Ludwig Engel Centre for Respiratory Research, Westmead Millennium Institute

Lab head: Kristina Kairaitis
Location: Department of Respiratory and Sleep Medicine, Westmead Hospital Westmead

Obstructive sleep apnoea (OSA) is characterised by recurrent nocturnal upper airway (UA) obstruction, airflow limitation and oxygen desaturation events. A low end-expiratory lung volume 
(EELV: the volume of gas remaining in the lung at the end of a tidal expiration), potentially arising as a consequence of obesity, supine posture and sleep, has been widely proposed as a key pathophysiological mechanism promoting increased UA collapsibility and nocturnal UA obstruction in OSA patients. The volume of the gas in the lung is also important in determining the severity of apnea related  oxygen desaturation, and may additionally influence the ability of the upper airway muscles to reopen the upper airway. Our recent published animal study suggests that the onset of upper airway closure occurs once there has been a threshold reduction in lung volume. We now propose to extend this work, and using both a well established animal model and human subjects with OSA we propose to test the following hypotheses:-
1.There is a critical EELV below which obstructive apnoeic events are likely to develop.
2. Low EELV levels promote more severe oxygen desaturation levels during apnoea.
3. Low EELV reduces UA dilator muscle fractional shortening for a given level of stimulus (input drive), reducing the ability of UA muscles to both dilate the UA lumen and lower its resistance to airflow.
4. In OSA patients, low EELV values during sleep are associated with more frequent and longer apnoeic events accompanied by more severe levels of oxygen desaturation.

Lab members: Assoc Prof Terence Amis Prof John Wheatley
Funding: None
Research approach equipment: Acute physiological studies in animal subjects Acute physiological studies in human subjects
Publications: Kairaitis K, Verma M, Fish V, Wheatley JR, and Amis TC. Pharyngeal muscle contraction modifies peri-pharyngeal tissue pressure in rabbits. Respir Physiol Neurobiol 166: 95-101, 2009. Kairaitis K, Verma M, Amatoury J, Wheatley JR, White DP, and Amis TC. A threshold lung volume for optimal mechanical effects on upper airway airflow dynamics: studies in an anesthetized rabbit model. J Appl Physiol 112: 1197-1205, 2012.

Pharyngeal wall folding:role in upper airway collapsibility

Primary supervisor: Kristina Kairaitis

Increased pharyngeal airway collapsibility, leading to upper airway narrowing and closure during sleep, is a defining patho-physiological characteristic of obstructive sleep apnoea (OSA), one of the most common chronic disorders occurring in middle-aged Australians. While the conditions under which the passive pharyngeal airway undergoes collapse during sleep have been extensively investigated, precise mechanisms by which pharyngeal lumen dimensions are reduced/olbliterated and the relationship between this mechanism and susceptibility to OSA, have both received little attention or analysis.

 

We will examine the following hypotheses:

1) Pharyngeal airway narrowing/collapse in humans occurs via pharyngeal wall folding.

2) Pharyngeal airway narrowing/collapse in patients with OSA is characterised by less folds than healthy subjects.

3) Pharyngeal wall folding behaviour can be modified and pharyngeal airway collapsibility is reduced when pharyngeal wall fold numbers are increased.

 

The AIMS of this project are:

1) establish the role played by pharyngeal wall folding in the process of pharyngeal lumen narrowing/collapse;

2) determine relationships between pharyngeal wall folding, pharyngeal airway collapsibility and OSA severity; and

3) investigate modification of pharyngeal wall folding processes as a potential therapy for OSA.

 

SIGNIFICANCE AND OUTCOME

This project will apply analytical techniques never previously deployed in upper airway physiology research to: 1) establish the role that pharyngeal wall folding plays in the process of upper airway collapse; 2) determine influences on pharyngeal folding behaviour; and 3) confirm that pharyngeal wall folding modification can stabilise the upper airway. By providing unique data defining the impact of pharyngeal wall folding on OSA severity, we will develop a new conceptual paradigm for enhanced understanding of OSA pathogenesis and a new therapeutic paradigm for clinical management of this common chronic disorder.


Discipline: Physiology
Co-supervisors: Terry Amis, John Wheatley
Keywords: Obstructive Sleep Apnoea, Sleep disorders, upper airway physiology
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