Personal View
Precision medicine in obstructive sleep apnoea

https://doi.org/10.1016/S2213-2600(19)30044-XGet rights and content

Summary

Obstructive sleep apnoea (OSA) is a heterogeneous and complex disease; however, diagnosis and management still rely on a simple set of tools and few therapeutic options. Precision medicine has emerged as the next goal for clinical practice, with the objective being to offer individually tailored treatments. Ways of implementing precision medicine in clinical practice have emerged for various respiratory disorders, and such an approach could also be readily exported to OSA. Here, we propose a control panel tool that describes OSA in four domains: disease severity, biological activity, impact on the patient, and pathophysiological traits. We also propose a graphical instrument, the clinical fingerprint tool, to enable the tracking of patients over time. These tools can address the complexity of OSA and guide a physician's course of action on the basis of the treatable traits of an individual patient, thereby facilitating clinical implementation of precision medicine in the disorder.

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

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