Personal ViewPrecision medicine in obstructive sleep apnoea
Introduction
Precision medicine is defined as treatment targeted to the needs of individual patients on the basis of genetic, biomarker, phenotypic, or psychosocial characteristics that distinguish a given patient from others with similar clinical presentations.1 This approach is most advanced in the field of cancer, in which molecular tumour markers are often used to guide individualised treatment.2 By contrast, precision medicine is seldom, if ever, applied to most chronic diseases, including obstructive sleep apnoea (OSA), a highly prevalent condition that is diagnosed on the basis of a simple set of clinical measures, including the Apnoea–Hypopnoea Index (AHI) and the subjective assessment of somnolence.3, 4 In patients with OSA, treatment primarily relies on weight loss interventions and the use of continuous positive airway pressure (CPAP), aimed at normalising the gas exchange abnormalities and sleep disruption that constitute the major pathophysiological processes underlying the systemic damage associated with OSA.5 The main results of the Sleep Apnoea Cardiovascular Endpoints (known as SAVE) trial, which is, to our knowledge, the largest trial in OSA, are an excellent example of the urgent need for precision medicine in the context of the disease. This need is particularly apparent when considering that the scarcity of any measurable or demonstrable cardiovascular benefits following OSA treatment might not be entirely explained by low CPAP adherence.6 A European expert working group met in 2016 to address the phenotypic heterogeneity of OSA and its consequences, advised against a common uniform approach to the patient, and instead advocated for development of novel multidimensional tools enabling precision medicine in OSA.3, 4
Implementing precision medicine in chronic diseases is not easy, as these disorders are complex (ie, they have many components with dynamic temporal interactions that are not linear) and heterogeneous (ie, not every one of these components is present in all patients at any given time).6, 7 In the past several years, various investigators have proposed a series of concepts to help transition the field of chronic airway diseases into precision medicine by identifying clinical and pathophysiological phenotype clusters8, endotypes,9 biomarkers,10 treatable traits,11 and by developing multipronged control dashboards (figure 1).13 As discussed in this Personal View, some of these elements could be adapted and incorporated into OSA diagnosis and treatment, and in so doing, we believe that the management of this disorder can effectively transition to precision medicine.
Section snippets
Terminology
Before discussing how to incorporate the various elements of precision medicine into OSA management, it is necessary to precisely define these components (figure 1). Most human diseases, including OSA, are the end-result of many dynamic and lifelong gene–environment interactions that are modulated by multilevel biological networks.14 In this context, the exposome is defined as the cumulative environmental exposures individuals encounter throughout life, whereas the genome is the genetic make-up
Moving OSA into precision medicine
Many of the previously described key concepts are not new to the field of OSA,15 but they have not yet been considered and integrated together as a combined strategy aimed at promoting precision medicine for the condition. A careful review of the available evidence from this perspective should also assist in identifying gaps in knowledge.3, 4
Conclusions
We propose that a treatable trait strategy in OSA can be implemented in practice by the use of control panel and clinical fingerprint tools, and that this approach can: help physicians understand the complexity and heterogeneity of OSA; facilitate the design of effective individualised management programmes via the identification of specific treatable traits present at a given timepoint in each individual patient; in comparison to current practice allow a simpler and better assessment of
References (78)
- et al.
Challenges in obstructive sleep apnoea
Lancet Respir Med
(2018) - et al.
Sleep apnea: types, mechanisms, and clinical cardiovascular consequences
J Am Coll Cardiol
(2017) - et al.
What does endotyping mean for treatment in chronic obstructive pulmonary disease?
Lancet
(2017) - et al.
The challenges of precision medicine in obstructive sleep apnea
Sleep Med Clin
(2016) Phenotypic approaches to obstructive sleep apnoea—new pathways for targeted therapy
Sleep Med Rev
(2018)- et al.
Positional patients (PP) and non positional patients (NPP) are two dominant phenotypes that should be included in the phenotypic approaches to obstructive sleep apnea
Sleep Med Rev
(2018) - et al.
Precision medicine in patients with resistant hypertension and obstructive sleep apnea. Blood pressure response to continuous positive airway pressure treatment
J Am Coll Cardiol
(2015) - et al.
Protective cardiovascular effect of sleep apnea severity in obesity hypoventilation syndrome
Chest
(2016) POINT: is the Apnea–Hypopnea Index the best way to quantify the severity of sleep-disordered breathing? Yes
Chest
(2016)- et al.
Occurrence of obstructive sleep apnea syndrome in patients with transient ischemic attack
J Stroke Cerebrovasc Dis
(2016)
Sleep, sleep apnea and atrial fibrillation: questions and answers
Sleep Med Rev
Obesity hypoventilation syndrome
Clin Chest Med
Sympathetic activation in resistant hypertension: theory and therapy
Semin Nephrol
Are automated blood pressure monitors comparable to ambulatory blood pressure monitors? A systematic review and meta-analysis
Can J Cardiol
Biomarkers of sleep apnea
Chest
Measurement properties of patient-reported outcome measures (PROMs) in adults with obstructive sleep apnea (OSA): a systematic review
Sleep Medicine Rev
A review of neurocognitive function and obstructive sleep apnea with or without daytime sleepiness
Sleep Med
Hypersomnolence and traffic safety
Sleep Med Clin
The effect of snoring and obstructive sleep apnea on the sleep quality of bed partners
Mayo Clin Proc
Sleep apnea is an independent correlate of erectile and sexual dysfunction
J Sex Med
Personalized management approach for OSA
Chest
Trajectories of emergent central sleep apnea during CPAP therapy
Chest
The role of big data in the management of sleep-disordered breathing
Sleep Med Clin
Uncertainty in the era of precision medicine
N Engl J Med
Molecular testing in lung cancer in the era of precision medicine
Transl Lung Cancer Res
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
CPAP for prevention of cardiovascular events in obstructive sleep apnea
N Engl J Med
The path to personalised medicine in COPD
Thorax
Chronic obstructive pulmonary disease phenotypes: the future of COPD
Am J Respir Crit Care Med
Biomarkers, the control panel and personalized COPD medicine
Respirology
Treatable traits: toward precision medicine of chronic airway diseases
Eur Respir J
Precision medicine in airway diseases: moving to clinical practice
Eur Respir J
The COPD control panel: towards personalised medicine in COPD
Thorax
Multi-level differential network analysis of COPD exacerbations
Eur Respir J
Quantifying the ventilatory control contribution to sleep apnoea using polysomnography
Eur Respir J
Clinical predictors of the respiratory arousal threshold in patients with obstructive sleep apnea
Am J Respir Crit Care Med
Defining phenotypic causes of obstructive sleep apnea. Identification of novel therapeutic targets
Am J Respir Crit Care Med
Polysomnographic phenotypes and their cardiovascular implications in obstructive sleep apnoea
Thorax
Incorporating polysomnography into obstructive sleep apnoea phenotyping: moving towards personalised medicine for OSA
Thorax
Cited by (84)
Upper airway assessment in obstructive sleep apnea patients: can computed tomography with lateral cephalometry replace drug-induced sleep endoscopy (DISE)?
2023, Acta Otorrinolaringologica EspanolaThe Development of New Interventional Clinical Trials on Obstructive Sleep Apnoea: Targeting the Outcome, Endotype and Trial Design
2023, Archivos de BronconeumologiaProteomic profiling for prediction of recurrent cardiovascular event in patients with acute coronary syndrome and obstructive sleep apnea: A post-hoc analysis from the ISAACC study
2023, Biomedicine and PharmacotherapyCitation Excerpt :OSA is caused by the appearance of repeated episodes of obstructive apneas and hypopneas that occur during sleep. OSA imposes important pathophysiological consequences that lead to impaired quality of life, increased traffic and occupational accidents, depression, cognitive impairment, cardiovascular and metabolic diseases and, more recently, cancer [2–5]. Epidemiological and clinical data, together with basic research support that OSA has a role in the initiation or progression of several cardiovascular diseases (CVDs) [6].
Future directions
2023, Snoring and Obstructive Sleep Apnea in ChildrenSustained periorbital edema following Mohs micrographic surgery in the setting of continuous positive airway pressure
2022, JAAD Case ReportsCitation Excerpt :Obstructive sleep apnea (OSA) is a common breathing disorder affecting 5% to 7% of the population and is associated with increasing age, obesity, and male gender.1-3