Download PDF
Semin Respir Crit Care Med
DOI: 10.1055/a-2591-5502
Review Article

Precision Medicine to Guide Obstructive Sleep Apnea Treatment Beyond the Continuous Positive Airway Pressure

Gonzalo Labarca
1   Department of Respiratory Diseases, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile
2   Division of Pulmonary, Allergy, and Sleep Medicine, Mayo Clinic, Jacksonville, Florida
,
Mario Henríquez-Beltrán
3   Translational Research in Respiratory Medicine, Hospital Universitari Arnau de Vilanova-Santa Maria, Biomedical Research Institute of Lleida (IRBLleida), Lleida, Spain
4   CIBER of Respiratory Diseases (CIBERES), Institute of Health Carlos III, Madrid, Spain
5   Núcleo de Investigación en Ciencias de la Salud, Universidad Adventista de Chile, Chillán, Chile
6   Escuela de Kinesiología, Facultad de Salud, Universidad Santo Tomás, Chile
,
Daniel Solomons
1   Department of Respiratory Diseases, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile
› Author Affiliations
Funding There was no specific funding for the current investigation. G.L. declares grant support from the National Institute of Health and the American Academy of Sleep Medicine, The Chest Foundation; The Sleep Research Society, The ResMed Foundation, and Agencia Nacional de Investigacion y Desarrollo (ANID, Chile, Fondecyt# 11240972).
› Further Information
   Permissions and Reprints

Abstract

Obstructive sleep apnea (OSA) is a widespread condition associated with an elevated risk of adverse outcomes. Continuous positive airway pressure (CPAP) is the gold standard treatment, particularly for moderate to severe OSA. However, in many instances, CPAP compliance falls short of expectations, necessitating physicians to consider additional interventions to alleviate patient symptoms. A comprehensive understanding of OSA endotypes and phenotypes can potentially enhance the confidence in selecting the appropriate combination or intervention to improve patient care. In this review, we will discuss various interventions and medications available to enhance the treatment of patients with OSA, following a precision medicine approach.

Keywords

sleep apnea - obstructive - precision medicine - OSA - sleep disorder breathing

Authors' Contributions

Study design: L.M., G.L., and M.H. Data abstraction and collection: D.S., G.L., and M.H. Initial draft: all authors. Review of the manuscript for important intellectual content: L.M., G.L., and M.H. All authors have seen and approved the manuscript.




Publication History

Article published online:
23 May 2025

© 2025. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

 

  • References

  • 1 Qaseem A, Holty JE, Owens DK, Dallas P, Starkey M, Shekelle P. Clinical Guidelines Committee of the American College of Physicians. Management of obstructive sleep apnea in adults: a clinical practice guideline from the American College of Physicians. Ann Intern Med 2013; 159 (07) 471-483
    PubMedSearch in Google Scholar
  • 2 Martinez-Garcia MA, Campos-Rodriguez F, Barbé F, Gozal D, Agustí A. Precision medicine in obstructive sleep apnoea. Lancet Respir Med 2019; 7 (05) 456-464
    CrossrefPubMedSearch in Google Scholar
  • 3 Labarca G, Dreyse J, Drake L, Jorquera J, Barbe F. Efficacy of continuous positive airway pressure (CPAP) in the prevention of cardiovascular events in patients with obstructive sleep apnea: systematic review and meta-analysis. Sleep Med Rev 2020; 52: 101312
    PubMedSearch in Google Scholar
  • 4 Malhotra A, Ayappa I, Ayas N. et al. Metrics of sleep apnea severity: beyond the apnea-hypopnea index. Sleep 2021; 44 (07) zsab030
    CrossrefPubMedSearch in Google Scholar
  • 5 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 (07) 911-922
    PubMedSearch in Google Scholar
  • 6 Ye L, Pien GW, Ratcliffe SJ. et al. The different clinical faces of obstructive sleep apnoea: a cluster analysis. Eur Respir J 2014; 44 (06) 1600-1607
    CrossrefPubMedSearch in Google Scholar
  • 7 Labarca G, Dreyse J, Salas C, Letelier F, Jorquera J. A validation study of four different cluster analyses of OSA and the incidence of cardiovascular mortality in a Hispanic population. Chest 2021; 160 (06) 2266-2274
    CrossrefPubMedSearch in Google Scholar
  • 8 Mazzotti DR, Keenan BT, Lim DC, Gottlieb DJ, Kim J, Pack AI. Symptom subtypes of obstructive sleep apnea predict incidence of cardiovascular outcomes. Am J Respir Crit Care Med 2019; 200 (04) 493-506
    CrossrefPubMedSearch in Google Scholar
  • 9 Allen AH, Beaudin AE, Fox N. et al. Symptom subtypes and cognitive function in a clinic-based OSA cohort: a multi-centre Canadian study. Sleep Med 2020; 74: 92-98
    PubMedSearch in Google Scholar
  • 10 Keenan BT, Kim J, Singh B. et al. Recognizable clinical subtypes of obstructive sleep apnea across international sleep centers: a cluster analysis. Sleep 2018; 41 (03) zsx214
    PubMedSearch in Google Scholar
  • 11 Thorarinsdottir EH, Pack AI, Gislason T. et al. Polysomnographic characteristics of excessive daytime sleepiness phenotypes in obstructive sleep apnea: results from the international sleep apnea global interdisciplinary consortium. Sleep 2024; 47 (04) zsae035
    PubMedSearch in Google Scholar
  • 12 Li Z, Cai S, Wang J, Chen R. Predictors of the efficacy for daytime sleepiness in patients with obstructive sleep apnea with continual positive airway pressure therapy: a meta-analysis of randomized controlled trials. Front Neurol 2022; 13: 911996
    PubMedSearch in Google Scholar
  • 13 Neshat SS, Heidari A, Henriquez-Beltran M. et al. Evaluating pharmacological treatments for excessive daytime sleepiness in obstructive sleep apnea: a comprehensive network meta-analysis and systematic review. Sleep Med Rev 2024; 76: 101934
    PubMedSearch in Google Scholar
  • 14 Labarca G, Singh B. Pitolisant: a game changer for managing sleepiness in OSA?. Chest 2024; 165 (03) 486-487
    PubMedSearch in Google Scholar
  • 15 Nassi TE, Oppersma E, Labarca G, Donker DW, Westover MB, Thomas RJ. Morphological prediction of CPAP associated acute respiratory instability. Ann Am Thorac Soc 2024; 22 (01) 138-149
    PubMedSearch in Google Scholar
  • 16 Pépin JL, Attali V, Caussé C. et al. Long-term efficacy and safety of pitolisant for residual sleepiness due to OSA. Chest 2024; 165 (03) 692-703
    PubMedSearch in Google Scholar
  • 17 Soreca I, Arnold N, Dombrovski AY. Bright light therapy for CPAP-resistant OSA symptoms. J Clin Sleep Med 2024; 20 (02) 211-219
    PubMedSearch in Google Scholar
  • 18 Martínez-García MA, Labarca G. Obstructive sleep apnea in women: scientific evidence is urgently needed. J Clin Sleep Med 2022; 18 (01) 1-2
    PubMedSearch in Google Scholar
  • 19 Schwarz EI, Schiza S. Sex differences in sleep and sleep-disordered breathing. Curr Opin Pulm Med 2024; 30 (06) 593-599
    PubMedSearch in Google Scholar
  • 20 Labarca G, Dreyse J, Salas C. et al. A clinic-based cluster analysis in patients with moderate-severe obstructive sleep apnea (OSA) in Chile. Sleep Med 2020; 73: 16-22
    CrossrefPubMedSearch in Google Scholar
  • 21 Sweetman A, Lack L, Catcheside PG. et al. Cognitive and behavioral therapy for insomnia increases the use of continuous positive airway pressure therapy in obstructive sleep apnea participants with comorbid insomnia: a randomized clinical trial. Sleep 2019; 42 (12) zsz178
    CrossrefPubMedSearch in Google Scholar
  • 22 Sweetman A, Lack L, McEvoy RD. et al. Bi-directional relationships between co-morbid insomnia and sleep apnea (COMISA). Sleep Med Rev 2021; 60: 101519
    CrossrefPubMedSearch in Google Scholar
  • 23 Messineo L, Sands SA, Labarca G. Hypnotics on obstructive sleep apnea severity and endotypes: a systematic review and meta-analysis. Am J Respir Crit Care Med 2024; 210 (12) 1461-1474
    PubMedSearch in Google Scholar
  • 24 Winkelman JW. Treating severe refractory and augmented restless legs syndrome. Chest 2022; 162 (03) 693-700
    PubMedSearch in Google Scholar
  • 25 Walters AS, LeBrocq C, Dhar A. et al; International Restless Legs Syndrome Study Group. Validation of the international restless legs syndrome study group rating scale for restless legs syndrome. Sleep Med 2003; 4 (02) 121-132
    CrossrefPubMedSearch in Google Scholar
  • 26 Sánchez-de-la-Torre M, Gracia-Lavedan E, Benitez ID. et al. Adherence to CPAP treatment and the risk of recurrent cardiovascular events: a meta-analysis. JAMA 2023; 330 (13) 1255-1265
    CrossrefPubMedSearch in Google Scholar
  • 27 Bailly S, Comte E, Malhotra A. et al. Impact of CPAP termination on permanent work disability in obstructive sleep apnea: a French nationwide Alaska database analysis. Ann Am Thorac Soc 2024; 21 (11) 1592-1599
    PubMedSearch in Google Scholar
  • 28 Labarca G, Schmidt A, Dreyse J, Jorquera J, Barbe F. Telemedicine interventions for CPAP adherence in obstructive sleep apnea patients: systematic review and meta-analysis. Sleep Med Rev 2021; 60: 101543
    PubMedSearch in Google Scholar
  • 29 Ellender CM, Samaranayake C, Reid N. et al. Randomized controlled trial on the efficacy of audio-visual health educational materials on CPAP adherence: the AHEAD trial. J Clin Sleep Med 2022; 18 (11) 2617-2625
    PubMedSearch in Google Scholar
  • 30 Schoebel C, Woehrle H, Ficker JH. et al. Effects of mask change/renewal on adherence to positive airway pressure therapy: analysis of a large telemedicine database. Ann Am Thorac Soc 2024
    PubMedSearch in Google Scholar
  • 31 Hudgel DW, Patel SR, Ahasic AM. et al; American Thoracic Society Assembly on Sleep and Respiratory Neurobiology. The role of weight management in the treatment of adult obstructive sleep apnea. an official American Thoracic Society clinical practice guideline. Am J Respir Crit Care Med 2018; 198 (06) e70-e87
    CrossrefPubMedSearch in Google Scholar
  • 32 Malhotra A, Heilmann CR, Banerjee KK, Dunn JP, Bunck MC, Bednarik J. Weight reduction and the impact on apnea-hypopnea index: a systematic meta-analysis. Sleep Med 2024; 121: 26-31
    PubMedSearch in Google Scholar
  • 33 Carneiro-Barrera A, Amaro-Gahete FJ, Guillén-Riquelme A. et al. Effect of an interdisciplinary weight loss and lifestyle intervention on obstructive sleep apnea severity: the INTERAPNEA randomized clinical trial. JAMA Netw Open 2022; 5 (04) e228212
    PubMedSearch in Google Scholar
  • 34 Sands SA, Alex RM, Mann D. et al. Pathophysiology underlying demographic and obesity determinants of sleep apnea severity. Ann Am Thorac Soc 2023; 20 (03) 440-449
    PubMedSearch in Google Scholar
  • 35 Malhotra A, Grunstein RR, Fietze I. et al; SURMOUNT-OSA Investigators. Tirzepatide for the treatment of obstructive sleep apnea and obesity. N Engl J Med 2024; 391 (13) 1193-1205
    CrossrefPubMedSearch in Google Scholar
  • 36 Labarca G. Novel markers of nocturnal hypoxemia in sleep apnea and heart failure with reduced ejection fraction (HFrEF). Am Heart J 2024; 280: 101-103
    PubMedSearch in Google Scholar
  • 37 Javaheri S, Brown LK, Abraham WT, Khayat R. Apneas of heart failure and phenotype-guided treatments: part one: OSA. Chest 2020; 157 (02) 394-402
    PubMedSearch in Google Scholar
  • 38 Phyu SL, Ercan S, Harriss E, Turnbull C. Nocturnal oxygen therapy in obstructive sleep apnoea: a systematic review and meta-analysis. Eur Respir Rev 2024; 33 (171) 230173
    PubMedSearch in Google Scholar
  • 39 Ni YN, Thomas RJ. Acetazolamide for residual apnea and periodic breathing on continuous positive airway pressure therapy. Sleep Med 2020; 71: 52-53
    PubMedSearch in Google Scholar
  • 40 Eskandari D, Zou D, Karimi M, Stenlöf K, Grote L, Hedner J. Zonisamide reduces obstructive sleep apnoea: a randomised placebo-controlled study. Eur Respir J 2014; 44 (01) 140-149
    PubMedSearch in Google Scholar
  • 41 Hoff E, Zou D, Schiza S. et al. Carbonic anhydrase, obstructive sleep apnea and hypertension: effects of intervention. J Sleep Res 2020; 29 (02) e12956
    PubMedSearch in Google Scholar
  • 42 Quinn T, Thomas RJ, Heckman E. Enhanced expiratory rebreathing space for high loop gain sleep apnea treatment. Front Sleep 2023 2. https://doi.org/10.3389/frsle.2023.1248371
    CrossrefPubMedSearch in Google Scholar
  • 43 Correa EJ, Conti DM, Moreno-Luna R, Sánchez-Gómez S, O'Connor Reina C. Role of nasal surgery in adult obstructive sleep apnea: a systematic review. Sleep Sci 2024; 17 (03) e310-e321
    PubMedSearch in Google Scholar
  • 44 Camacho M, Malu OO, Kram YA. et al. Nasal dilators (breathe right strips and NoZovent) for snoring and OSA: a systematic review and meta-analysis. Pulm Med 2016; 2016: 4841310
    CrossrefPubMedSearch in Google Scholar
  • 45 Labarca G, Sands SA, Cohn V. et al. Mouth closing to improve the efficacy of mandibular advancement devices in sleep apnea. Ann Am Thorac Soc 2022; 19 (07) 1185-1192
    PubMedSearch in Google Scholar
  • 46 Law M, Villar S, Oscroft N. et al. Continuous positive airway pressure plus mandibular advancement therapy (PAPMAT): study protocol for an adaptive randomised crossover trial comparing the benefits and costs of combining two established treatments for obstructive sleep apnoea. Trials 2023; 24 (01) 474
    PubMedSearch in Google Scholar
  • 47 Saboisky JP, Stashuk DW, Hamilton-Wright A, Trinder J, Nandedkar S, Malhotra A. Effects of aging on genioglossus motor units in humans. PLoS One 2014; 9 (08) e104572
    PubMedSearch in Google Scholar
  • 48 Saba ES, Kim H, Huynh P, Jiang N. Orofacial myofunctional therapy for obstructive sleep apnea: a systematic review and meta-analysis. Laryngoscope 2024; 134 (01) 480-495
    PubMedSearch in Google Scholar
  • 49 Ulualp SO, Kezirian EJ. Advanced diagnostic techniques in obstructive sleep apnea. Otolaryngol Clin North Am 2024;
    CrossrefPubMedSearch in Google Scholar
  • 50 Wray CM, Thaler ER. Hypoglossal nerve stimulation for obstructive sleep apnea: a review of the literature. World J Otorhinolaryngol Head Neck Surg 2016; 2 (04) 230-233
    PubMedSearch in Google Scholar
  • 51 Lorenzi-Filho G, Almeida FR, Strollo PJ. Treating OSA: Current and emerging therapies beyond CPAP. Respirology 2017; 22 (08) 1500-1507
    CrossrefPubMedSearch in Google Scholar
  • 52 Schwartz AR, Jacobowitz O, Eisele DW. et al. Targeted hypoglossal nerve stimulation for patients with obstructive sleep apnea: a randomized clinical trial. JAMA Otolaryngol Head Neck Surg 2023; 149 (06) 512-520
    PubMedSearch in Google Scholar
  • 53 Choi JH, Cho SH, Kim SN, Suh JD, Cho JH. Predicting outcomes after uvulopalatopharyngoplasty for adult obstructive sleep apnea: a meta-analysis. Otolaryngol Head Neck Surg 2016; 155 (06) 904-913
    PubMedSearch in Google Scholar
  • 54 MacKay S, Carney AS, Catcheside PG. et al. Effect of multilevel upper airway surgery vs medical management on the apnea-hypopnea index and patient-reported daytime sleepiness among patients with moderate or severe obstructive sleep apnea: the SAMS randomized clinical trial. JAMA 2020; 324 (12) 1168-1179
    PubMedSearch in Google Scholar
  • 55 de Vries GE, Hoekema A, Doff MH. et al. Usage of positional therapy in adults with obstructive sleep apnea. J Clin Sleep Med 2015; 11 (02) 131-137
    PubMedSearch in Google Scholar
  • 56 Rahimi MM, Vakulin A, McEvoy RD. et al. Comparative effectiveness of supine avoidance versus continuous positive airway pressure for treating supine-isolated sleep apnea: a clinical trial. Ann Am Thorac Soc 2024; 21 (02) 308-316
    PubMedSearch in Google Scholar