LAUSR

Obstructive sleep apnoea (OSA) is characterised by recurrent episodes of complete or partial obstruction of the upper airway during sleep. OSA syndrome (OSAS) is used when OSA is associated with symptoms such as excessive daytime sleepiness, anxiety and depression. OSAS is a common condition which is associated with several comorbidities. The prevalence of OSA and OSAS has increased globally over the past decade reflecting an increased prevalence of obesity. Currently, the mainstay of treatment for OSAS is continuous positive airway pressure (CPAP) applied via a nasal mask. CPAP therapy has a strong evidence base and has recently been endorsed in the UK by the National Institute of Clinical Excellence, yet it is seldom greeted by patients with enthusiasm and adherence rates in clinical practice remain suboptimal. Thus, there is great interest in alternative therapies for OSAS which entails understanding the underlying pathophysiology. Absent airflow, apnoea and the related phenomenon of reduced airflow (hypopnea) causing arousal and sleep fragmentation is the hallmark of OSAS, yet the mechanism underlying apnoea in OSA remains unclear. Clinically, obstructive events are defined as absent (or reduced) airflow combined with persistent respiratory muscle activity usually evidenced by rib cage or abdominal movements detected by effort bands. This approach is somewhat inaccurate because effort bands may fail to show movement despite inspiratory muscle activity being demonstrable as oesophageal pressure change or diaphragm electromyographic (EMG). Indeed, we have shown that up to 30% of apparently central events may be misclassified. Nevertheless, the presence of absent airflow and persistent respiratory muscle activity led to the conclusion that these events primarily occurred because of airway closure. However, data from Gell and coworkers suggest that while this is the case in a substantial minority of patients with OSA, in the majority (60%) of patients, apnoea occurs because of reduced neural drive. They were able to show this by applying innovative technology to more accurately measure inspiratory muscle activity by diaphragm EMG while simultaneously measuring in a quantitative fashion both the volume of air and the neural drive to a pharyngeal dilator muscle (genioglossus). The main findings of their study confirmed a classical OSA phenotype (ie, flow fell or was abolished and drive rose in an attempt to overcome obstruction) only in a minority of patients. More commonly, however, when flow fell, drive also fell suggesting that the primary abnormality was loss of neural drive to both the inspiratory muscles and pharyngeal dilators. This observation comes in contrast to current received wisdom but is consistent with our own prior study and other data highlighted by the Gell and coworkers including the successful use of neural stimulants (CO2 and acetazolamide) to treat OSA. It may also, at least partially, explain why inspiratory muscle fatigue is not a feature of OSA. Similarly, it also suggests an alternative explanation as to why agents (eg, alcohol, benzodiazepines) which suppress neural drive frequently worsen sleep apnoea—this would not be expected if the mechanism were simply gravitational induced collapse. A novel paradigm of course raises some questions; the authors suggest some possible solutions, but key questions include the following. First, why does CPAP (or other upper airway dilator therapies such as hypoglossal nerve stimulation) work in OSA if the issue is neural inspiratory drive? Here, the suggestion is that reduced neural drive to the dilators is offset by the increased airway patency conferred by CPAP and is then sufficient that reduced neural drive is still sufficient to maintain ventilation. This would be supported and, in keeping, with the load– capacity–drive relationship. Second, do we need to rethink upper airway resistance syndrome? Conventionally, increased respiratory effort is thought to cause arousal despite a patent airway; however, this calculation is conventionally based on recording of oesophageal pressure swings which are influenced by airflow and lung volume as highlighted by Gell and coauthors. Future studies need to enquire whether neural drive in upper airway resistance syndrome is genuinely increased if flow and inspiratory drive are accurately measured. Indeed, although we studied many patients with OSA and recorded both diaphragm EMG and oesophageal pressure during respiratory events, we seldom detected the increased diaphragm EMG that should be evident in the upper airway resistance syndrome. Third, the major pathophysiological change of OSA is arousal and sleep fragmentation contributes to daytime sleepiness. Since this does not clearly relate to hypoxia, it has been hypothesised that there is threshold of respiratory muscle effort which triggers arousal. This hypothesis is largely based on oesophageal pressure measurements and again this concept needs reevaluation using quantitative diaphragm EMG, since the current data suggest that in a majority, neural inspiratory drive actually decreases during apnoeic events. Consistent with this, we previously demonstrated that arousal actually is independent of neural respiratory drive based on the amplitude of the diaphragm EMG. In summary, therefore, Gell and colleagues provide important new data concerning the pathophysiology of apnoea; these insights may in time offer new therapeutic alternatives to CPAP.