Sleep, 20(12):1157-1161 © 1997 American Sleep Disorders Association and Sleep Research Society Arousals and Nocturnal Respiration in Symptomatic Snorers and NonSnorers *Soren Berg, tSusan Nash, tPhilip Cole and tVictor Hoffstein Summary: The purpose of the present investigation was to examine the relationship among upper airway resistance, snoring, and arousals, all measured simultaneously, in non apneic snorers complaining of excessive daytime sleepiness (EDS). To accomplish this task, we selected a group of nine nonapneic snorers who presented because of snoring, EDS, tiredness, or fatigue. Ten healthy, alert, nonapneic, nonsnoring subjects recruited from among the hospital personnel acted as a comparison group. All subjects had nocturnal polysomnography, which included measurements of snoring, nasal and pharyngeal airway pressure, esophageal pressure, and total respiratory flow. Each polysomnogram was analyzed to identify all arousals and all respiratory events, i.e. apneas, hypopneas, and periods of increased upper airway resistance. Each arousal was examined to determine whether it was associated with a respiratory event, and each respiratory event was examined to determine whether it was associated with an arousal. The results were compared between snorers and nonsnorers. There was no significant difference between the two groups in the total sleep time (182 :!: 61 minutes in controls vs. 188 :!: 50 minutes in patients) or the total number of arousals per hour of sleep (24 :!: 12 in controls vs. 28 :!: 10 in snorers). However, the distribution of arousals, i.e. electroencephalogram (EEG) vs. respiratory, was different in snorers and nonsnorers. In snorers 55% of arousals were respiratory, whereas in nonsnorers only 17% of arousals were associated with respiratory events. Not unexpectedly, the snorers had significantly more respiratory events during the night (512) than controls (112). However, the relative proportion of these events that was accompanied by arousals was similar in both groups. We conclude that the difference in daytime function between symptomatic snorers and asymptomatic non snorers is unlikely to be due strictly to the number of arousals during the night; however, it is possible that respiratory and EEG arousals have different impacts on daytime performance, which may explain the difference in daytime function between our two groups. Key Words: Upper airway resistance syndrome-Snoring-Sleepiness-Arousals. Many habitual snorers referred to sleep disorders centers complain of excessive daytime tiredness, fatigue, or sleepiness, thus raising a possibility of obstructive sleep apnea. However, in many of them nocturnal polysomnography does not demonstrate sleep apnea but confirms loud and continuous snoring. Guillerninault et al. (1,2) postulated that these patients may have cyclical increases of upper airway resistance throughout the night, causing arousals from sleep, thus leading to sleep fragmentation and daytime dysfunction. However, no simultaneous measurements of upper airway resistance, snoring, and arousals have been performed in well-defined groups of nonapneic snorers with daytime sleepiness and nonsnoring healthy controls, Such measurements would help to determine how frequently episodes of increased upper airway resistance are associated with arousals, and whether there are any differences in the Accepted for publication August 1997. Address correspondence and reprint requests to Dr. V. Hoffstein, St. Michael's Hospital, 30 Bond Street, Toronto, ON M5B 1W8, Canada number and pattern of arousals in sleepy snorers vs. asymptomatic nonsnorers. Consequently, the present investigation was designed to test the hypothesis that nonapneic snorers who complain of excessive daytime sleepiness have more arousals than healthy nonsnorers, and that most of the arousals in the former group are associated with respiratory events, i.e. apneas, hypopneas, and episodes of elevated upper airway resistance. METHODS Patients We searched our database to select patients who satisfied the following criteria: 1) chief presenting complaint was excessive daytime sleepiness, tiredness, or fatigue; 2) all admitted to being habitual snorers, thus raising a possibility of sleep apnea; 3) all had undergone diagnostic nocturnal polysomnography that confirmed the snoring and demonstrated the absence of sleep apnea, 1157 Downloaded from https://academic.oup.com/sleep/article-abstract/20/12/1157/2749992 by guest on 13 June 2020 *University Hospital, Lund, Sweden; and tSt, Michael's Hospital, University of Toronto, Toronto, Ontario, Canada 1158 S. BERG ET AL. Polysomnography All patients and controls had nocturnal polysomnography which included monitoring of electroencephalogram (EEG), electromyogram (chin and legs), electrooculogram, electrocardiogram, oxygen saturation, chest wall and abdominal movements, and snoring sounds, as described previously (3). Upper airway pressures at 8, 12, and 16 cm from the nares, corresponding to the posterior nasal cavity, rhinopharynx, and hypopharynx, respectively, were also monitored using open catheters (infant feeding tubes, 8F). Esophageal pressure was measured using a specially designed microchip sensor catheter (Reditech Corp., Copenhagen, Denmark), with the sensor head placed in the middle third of the esophagus (4). Flow was measured using a tight-fitting, full-face continuous positive airway pressure (CPAP) mask modified to serve as a pneumotachograph. Pressure and flow signals, displayed on a chart recorder together with other polysomnographic variables, were digitized at 50 Hz and processed using appropriate software to calculate airway resistance. All measurements were performed during stable periods of well-defined non-rapid eye movement (nonREM) sleep and a minimum of 3 minutes after the latest sleep stage shift. Polysomnograms were scored three times: 1) to identify the arousals, 2) to identify respiratory events, and 3) to identify the linkages between the two. The person Sleep. Vol. 20. No. 12. 1997 scoring polysomnograms (S.N.) was not aware of whether it belonged to a snorer or to a control subject. Definition of respiratory events Respiratory events were classified as apneas, hypopneas, or episodes of increased upper airway resistance. Apneas were defined as a complete cessation of oronasal flow lasting 10 seconds or more. Hypopneas were defined as a reduction of at least 50% in oronasal flow lasting 10 seconds or longer and reduction in oxygen saturation by at least 4% from baseline. Increased upper airway resistance events were differentiated from hypopneas as follows: they were defined as episodes during which there was an increase of 20% or more in peak-to-peak pressure amplitude, compared with baseline, lasting at least 15 seconds, with reduction in flow not exceeding 50% of baseline; these events were usually not accompanied by significant oxygen desaturation. Baseline peak-to-peak esophageal pressure fluctuations were obtained during awake, unobstructed breathing. Initially, we also identified snoring events as episodes of snoring lasting at least 15 seconds; however, it soon became apparent that this identification was redundant, because all snoring events were associated with increased upper airway resistance, although the opposite was not always true. We then examined each respiratory event to see whether it was associated with an arousal. Definition of arousals Arousals were defined according to American Sleep Disorders Association criteria as 3-15 seconds of alpha and fast theta EEG frequency (5). Each arousal was examined to decide whether it was associated with a respiratory event. This was determined by checking for the presence of apnea, hypopnea, or increased esophageal pressure, i.e. upper airway resistance, in the 30-second period preceding each arousal. If a respiratory event was not accompanied by an arousal as defined above, we examined the EEG to determine if there was a shorter burst of alpha activity lasting between 1 and 3 seconds. These EEG events were termed "microarousals". No effort was made to count all such events but only those that were associated with episodes of increased upper airway resistance. Arousals that were not associated with respiratory events were termed "EEG arousals". Data analysis Anthropometric and sleep data, including apnea index, hypopnea index, upper airway resistance index, Downloaded from https://academic.oup.com/sleep/article-abstract/20/12/1157/2749992 by guest on 13 June 2020 as defined by the apnea/hypopnea index as < 10; and 4) none had any concurrent disease or were taking any medication. The patients were contacted and asked to undergo another polysomnography with measurements of upper airway resistance. Twenty-five patients were contacted, 12 of whom agreed to participate. Subsequently, three patients were excluded because of failure to complete the required investigations. The remaining nine patients were used for data analysis. We also selected a comparison group consisting of 13 hospital personnel who were healthy and had no complaints whatsoever. Polysomnography revealed that three individuals snored lightly, whereas the remaining 10 had no snoring or sleep apnea. These 10 individuals formed the comparison group. Although comparing a group of healthy subjects to a group of snorers with complaints of daytime sleepiness may at first seem inappropriate, we wanted to compare the groups from the "opposite ends of the arousal spectrum", i.e. the group that is expected to have the lowest number of arousals (healthy, asymptomatic subjects) with the group that is expected to have the highest number of arousals (snoring, symptomatic patients). 1159 SNORING, AROUSALS, AND DAYTIME DYSFUNCTION TABLE 1. Variable Age (years) Body mass index (kg/m') Weight (kg) TABLE 3. Anthropometric data Controls (mean:!: SO) Patients (mean:!: SO) 30 :!: 5 25 :!: 2 77 :!: 8 47 :!: 12* 27 :!: 4 84 :!: 15 Sleep architecture and Epworth sleepiness score Controls Patients (mean:!: SD) (mean:!: SO) Variable * Significantly (p < 0.05) different from controls. 182 66 14 38 9 10 6 :!: :!: :!: :!: :!: :!: :!: 188 :!: 63 :!: 19 :!: 36 :!: 2:!: 10 :!: 13 :!: 61 21 7 13 7 5 3 50 20 6 20 1* 6 3* * Significantly (p < 0.05) different from controls. trast, such events (a total of 10) were identified in only two of 10 controls. NC). DISCUSSION RESULTS All snorers and nonsnorers were males. On the average, snorers were 17 years older than nonsnorers. Body mass index was not significantly different between both groups (Table 1). Respiratory data (Table 2) confirm that both groups were nonapneics, although snorers had significantly more respiratory events (apneas, hypopneas, and episodes of elevated upper airway resistance) than nonsnorers. Baseline esophageal pressure and maximum pressure during an episode with elevated upper airway resistance were not different between the groups. Sleep architecture (Table 3) shows that the amount of slow-wave sleep (expressed as a percent of total sleep time) was significantly lower in snorers than nonsnorers. Epworth sleepiness score was significantly higher in snorers. Relatively low total sleep time and sleep efficiency in snorers and controls were probably due to invasive instrumentation. Total arousal index was similar in both groups, but the types of arousals were different (Table 4). Snorers had significantly more arousals associated with respiratory events than nonsnorers. Although the latter group had fewer respiratory events, a similar percentage of them were associated with arousals (Table 5). In seven of nine patients, a total of 35 respiratory events were associated with microarousals; by conTABLE 2. Variable Apnea index Hypopnea index Upper airway resistance index Baseline esophageal pressure (cm H 20) Maximum esophageal pressure (% of baseline) This study indicates that snorers with daytime dysfunction have similar arousal index values but different types of arousals than nonsnoring, asymptomatic controls; most arousals in symptomatic snorers occur in association with respiratory events, whereas controls have mostly "pure EEG" arousals. The similarity in the numbers of arousals in both groups is surprising and unexpected, particularly because our snorers were older than the controls, which should further accentuate the difference in arousals. On the basis of the existing data (1,2,6-8), we expected the opposite, i.e. symptomatic snoring patients would have more arousals than controls, consistent with the currently accepted view that arousals lead to sleep fragmentation causing daytime dysfunction. Consequently, we must consider the possibility that our study design and patient selection simply failed to detect the difference in arousals, where in fact such a difference exists. One possibility is that, despite patients' complaints, our groups were in fact not different with respect to their daytime function, which would explain why we found similar numbers of arousals in both of them. This is a difficult issue to resolve, because we defined sleepiness strictly on the basis of subjective complaint rather than objective measurements such as the multiple sleep latency test (MSLT). However, there is no Respiratory data Controls (mean:!: SO) 0.2 1.1 2.2 7 195 :!: :!: :!: :!: :!: 0.4 3 2 2 53 Patients (mean:!: SO) 2 3 12 9 195 :!: :!: :!: :!: :!: 2* 2* 8* 4 44 * Significantly (p < 0.05) different from controls. Sleep, Vol. 20, No. 12, 1997 Downloaded from https://academic.oup.com/sleep/article-abstract/20/12/1157/2749992 by guest on 13 June 2020 and arousal index, were compared between patients and controls using unpaired t tests. Frequency of different arousals (i.e. the percentage of EEG and respiratory arousals) in both groups was compared using chi-square tests. All statistical analysis was performed using SAS software, release 6.10 (SAS Institute, Cary, Total sleep time (minutes) % Sleep efficiency % Stage I time % Stage II time % Slow-wave sleep time % REM sleep time Epworth sleepiness score S. BERG ET AL. 1160 TABLE 4. Variable Total arousal index EEG arousal index Apnea arousal index Hypopnea arousal index DAR arousal index TABLE 5. Arousals Controls (mean:':: SD) 24 20 0.1 1 1.8 :':: 12 :':: 9 :':: 0.3 :!: 3 :':: 1.6 Patients (mean:':: SD) 28:':: 13 :':: 2 :':: 3 :!: 10 :':: 10 7* 2* 2* 7* EEG, electroencephalogram; DAR, upper airway resistance. * Significantly (p < 0.05) different from controls. Sleep, Vol. 20, No. 12, 1997 Variable Controls Patients Total number of arousals % associated with respiratory events 678 17 748 55* Total number of respiratory events % associated with arousals 129 89 512 81 * Significantly (p < 0.05) different from controls. (12), which may explain why our group of sleepy snorers did not have more arousals than nonsnorers. Furthermore, the effect of sleepiness on the arousal response is not well understood and may alter the arousal threshold (13). Another possibility is that the "arousal strength", i.e. duration of arousals, is longer in snoring patients compared with controls. We did not systematically record the duration of each arousal (other than to confirm that it was within the range of 315 seconds), but the possibility that arousals are longer in snorers than in controls, and that this may account for their daytime symptoms, clearly needs to be explored further. Is it possible that daytime sleepiness among nonapneic snorers is unrelated to either snoring or arousals? For example, Downey et al. (14), in their retrospective analysis of children with upper airway resistance syndrome, were unable to demonstrate a statistically significant difference in the arousal index between children with UARS and either normal controls or children with sleep apnea. Jennum and Sj~l (15) examined daytime sleepiness and cognitive function in snorers and patients with sleep apnea and found that many snorers (almost 10%) complained of unintended sleepiness; however, because only respiratory measurements were performed during sleep, the authors were unable to comment on the arousals and their possible relationship to cognitive function. Philip et al. (16) examined sleep latency and performance tests in normal volunteers subjected to one night of sleep disturbance induced by repetitive short auditory stimuli sufficient to cause an arousal. The authors found that one night of sleep fragmentation was sufficient to reduce significantly sleep latency the following day but did not affect performance tests. Martikainen et al. (17) examined evolution of symptoms among habitual snorers over a period of 5 years. These authors found that approximately 14% of habitual snorers complain of daytime sleepiness, with 2.44.5% reporting traffic accidents due to sleepiness. However, when a small sample, consisting of 22 men, had nocturnal polysomnography, almost 30% were found to have sleep apnea. This raises the question of whether it was only patients with unsuspected obstructive sleep apnea who had problems with excessive Downloaded from https://academic.oup.com/sleep/article-abstract/20/12/1157/2749992 by guest on 13 June 2020 evidence that the MSLT can resolve between "mild" sleepiness and "no" sleepiness (1,2). Furthermore, measurement of sleep latencies in this situation is not helpful. Finding a significantly shorter sleep latency among symptomatic snorers would strengthen our conclusion, but finding similar sleep latencies in both groups would still leave us with the problem of having to explain the definite complaint of sleepiness, tiredness, or fatigue consistently voiced by this group. Another possibility is that airway resistance in our group of snorers was not as high as that in the group of patients with upper airway resistance syndrome (UARS) studied by Guilleminault et al. (2). In our patients, the mean esophageal pressure nadir was only -15 cm H 20, compared with -33 cm H 20 in the group studied by Guilleminault et al. (2). Only during frank apneas did we observe more negative esophageal pressures, comparable to those measured in patients studied by other investigators. It is quite possible that stronger respiratory efforts coupled with higher upper airway resistance would produce more arousals. Can our results explain the fundamental difference between our groups, i.e. daytime dysfunction? The answer to this question is a speculative one and depends on the interpretation of arousals. If we assume that all arousals, independent of whether or not they are associated with respiratory events, are equivalent, then our results do not indicate a relationship between arousals and daytime dysfunction. However, if we assume that all arousals are not equivalent, and in particular that those associated with increased work in breathing and reduction in oxygen saturation may lead to daytime dysfunction, whereas pure EEG arousals do not, then our results could explain why the patients are more sleepy than the controls. The possibility that respiratory arousals may lead to daytime dysfunction is implicit in the results of previous investigations (911); e.g. Telakivi et al. (9) found that in nonapneic snorers it was not the total number of arousals but rather the number of desaturations exceeding 4% that correlated best with certain indices of daytime dysfunction. Arousal responses appear to be mediated by brain stem mechanisms and are not necessarily accompanied by cortical effects, such as typical EEG pattern Distribution of arousals and their association with respiratory events SNORING, AROUSALS, AND DAYTIME DYSFUNCTION REFERENCES 1. Guilleminault C, Stoohs R, Duncan S. Snoring (I): daytime sleepiness in regular heavy snorers. Chest 1991;99:40-8. 2. Guilleminault C, Stoohs R, Clerk A, Cetel M, Maistros P. A cause of excessive daytime sleepiness: the upper airway resistance syndrome. Chest 1993;104:781-87. 3. Hoffstein Y, Mateika S, Anderson D. Snoring: is it in the ear of the beholder? Sleep 1994; 17:522-6. 4. Berg S, Hybbinette JC, Gislason T, Hawke M. Continuous intrathoracic pressure monitoring with a new esophageal microchip catheter in sleep-related upper airway obstructions. J 010laryngoI1995;24:160-4. 5. American Sleep Disorders Association. EEG arousals: scoring rules and examples. Sleep 1992;15:173-84. 6. Guilleminault C, Stoohs R, Clerk A, Simmons J, Labanowski M. From obstructive sleep apnea syndrome to upper airway resistance syndrome: consistency of daytime sleepiness. Sleep 1992;15:S13-6. 7. Stoohs R, Guilleminault C. Obstructive sleep apnea syndrome or abnormal upper airway resistance during sleep? J Clin Neurophysiol 1990;7:83-92. 8. Mathur R, Douglas NJ. Frequency of EEG arousals from nocturnal sleep in normal subjects. Sleep 1995;18:330-3. 9. Telakivi T, Kajaste S, Partinen M, Koskenvuo M, Salmi T, Kaprio J. Cognitive function in middle-aged snorers and controls: role of excessive daytime sClmnolence and sleep-related hypoxic events. Sleep 1988; II :454-62. 10. Poceta JC, Timms RM, Jeong DU, Ho S, Erman MK, Mitler MM. Maintenance of wakefulness test in obstructive sleep apnea syndrome. Chest 1992;101:893-7. II. Roehrs T, Zorick F, Wittig R, Conway W, Roth T. Predictors of objective level of daytime sleepiness in patients with sleep-related breathing disorders. Chest 1989;95:1202-6. 12. Rees K, Spence DPS, Earis JE, Calverley PMA. Arousal responses from apneic events during non-rapid-eye-movement sleep. Am J Respir Crit Care Med 1995;152:1016-21. 13. Stoohs RA. Picking up the pieces: the consequences of sleep fragmentation. Chest 1996;109:1417-9. 14. Downey R, Perkin RM, MacQuarrie J. Upper airway resistance syndrome: sick, symptomatic but under-recognized. Sleep 1993; 16:620-3. 15. Jennum P, Sj¢1 A. Self-assessed cognitive function in snorers and sleep apneics. Eur Neurol 1994;34:204-8. 16. Philip P, Stoohs R, Guilleminault C. Sleep fragmentation in normals: a model for sleepiness associated with upper airway resistance syndrome. Sleep 1994;17:242-7. 17. Martikainen K, Partinen M, Urponen H, Yuori I, Laippala P, Hasan J. Natural evolution of snoring: a 5-year follow-up study. Acta Neural Scand 1994;90:437-42. 18. Lofaso F, Coste A, Gilain L, Harf A, Guilleminault C, Goldenberg F. Sleep fragmentation as a risk factor for hypertension in middle-aged non-apneic snorers. Chest 1996; 109:896-900. 19. Martin SE, Engleman HM, Deary II, Douglas NJ. The effect of sleep fragmentation on daytime function. Am J Respir Crit Care Med 1996;153:1328-32. 20. Fietze I, Quispe-Bravo S, Hansch T, Rottig J, Baumann G, Witt C. Arousals and sleep stages in patients with obstructive apnea syndrome: changes under nCPAP treatment. J Sleep Res 1977; 6:128-33. Sleep, Vol. 20, No. 12, 1997 Downloaded from https://academic.oup.com/sleep/article-abstract/20/12/1157/2749992 by guest on 13 June 2020 daytime sleepiness. Recently, Lofaso et al. (18) was unable to find any difference in complaints of daytime sleepiness, fatigue, and Epworth sleepiness scale scores between two groups of snorers with and without fragmented sleep. On the other hand, Martin et al. (19) found that in normal individuals one night of sleep fragmentation induced by repetitive sound stimuli leads to reduction in sleep latency and impairment of daytime function. The results presented above illustrate that the relationship among snoring, arousals, and daytime sleepiness continues to be a matter of debate, not necessarily because such an association does not exist, but perhaps because it is masked by the lack of uniform definition of snoring, arousals, and daytime sleepiness. Recently, Fietze et al. (20) studied respiratory and movement arousals in patients with sleep apnea at baseline and while on nasal CPAP. The latter abolished abnormal respiratory events and reduced the number of respiratory arousals but had no effect on movement arousals. Because daytime function of these patients improves when they are treated with CPAp, the implication is that respiratory arousals, rather than movement arousals, may be responsible for daytime dysfunction. In summary, we found that nonapneic snoring patients complaining of excessive daytime sleepiness have similar total numbers of arousals as asymptomatic controls. However, these patients have significantly more respiratory events. We speculate that it is not the number of arousals per se but the type of arousal (pure EEG vs. respiratory) that may lead to daytime symptoms. 1161