NOTE: By submitting this form and registering with us, you are providing us with permission to store your personal data and the record of your registration. In addition, registration with the Medical Independent includes granting consent for the delivery of that additional professional content and targeted ads, and the cookies required to deliver same. View our Privacy Policy and Cookie Notice for further details.

You can opt out at anytime by visiting our cookie policy page. In line with the provisions of the GDPR, the provision of your personal data is a requirement necessary to enter into a contract. We must advise you at the point of collecting your personal data that it is a required field, and the consequences of not providing the personal data is that we cannot provide this service to you.


[profilepress-login id="1"]

Don't have an account? Subscribe

Moving towards personalised therapy for obstructive sleep apnoea

By Dermot - 14th Dec 2020

woman using cpap machine to stop choking and snoring from obstructive sleep apnea

Irish Thoracic Society, Annual Scientific Meeting, 3-4 December 2020

Prof Atul Malhotra from the University of California, San Diego, was a keynote speaker at the Irish Thoracic Society Annual Scientific Meeting 2020. He spoke about the need for personalised therapeutics in obstructive sleep apnoea (OSA), and informed the audience on the current research surrounding this field.

It is estimated that OSA affects approximately one billion people worldwide, and it has been related to increased risk for hypertension, diabetes and depression, even when asymptomatic. Currently, nasal continuous positive airway pressure (CPAP) is the “treatment of choice” for OSA. It has been transformative for some patients, where it has been demonstrated to improve symptoms and blood pressure.

However, Dr Malhotra argued new therapies based on ongoing research are necessary, as CPAP does not work for all OSA patients. Prof Malhotra told the audience that OSA can vary in clinical expression. Three clinical presentation clusters have been identified: Disturbed sleep, minimally symptomatic, and severe excessive daytime sleepiness.

It has been demonstrated that the OSA group suffering from severe excessive daytime sleepiness appear to be the most at risk for cardiovascular disease compared to the other groups. Prof Malhotra continued that it therefore “doesn’t make sense” to treat all OSA patients in the same way even in terms of related risk factors.

OSA also has a number of different causes. Prof Malhotra and his research team study the mechanisms that underpin this condition. At least five different mechanisms have been shown to cause OSA thus far, including anatomy, pharyngeal dilator muscle control during sleep, arousal threshold, loop gain, and lung volume.

Understanding these underlying causes “may help guide individualised therapy”, as the mechanism underlying OSA might affect disease expression or risk of complications. For example, anatomically driven OSA might be clinically expressed differently and have different consequences than ventilatory control driven OSA. Therefore understanding the underlying causes of OSA may guide therapeutic interventions.

Prof Malhotra then continued to provide a more detailed explanation on some of the different causes of OSA. The anatomy of some individuals with OSA results in a compromised velopharynx and retronasal airway when sleeping, which affects the airflow into the lungs. Surgery would perhaps be a good treatment for these patients.

Pharyngeal dilator muscle control during sleep is another cause of OSA found in some patients. The genioglossus, the largest upper airway dilator muscle, has been demonstrated to be required for stable breathing. Prof Malhotra and his research team demonstrated that low genioglossus activity results in repetitive apnoea, and that high genioglossus activity is sufficient to stabilise breathing spontaneously in OSA.

This knowledge provides a therapeutic target for OSA patients with an underactive genioglossus muscle, as the upper airway muscles can be activated by endogenous stimuli such as carbon dioxide if provided in sufficient magnitude and duration.

Application of this knowledge could prove useful to OSA patients resulting from an underactive genioglossus. In other cases, Prof Malhotra and his team believe that a low arousal threshold in some patients results in OSA. These individuals awaken just before the body naturally restores airflow. This low arousal threshold results in premature arousal with inadequate time to accumulate respiratory stimuli.

For these patients, increasing the arousal threshold would give the body sufficient time to restore airflow during stable sleep, and the patient would have a restful night. There are medications available that increase the arousal threshold. However, an arousal threshold that is too high could lead to substantial hypoxemia and hypercapnia with end-organ impact.

Therefore therapies to manipulate arousal threshold are likely to benefit some OSA patients and theoretically hurt others.

Another defined set of OSA patients have a high loop gain. Loop gain is a ratio of the ventilatory response to carbon dioxide, the blood gas response to a change in ventilation, and the speed of the feedback signal back to the controller. It is essentially a measurement of stability for the respiratory control system, and a high loop gain symbolises an unstable respiratory control system.

If an individual wakes up short of breath, it is usually due to a high loop gain. For these patients, therapies that reduce loop gain such as oxygen and acetazolamide would be beneficial.

Prof Malhotra concluded by highlighting the fact that OSA occurs for varying reasons, and that the mechanisms underlying this could be used to tailor therapeutic strategies. In order for this to happen however, new models and technologies will need to be embraced, and coordinated efforts will be required.

Leave a Reply

Latest
Latest Issue
The Medical Independent – 24 June 2021

You need to be logged in to access this content. Please login or sign up using the links below.

Most Read