may occur. However, the risk of upper airway collapse for a given loop gain (or, for a given amount of fluctuation in ventilatory drive) is less, and it is likely that loop gain needs to be highly elevated before an association with AHI is seen. (C) Positive Pcrit group. The airway closes at sleep onset (C₁) due to a net collapsing force on the pharynx. Increases in chemical drive, while producing a large dilating force (C₂), are ineffective at opening the airway (C₃), and arousal is necessary to reestablish flow. In this condition, ventilatory instability cannot be responsible for cycling, given that repeated airway closure and arousal are inevitable despite a high or low loop gain.