Abstract
Background
Patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) present with a variety of sleep-related symptoms. In polysomnography, sleep architecture is almost always abnormal, but it is not known which of the sleep-stage abnormalities are related to symptoms. Finding key sleep-stage abnormality that cause symptoms may be of therapeutic importance to alleviate symptoms. So far the mainstay of treatment is continuous positive airway pressure (CPAP)/bi-level positive airway pressure (BIPAP) therapy, but many patients are non-compliant to it. Correcting the sleep-stage abnormality that cause symptoms by pharmacotherapy may become an important adjunct to CPAP/BIPAP therapy.
Methods
A cross-sectional study. Adult subjects who attended a sleep laboratory for diagnostic polysomnography for a period of 1 month were recruited consecutively. OSAHS was diagnosed using American Academy of Sleep Medicine criteria. Subjects filled a questionnaire for symptoms prior to polysomnography.
Results
Thirty subjects, of whom 83.3% were obese, met diagnostic criteria, with males constituting 46.7% and females constituting 53%. Mean age was 53.40±11.60 years. Sleep architecture comprised N1 19.50±19.00%, N2 53.93±13.39%, N3 3.90±19.50%, and rapid eye movement 8.92±6.21%. Excessive fatigue or sleepiness, waking up tired, falling asleep during the day, trouble paying attention, snoring and insomnia were significantly related to decreased N3 sleep.
Conclusions
Most of the symptoms in OSAHS in adults are related to decreased stage N3 sleep. If confirmed by larger controlled studies, correcting N3 sleep deficiency by pharmacotherapy may become an important adjunct to CPAP/BIPAP therapy to alleviate symptoms.
Keywords: obstructive sleep apnea-hypopnea syndrome, sleep architecture, stage, symptom
Sleep architecture refers to the basic structural organization of normal sleep (1). There are two types of sleep, non-rapid eye movement (NREM) sleep and rapid eye movement (REM) sleep. NREM sleep is further divided into three sub-stages: stage N1, stage N2, and stage N3, according to current sleep scoring rules by American Academy of Sleep Medicine (AASM) (2). To note that, older sleep scoring rules had four stages of NREM sleep, but in the current scoring system, stage N3 and stage N4 combined as stage N3 (3). Each stage has its unique characteristics including variations in brain wave patterns, eye movements, and muscle tone. A sleep episode normally begins with a short period of NREM stage 1 progressing through stage 2, followed by stage 3 and finally to REM (1). Over the course of the sleep period, NREM sleep and REM sleep alternate cyclically every 90–120 min. Normal sleep architecture comprises stage N1 2–5%, stage N2 45–55%, stage N3 15–25%, and REM 20–25% of total sleep time (TST) (4–7).
Obstructive sleep apnea-hypopnea syndrome (OSAHS) is a common disorder affecting at least 2 to 4% of the adult population in the United States (8, 9). Sleep is fragmented by frequent arousals with increase in stage N1 sleep and decrease in stage N3 sleep and REM sleep (10–18). Patients with OSAHS experience many sleep-related symptoms, including poor cognitive performance, and are subject to various complications. Positive airway pressure in the form of continuous positive airway pressure (CPAP)/bi-level positive airway pressure (BIPAP) is the mainstay of treatment to prevent airway collapse during sleep, which is the fundamental abnormality in OSAHS. Unfortunately, many patients are non-compliant to CPAP/BIPAP mainly due to discomfort of using the machine. If the symptoms can be attributed to a particular sleep-stage abnormality, therapeutic modality to correct that abnormality may become an important adjunct to CPAP/BIPAP therapy to alleviate symptoms and or complications.
Materials and methods
This is a cross-sectional study. Subjects aged 18 years or older who attended a hospital sleep laboratory for diagnostic polysomnography during a 1-month period were recruited consecutively. A diagnosis of OSAHS was made if apnea-hypopnea index (AHI) score was 5 or more, according to AASM criteria (8). Those who met the diagnostic criteria for OSAHS were included for analysis. Mild, moderate, and severe OSAHS were defined as AHI of 5 to <15, 15 to 30, and >30, respectively (8).
Subjects filled a questionnaire for symptoms before the overnight polysomnography. Following symptoms were assessed in the questionnaire: excessive fatigue or sleepiness, falling asleep during the day, waking up tired, inattention (trouble paying attention due to sleepiness), snoring, stopped breathing during sleep, insomnia and leg jerks during sleep. Symptoms were graded as 0 if absent, 1 if sometimes, 2 if usually, and 3 if almost always present. This ranking of severity of symptoms was used in Spearman's correlation test.
Subjects who attended for positive airway pressure (PAP) titration studies were excluded from the study. This is because polysomnograhic abnormalities during titration studies do not reflect the baseline abnormalities.
Polysomnograms were scored manually following AASM scoring manual (2). Data were analyzed using SPSS version 20. Sleep stages were presented as percentages of TST. Mean and standard deviation were used for normally distributed data and median and interquartile ranges were used for non-normally distributed data. Shapiro–Wilk test was used for normality of data distribution. Spearman's test was used to see any significant correlation. P<0.05 was considered significant.
Results
Thirty subjects met diagnostic criteria for OSAHS, of which males constituted 46.7% and females constituted 53.3%. Mean age was 53.87±10.73 years. Mean BMI was 39.10±9.10. Majority (83.3%) were obese with BMI ≥30. Mild, moderate, and severe OSAHS were present in 30.0, 23.3, and 46.7%, respectively. Symptoms reported by patients or observed by partners are presented in Table 1.
Table 1.
Frequency of symptoms
| Present | ||||||
|---|---|---|---|---|---|---|
| Symptoms | Absent (%) | Sometimes (%) | Usually (%) | Almost always (%) | Total present (%) | Total |
| Snoring | 3.7 | 14.8 | 7.4 | 74 | 96.3 | 27 |
| Falling asleep during the day | 15.4 | 53.8 | 15.4 | 15.4 | 84.6 | 26 |
| Waking up tired | 19.2 | 34.6 | 26.9 | 19.2 | 80.8 | 26 |
| Excessive fatigue or sleepiness | 20.0 | 28.0 | 24.0 | 28.0 | 80 | 25 |
| Stopped breathing during sleep | 32.0 | 32.0 | 24.0 | 12.0 | 68 | 25 |
| Insomnia | 34.6 | 38.5 | 19.2 | 7.7 | 65.4 | 26 |
| Trouble paying attention | 34.6 | 42.3 | 15.4 | 7.7 | 65.4 | 26 |
| Leg jerks during sleep | 59.1 | 36.4 | 4.5 | 0 | 40.9 | 22 |
Sleep architecture and AHI are presented in Table 2.
Table 2.
Sleep architecture and AHI
| Variable | Mean | SD | 95% CI | Median | IQR |
|---|---|---|---|---|---|
| Sleep onset (min) | 10.00 | 15.25 (2.50–17.75) | |||
| Total sleep time (min) | 334.0 | 83.75 (276.25–360.00) | |||
| Sleep efficiency (%) | 84.00 | 21.00 (70.00–91.00) | |||
| Arousal index | 15.50 | 41.65 (8.75–50.40) | |||
| Stage N1 sleep (% of TST) | 19.50 | 19.00 (13.40–32.40) | |||
| Stage N2 sleep (% of TST) | 53.93 | 13.39 | 48.40–59.46 | ||
| Stage N3 sleep (% of TST) | 3.90 | 19.50 (0.00–19.50) | |||
| REM sleep (% of TST) | 8.92 | 6.21 | 6.35–11.48 | ||
| AHI | 19.40 | 65.60 (10.60–76.20) |
AHI=apnea-hypopnea index; IQR=interquartile range; TST=total sleep time.
We did Spearman's rank correlation between symptoms and sleep architecture. Results are presented in Table 3.
Table 3.
Correlations of symptoms with sleep architecture and AHI
| N1 | N2 | N3 | REM | Sleep onset | Sleep time | Sleep efficiency | Arousal index | AHI | ||
|---|---|---|---|---|---|---|---|---|---|---|
| Snoring | Correlation coefficient | 0.267 | 0.062 | −0.417 | −0.089 | 0.264 | 0.065 | 0.091 | 0.185 | 0.223 |
| p | 0.178 | 0.760 | 0.031 | 0.660 | 0.184 | 0.748 | 0.650 | 0.356 | 0.264 | |
| Falling asleep during the day | Correlation coefficient | 0.234 | 0.105 | −0.571 | 0.175 | −0.302 | 0.246 | 0.236 | 0.146 | 0.104 |
| p | 0.249 | 0.609 | 0.002 | 0.393 | 0.134 | 0.225 | 0.246 | 0.477 | 0.613 | |
| Waking up tired | Correlation coefficient | 0.075 | 0.061 | −0.346 | 0.090 | −0.226 | 0.357 | 0.423 | 0.224 | 0.062 |
| p | 0.716 | 0.765 | 0.083 | 0.662 | 0.267 | 0.074 | 0.031 | 0.271 | 0.763 | |
| Excessive fatigue or sleepiness | Correlation coefficient | 0.355 | −0.054 | −0.449 | −0.161 | 0.214 | −0.045 | −0.059 | 0.170 | 0.148 |
| p | 0.082 | 0.798 | 0.024 | 0.443 | 0.305 | 0.830 | 0.780 | 0.416 | 0.479 | |
| Stopped breathing during sleep | Correlation coefficient | 0.163 | 0.070 | −0.200 | 0.083 | 0.019 | 0.077 | 0.161 | 0.058 | 0.178 |
| p | 0.436 | 0.740 | 0.337 | 0.693 | 0.929 | 0.714 | 0.442 | 0.784 | 0.396 | |
| Insomnia | Correlation coefficient | 0.281 | −0.078 | −0.426 | −0.264 | −0.213 | −0.336 | −0.264 | 0.445 | 0.151 |
| p | 0.164 | 0.707 | 0.030 | 0.192 | 0.297 | 0.093 | 0.193 | 0.023 | 0.463 | |
| Trouble paying attention | Correlation coefficient | 0.245 | 0.026 | −0.479 | −0.215 | −0.296 | 0.042 | 0.104 | 0.318 | 0.249 |
| p | 0.227 | 0.899 | 0.013 | 0.291 | 0.141 | 0.837 | 0.612 | 0.113 | 0.220 | |
| Leg jerks during sleep | Correlation coefficient | −0.161 | 0.351 | 0.069 | 0.294 | −0.008 | 0.250 | 0.278 | −0.145 | −0.178 |
| p | 0.475 | 0.109 | 0.760 | 0.183 | 0.972 | 0.262 | 0.211 | 0.520 | 0.427 | |
| AHI | Correlation coefficient | 0.605 | −0.364 | −0.484 | −0.552 | −0.012 | −0.388 | −0.394 | 0.775 | – |
| p | 0.000 | 0.048 | 0.007 | 0.002 | 0.949 | 0.034 | 0.031 | 0.000 |
AHI=apnea-hypopnea index.
Only statistically significant values are highlighted.
Discussion
Most of the patients were obese older adults with slight female predominance. Sleep onset was normal but TST and sleep efficiency were low. There were frequent arousals with increased stage N1 and high normal stage N2 sleep. Stage N3 and REM sleep were low. Most patients were symptomatic and snoring was present in almost all of them. In Spearman's rank correlation, the more the subjects were deprived of N3 sleep, the more they complained of snoring, excessive fatigue, sleepiness, falling asleep during the day, trouble paying attention, and insomnia. None of the symptoms were related to other sleep-stage abnormalities. Frequent arousal during sleep correlated with frequent complaints of insomnia. Median sleep efficiency was low, but those who had relatively better sleep efficiency, they complained more of waking up tired. Although AHI correlated with most of the sleep architecture abnormalities, it had no relationship with any of the symptoms. AHI also did not correlate with Epworth sleepiness scale, which is on par with findings described in other studies (19, 20). If the findings of this study can be confirmed by larger controlled studies, correcting stage N3 sleep deficiency by PAP or pharmacotherapy may result in symptomatic improvement in patients with obstructive sleep apnea-hypopnea syndrome.
Conclusions
Most of the symptoms in obstructive sleep apnea-hypopnea syndrome in adults are related to decreased stage N3 sleep. If confirmed by larger controlled studies, correcting stage N3 sleep deficiency by pharmacological means may become an important adjunct to PAP therapy to alleviate symptoms.
Conflict of interest and funding
The authors have not received any funding or benefits from industry or elsewhere to conduct this study.
References
- 1.Institute of Medicine (US) Committee on Sleep Medicine and Research. Colten HR, Altevogt BM., editors . Washington, DC: National Academies Press (US); 2006. Sleep disorders and sleep deprivation: An unmet public health problem; p. 2. [PubMed] [Google Scholar]
- 2.Berry RB, Brooks R, Gamaldo CE, Harding SM, Lloyd RM, Marcus CL, et al. 2nd ed. Darien, CT: American Academy of Sleep Medicine; 2014. The AASM manual for the scoring of sleep and associated events: Rules, terminology and technical specifications. [Google Scholar]
- 3.Kales A, Rechtschaffen A. Bethesda, MD: Public Health Service, U.S. Government Printing Office; 1968. A manual of standardized terminology, techniques and scoring system for sleep stages of human subjects; p. 58. [Google Scholar]
- 4.Ohayon MM, Carskadon MA, Guilleminault C, Vitiello MV. Meta-analysis of quantitative sleep parameters from childhood to old age in healthy individuals: Developing normative sleep values across the human lifespan. Sleep. 2004;27(7):1255–73. doi: 10.1093/sleep/27.7.1255. [DOI] [PubMed] [Google Scholar]
- 5.Mitterling T, Högl B, Schönwald SV, Hackner H, Gabelia D, Biermayr M, et al. Sleep and respiration in 100 healthy Caucasian sleepers – A polysomnographic study according to American Academy of Sleep Medicine standards. Sleep. 2015;38(6):867–75. doi: 10.5665/sleep.4730. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Hirshkowitz M, Moore CA, Hamilton CR, Rando KC, Karacan I. Polysomnography of adults and elderly: Sleep architecture, respiration, and leg movement. J Clin Neurophysiol. 1992;9(1):56–62. [PubMed] [Google Scholar]
- 7.Keenan S, Hirshkowitz M. Monitoring and staging human sleep. In: MH Kryger, T Roth, WC, Dement., editors. Principles and practice of sleep medicine. 5th ed. St. Louis, MO: Elsevier Saunders; 2011. pp. 1602–9. [Google Scholar]
- 8.Epstein LJ, Kristo D, Strollo PJ, Jr, Friedman N, Malhotra A, Patil SP, et al. Clinical guideline for the evaluation, management and long-term care of obstructive sleep apnea in adults. J Clin Sleep Med. 2009;5(3):263–76. [PMC free article] [PubMed] [Google Scholar]
- 9.Young T, Peppard PE, Gottlieb DJ. Epidemiology of obstructive sleep apnea: A population health perspective. Am J Respir Crit Care Med. 2002;165(9):1217–39. doi: 10.1164/rccm.2109080. [DOI] [PubMed] [Google Scholar]
- 10.Kappus MR, Leszczyszyn DJ, Moses L, Raman S, Heuman DM, Bajaj JS. Effect of obstructive sleep apnea on the sleep architecture in cirrhosis. J Clin Sleep Med. 2013;9(3):247–51. doi: 10.5664/jcsm.2488. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Jalilolghadr S, Yazdi Z, Mahram M, Babaei F, Esmailzadehha N, Nozari H, et al. Sleep architecture and obstructive sleep apnea in obese children with and without metabolic syndrome: A case control study. Sleep Breath. 2015;20(2):845–51. doi: 10.1007/s11325-015-1291-y. doi: http://dx.doi.org/10.1007/s11325-015-1291-y. [DOI] [PubMed] [Google Scholar]
- 12.Bardwell WA, Moore P, Ancoli-Israel S, Dimsdale JE. Does obstructive sleep apnea confound sleep architecture findings in subjects with depressive symptoms? Biol Psychiatry. 2000;48(10):1001–9. doi: 10.1016/s0006-3223(00)00887-8. doi: http://dx.doi.org/10.1016/S0006-3223(00)00887-8. [DOI] [PubMed] [Google Scholar]
- 13.Chung F, Liao P, Yegneswaran B, Shapiro CM, Kang W. Postoperative changes in sleep-disordered breathing and sleep architecture in patients with obstructive sleep apnea. Anesthesiology. 2014;120(2):287–98. doi: 10.1097/ALN.0000000000000040. doi: http://dx.doi.org/10.1097/ALN.0000000000000040. [DOI] [PubMed] [Google Scholar]
- 14.Wang G, He B, Chi C. Severity of obstructive sleep apnea syndrome relates to sleep architecture changes. Zhonghua Jie He He Hu Xi Za Zhi. 1998;21(8):477–9. (in Chinese) [PubMed] [Google Scholar]
- 15.McArdle N, Douglas NJ. Effect of continuous positive airway pressure on sleep architecture in the sleep apnea–hypopnea syndrome: a randomized controlled trial. Am J Respir Crit Care Med. 2001;164(8):1459–63. doi: 10.1164/ajrccm.164.8.2008146. doi: http://dx.doi.org/10.1164/ajrccm.164.8.2008146. [DOI] [PubMed] [Google Scholar]
- 16.Xiao YL, Richter F, Brunner F, Lerche B, Zhang DP, Zheng PD. Short-term and long-term influences of nasal continuous positive airway pressure to sleep architecture of obstructive sleep apnea hypopnea syndrome. Zhonghua Nei Ke Za Zhi. 2004;43(9):651–3. (in Chinese) [PubMed] [Google Scholar]
- 17.Goh DY, Galster P, Marcus CL. Sleep architecture and respiratory disturbances in children with obstructive sleep apnea. Am J Respir Crit Care Med. 2000;162(2):682–6. doi: 10.1164/ajrccm.162.2.9908058. doi: http://dx.doi.org/10.1164/ajrccm.162.2.9908058. [DOI] [PubMed] [Google Scholar]
- 18.Bianchi MT, Cash SS, Mietus J, Peng C-K, Thomas R. Obstructive sleep apnea alters sleep stage transition dynamics. PLoS One. 2010;5(6):e11356. doi: 10.1371/journal.pone.0011356. doi: http://dx.doi.org/10.1371/journal.pone.0011356. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Guimarães C, Martins MV, Vaz Rodrigues L, Teixeira F, Moutinho Dos Santos J. Epworth sleepiness scale in obstructive sleep apnea syndrome – An underestimated subjective scale. Rev Port Pneumol. 2012;18(6):267–71. doi: 10.1016/j.rppneu.2012.04.009. doi: http://dx.doi.org/10.1016/j.rppneu.2012.04.009. (in English, Portuguese) [DOI] [PubMed] [Google Scholar]
- 20.Nguyen ATD, Baltzan MA, Small D, Wolkove N, Guillon S, Palayew M. Clinical reproducibility of the Epworth Sleepiness Scale. J Clin Sleep Med. 2006;2(2):170–4. [PubMed] [Google Scholar]