Phenotypic approaches to obstructive sleep apnoea - New pathways for targeted therapy

Abstract

People develop obstructive sleep apnoea (OSA) for different reasons. The ability to understand these reasons, easily identify them in individual patients, and develop therapies that target one or more of these reasons are the keys to unlocking new approaches for the treatment of OSA. In line with this approach, recent advances in OSA pathogenesis using upper airway and respiratory phenotyping techniques have identified four key causes of OSA. A narrow or collapsible upper airway ('impaired anatomy') is the primary cause. However, the anatomical contribution to OSA varies substantially. Indeed, impairment in pharyngeal anatomy can be modest and in many patients (∼20%), pharyngeal collapsibility asleep is not different to people without OSA. Thus, non-anatomical factors or 'phenotypes' that modulate pharyngeal patency are crucial determinants of OSA for many people. These include impairment in pharyngeal dilator muscle control and function during sleep, increased propensity for awakening during airway narrowing (low respiratory arousal threshold) and respiratory control instability (high loop gain). Each phenotype is a potential therapeutic target. This review summarises the recent advances in the understanding of OSA pathogenesis according to a phenotypic approach, emerging tools to identify the phenotypes, and potential new therapeutic pathways and interventions to treat this common disorder.

Keywords: Arousal; Lung; Pathophysiology; Personalised medicine; Precision medicine; Respiratory control; Sleep-disordered breathing; Treatment; Upper airway muscles; Upper airway physiology.