Upper Airway Collapsibility in Snorers and in Patients with Obstructive Hypopnea and Apnea 1- 3

lAIN C. GLEADHILL, ALAN R. SCHWARTZ: NORMAN SCHUBERT, ROBERT A. WISE, SOLBERT PERMUTT, and PHILIP L. SMITH

Introduction

Sleep-disordered breathing is a common disorder (1) characterized by periodic obstruction of the upper airway during sleep (2). Patients may exhibit obstructive sleep apnea with complete occlusion of the upper airway during sleep (2, 3) or they may demonstrate hypopnea with severereductions in inspiratory airflow (4). Furthermore, in patients with both apnea and hypopnea, loud snoring has generally been regarded as evidence of reduced airflow (5); yet snoring is also common in asymptomatic persons who do not exhibit apneas or hypopneas during sleep (5,6). Therefore, asymptomatic snoring may represent a mild degree of reduced airflow, whereas hypopnea and apnea represent greater degrees of reduced airflow. We hypothesized that nocturnal reductions in upper airway inspiratory flow are due to increases in upper airway collapsibility. On the basis of previous studies (7-10), collapsibility can be defined by the upper airway critical pressure (Pcrit) that surrounds the locus of pharyngeal collapse, as illustrated in the mechanical analogue in figure 1. When Pcrit is positive relative to atmospheric nasal pressure, the mechanical analogue would allow us to predict that the upper airway should occlude. In contrast, an increasingly negative Pcrit should be associated with greater degrees of upper airway inspiratory airflow. In fact, previous studies have confirmed that Pcrit is positive in patients with obstructive sleep apnea who demonstrated recurrent complete occlusions of the upper airway during sleep (7-9). In contrast, a negative Pcrit has been demonstrated in normal subjects whose upper airway remains patent during sleep (10). Because reduced airflow has been observed in patients with obstructive hypopnea and in normal subjects who snore, we hypothesized that Pcrit in these groups would be intermediate between 1300

SUMMARY During sleep, mild reduction In Inspiratory airflow Is associated with snoring, whereas obstructive hypopneas and apneas are associated with more marked reductions In airflow. We determined whether the degree of Inspiratory airflow reduction was associated with differences In the collapsibility of the upper airway during sleep. Upper airway collapsibility was defined by the critical pressure (Pcrlt) derived from the relationship between maximal Inspiratory airflow and nasal pressure. In 10 asymptomatic snorers, six patients with obstructive hypopneas, and 10 patients with obstructive apneas, during nonrapld aye movement sleep, Perlt ranged from -6.5 ± 2.7 em H20 to -1.6 ± 1.4 and 2.5 ± 1.5 em H20, respectively (mean ± SO, P < 0.001). Moreover, higher 18'18ls of Perlt were associated with lower levels of maximal Inspiratory airflow during tidal breathing durIng sleep (p < 0.005). Weconclude that differences In upper airway collapsibility distinguish among groups of normal SUbjectswho snore and patIents with periodic hypopneas and apneas. Moreover. the findings suggest that small differences In collapsibility (Perlt) along a continuum are associated with reduced airflow and altered changes In pattern of breathing. AM REV RESPIR DIS 1991; 143:1300-1303

normal subjects and those with obstructive sleep apnea. Methods Subject Selection Patients with obstructive hypopneas and apneas were recruited from the patient referral population at the Johns Hopkins Sleep Disorders Center. Normal volunteers who snored were recruited from the local community. Subjects were excluded if concomitant medical illness, concurrent chronic medications, or abnormal pulmonary function were in evidence on the screening history, physical examination, or spirometry. Subjects who snored were also excluded if they complained of any nocturnal breathing difficulties or daytime hypersomnolence. Of these asym ptomatic snorers, 48070 of the subjects who snored were also excluded because they demonstrated significant obstructive apneas and hypopneas (29.4 ± 20.8 episodes/h of non-REM sleep, mean ± SD). Subjects who snored, patients with obstructive hypopnea, and patients with obstructive apnea were age-, weight-, and sexmatched. Written consent was obtained from each subject for the protocols below, which were approved by the Human Investigations Review Board in our institution.

Subject Classification 1\vo sleep studies were performed. The initial screening full-night sleep study was used to characterize the type of upper airway obstruction during sleep. Subjects were moni-

tored in the supine position in a sleep laboratory between the hours of 10:00 P.M. and 7:00 A.M. as previously described (ll). During this study. the following physiologic parameters were monitored during sleep. Thoracoabdominal movements were qualitativelyassessed by mercury strain gauges placed at the second intercostal space and at the level of the umbilicus. Airflow was qualitatively detected at both the nose and mouth with thermistors (Grass TCT lR; Grass Instruments. Quincy, MA) clipped to one nostril and the lip in the midline position. Surface electroencephalographic electrodes placed at C 3-A, and c.-a.. a submental electrode, and left and right electrooculograms were used to stage

(Receivedin originalform September 22, 1989and in revisedform January 11, 1991) 1 From the Johns Hopkins Sleep Disorders Center, Division of Pulmonary Medicine, Department of Medicine, Francis Scott Key Medical Center, Johns Hopkins Medical Institutions, Baltimore, Maryland. 2 Supported by Grant HL-37379-01 from the National Institutes of Health and by the Maryland Chapter of the American Lung Association. 3 Correspondence and requests for reprints should be addressed to lain C. Gleadhill, M.D., Division of Respiratory Medicine, Belfast City Hospital, Lisburn Road, Belfast, North Ireland BT97AB. 4 Recipient of Clinical Investigator Award HL-02031-OiAI from the National Institutes of Health.

1301

UPPER AIRWAY COLLAPSIBILITY IN SNORERS AND IN HYPOPNEA AND APNEA

sleep. An ear oximeter (Biox II; Ohmeda; Boulder, CO) recorded oxygen saturation and a continuous electrocardiogram was employed to record heart rate and rhythm. A polygraph (Model No. 78D; Grass Instruments) ran continuouslyat 10 mmls to record all physiologic data simultaneously throughout the night. An infrared closed-circuit television camera recorded in time lapse and real time all nighttime events so they could be reviewed and correlated with the results of the physiologic recordings. A technician was in attendance throughout the night co record any special events (e.g., snoring, electrode displacement, etc.). The pattern of breathing during sleep was evaluated according to standard techniques as follows. Disordered breathing episodes were defined by reductions in airflow at the nose and mouth lasting more than 10 s, which were associated with ~ 40/D oxyhemoglobin desaturations or a movement arousal (12). The type of disordered breathing episode was classified as: (1) central apnea when there was complete absence of airflow and thoracoabdominal movements, (2) obstructive apnea when airflow was absent and paradoxical thoracoabdominal respiratory movements were observed, (3) mixed apnea if both central and obstructive periods were noted during the disordered breathing event, or (4) obstructive hypopnea when there was a 50070 reduction in airflow with paradoxical thoracoabdominal movements associated with either a fall in oxygen saturation of at least 4% or was terminated by an arousal from sleep. During this first sleep study, snoring was monitored in normal volunteers who snored with a sound level meter (Model 155; Quest Electronics, Oconomowoc, WI) positioned I m above the subject's head. Snoring was defined by the presence of inspiratory sound greater than 40 dB, which corresponded to audible snoring. Ambient background noise in our laboratory is approximately 30 dB. In these subjects, snoring was present in 58 ± 15% (mean ± SD) of breaths during sleep at a mean peak level of 44.2 ± 3.2 dB. Patients were divided into three groups on the basis of their breathing patterns derived from the first sleep study. Snorers were defined as those who had greater than 40 disordered breathing events and no evidence of hypopnea or apnea. Patients were defined as having hypopnea if greater than five sleepdisordered events/h of non-REM sleep were recorded and if greater than 90% of the events had hypopnea as defined above. Patients were defined as having obstructive sleep apnea if greater than five disordered breathing events were recorded and if 90% of the events were apnea as defined above.

Determination of Critical Pressure and Nasal Resistance On the second night during non-REM sleep, upper airway pressure- flow relationships were measured in each subject as previously de-

Fig. ~. Mechanicalanalogueot tne upper airway consists of a collapsible 10· cus surrounded by a tissue or critical pressure (Perit)and relatively rigid seg· ments upstream in the nose and downstream in the hypopharynx with pressures, Pn and Php, and resistances, Rn and Rhp, respectively.

NASAL SEGMENT COLLAPSIBLE SEGMENT

600 Fig. 2. Maximal airflow (Vlmaxl versus nasal prlJsslJfe(Pn) in a representative patient with obstructive hypopnea demonstrates a Pcrit of -1.2 cm H2O (defined by the nasal pressure at which airflow ceases). Vlmax during tidal breathing at atmospheric Pn is shown by the level 01flow at the intercept with the vertical dashed line. Each point represents the mean ± SO for breaths sampled at each level of Pn shown.

HYPOPHARYNGEAL SEGMENT

JC 48 M

500 400 Virna. (mils)

300 200

100 pcrit\

-6

-4

-2

0

2

4

6

8

PN (ern H 2O)

scribed (9. 10). Briefly, each subject was studied in the supine position and breathed through a tight-fitting nasal mask (Vital Signs, East Rutherford, NJ), which was connected to a variable pressure source at the inflow port and a variable resistor at the outflow port. Pressure in the nasal mask was measured with . a catheter connected to a port in the mask, and esophageal pressure was measured with a 1O-cm latex balloon catheter prepared as previously described (9) and passed perinasally and positioned 10 em above the gastroesophageal junction. Nasal airflow was measured with a pneumotachograph (Hans Rudolf, Kansas City. MO), which was inserted in the breathing circuit. A thermistor (Dual probe, Model 1110; Somnitec, Van Nuys, CA) was placed at the mouth, and patients were monitored visually to assure that oral breathing did not occur. All pressures, flows, and neurophysiologic parameters were recorded continuously on the polygraph recorder (Model 780; Grass Instruments). After the initiation of stable non-REM sleep, nasal pressure was varied every 15 min over a range that included the nasal pressure at which inspiratory airflow became zero, i.e., the upper airway completely occluded (9, 10). During spontaneous inspirations, maximal inspiratory airflow (Vnnax) was measured at each level of nasal pressure as previously described (9, 10). Briefly, all measurements were made during steady-state periods of nonREM sleep. Transitional states were not examined. An average of three to five apnea or hypopnea cycles were measured at each level of CPAP. We averaged the maximal flow for the last four breaths during apneas or hypopneas before arousal. Pressure-flow curves were constructed by plotting maximal inspiratory

airflow against mask pressure. Flow limitation was present during all periods in which nasal pressure was above Pcrit. The relationship between maximal airflow and nasal pressure was also examined and is illustrated for a representative patient with obstructive hypopnea (figure 2).

Data Analysis Pcrit was defined as nasal at zero flow, which was determined by least squares linear regression of Vlmax and nasal pressure as previously described (9, IO). Vlmax during tidal breathing at atmospheric nasal pressure was also derived for each subject from intercept at atmospheric pressure of the least squares regression line of maximal airflow versus nasal pressure (9, 1O). Comparisons among the groups were made with one-way ANOVA. Post-hoc analysis of significant comparisons .was performed with Newman-Keuls multiple range test to determine the source of these differences. Statistical significance was inferred when p < 0.05.

Results

Anthropometric and sleeprespiratory data are shown in table 1. Subjects in each group were age-, weight-, and sexmatched. Moreover, the patients with hypopnea and apnea were also matched for the frequency of non-REM disordered-breathing episodes. In figure 3, Pcrit during non-REM sleep is demonstrated for the subjects of each group. In patients with obstructive sleep apnea, Perit was positive. In contrast, lower(more negative) levels of Pcrit

1302

GLEADHILL, SCHWARTZ. SCHUBERT. WISE. PERMUTT, AND SMITH

tient 12)with hypopnea was noted to have zero flow at atmospheric pressure.

TABLE 1 ANTHROPOMETRIC AND SLEEP RESPIRATORY DATA-

(yr)

Group I (OSA), n

Baseline Sao,

Average low Sao,

Sex

Non-REM DBR (episodeslh)

(%)

(%)

M M M M M F M M M M

28.6 29.6 32.8 27.5 30.7 36.3 27.3 26.3 27.0 26.7

92.2 55.6 35.6 61.7 62.2 110.0 75.5 86.0 34.4 63.0

95.6 96.2 97.6 94.4 96.0 93.4 94.9 95.4 96.6 95.5

89.8 86.7 89.1 91.7 83.3 79.9 85.0 91.0 88.6 92.0

4.1 1.2 2.1 0.4 4.2 1.2 3.5 3.7 3.8 0.8

0 0 0 0 0 0 0 0 0 0

29.3 3.2

67.6 23.9

96.6 1.2

87.7 4.0

2.5 1.5

0 0

38.9 38.7 34.1 37.4 25.4 32.7

37.5 51.1 72.0 63.9 25.0 39.2

96.3 92.7 96.8 94.2 96.8 95.9

91.0 84.5 91.2 87.4 91.0 90.4

-2.5 0.9 -1.2 -2.0 -1.8 -3.2

72.2 0 83.3 40.0 44.4 100.0

35 27 39 31 51 46 49 45 30 43

34.5 5.1

48.1 17.6

95.5 1.7

89.3 2.7

-1.6 1.4

56.7 36.0

27.3 26.8 33.1 26.7 28.8 39.5 33.7 29.0 29.4 34.5

1.3 0.0 0.0 1.2 0.0 0.4 3.2 3.8 0.2 0.0

92.7 96.0 98.0 99.3 96.0 91.0 93.7 95.2 98.0 95.0

-5.7 -5.8 -2.3 -2.4 -7.1 -7.9 -7.0 -6.8 -8.4 -11.4

159.2 162.5 81.9 91.3 161.4 204.1 148.3 175.7 215.4 186.0

30.9 4.2

1.0 1.4

95.5 2.6

-6.5 2.7

158.6 43.3

39.6 8.5

=6 52 39 48 43 39 36

11 12 13 14 15 16 Mean ± SO Group III (NS), n

Peritt (cm H2O)

= 10

1 2 3 4 5 6 7 8 9 10 Mean ± SO Group II (OH), n

Vlmax at Pn = 0:1=

BMI (kglmZj

Age

Subject No.

M M M F M F

42.8 6.1

= 10

17 18 19 20 21 22 23 24 25 26

36 35 43 43

Mean ± SO

39.4 5.5

M M

M M M F M M M F

44

36 34 51 36 36

Definition of abbreviations: BMI = body mass index; oBR = disordered breathing rate; Vrmax OSA = obstructive sleep apnea; OH = obstructive hypopnea; NS = nonsnorer. • Values represent mean ± SO.

= maximal

inspiratoryflow;

t p < 0.001 between each pair of groups.

*p < 0.005 between each pair of groups. were demonstrated in the patients with obstructive hypopneas and in those who snored, respectively. Significant differences in Pcrit weredemonstrated between 8

4

Perit (em H2 O)

•

0

I

• -4

-B

-12

.•,

• •

I

SNORER

*p