In 106 patients with COPD, 56 patients (52.8%) had an AHI ≥10 events/h and were considered to have COPD with OSA. Individuals in the COPD without OSA and COPD with OSA groups did not differ by sex, age, BMI, neck circumference, or exposure history of noxious particles. The proportion of patients undergoing drug therapy for stable COPD in the COPD without OSA and COPD with OSA groups was 84.0% and 73.2%, respectively (χ2 = 0.501, P = 0.639). However, the use of theophylline in the COPD without OSA group was 20.4% higher than that in COPD with OSA group (5.4% vs. 26.0%, χ2 = 8.783, P = 0.005). Spirometry demonstrated on an average, moderate and severe COPD. The post-bronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio and FEV1% predicted of the two groups were similar (56.54% vs. 56.70%, t = −0.061, P = 0.951; 54.19% vs. 57.98%, t = −0.897, P = 0.372, respectively) [Table 1].
Eighty-four participants (79.2%) with COPD snored and 37 participants (34.9%) with COPD were daytime sleepiness. The prevalence of snoring in the COPD without OSA group was similar to that in the COPD with OSA group (82.1% vs. 76.0%, χ2 = 0.606, P = 0.479). The prevalence of sleepiness between the COPD with and without OSA groups did not show statistical differences (42.9% vs. 26.0%, χ2 = 1.231, P = 0.102). Compared with COPD individuals without OSA, individuals with OSA had elevated AHI (20.00 [13.13–34.50] events/h vs. 5.05 [3.00–6.83] events/h, Z = −0.861, P < 0.001), more severe minimal oxygen desaturation (minimal SpO2) (83.50 [76.00–87.00]% vs. 88.50 [86.00–91.00] %, Z = −5.429, P < 0.001), and greater percentage of night-time spent with oxygen saturation below 90% (T90) (3.10 [0.50–26.25] % vs. 0 [0–1.00] %, Z = −5.054, P < 0.001) [Table 2].
The left ventricular ejection fraction (LVEF) did not show significant difference between the two study groups (70.00 [67.50–72.00] % vs. 70.00 [66.00–73.00] %, Z = −0.203, P = 0.839). The mean peak TRV (2.61 ± 0.52 m/s vs. 2.58 ± 0.40 m/s, t = −0.066, P = 0.947) and median PAP (31.00 [26.00–38.00] mmHg vs. 32.00 [25.00–36.50] mmHg, Z = −0.172, P = 0.846) were similar in the COPD with OSA group and the COPD without OSA group. In total, 10 of 50 (20.0%) COPD without OSA participants and 14 of 56 (25.0%) COPD with OSA participants had PH (χ2 = 0.377, P = 0.644) [Table 3].
Patients with COPD were divided into four categories based on their AHI: COPD without OSA group (AHI < 5), COPD with mild OSA group (5 ≤ AHI < 15), COPD with moderate OSA group (15 ≤ AHI < 30), and COPD with severe OSA group (AHI ≥ 30). Compared with COPD without OSA group, the median PAP in COPD with severe OSA group increased by 5 mmHg (36.00 [26.00–50.00] mmHg vs. 31.00 [24.00–34.00] mmHg, P = 0.036). The mean peak TRV (2.88 ± 0.63 m/s vs. 2.53 ± 0.39 m/s, P = 0.047), median PAP (36.00 [26.00–50.00] mmHg vs. 30.50 [26.00–35.75] mmHg, P = 0.024), and Charlson index (1.00 [0.25–2.75] vs. 0 (0–1.75), P = 0.022) in the COPD with severe OSA group were higher than those in the COPD with mild OSA group [Table 5].
According to the degree of nocturnal hypoxemia, patients with COPD were divided into COPD without hypoxemia group (minimal SpO2 ≥ 90%), COPD with mild hypoxemia group (85% ≤ minimal SpO2 < 90%), COPD with moderate hypoxemia group (80% ≤ minimal SpO2 < 85%), and COPD with severe hypoxemia group (minimal SpO2 < 80%). There were no statistical differences in the median PAP, proportion of PH, and secondary outcomes between the four groups [Table 6].
Based on T90, the patients were also divided into three groups, including COPD with T90 ≤ 1%, 1% < T90 ≤ 10% and T90 > 10%. We found that the mean peak TRV (2.87 ± 0.54 m/s vs. 2.51 ± 0.40 m/s, P = 0.008), median PAP (36.00 [29.00–50.00] mmHg vs. 29.00 [25.50–34.00] mmHg, P = 0.007), and Charlson index (1.00 [0–3.00] vs. 0 [0–1.00], P = 0.019) in the COPD with T90 > 10% group were significantly higher than those in COPD with T90 ≤ 1% group [Table 7].
Univariate analysis performed on data in patients with COPD revealed significant effects of age, FEV1% predicted, T90, and Charlson index on PH. According to the regression model, FEV1% predicted <50% increased the risk of PH by 3.46 times (odds ratio [OR] = 3.46; 95% confidence interval [CI]: 1.15–10.46; P = 0.028) and AHI ≥15 events/h increased the risk of PH by 3.20 times (OR = 3.20; 95% CI: 1.09–19.35; P = 0.034). Moderate to severe OSA and GOLD stage 2 or higher were independent factors contributing to PH in subjects with COPD [Table 8].
This study demonstrated that patients with COPD with OSA were more susceptible to PH, which might be associated with declining lung function and increased OSA severity. The main findings of this study are: (1) 56 patients (52.8%) with COPD were diagnosed as OSA, and 24 patients (22.6%) with COPD had PH; (2) COPD with severe OSA group and COPD with T90 >10% group had higher PAP; (3) multiple regression analysis revealed significant and independent effects of both FEV1% predicted and AHI on PH. These findings were consistent with our hypothesis that OSA is an aggravating factor of PAP and PH in patients with COPD.
In our study, we showed a high prevalence of OSA in patients with COPD, which was similar to the high prevalence reported in other studies.[26–28] This might be related to the fact that most of the subjects were elderly and had moderate to severe lung injury. Previous studies have found that the prevalence of OSA increased with age.[29,30] Considering the average age was 70 years in our study, we used AHI ≥10 events/h as a diagnostic criterion. Moreover, we found that the use of theophylline in COPD with OSA group was higher than that in COPD without OSA group. Previous studies have shown that theophylline could improve AHI, nocturnal hypoxia and sleep-related gas exchange in OSA.[31,32] Theophylline may have a stimulant effect on central respiratory drive and the upper airway muscles. It is unclear if theophylline is a more suitable drug for patients with COPD with OSA. In addition, 79.2% of patients with COPD snored and 34.9% of patients with COPD were daytime sleepiness. However, snoring and daytime sleepiness were not significant clinical features for identifying OSA in patients with COPD. At present, there is no recognized tool for screening OSA in patients with COPD. For patients with COPD, we need to further explore simpler identifiable features and screening methods for OSA. Sleep monitoring is needed to diagnose OSA for patients with COPD.
The present study revealed the prevalence of PH in 22.6% patients with COPD. Previous studies showed 38.7% to 62.4% cases of PH in patients with COPD.[33–35] In patients with COPD, increased PAP is an independent predictor of future exacerbations and life expectancy reduction. Decrease in the pulmonary vascular bed and chronic hypoxia are two main mechanisms of increased pulmonary vascular resistance and subsequent PH COPD.[7,36] In the present study, with increasing duration of hypoxemia, a significant increase in PAP was observed. However, we did not directly observe a significant increase in PAP with increasing severity of OSA and hypoxemia. Compared with AHI, the duration of hypoxemia may be more relevant to PH. Therefore, further studies involving larger sample size are needed to understand better clinical and biochemical profile of patients with OSA.
The prevalence of OSA-related PH varies from 17% to 53% in studies using right heart catheterization.[10,13,37] In general, older age, high BMI, worse nocturnal desaturations, and poor lung function are closely related to PH in OSA.[10,38] The occurrence of PH was mainly related to BMI and nocturnal hypoxia, and AHI was not an independent risk factor for PH. However, those studies were not limited to patients with OSA alone and subjects might have chronic cardiopulmonary disease, such as COPD. It is difficult to determine whether PH is due to intermittent hypoxemia caused by sleep apnea or persistent hypoxemia associated with chronic cardiopulmonary disease. Some studies have attempted to control the effect of cardiopulmonary disease as a confounding factor. Small sample studies have shown that the prevalence of PH in OSA without lung or heart disease was 20.7% to 41.0%. Most studies have found that OSA-induced PH was mild to moderate, and some studies have challenged the effect of AHI on PH.[11,12,37,40] Few studies have focused on PH in patients with COPD with OSA. The coexistence of OSA may have a synergistic adverse effect on pulmonary hemodynamics leading to right ventricular dysfunction in patients with COPD. Chaouat et al have reported that the prevalence of PH in patients with overlap syndrome is 29% higher than that in patients with OSA alone. Hawrylkiewicz et al have suggested that PH was very common (14/17, 82.4%) in patients with OS, but did not correlate with the severity of nocturnal desaturation in OS patients. Consistent with other research reports, we also found that patients with COPD with OSA developed more severe hypoxemia at night. In a study by Kendzerska et al, the degree of hypoxemia had a better ability to predict PH than did AHI in individuals with COPD and OSA. In addition, they demonstrated that co-occurrence of COPD and severe OSA has a synergistic effect on cardiovascular events and mortality.
Although our results suggested that apnea-hypopnea was an independent risk factor for PH in patients with COPD, this observation is still controversial. In this present study, we found that AHI and oxygen desaturation index (ODI) did not differ between the groups. This might be explained by the fact that patients with COPD were more likely to experience hypoxemia at night. An increase in upper respiratory resistance during night sleep in patients with COPD is almost always accompanied by hypoxemia. Therefore, hypoxemia occurs with apnea-hypopnea in COPD. Previous studies found the primary determinant of oxygen desaturation during repetitive airway obstruction was the duration of obstruction rather than the number of obstructions, and that hypoxemia was a main factor in elevating PAP. However, repetitive airway obstruction can cause repeated negative changes in intrathoracic pressure, which can lead to increased intrathoracic venous reflux, resulting in right ventricular hypertrophy and PH. A systematic review and meta-analysis showed that patients with OSA exhibited right ventricular dilatation, increased wall thickening, and altered RV function.  Repetitive airway obstruction can also cause microarousal and changes in sleep structure. The average PAP during rapid eye movement (REM) sleep is higher than that during non-REM sleep.[46,47] The increase in sympathetic nerve excitation and catecholamine secretion caused by apnea-hypopnea, as well as inflammation, oxidative stress, and endothelial dysfunction caused by intermittent hypoxia have been suggested to play a role in the pathogenesis of PH in OSA.
Our study has a few limitations. This study was cross-sectional, and we did not observe the compliance and efficacy of positive pressure ventilation therapy in patients with COPD with OSA. We failed to diagnose OSA using polysomnography, and could not assess the quality and stage of sleep in patients with COPD. Compared with polysomnography, the ApneaLink device is a simple, easy-to-use and reliable device with high sensitivity and specificity in calculating AHI. Apnea Link has been shown to underestimate and overestimate the AHI of OSA patients;[16,48] however, we used AHI ≥10 events/h as a criterion for diagnosing OSA to reduce errors. In recent years, echocardiography has been recommended as a first non-invasive screening and diagnostic technique for PH. The accuracy of Doppler echocardiography in evaluating PAP has been verified using right heart catheterization. Patients with TRV-estimated elevated PAP have an intermediate or high risk of PH. This study can help in diagnosis and treatment of these patients with COPD in a timely manner.
In conclusion, we observe that patients with COPD have a high prevalence of OSA. COPD with OSA patients are more susceptible to PH, which is associated with declining lung function and increased OSA severity. The severity of airflow obstruction, apnea-hypopnea and nocturnal hypoxia play important roles in the pathogenesis of PH in patients with COPD. Our observations can help understand the clinical and physiologic characteristics of individuals with COPD, with and without OSA and to identify suspected PH in COPD. Moreover, OSA and nocturnal hypoxemia deserve attention in elderly patients with COPD. The effect of the interaction between COPD and OSA on PH needs further confirmation. Furthermore, whether sleep apnea can promote PAP, or whether this interaction is bidirectional needs further study.
This work was supported by the grants from the Chronic Non-Communicable Diseases Prevention and Control Research of National Key Research and Development Program of China (No. 2016YFC1304301), Precision Medical Project of National Key Research and Development Program (No. 2016YFC0903601 and 2016YFC0901102), and the Beijing New-star Plan of Science and Technology program (No. Z171100001117124).
1. Wang C, Xu J, Yang L, Xu Y, Zhang X, Bai C, et al. Prevalence and risk factors of chronic obstructive pulmonary disease
in China (the China Pulmonary Health [CPH] study): a national cross-sectional study. Lancet
2018; 391:1706–1717. doi: 10.1016/s0140-6736(18)30841-9.
2. Zhou M, Wang H, Zhu J, Chen W, Wang L, Liu S, et al. Cause-specific mortality for 240 causes in China during 1990–2013: a systematic subnational analysis for the Global Burden of Disease Study 2013. Lancet
2016; 387:251–272. doi: 10.1016/s0140-6736(15)00551-6.
3. Ip SM, Lam B, Lauder IJ, Tsang KW, Chung K-F, Mok Y-W, et al. A community study of sleep-disordered breathing in middle-aged Chinese men in Hong Kong. Chest
2001; 119:62–69. doi: 10.1378/chest.119.1.62.
4. Liu J, Wei C, Huang L, Wang W, Liang D, Lei Z, et al. Prevalence of signs and symptoms suggestive of obstructive sleep apnea
syndrome in Guangxi, China. Sleep Breath
2014; 18:375–382. doi: 10.1007/s11325-013-0896-2.
5. Bednarek M, Plywaczewski R, Jonczak L, Zielinski J. There is no relationship between chronic obstructive pulmonary disease
and obstructive sleep apnea
syndrome: a population study. Respiration
2005; 72:142–149. doi: 10.1159/000084044.
6. Hoeper MM, Bogaard HJ, Condliffe R, Frantz R, Khanna D, Kurzyna M, et al. Definitions and diagnosis of pulmonary hypertension
. J Am Coll Cardiol
2013; 62:42–50. doi: 10.1016/j.jacc.2013.10.032.
7. Sakao S, Voelkel NF, Tatsumi K. The vascular bed in COPD: pulmonary hypertension
and pulmonary vascular alterations. Eur Respir Rev
2014; 23:350–355. doi: 10.1183/09059180.00007913.
8. Bady E, Achkar A, Pascal S, Orvoen-Frija E, Laaban JP. Pulmonary arterial hypertension in patients with sleep apnoea syndrome. Thorax
2000; 55:934–939. doi: 10.1136/thorax.55.11.934.
9. Wong HT, Chee KH, Chong AW. Pulmonary hypertension
and echocardiogram parameters in obstructive sleep apnea
. Eur Arch Otorhinolaryngol
2017; 274:2601–2606. doi: 10.1007/s00405-017-4491-1.
10. Minai OA, Ricaurte B, Kaw R, Hammel J, Mansour M, McCarthy K, et al. Frequency and impact of pulmonary hypertension
in patients with obstructive sleep apnea
syndrome. Am J Cardiol
2009; 104:1300–1306. doi: 10.1016/j.amjcard.2009.06.048.
11. Sanner BM, Doberauer C, Konermann M, Sturm A, Zidek W. Pulmonary hypertension
in patients with obstructive sleep apnea
syndrome. Arch Intern Med
1997; 157:2483–2487. doi: 10.1001/archinte.1997.00440420115011.
12. Alchanatis M, Tourkohoriti G, Kakouros S, Kosmas E, Podaras S, Jordanoglou JB. Daytime pulmonary hypertension
in patients with obstructive sleep apnea
: the effect of continuous positive airway pressure on pulmonary hemodynamics. Respiration
2001; 68:566–572. doi: 10.1159/000050574.
13. Wong HS, Williams AJ, Mok Y. The relationship between pulmonary hypertension
and obstructive sleep apnea
. Curr Opin Pulm Med
2017; 23:517–521. doi: 10.1097/MCP.0000000000000421.
14. Chronic Obstructive Pulmonary Disease
Group, Chinese Medical Association. Guideline for diagnosis and treatment of chronic obstructive pulmonary disease
[in Chinese]. Chin J Tuberc Respir Dis
2013; 36:255–264. doi: 10.3760/cma.j.issn.1001-0939.2013.04.007.
16. Nigro CA, Dibur E, Malnis S, Grandval S, Nogueira F. Validation of ApneaLink Ox( for the diagnosis of obstructive sleep apnea
. Sleep Breath
2013; 17:259–266. doi: 10.1007/s11325-012-0684-4.
17. Berry RB, Brooks R, Gamaldo C, Harding SM, Lloyd RM, Quan SF, et al. AASM scoring manual updates for 2017 (Version 2.4). J Clin Sleep Med
2017; 13:665–666. doi: 10.5664/jcsm.6576.
18. Galiè N, Humbert M, Vachiery J-L, Gibbs S, Lang I, Torbicki A, et al. 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension
. Eur Heart J
2016; 37:67–119. doi: 10.1093/eurheartj/ehv317.
19. Kendzerska TB, Smith PM, Brignardello-Petersen R, Leung RS, Tomlinson GA. Evaluation of the measurement properties of the Epworth sleepiness scale: a systematic review. Sleep Med Rev
2014; 18:321–331. doi: 10.1016/j.smrv.2013.08.002.
20. Bestall JC, Paul EA, Garrod R, Garnham R, Jones PW, Wedzicha JA. Usefulness of the Medical Research Council (MRC) dyspnoea scale as a measure of disability in patients with chronic obstructive pulmonary disease
1999; 54:581–586. doi: 10.1136/thx.54.7.581.
21. Jones PW, Harding G, Berry P, Wiklund I, Chen WH, Kline Leidy N. Development and first validation of the COPD assessment test. Eur Respir J
2009; 34:648–654. doi: 10.1183/09031936.00102509.
22. Dowson C, Laing R, Barraclough R, Town I, Mulder R, Norris K, et al. The validity of the Hospital Anxiety and Depression Scale. An updated literature review. J Psychosom Res
2002; 52:69–77. doi: 10.1016/S0022-3999(01)00296-3.
23. Nishimura K, Mitsuma S, Kobayashi A, Yanagida M, Nakayasu K, Hasegawa Y, et al. COPD and disease-specific health status in a working population. Respir Res
2013; 14:61doi: 10.1186/1465-9921-14-61.
24. Roffman CE, Buchanan J, Allison GT. Charlson comorbidities index. J Physiother
2016; 62:171doi: 10.1016/j.jphys.2016.05.008.
25. Degroot V, Beckerman H, Lankhorst G, Bouter L. How to measure comorbiditya critical review of available methods. J Clin Epidemiol
2003; 56:221–229. doi: 10.1016/s0895-4356(02)00585-1.
26. Basoglu OK, Gunduz C, Tasbakan MS. Prevalence of overlap syndrome in chronic obstructive pulmonary disease
patients without sleep apnea symptoms. Clin Respir J
2016; 8:236–242. doi: 10.1111/crj.12493.
27. Soler X, Gaio E, Powell FL, Ramsdell JW, Loredo JS, Malhotra A, et al. High prevalence of obstructive sleep apnea
in patients with moderate to severe chronic obstructive pulmonary disease
. Ann Am Thorac Soc
2015; 12:1219–1225. doi: 10.1513/AnnalsATS.201407-336OC.
28. Shawon MS, Perret JL, Senaratna CV, Lodge C, Hamilton GS, Dharmage SC. Current evidence on prevalence and clinical outcomes of co-morbid obstructive sleep apnea
and chronic obstructive pulmonary disease
: a systematic review. Sleep Med Rev
2017; 32:58–68. doi: 10.1016/j.smrv.2016.02.007.
29. Gamaldo AA, Beydoun MA, Beydoun HA, Liang H, Salas RE, Zonderman AB, et al. Sleep disturbances among older adults in the United States, 2002–2012: nationwide inpatient rates, predictors, and outcomes. Front Aging Neurosci
2016; 8:266doi: 10.3389/fnagi.2016.00266.
30. Leppanen T, Toyras J, Mervaala E, Penzel T, Kulkas A. Severity of individual obstruction events increases with age in patients with obstructive sleep apnea
. Sleep Med
2017; 37:32–37. doi: 10.1016/j.sleep.2017.06.004.
31. Mulloy E, McNicholas WT. Theophylline in obstructive sleep apnea
a double-blind evaluation. Chest
1992; 101:753–757. doi: 10.1378/chest.101.3.753.
32. Mulloy E, McNicholas WT. Theophylline improves gas exchange during rest, exercise, and sleep in severe chronic obstructive pulmonary disease
. Am Rev Respir Dis
1993; 148:1030–1036. doi: 10.1164/ajrccm/148.4_Pt_1.1030.
33. Schreiber A, Cemmi F, Ambrosino N, Ceriana P, Lastoria C, Carlucci A. Prevalence and predictors of obstructive sleep apnea
in patients with chronic obstructive pulmonary disease
undergoing inpatient pulmonary rehabilitation. COPD
2018; 1–6. doi: 10.1080/15412555.2018.1500533.
34. Gupta KK, Roy B, Chaudhary S, Mishra A, Patel ML, Singh J, et al. Prevalence of pulmonary artery hypertension in patients of chronic obstructive pulmonary disease
and its correlation with stages of chronic obstructive pulmonary disease
, exercising capacity, and quality of life. J Family Med Prim Care
2018; 7:53–57. doi: 10.4103/jfmpc.jfmpc_18_17.
35. Soler X, Liao SY, Marin JM, Lorenzi-Filho G, Jen R, DeYoung P, et al. Age, gender, neck circumference, and Epworth sleepiness scale do not predict obstructive sleep apnea
(OSA) in moderate to severe chronic obstructive pulmonary disease
(COPD): the challenge to predict OSA in advanced COPD. PLoS One
2017; 12:e0177289doi: 10.1371/journal.pone.0177289.
36. Chaouat A, Naeije R, Weitzenblum E. Pulmonary hypertension
in COPD. Eur Respir J
2008; 32:1371–1385. doi: 10.1183/09031936.00015608.
37. Sajkov D, Wang T, Saunders NA, Bune AJ, Neill AM, Douglas Mcevoy R. Daytime pulmonary hemodynamics in patients with obstructive sleep apnea
without lung disease. Am J Respir Crit Care Med
1999; 159:1518–1526. doi: 10.1164/ajrccm.159.5.9805086.
38. Chaouat A, Weitzenblum E, Krieger J, Oswald M, Kessler R. Pulmonary hemodynamics in the obstructive sleep apnea
syndrome. Results in 220 consecutive patients. Chest
1996; 109:380–386. doi: 10.1378/chest.109.2.380.
39. Sajkov D, McEvoy RD. Obstructive sleep apnea
and pulmonary hypertension
. Prog Cardiovasc Dis
2009; 51:363–370. doi: 10.1016/j.pcad.2008.06.001.
40. Nagaoka M, Goda A, Takeuchi K, Kikuchi H, Finger M, Inami T, et al. Nocturnal hypoxemia, but not sleep apnea, is associated with a poor prognosis in patients with pulmonary arterial hypertension. Circ J
2018; 82:3076–3081. doi: 10.1253/circj.CJ-18-0636.
41. Chaouat A, Weitzenblum E, Warrior J, Ifoundza T, Oswald M, Kessler R. Association of chronic obstructive pulmonary disease
and sleep apnea syndrome. Am J Respir Crit Care Med
1995; 151:82–86. doi: 10.1164/ajrccm.151.1.7812577.
42. Hawryłkiewicz I, Sliwiński P, Górecka D, Plywaczewski R, Zieliński JZ. Pulmonary haemodynamics in patients with OSAS or an overlap syndrome. Monaldi Arch Chest Dis
2004; 61:148–152. doi: 10.4081/monaldi.2004.693.
43. Kendzerska T, Leung RS, Aaron SD, Ayas N, Sandoz JS, Gershon AS. Cardiovascular outcomes and all-cause mortality in patients with obstructive sleep apnea
and chronic obstructive pulmonary disease
(overlap syndrome). Ann Am ThoracSoc
2019; 16:71–81. doi: 10.1513/AnnalsATS.201802-136OC.
44. Iwase N, Kikuchi Y, Hida W, Miki H, Taguchi O, Satoh M, et al. Effects of repetitive airway obstruction on O2 saturation and systemic and pulmonary arterial pressure in anesthetized dogs. Am Rev Respir Dis
1992; 146:1402–1410. doi: 10.1164/ajrccm/146.6.1402.
45. Maripov A, Mamazhakypov A, Sartmyrzaeva M, Akunov A, MurataliUulu K, Duishobaev M, et al. Right ventricular remodeling and dysfunction in obstructive sleep apnea
: a systematic review of the literature and meta-analysis. Can Respir J
2017; 2017:1587865doi: 10.1155/2017/1587865.
46. Niijima M, Kimura H, Edo H, Shinozaki T, Kang J, Masuyama S, et al. Manifestation of pulmonary hypertension
during REM sleep in obstructive sleep apnea
syndrome. Am J Respir Crit Care Med
1999; 159:1766–1772. doi: 10.1164/ajrccm.159.6.9808064.
47. Choi E, Park DH, Yu JH, Ryu SH, Ha JH. The severity of sleep disordered breathing induces different decrease in the oxygen saturation during rapid eye movement and non-rapid eye movement sleep. Psychiatry Investig
2016; 13:652–658. doi: 10.4306/pi.2016.13.6.652.
48. Ragette R, Wang Y, Weinreich G, Teschler H. Diagnostic performance of single airflow channel recording (ApneaLink) in home diagnosis of sleep apnea. Sleep Breath
2010; 14:109–114. doi: 10.1007/s11325-009-0290-2.