Generic placeholder image

Current Respiratory Medicine Reviews


ISSN (Print): 1573-398X
ISSN (Online): 1875-6387

Review Article (Mini-Review)

Phenotypes of Obstructive Sleep Apnea and Direct Targeted Therapy: A Literature Review

Author(s): Shi Nee Tan* and Baharudin Abdullah

Volume 16 , Issue 2 , 2020

Page: [76 - 83] Pages: 8

DOI: 10.2174/1573398X16999201016095352

Price: $65


Obstructive sleep apnea (OSA) is a heterogenous chronic disorder causing hypoxemia, excessive daytime sleepiness, non-refreshing sleep, nocturia, morning headache, irritability, and memory loss. Cardiovascular disease, cognitive impairment, metabolic disorders, and depression are its long-term consequences. The difficulty in treating patients is due to poor compliance, failure to obtain the desired outcome, and complication arising from the multimodality treatment. Direct targeted therapy may overcome these issues. Identification of its phenotypes improves understanding of the disease mechanism, the risk for adverse effects, and predicting response to targeted therapy. Phenotyping of OSA allows treating patients according to their inherent disease and not based on a “one size fits all” method, which may not be applicable for all patients. This approach may improve patients’ compliance with treatment, minimize the associated morbidities, and consequently improve their quality of life.

Keywords: Obstructive sleep apnea, phenotypes, anatomy, polysomnography, continuous positive airway pressure, surgery.

Graphical Abstract
Heinzer R, Vat S, Marques-Vidal P, et al. Prevalence of sleep-disordered breathing in the general population: the HypnoLaus study. Lancet Respir Med 2015; 3(4): 310-8.
Subramani Y, Singh M, Wong J, Kushida CA, Malhotra A, Chung F. Understanding phenotypes of obstructive sleep apnea: applications in anesthesia, surgery, and perioperative medicine. Anesth Analg 2017; 124(1): 179-91.
Antic NA, Catcheside P, Buchan C, et al. The effect of CPAP in normalizing daytime sleepiness, quality of life, and neurocognitive function in patients with moderate to severe OSA. Sleep (Basel) 2011; 34(1): 111-9.
Walia HK, Li H, Rueschman M, et al. Association of severe obstructive sleep apnea and elevated blood pressure despite antihypertensive medication use. J Clin Sleep Med 2014; 10(8): 835-43.
Sateia MJ. International classification of sleep disorders-third edition: highlights and modifications. Chest 2014; 146(5): 1387-94.
Joosten SA, Hamza K, Sands S, Turton A, Berger P, Hamilton G. Phenotypes of patients with mild to moderate obstructive sleep apnoea as confirmed by cluster analysis. Respirology 2012; 17(1): 99-107.
Eckert DJ. Phenotypic approaches to obstructive sleep apnoea - New pathways for targeted therapy. Sleep Med Rev 2018; 37: 45-59.
Ye L, Pien GW, Ratcliffe SJ, et al. The different clinical faces of obstructive sleep apnoea: a cluster analysis. Eur Respir J 2014; 44(6): 1600-7.
Osman AM, Carter SG. Obstructive sleep apnea: current perspectives. Nat Sci Sleep 2018; 10: 21-34.
Gray EL, McKenzie DK, Eckert DJ. Obstructive sleep apnea without obesity is common and difficult to treat: evidence for a distinct pathophysiological phenotype. J Clin Sleep Med 2016.
Silvia Matarredona-Q. Andrea De V, Khai BC, Claudio V. Drug-induced sleep endoscopy: technique, indications, tips and pitfalls. Healthcare (Basel) 2019; 7(3): 93.
Op de Beeck S, Dieltjens M, Verbruggen AE, et al. Phenotypic labelling using drug-induced sleep endoscopy improves patient selection for mandibular advancement device outcome: a prospective study. J Clin Sleep Med 2019; 15(8): 1089-99.
Chirinos JA, Gurubhagavatula I, Teff K, et al. CPAP, weight loss, or both for obstructive sleep apnea. N Engl J Med 2014; 370(24): 2265-75.
Alberto RR, Pedro F, Shirin S, Alejandro DC, Alexandre RA, Salim ID. Carlos TDMW. Obstructive sleep apnea phenotypes and markers of vascular disease: a review. Front Neurol 2017; 5
Zinchuk AV, Gentry MJ, Concato J, Yaggi HK. Phenotypes in obstructive sleep apnea: a definition, examples and evolution of approaches. Sleep Med Rev 2017; 35: 113-23.
Bjorvatn B, Lehmann S, Gulati S, Aurlien H, Pallesen S, Saxvig IW. Prevalence of excessive sleepiness is higher whereas insomnia is lower with greater severity of obstructive sleep apnea. Sleep Breath 2015; 19(4): 1387-93.
Appleton SL, Gill TK, Lang CJ, et al. Prevalence and comorbidity of sleep conditions in Australian adults: 2016 Sleep Health Foundation national survey. Sleep Health 2018; 4(1): 13-9.
Tveit RL, Lehmann S, Bjorvatn B. Prevalence of several somatic diseases depends on the presence and severity of obstructive sleep apnea. PLoS One 2018; 13(2): e0192671.
Ruel G, Martin SA, Lévesque JF, et al. Association between multimorbidity and undiagnosed obstructive sleep apnea severity and their impact on quality of life in men over 40 years old. Glob Health Epidemiol Genom 2018; 3e10.
[] [PMID: 30263134]
Francesco DM, et al. The Epworth Sleepiness Scale. Chest 2013; 43(6): 1569-75.
Dudley KA, Patel SR. Disparities and genetic risk factors in obstructive sleep apnea. Sleep Med 2016; 18: 96-102.
Shao C, Qi H, Lang R, et al. Clinical features and contributing factors of excessive daytime sleepiness in Chinese obstructive sleep apnea patients: the role of comorbid symptoms and polysomnographic variables. Can Respir J 2019; 1: 1-10.
Chiang CL, Chen YT, Wang KL, et al. Comorbidities and risk of mortality in patients with sleep apnea. Ann Med 2017; 49(5): 377-83.
Riha RL, Gislasson T, Diefenbach K. The phenotype and genotype of adult obstructive sleep apnoea/hypopnoea syndrome. Eur Respir J 2009; 33(3): 646-55.
Carberry JC, Jordan AS, White DP, Wellman A, Eckert DJ. Upper airway collapsibility (Pcrit) and pharyngeal dilator muscle activity are sleep stage dependent. Sleep (Basel) 2016; 39(3): 511-21.
Ha J-G, Lee Y, Nam JS, et al. Can drug-induced sleep endoscopy improve the success rates of tongue base surgery? J Otolaryngol Head Neck Surg 2020; 49(1): 8.
Eckert DJ, Malhotra A, Lo YL, White DP, Jordan AS. The influence of obstructive sleep apnea and gender on genioglossus activity during rapid eye movement sleep. Chest 2009; 135(4): 957-64.
Kubin L. Neural control of the upper airway: respiratory and state dependent mechanisms. Compr Physiol 2016; 6(4): 1801-50.
Brown EC, Cheng S, McKenzie DK, Butler JE, Gandevia SC, Bilston LE. Respiratory movement of upper airway tissue in obstructive sleep apnea. Sleep (Basel) 2013; 36(7): 1069-76.
Dotan Y, Pillar G, Schwartz AR, Oliven A. Asynchrony of lingual muscle recruitment during sleep in obstructive sleep apnea. J Appl Physiol 2015; 118(12): 1516-24.
Eckert DJ, White DP, Jordan AS, Malhotra A, Wellman A. Defining phenotypic causes of obstructive sleep apnea. Identification of novel therapeutic targets. Am J Respir Crit Care Med 2013; 188(8): 996-1004.
Edwards BA, Eckert DJ, McSharry DG, et al. Clinical predictors of the respiratory arousal threshold in patients with obstructive sleep apnea. Am J Respir Crit Care Med 2014; 190(11): 1293-300.
Gray EL, McKenzie DK, Eckert DJ. Obstructive sleep apnea without obesity is common and difficult to treat: evidence for a distinct pathophysiological phenotype. J Clin Sleep Med 2017; 13(1): 81-8.
Mateika JH, Panza G, Alex R, El-Chami M. The impact of intermittent or sustained carbon dioxide on intermittent hypoxia initiated respiratory plasticity. What is the effect of these combined stimuli on apnea severity? Respir Physiol Neurobiol 2018; 256: 58-66.
Kastoer C, Op de Beeck S, Dom M, et al. Drug-induced sleep endoscopy upper airway collapse patterns and maxillomandibular advancement. Laryngoscope 2020; 130(4): E268-74.
Edwards BA, Andara C, Landry S, et al. Upper-airway collapsibility and loop gain predict the response to oral appliance therapy in patients with obstructive sleep apnea. Am J Respir Crit Care Med 2016; 194(11): 1413-22.
Ustun B, Westover MB, Rudin C, Bianchi MT. Clinical prediction models for sleep apnea: the importance of medical history over symptoms. J Clin Sleep Med 2016; 12(2): 161-8.
Randerath W, Bassetti CL, Bonsignore MR, et al. Challenges and perspectives in obstructive sleep apnoea: Report by an ad hoc working group of the sleep disordered breathing group of the European Respiratory Society and the European Sleep Research Society. Eur Respir J 2018; 52(3): 1702616.
Cade BE, Chen H, Stilp AM, et al. Genetic associations with obstructive sleep apnea traits in Hispanic/Latino Americans. Am J Respir Crit Care Med 2016; 194(7): 886-97.
Zinchuk A, Yaggi HK. Phenotypic subtypes of OSA: a challenge and opportunity for precision medicine. Chest 2020; 157(2): 403-20.
Billings ME, Rosen CL, Auckley D, et al. Psychometric performance and responsiveness of the functional outcomes of sleep questionnaire and sleep apnea quality of life instrument in a randomized trial: the HomePAP study. Sleep (Basel) 2014; 37(12): 2017-24.
Edwards BA, Redline S, Sands SA, Owens RL. More than the sum of the respiratory events: personalized medicine approaches for obstructive sleep apnea. Am J Respir Crit Care Med 2019; 200(6): 691-703.
Gottlieb DJ, Punjabi NM, Mehra R, et al. CPAP versus oxygen in obstructive sleep apnea. N Engl J Med 2014; 370(24): 2276-85.
McEvoy RD, Antic NA, Heeley E, et al. SAVE investigators and coordinators. CPAP for prevention of cardiovascular events in obstructive sleep apnea. N Engl J Med 2016; 375(10): 919-31.
Wolfe BM, Kvach E, Eckel RH. Treatment of obesity: weight loss and bariatric surgery. Circ Res 2016; 118(11): 1844-55.
Taranto-Montemurro L, Edwards BA, Sands SA, et al. Desipramine increases genioglossus activity and reduces upper airway collapsibility during Non-REM sleep in healthy subjects. Am J Respir Crit Care Med 2016; 194(7): 878-85.
Taranto-Montemurro L, Sands SA, Edwards BA, et al. Desipramine improves upper airway collapsibility and reduces OSA severity in patients with minimal muscle compensation. Eur Respir J 2016; 48(5): 1340-50.
Horner RL, Grace KP, Wellman A. A resource of potential drug targets and strategic decision-making for obstructive sleep apnoea pharmacotherapy. Respirology 2017; 22(5): 861-73.
Taranto-Montemurro L, Messineo L, Wellman A. Targeting endotypic traits with medications for the pharmacological treatment of obstructive sleep apnea. A review of the current literature. J Clin Med 2019; 8(11): 1846.
Eskandari D, Zou D, Grote L, Hoff E, Hedner J. Acetazolamide reduces blood pressure and sleep-disordered breathing in patients with hypertension and obstructive sleep apnea: a randomized controlled trial. J Clin Sleep Med 2018; 14(3): 309-17.
Wellman A, Malhotra A, Jordan AS, Stevenson KE, Gautam S, White DP. Effect of oxygen in obstructive sleep apnea: role of loop gain. Respir Physiol Neurobiol 2008; 162(2): 144-51.
Edwards BA, Sands SA, Eckert DJ, et al. Acetazolamide improves loop gain but not the other physiological traits causing obstructive sleep apnoea. J Physiol 2012; 590(5): 1199-211.
Carberry JC, Fisher LP, Grunstein RR, et al. Role of common hypnotics on the phenotypic causes of OSA: paradoxical effects of zolpidem. Eur Respir J 2017; 50(6): 1701344.
Carberry JC, Amatoury J, Eckert DJ. Personalized management approach for OSA. Chest 2018.
Wellman A, Edwards BA, Sands SA, et al. A simplified method for determining phenotypic traits in patients with obstructive sleep apnea. J Appl Physiol 2013; 114(7): 911-22.

Rights & Permissions Print Export Cite as
© 2022 Bentham Science Publishers | Privacy Policy