Skip to main content
Erschienen in: Sleep and Breathing 1/2021

27.03.2020 | Sleep Breathing Physiology and Disorders • Original Article

Multi-perspective clustering of obstructive sleep apnea towards precision therapeutic decision including craniofacial intervention

verfasst von: Su-Jung Kim, Waleed Maqbul Alnakhli, Ali Saeed Alfaraj, Kyung-A Kim, Sung-Wan Kim, Stanley Yung-Chuan Liu

Erschienen in: Sleep and Breathing | Ausgabe 1/2021

Einloggen, um Zugang zu erhalten

Abstract

Purpose

Previous studies focusing on phenotyping obstructive sleep apnea (OSA) have outlined its heterogeneity in clinical symptoms, comorbidities, and polysomnographic features. However, the role of anatomical or pathophysiological causality including craniofacial skeletal deformity has not been studied. We aimed to identify and characterize phenotypes of OSA based on multi-perspective clustering by incorporating craniofacial risks with obesity, apnea severity, arousability, symptom, and comorbidity.

Methods

A total of 421 Korean patients with OSA (apnea-hypopnea index, AHI ≥ 5; age ≥ 20 years old) were recruited. A K-means cluster analysis was performed following principal component analysis with sagittal and vertical skeletal variables (ANB and mandibular plane angle), AHI, body mass index, and Epworth sleepiness scale. Inter-cluster comparison was conducted using demographic, cephalometric, and polysomnographic variables in addition to presence of diabetes and hypertension. Risk factors contributing to OSA severity were evaluated in each cluster using multivariable regression analysis with adjustment for age and gender.

Results

Three phenotypic clusters were identified and characterized as follows: Cluster-1 (noncraniofacial phenotype, 39%), non-obese moderate-to-severe OSA with no skeletal discrepancy representing low arousal threshold (ArTh), little sleepiness, and low comorbidity; Cluster-2 (craniofacial skeletal phenotype, 33%), non-obese moderate OSA with definite skeletal discrepancy showing low ArTh, mild sleepiness, and low comorbidity; and Cluster-3 (complicated phenotype, 28%), obese severe OSA with skeletal discrepancy exhibiting high ArTh, excessive daytime sleepiness, and high incidence of hypertension.

Conclusions

The three OSA phenotypes from multi-perspective clustering may provide a basis for precise therapeutic decision-making including craniofacial skeletal intervention beyond usual characterization of OSA subgroups.
Literatur
1.
Zurück zum Zitat Park JG, Ramar K, Olson EJ (2011) Updates on definition, consequences, and management of obstructive sleep apnea. In: Mayo Clinic Proceedings. vol 6. Elsevier, pp 549–555 Park JG, Ramar K, Olson EJ (2011) Updates on definition, consequences, and management of obstructive sleep apnea. In: Mayo Clinic Proceedings. vol 6. Elsevier, pp 549–555
2.
Zurück zum Zitat Eckert DJ (2018) Phenotypic approaches to obstructive sleep apnoea–new pathways for targeted therapy. Sleep Med Rev 37:45–59 CrossRef Eckert DJ (2018) Phenotypic approaches to obstructive sleep apnoea–new pathways for targeted therapy. Sleep Med Rev 37:45–59 CrossRef
3.
Zurück zum Zitat Bailly S, Destors M, Grillet Y, Richard P, Stach B, Vivodtzev I, Timsit J-F, Lévy P, Tamisier R, Pépin J-L (2016) Obstructive sleep apnea: a cluster analysis at time of diagnosis. PLoS One 11(6):e0157318 CrossRef Bailly S, Destors M, Grillet Y, Richard P, Stach B, Vivodtzev I, Timsit J-F, Lévy P, Tamisier R, Pépin J-L (2016) Obstructive sleep apnea: a cluster analysis at time of diagnosis. PLoS One 11(6):e0157318 CrossRef
4.
Zurück zum Zitat Keenan BT, Kim J, Singh B, Bittencourt L, Chen N-H, Cistulli PA, Magalang UJ, McArdle N, Mindel JW, Benediktsdottir B (2018) Recognizable clinical subtypes of obstructive sleep apnea across international sleep centers: a cluster analysis. Sleep 41(3):zsx214 CrossRef Keenan BT, Kim J, Singh B, Bittencourt L, Chen N-H, Cistulli PA, Magalang UJ, McArdle N, Mindel JW, Benediktsdottir B (2018) Recognizable clinical subtypes of obstructive sleep apnea across international sleep centers: a cluster analysis. Sleep 41(3):zsx214 CrossRef
5.
Zurück zum Zitat Wang Q, Zhang C, Jia P, Zhang J, Feng L, Wei S, Luo Y, Su L, Zhao C, Dong H (2014) The association between the phenotype of excessive daytime sleepiness and blood pressure in patients with obstructive sleep apnea-hypopnea syndrome. Int J Med Sci 11(7):713–720 CrossRef Wang Q, Zhang C, Jia P, Zhang J, Feng L, Wei S, Luo Y, Su L, Zhao C, Dong H (2014) The association between the phenotype of excessive daytime sleepiness and blood pressure in patients with obstructive sleep apnea-hypopnea syndrome. Int J Med Sci 11(7):713–720 CrossRef
6.
Zurück zum Zitat Kuang J (2016) Obstructive sleep apnea-hypopnea syndrome clinical in subtypes a principal component analysis-based cluster analysis. Chest 149(4):A566 CrossRef Kuang J (2016) Obstructive sleep apnea-hypopnea syndrome clinical in subtypes a principal component analysis-based cluster analysis. Chest 149(4):A566 CrossRef
7.
Zurück zum Zitat Ye L, Pien GW, Ratcliffe SJ, Björnsdottir E, Arnardottir ES, Pack AI, Benediktsdottir B, Gislason T (2014) The different clinical faces of obstructive sleep apnoea: a cluster analysis. Eur Respir J 44(6):1600–1607 CrossRef Ye L, Pien GW, Ratcliffe SJ, Björnsdottir E, Arnardottir ES, Pack AI, Benediktsdottir B, Gislason T (2014) The different clinical faces of obstructive sleep apnoea: a cluster analysis. Eur Respir J 44(6):1600–1607 CrossRef
8.
Zurück zum Zitat Saaresranta T, Hedner J, Bonsignore MR, Riha RL, McNicholas WT, Penzel T, Anttalainen U, Kvamme JA, Pretl M, Sliwinski P (2016) Clinical phenotypes and comorbidity in European sleep apnoea patients. PLoS One 11(10):e0163439 CrossRef Saaresranta T, Hedner J, Bonsignore MR, Riha RL, McNicholas WT, Penzel T, Anttalainen U, Kvamme JA, Pretl M, Sliwinski P (2016) Clinical phenotypes and comorbidity in European sleep apnoea patients. PLoS One 11(10):e0163439 CrossRef
9.
Zurück zum Zitat Vavougios GD, Natsios G, Pastaka C, Zarogiannis SG, Gourgoulianis KI (2016) Phenotypes of comorbidity in OSAS patients: combining categorical principal component analysis with cluster analysis. J Sleep Res 25(1):31–38 CrossRef Vavougios GD, Natsios G, Pastaka C, Zarogiannis SG, Gourgoulianis KI (2016) Phenotypes of comorbidity in OSAS patients: combining categorical principal component analysis with cluster analysis. J Sleep Res 25(1):31–38 CrossRef
10.
Zurück zum Zitat Gagnadoux F, Le Vaillant M, Paris A, Pigeanne T, Leclair-Visonneau L, Bizieux-Thaminy A, Alizon C, Humeau M-P, Nguyen X-L, Rouault B (2016) Relationship between OSA clinical phenotypes and CPAP treatment outcomes. Chest 149(1):288–290 CrossRef Gagnadoux F, Le Vaillant M, Paris A, Pigeanne T, Leclair-Visonneau L, Bizieux-Thaminy A, Alizon C, Humeau M-P, Nguyen X-L, Rouault B (2016) Relationship between OSA clinical phenotypes and CPAP treatment outcomes. Chest 149(1):288–290 CrossRef
11.
Zurück zum Zitat Burgel P-R, Paillasseur J-L, Janssens W, Piquet J, Ter Riet G, Garcia-Aymerich J, Cosio B, Bakke P, Puhan MA, Langhammer A (2017) A simple algorithm for the identification of clinical COPD phenotypes. Eur Respir J 50(5):1701034 CrossRef Burgel P-R, Paillasseur J-L, Janssens W, Piquet J, Ter Riet G, Garcia-Aymerich J, Cosio B, Bakke P, Puhan MA, Langhammer A (2017) A simple algorithm for the identification of clinical COPD phenotypes. Eur Respir J 50(5):1701034 CrossRef
12.
Zurück zum Zitat Nakayama H, Kobayashi M, Tsuiki S, Yanagihara M, Inoue Y (2019) Obstructive sleep apnea phenotypes in men based on characteristics of respiratory events during polysomnography. Sleep and Breathing 23(4):1087–1094 1–8 CrossRef Nakayama H, Kobayashi M, Tsuiki S, Yanagihara M, Inoue Y (2019) Obstructive sleep apnea phenotypes in men based on characteristics of respiratory events during polysomnography. Sleep and Breathing 23(4):1087–1094 1–8 CrossRef
13.
Zurück zum Zitat An H-J, Baek S-H, Kim S-W, Kim S-J, Park Y-G (2019) Clustering-based characterization of clinical phenotypes in obstructive sleep apnoea using severity, obesity, and craniofacial pattern. Eur J Orthod 42(1):93–100 An H-J, Baek S-H, Kim S-W, Kim S-J, Park Y-G (2019) Clustering-based characterization of clinical phenotypes in obstructive sleep apnoea using severity, obesity, and craniofacial pattern. Eur J Orthod 42(1):93–100
14.
Zurück zum Zitat Berry RB, Brooks R, Gamaldo CE, Harding SM, Marcus C, Vaughn BV (2012) The AASM manual for the scoring of sleep and associated events. Rules, terminology and technical specifications. American Academy of Sleep Medicine, Darien, p 176 Berry RB, Brooks R, Gamaldo CE, Harding SM, Marcus C, Vaughn BV (2012) The AASM manual for the scoring of sleep and associated events. Rules, terminology and technical specifications. American Academy of Sleep Medicine, Darien, p 176
15.
Zurück zum Zitat Joosten SA, Leong P, Landry SA, Sands SA, Terrill PI, Mann D, Turton A, Rangaswamy J, Andara C, Burgess G (2017) Loop gain predicts the response to upper airway surgery in patients with obstructive sleep apnea. Sleep 40(7):zsx094 CrossRef Joosten SA, Leong P, Landry SA, Sands SA, Terrill PI, Mann D, Turton A, Rangaswamy J, Andara C, Burgess G (2017) Loop gain predicts the response to upper airway surgery in patients with obstructive sleep apnea. Sleep 40(7):zsx094 CrossRef
16.
Zurück zum Zitat Cho YW, Lee JH, Son HK, Lee SH, Shin C, Johns MW (2011) The reliability and validity of the Korean version of the Epworth sleepiness scale. Sleep and Breathing 15(3):377–384 CrossRef Cho YW, Lee JH, Son HK, Lee SH, Shin C, Johns MW (2011) The reliability and validity of the Korean version of the Epworth sleepiness scale. Sleep and Breathing 15(3):377–384 CrossRef
17.
Zurück zum Zitat Dahlberg G (1940) Statistical methods for medical and biological students. Br Med J 2(4158):358–359 Dahlberg G (1940) Statistical methods for medical and biological students. Br Med J 2(4158):358–359
18.
Zurück zum Zitat Kim J, Keenan BT, Lim DC, Lee SK, Pack AI, Shin C (2018) Symptom-based subgroups of Koreans with obstructive sleep apnea. J Clin Sleep Med 14(03):437–443 CrossRef Kim J, Keenan BT, Lim DC, Lee SK, Pack AI, Shin C (2018) Symptom-based subgroups of Koreans with obstructive sleep apnea. J Clin Sleep Med 14(03):437–443 CrossRef
19.
Zurück zum Zitat Eckert DJ, White DP, Jordan AS, Malhotra A, Wellman A (2013) Defining phenotypic causes of obstructive sleep apnea. Identification of novel therapeutic targets. Am J Respir Crit Care Med 188(8):996–1004 CrossRef Eckert DJ, White DP, Jordan AS, Malhotra A, Wellman A (2013) Defining phenotypic causes of obstructive sleep apnea. Identification of novel therapeutic targets. Am J Respir Crit Care Med 188(8):996–1004 CrossRef
20.
Zurück zum Zitat Zinchuk A, Edwards BA, Jeon S, Koo BB, Concato J, Sands S, Wellman A, Yaggi HK (2018) Prevalence, associated clinical features, and impact on continuous positive airway pressure use of a low respiratory arousal threshold among male United States veterans with obstructive sleep apnea. J Clin Sleep Med 14(05):809–817 CrossRef Zinchuk A, Edwards BA, Jeon S, Koo BB, Concato J, Sands S, Wellman A, Yaggi HK (2018) Prevalence, associated clinical features, and impact on continuous positive airway pressure use of a low respiratory arousal threshold among male United States veterans with obstructive sleep apnea. J Clin Sleep Med 14(05):809–817 CrossRef
21.
Zurück zum Zitat Sands SA, Edwards BA, Terrill PI, Taranto-Montemurro L, Azarbarzin A, Marques M, Hess LB, White DP, Wellman AJ (2018) Phenotyping pharyngeal pathophysiology using polysomnography in patients with obstructive sleep apnea. Am J Respir Crit Care Med 197(9):1187–1197 CrossRef Sands SA, Edwards BA, Terrill PI, Taranto-Montemurro L, Azarbarzin A, Marques M, Hess LB, White DP, Wellman AJ (2018) Phenotyping pharyngeal pathophysiology using polysomnography in patients with obstructive sleep apnea. Am J Respir Crit Care Med 197(9):1187–1197 CrossRef
22.
Zurück zum Zitat Sforza E, Petiau C, Weiss T, Thibault A, Krieger JJ (1999) Pharyngeal critical pressure in patients with obstructive sleep apnea syndrome: clinical implications. Am J Respir Crit Care Med 159(1):149–157 CrossRef Sforza E, Petiau C, Weiss T, Thibault A, Krieger JJ (1999) Pharyngeal critical pressure in patients with obstructive sleep apnea syndrome: clinical implications. Am J Respir Crit Care Med 159(1):149–157 CrossRef
23.
Zurück zum Zitat Lee RW, Vasudavan S, Hui DS, Prvan T, Petocz P, Darendeliler MA, Cistulli PA (2010) Differences in craniofacial structures and obesity in Caucasian and Chinese patients with obstructive sleep apnea. Sleep 33(8):1075–1080 CrossRef Lee RW, Vasudavan S, Hui DS, Prvan T, Petocz P, Darendeliler MA, Cistulli PA (2010) Differences in craniofacial structures and obesity in Caucasian and Chinese patients with obstructive sleep apnea. Sleep 33(8):1075–1080 CrossRef
24.
Zurück zum Zitat Sutherland K, Keenan BT, Bittencourt L, Chen N-H, Gislason T, Leinwand S, Magalang UJ, Maislin G, Mazzotti DR, McArdle N (2019) A global comparison of anatomic risk factors and their relationship to obstructive sleep apnea severity in clinical samples. J Clin Sleep Med 15(04):629–639 CrossRef Sutherland K, Keenan BT, Bittencourt L, Chen N-H, Gislason T, Leinwand S, Magalang UJ, Maislin G, Mazzotti DR, McArdle N (2019) A global comparison of anatomic risk factors and their relationship to obstructive sleep apnea severity in clinical samples. J Clin Sleep Med 15(04):629–639 CrossRef
25.
Zurück zum Zitat Edwards BA, Wellman A, Sands SA, Owens RL, Eckert DJ, White DP, Malhotra A (2014) Obstructive sleep apnea in older adults is a distinctly different physiological phenotype. Sleep 37(7):1227–1236A CrossRef Edwards BA, Wellman A, Sands SA, Owens RL, Eckert DJ, White DP, Malhotra A (2014) Obstructive sleep apnea in older adults is a distinctly different physiological phenotype. Sleep 37(7):1227–1236A CrossRef
26.
Zurück zum Zitat Ferguson KA, Ono T, Lowe AA, Ryan CF, Fleetham JA (1995) The relationship between obesity and craniofacial structure in obstructive sleep apnea. Chest 108(2):375–381 CrossRef Ferguson KA, Ono T, Lowe AA, Ryan CF, Fleetham JA (1995) The relationship between obesity and craniofacial structure in obstructive sleep apnea. Chest 108(2):375–381 CrossRef
27.
Zurück zum Zitat Chi L, Comyn F-L, Mitra N, Reilly MP, Wan F, Maislin G, Chmiewski L, Thorne-FitzGerald MD, Victor UN, Pack AI (2011) Identification of craniofacial risk factors for obstructive sleep apnoea using three-dimensional MRI. Eur Respir J 38(2):348–358 CrossRef Chi L, Comyn F-L, Mitra N, Reilly MP, Wan F, Maislin G, Chmiewski L, Thorne-FitzGerald MD, Victor UN, Pack AI (2011) Identification of craniofacial risk factors for obstructive sleep apnoea using three-dimensional MRI. Eur Respir J 38(2):348–358 CrossRef
Metadaten
Titel
Multi-perspective clustering of obstructive sleep apnea towards precision therapeutic decision including craniofacial intervention
verfasst von
Su-Jung Kim
Waleed Maqbul Alnakhli
Ali Saeed Alfaraj
Kyung-A Kim
Sung-Wan Kim
Stanley Yung-Chuan Liu
Publikationsdatum
27.03.2020
Verlag
Springer International Publishing
Erschienen in
Sleep and Breathing / Ausgabe 1/2021
Print ISSN: 1520-9512
Elektronische ISSN: 1522-1709
DOI
https://doi.org/10.1007/s11325-020-02062-9

Weitere Artikel der Ausgabe 1/2021

Sleep and Breathing 1/2021 Zur Ausgabe

Update Innere Medizin

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert – ganz bequem per eMail.