Effect of Expiratory Positive Airway Pressure on Sleep Disordered Breathing

Abstract

Study Objectives:

We sought to determine the effect of expiratory positive airway pressure on end expiratory lung volume (EELV) and sleep disordered breathing in obstructive sleep apnea patients.

Design:

Observational physiology study

Participants:

We studied 10 OSA patients during sleep wearing a facial mask. We recorded 1 hour of NREM sleep without treatment (baseline) and 1 hour with 10 cm H₂O EPAP in random order, while measuring EELV and breathing pattern.

Results:

The mean EELV change between baseline and EPAP was only 13.3 mL (range 2–25 mL). Expiratory time was significantly increased with EPAP compared to baseline 2.64±0.54 vs 2.16±0.64 sec (P = 0.002). Total respiratory time was longer with EPAP than at baseline 4.44±1.47 sec vs 3.73±0.88 sec (P = 0.3), and minute ventilation was lower with EPAP vs baseline 7.9±4.17 L/min vs 9.05±2.85 L/min (P = 0.3). For baseline (no treatment) and EPAP respectively, the mean apnea+hypopnea index (AHI) was 62.6±28.7 and 56.8±30.3 events per hour (P = 0.4).

Conclusion:

In OSA patients during sleep, the application of 10 cm H₂O EPAP led to prolongation of expiratory time with only marginal increases in FRC. These findings suggest important mechanisms exist to avoid hyperinflation during sleep.

Citation:

Heinzer R; White DP; Malhotra A; Lo YL; Dover L; Stevenson KE; Jordan AS. Effect of expiratory positive airway pressure on sleep disordered breathing. SLEEP 2008;31(3):429-432.

OBSTRUCTIVE SLEEP APNEA (OSA) IS A COMMON DISORDER CHARACTERIZED BY RECURRENT COLLAPSE OF THE UPPER AIRWAY LEADING TO REPETITIVE episodes of hypoxemia, hypercapnia, and arousal from sleep. Sleep-induced decrements in lung volume are believed to result in increased upper airway collapsibility and contribute to inspiratory flow limitation,¹ although the exact mechanisms have not been clearly delineated. Our group has recently demonstrated that, in OSA patients, increased end expiratory lung volume (EELV) decreases the number of respiratory events during sleep.^2,3 These data suggest that increments in lung volume have a stabilizing effect on the upper airway during sleep in OSA patients. In these studies, lung volume was increased using an iron lung with a constant negative extrathoracic pressure, which would be impractical to use at home. We therefore sought to determine the effect of expiratory positive airway pressure (EPAP) on EELV and sleep disordered breathing in OSA patients, under the assumption that such an approach may be easier to achieve in the home than an iron lung apparatus.

METHODS

We recruited sleep apnea patients with moderate to severe OSA determined by overnight diagnostic polysomnogram. Wake/sleep states were determined using standard electroencephalography (EEG), chin electromyogram (EMG), and electrooculogram (EOG). Apneas and hypopneas were scored using AASM defined criteria,⁴ with the respiratory effort being determined with abdominal and thoracic magnetometers instead of bands. The protocol was approved by the Human Subjects' Committee at Brigham and Women's Hospital. All subjects provided informed written consent prior to participation in the study. Subjects with medical disorders potentially affecting lung or chest wall compliance or the upper or lower airway (other than obstructive sleep apnea and obesity) were excluded. During the night study, subjects breathed through a facial mask (Respironics, Murraysville, PA) connected to a pneumotachograph (Hans Rudolph, Kansas City, MO) and a two-way valve, while supine. To induce 10 cm H₂O EPAP we used a constant positive pressure device (Respironics, Murraysville, PA) connected to the expiratory line of the two-way valve. During baseline (no EPAP) the positive pressure was disconnected from the expiratory line. Subjects also had pulmonary function testing sitting and supine, with measurement of FRC with the helium dilution technique.

Changes in EELV were measured with two pairs of magnetometers (EOL Eberhard, Oberwil, Switzerland) placed in the anteroposterior axis of the chest and abdomen using a standardized formula previously validated by Kono and Mead.^5,6 Calibration was performed during quiet breathing supine: the changes in chest wall and abdomen anteroposterior diameter were averaged over 12 breaths of stable breathing and combined with the pneumotachograph data. Each change in AP diameter values was entered into the following equation describing the relationship between tidal volume and chest (RC)/abdominal (AB) excursion: TV = X (4 RC + AB). Tidal volume (TV) was determined using X, a coefficient determined in the calibration procedure for a given individual. All calibration maneuvers were performed with subjects instrumented and supine. This posture was maintained throughout the study.

Subjects were allowed to fall asleep with CPAP at the level they had been previously prescribed during in-laboratory titration. When they reached stable stage 2 NREM sleep, CPAP was stopped, and they were studied for 1 hour in NREM sleep with 10 cm H₂0 EPAP and for 1 hour in NREM sleep without any pressure applied, in random order. Variations in FRC were constantly monitored using chest and abdomen magnetometers. Mask pressure was constantly measured, so that 10 cm H₂O expiratory pressure was maintained at all times during the EPAP part of the study.

Data Analysis

The above-mentioned signals were recorded on both a 16-channel polygraph (Grass model 78) and a personal computer. Each signal (EEG, EOG, EMG, EKG, abdominal and rib cage magnetometers, flow, tidal volume) was analyzed using signal-processing software (Spike 2, CED Ltd, Cambridge, UK).

The recording of both conditions (baseline and EPAP) was analyzed blindly by the same experienced technician (LD). Inspiratory and expiratory time, as well as total respiratory time, were analyzed using custom written software (Spike 2 CED Ltd, Cambridge, UK). The two one-hour segments were also staged for sleep and breathing disturbances (apnea-hypopnea index (AHI), 3% oxygen desaturation index, arousal index, mean oxygen saturation, and sleep stage distribution). Minute ventilation, tidal volume, inspiratory, and expiratory and total respiratory time were calculated from the calibrated pneumotachograph signal. Calibrated magnetometers were used to determine relative changes in EELV. Results are reported as mean ± standard deviation. We used a paired t-test to assess the differences in the measured sleep parameters between the two conditions.

RESULTS

A total of 15 patients were included in the study. Five could not complete the protocol because they were unable to fall or to stay asleep with the EPAP. Thus, night time data from 10 OSA patients were analyzed (Table 1). These patients were aged 48.6 ± 8.9 years and were obese BMI = 36.9 ± 5.0. They had moderate to severe obstructive sleep apnea: AHI (diagnostic night) was 33.6 ± 13.3 events per hour. During sleep the mean FRC increase between baseline and EPAP was negligible 13.3 mL (range 2–25 mL). However, respiratory pattern did change. Expiratory time was significantly increased with EPAP compared to baseline: 2.6 ± 0.54 seconds vs. 2.2 ± 0.64 seconds (P = 0.002). Total respiratory time was slightly increased with EPAP compared to baseline 4.4 ± 1.47 sec vs. 3.7 ± 0.88 sec (P = 0.3) and minute ventilation lower with EPAP vs. baseline 7.9 ± 4.17 L/min vs. 9.0 ± 2.8 L/min (P = 0.3). Breathing frequency also tended to be lower with EPAP compared with baseline 14.5 ± 3.5 vs. 16.9 ± 4.0 (P = 0.13) breaths per minute.

Table 1.

Demographic Data of the Subjects, Pulmonary Function Testing Results and Effect of 10 cm H₂O Expiratory Postive Airway Pressure (EPAP) on Breathing Cycle and Sleep Disordered Breathing

Subjects	1	2	3	4	5	6	7	8	9	10	Mean	SD
Sex	f	m	f	m	f	m	f	m	m	m
Age (years)	47.0	36.0	47.0	52.0	59.0	60.0	52.0	45.0	55.0	33.0	48.6	8.9
BMI (kg/m2)	32.4	37.0	36.1	44.5	32.3	36.5	45.2	33.1	33.2	39.0	36.9	4.7
AHI (events/hr, diagnostic night)	27	42	15	41	32	25	23	52	55	24	33.60	13.3
Prescribed CPAP (cm H2O)	5.0	11.0	5.0	10.0	8.0	10.0	10.0	10.0	10.0	10.0	8.9	2.2
Lung volume increase on EPAP (mL)	9.3	17.0	11.3	24.0	20.0	16.5	13.3	2.0	9.2	10.0	13.3	6.3
FRC Sitting (liter)	1.8	1.7	1.7	2.6	2.5	2.7	1.8	NA	2.3	1.6	2.1**	0.4
FRC % predicted	59.0	54.0	62.0	67.0	82.0	72.0	70.0	NA	69.0	52.0	65.2	9.5
FRC Supine (liter)	1.4	1.9	1.3	2.5	1.9	2.3	1.8	NA	1.8	1.2	1.8**	0.4
FRC % diff sitting/supine	−23.0	12.0	−20.0	−2.0	−24.0	−14.0	0.0	NA	−23.0	−24.0	−13.1	13.3
Baseline
AHI (Events/hr)	100.0	49.0	27.8	81.0	78.0	47.8	26.0	101.0	80.0	36.0	62.7	28.7
Oxygen Desat (3% desaturations/hr)	1.0	16.0	17.7	73.0	67.0	21.9	6.5	94.0	74.0	25.0	39.6	33.6
Inspiratory time (Ti)	1.1	1.8	1.6	1.3	1.6	2.0	1.5	1.6	1.6	1.8	1.6	0.3
Expiratory time (Te)	1.4	3.0	1.7	1.6	2.4	3.2	2.4	2.2	2.0	1.8	2.2*	0.6
Total respiratory time (Ttot)	2.5	4.9	3.2	2.9	4.0	5.2	3.9	3.7	3.5	3.6	3.7	0.8
Breathing freq (breaths/min)	24.4	12.3	18.6	21.0	15.1	11.6	15.2	16.9	17.0	16.8	16.9	4.0
Tidal volume (liter)	0.4	0.6	0.3	0.6	0.2	0.5	0.6	0.5	0.5	0.7	0.5	0.2
EPAP
AHI (Events/hour)	49.5	49.2	10.5	77.0	85.9	53.4	8.4	88.0	94.0	52.5	56.8	30.3
Oxygen Desat (3% desaturations/hr)	0.0	28.8	4.8	54.0	66.3	23.9	6.5	81.0	87.0	41.9	39.4	31.8
Inspiratory time (Ti)	1.5	1.9	1.5	1.3	1.5	2.0	1.3	4.7	1.1	1.3	1.8	1.1
Expiratory time (Te)	2.8	2.8	2.0	2.0	3.1	3.3	2.6	3.4	2.4	2.0	2.6*	0.5
Total respiratory time (Ttot)	4.3	4.7	3.5	3.3	4.5	5.2	3.9	8.2	3.5	3.3	4.4	1.5
Breathing freq (breaths/min)	13.9	12.7	17.1	18.3	13.2	11.5	15.4	7.3	17.2	18.3	14.5	3.5
Tidal volume (liter)	0.5	0.7	0.2	0.5	0.6	0.5	0.5	1.1	0.4	0.5	0.5	0.2

* P = 0.0018; ** P = 0.0015 (paired t-test)

AHI = apnea-hypopnea index; BMI= body mass index; CPAP = continuous positive airway pressure; FRC = functional residual capacity.

In terms of clinical outcomes, there was little effect of EPAP. For baseline and EPAP respectively the mean apnea hypopnea index (supine) was 62.6 ± 28.7 and 56.8 ± 30.3 events per hour (P = 0.4), the mean 3% desaturation index was 39.6 ± 33.6 and 39.4 ± 31.8 events per hour (P = 0.9), the microarousal index was 63.3 ± 27.9 and 58.0 ± 26.6 events per hour (P = 0.3). Even though it was difficult for some subjects to sleep with the EPAP, the percentage of epochs scored as stage 1 NREM sleep was not different between the conditions (Baseline 9.5% ± 7.5%, EPAP 10.9% ± 8.6%).

Nine subjects also had sitting and supine PFTs: For the sitting PFT, there was a decrease in FRC and ERV compared to reference values for the height, sex, and age. When PFTs were repeated supine we measured a significant decreased in FRC (P = 0.0015), vital capacity (P = 0.03), total lung capacity (P = 0.009) and expiratory reserve volume (P = 0.03) compared to sitting measurements. There was however no correlation between baseline PFT values (nor PFT changes between sitting vs. supine) and the magnitude of the EPAP effect on AHI or FRC.

DISCUSSION

In this study we observed that EPAP only marginally increases EELV but that expiratory time is extended when EPAP is applied during sleep. These findings could represent a physiological mechanism by which FRC is maintained at a constant level during sleep in order to avoid hyperinflation.

We were surprised by the negligible effect of EPAP on EELV during sleep. EPAP along with CPAP have been shown to increase EELV in humans and in dogs during wakefulness.^7,8 We therefore expected that the same would occur during sleep, but this was clearly not the case when we applied EPAP. Deegan et al⁹ previously reported a lesser EELV increase with EPAP compared to CPAP during wakefulness and a nonsignificant EELV increase during sleep in nonobese individuals. There could be two explanations for this. First, expiratory time (TE) was significantly extended in our study when EPAP was applied. With an increased TE, expired volume could be preserved despite a decrease in expiratory flow due to EPAP. Interestingly Deegan et al.⁹ reported that one subject decreased his EELV during sleep with EPAP and they also attributed this to an extended TE. Second, Schlobohm et al¹⁰ demonstrated an activation of expiratory muscles with EPAP (in intubated patients), which was not found with CPAP. Even though we did not measure muscle activity, we suspect that an activation of expiratory muscles was also present: To oppose a 10 cm H₂O EPAP and exhale the tidal volume certainly requires both extended expiratory time and expiratory muscle activity as there was no hyperinflation.

We do not believe that the lack of increase in EELV was due to technical problems with the measurement EELV, as we have successfully used the magnetometers in previous studies and measured a marked increase in EELV with CPAP and extrathoracic negative pressure.³ Moreover, the magnetometer technique (with a fixed rib cage/abdomen ratio) has been validated and widely used by others groups with a sensitivity for a lung volume change of ~ 100 mL.^5,6,11 We are thus reasonably confident not to have missed a clinically significant EELV increase with this technique, but cannot exclude a minor change in EELV with EPAP. It is however possible that the lack of increase in EELV was related to the higher BMI in our subjects compared to prior studies, such that greater abdominal mass facilitated expiration.

We were also surprised by the difference between our results showing a very small decrease in sleep disordered breathing with EPAP and the results of Mahadevia et al. results, which showed an important reduction in apnea and desaturation index with EPAP (10 cm H₂O).¹² There are several possible explanations for this. First, they used a different technique to induce the EPAP. For some of their subjects, the expiratory line was dipped into a bucket of water (10 cm depth) and for others they used a threshold valve, both inducing a “passive” expiratory resistance. We chose to use a CPAP machine (at 10 cm H₂O) connected to the expiratory line to yield a constant “active” pressure. Second, the definition of respiratory events has evolved since 1983: Mahadevia et al. only reported the apnea index and not the apnea + hypopnea index as is done currently. We therefore suspect that some apneas may have changed into hypopneas with EPAP therapy in the Mahadevia study, and that this could explain the decrease in apnea index with 10 cm H₂O EPAP. Third, we studied our subjects only for one hour in each condition and exclusively during NREM sleep, while Mahadevia et al. recorded a whole night for both baseline and EPAP, which certainly included REM and NREM sleep.

One limitation of the present study is that we only recorded NREM sleep. Because expiratory muscles have been shown to be activated with EPAP, one could argue that EPAP could have a greater effect on EELV during REM sleep (compared to NREM sleep) because of the atonia of the most skeletal muscles during REM. The absence of an active expiratory phase could have yielded the expected increase in EELV with a possible effect on sleep disordered breathing in this sleep stage. This interesting question should be addressed in a future protocol. Another limitation is that our patients had moderate to severe OSA. Our results can thus only apply to this population. Only one patient had an AHI below 20 (diagnostic night) and his response to EPAP on AHI was interesting (baseline AHI 27.7/h compared to 10.5/h with 10 cm H₂O EPAP), but obviously we cannot draw conclusions from a single case. Moreover EPAP was applied only for one hour. We cannot exclude that after a period longer than an hour on EPAP the compensatory mechanisms preventing hyperinflation could have weakened and an increase in EELV could have occurred.

In summary these results show that, in OSA patients during sleep, the application EPAP, unlike CPAP, only marginally increases FRC, probably because of an increase in expiratory time. These findings suggest important physiological mechanisms are present to prevent hyperinflation during sleep.