Ludwig Engel Centre for Respiratory Research

Lab head: Professor John Wheatley
Location: Westmead Millennium Institute, Westmead Hospital

The Ludwig Engel Centre for Respiratory Research (LECRR) is the research arm of the Department of Respiratory and Sleep Medicine at Westmead Hospital and was named after the founding Director, Professor Ludwig Engel. LECRR combines both laboratory research and clinical studies aimed at identifying the pathophysiological basis of respiratory and sleep disorders.

Sleep disordered breathing

The centre has a particular emphasis on sleep disordered breathing with an international reputation for researching the mechanisms underlying the obstructive sleep apnoea syndrome (OSAS). In this disorder, patients experience repetitive episodes of throat blockage during sleep leading to complete cessation of breathing for short periods of time. In the short term, this leads to daytime fatigue, poor concentration, and an increased risk of work and motor vehicle accidents. In the long term it has been linked to the occurrence of heart disease, high blood pressure and stroke.

LECRR researchers are working to understand the processes associated with the occurrence of obstructed breathing during sleep in order to improve the treatments available for this important disorder.

Snoring has long been thought of as mainly a social nuisance, but there is growing evidence world wide of the possible health implications of habitual snoring. We have published a large study showing an increased prevalence of carotid artery atherosclerosis in heavy snorers. Studies undertaken this year have demonstrated that snoring like vibrations may be a factor responsible for triggering endothelial dysfunction. We are continuing this line of research to further explore the mechanisms by which snoring vibration energy may trigger the endothelial dysfunction and inflammation that may lead to carotid artery atherosclerosis, which is the leading cause of stroke.

Studies undertaken in 2009 include investigation of nasal dilator splints as a treatment to reduce disturbed sleep and sleep disordered breathing, measurements of the surface tension of the upper airway lining liquid in healthy subjects and OSAS patients, the impact of breathing route on the development of sleep disordered breathing, and the development of a computer model aimed at defining the relationships between peri-pharyngeal tissue pressure and upper airway patency. Ongoing studies have continued to explore the role of peri-pharyngeal tissue pressure in the pathogenesis of upper airway collapse, which is the major underlying cause of OSAS. We have also developed and published a new model of the upper airway functioning as a muscular hydrostat.

LECRR also participated in a study in Samoa demonstrating that CPAP treatment can effectively reduce blood pressure  in patients with untreated severe sleep apnoea and hypertension.

Cystic fibrosis

Cystic Fibrosis (CF) is the most common lethal inherited disease affecting Australians.  CF is caused by mutations in the body’s major chloride channel.  In the airway, this limits the movement of chloride (salt), which then dries the airway, resulting in chronic chest infections and ultimately death from lung disease. 

LECRR researchers have been working on the nasal potential difference (NPD) technique which can diagnose CF, and LECRR is part of the European CF Diagnostic Network which is examining different groups of patients and comparing the nasal potential difference recordings with the severity of their disease.  LECRR staff have recently compared different testing solutions in the NPD test which will allow the NPD to be used more effectively in multi-centre trials.

This NPD test also provides better understanding of the mechanisms involved in salt movement across the human airway and is helping to find new therapies which may bypass the defect in CF by stimulating different chloride channels to move salt in the right direction. 

LECRR has just published a study of fungi in CF, showing the importance of correct analysis for new species of fungi, such as Scedosporium.

Asthma and chronic obstructive pulmonary disease

Asthma now affects the lives of over 2 million Australian children and adults. Despite decades of research into the causes and treatment of asthma the prevalence of asthma in the population continues to rise. A major research interest of the centre is the influence of mouth versus nose breathing on the occurrence of asthmatic symptoms.

Chronic Obstructive Pulmonary Disease is the fourth leading cause of death and third leading cause of disease burden and it has been estimated that 2.1 million Australians have some form of COPD.  Research in the Respiratory Ambulatory Care Service focuses on improving the quality of life of patients with COPD and their carers by the prevention of crisis situations in the community, reducing the frequency of avoidable admissions to hospital and improved integration of services. 

Research completed over the past 12 months include the outcomes of a community outreach program for patients with COPD and a review of whether patients recently admitted to hospital with an acute exacerbation of their COPD will benefit most from pulmonary rehabilitation. Our study demonstrated that admission to hospital does not necessarily predict a favourable response to pulmonary rehabilitation.

Translational Clinical Research:

LECRR has a very active clinical trials programme and during 2009 has been involved in many trials testing new clinical treatments including a surgically implanted nerve stimulator to treat sleep apnoea, nasal dilator splints to treat snoring, antibiotics and bronchodilators for cystic fibrosis, new bronchodilators for COPD and asthma as well as new drug treatments for insomnia.

Website: http://www.wmi.usyd.edu.au/research/respitory.htm
Lab members: Assoc Prof Terry Amis Assoc Prof Peter Middleton Dr Kristina Kairaitis Dr Tracey Robinson
Funding: NH&MRC, Clinical Trials
Research approach equipment: Our fundamental approach is to make physiological measurements in normal human subjects as well as selected patient groups, to better understand the mechanisms of respiratory and sleep disorders, in order to develop more effective new therapies. We make extensive use of clinical monitoring in the Sleep Disorders Laboratory, the Respiratory Function Laboratory as well as physiological parameters in the LECRR research laboratories. We have international expertise in the measurement of surface tension in the upper airway, the measurement of snoring and the nasal potential difference test for Cystic Fibrosis. We are interested in translational research, and maintain an active involvement in clinical trials of devices and drugs as new therapies for respiratory and sleep disorders.
Publications:

2009

  • Kairaitis, K., Howitt, L., Wheatley, J., Amis, T. Mass loading of the upper airway extraluminal tissue space in rabbits: effects on tissue pressure and pharyngeal airway lumen geometry. Journal of applied physiology (Bethesda, Md. : 1985). 2009; 106:887-92. [Abstract]

2008

  • Lam, J., Kairaitis, K., Verma, M., Wheatley, J., Amis, T. Saliva production and surface tension: influences on patency of the passive upper airway. The Journal of Physiology. 2008; 586:5537-5547. [Abstract]
  • Lee, S., Amis, T., Byth, K., Larcos, G., Kairaitis, K., Robinson, T., Wheatley, J. Heavy snoring as a cause of carotid artery atherosclerosis. Sleep. 2008; 31:1207-1213. [Abstract]
  • Hallani, M., Wheatley, J., Amis, T. Enforced mouth breathing decreases lung function in mild asthmatics. Respirology. 2008; 13:553-558. [Abstract]
  • Hallani, M., Wheatley, J., Amis, T. Initiating oral breathing in response to nasal loading: asthmatics versus healthy subjects. The European respiratory journal : official journal of the European Society for Clinical Respiratory Physiology. 2008; 31:800-6. [Abstract]

2007

  • Howitt, L., Kairaitis, K., Kirkness, J., Garlick, S., Wheatley, J., Byth, K., Amis, T. Oscillatory Pressure Wave Transmission from the Upper Airway to the Carotid Artery. Journal of applied physiology (Bethesda, Md. : 1985). 2007; 103:1622-7. [Abstract] [Cited: 1]
  • Marshall, N., Wilsmore, B., McEvoy, R., Wheatley, J., Dodd, M., Grunstein, R. Polysomnography in Australia--trends in provision. Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine. 2007; 3:281-284. [Abstract]
  • Kairaitis, K., Byth, K., Parikh, R., Stavrinou, R., Wheatley, J., Amis, T. Tracheal traction effects on upper airway patency in rabbits: the role of tissue pressure. Sleep. 2007; 30:179-186. [Abstract]

2006

  • Verma, M, Seto-Poon, M, Wheatley, J, Amis, T, Kirkness, J. Influence of breathing route on upper airway lining liquid surface tension. The Journal of physiology. 2006; 574:859-66 [Abstract]
  • Amatoury, J, Howitt, L, Wheatley, J, Avolio, A, Amis, T. Snoring-related energy transmission to the carotid artery in rabbits. Journal of applied physiology (Bethesda, Md. : 1985). 2006; 100:1547-53 [Abstract]
  • Kairaitis, K, Stavrinou, R, Parikh, R, Wheatley, J, Amis, T. Mandibular advancement decreases pressures in the tissues surrounding the upper airway in rabbits. Journal of applied physiology (Bethesda, Md. : 1985). 2006; 100:349-56 [Abstract]
  • Marshall, N, Wilsmore, B, McEvoy, R, Wheatley, J, Dodd, M, Grunstein, R. Polysomnography in Australia- Trends in Provision. Journal of Clinical Sleep Medicine. 2006; 0:0
  • Kirkness, J, Verma, M, Maly, J, Wheatly, J, Amis, T, Smith, P, Schwartz, A, Schneider, H. Quantification of inspiratory airflow obstruction using a novel light-weight flowmeter. Sleep. 2006; 29:A340-A340

2005

  • Kirkness, J, Christenson, H, Wheatley, J, Amis, T. Application of the 'pull-off' force method for measurement of surface tension of upper airway mucosal lining liquid. Physiological measurement. 2005; 26:677-88 [Abstract]
  • Jenkins, C, Thien, F, Wheatley, J, Reddel, H. Traditional and patient-centred outcomes with three classes of asthma medication. The European respiratory journal: official journal of the European Society for Clinical Respiratory Physiology. 2005; 26:36-44 [Abstract]
  • Britton, W, Gilbert, G, Wheatley, J, Leslie, D, Rothel, J, Jones, S, Bradley, P. Sensitivity of human gamma interferon assay and tuberculin skin testing for detecting infection with Mycobacterium tuberculosis in patients with culture positive tuberculosis. Tuberculosis (Edinburgh, Scotland). 2005; 85:137-45 [Abstract]
  • Kirkness, J, Madronio, M, Stavrinou, R, Wheatley, J, Amis, T. Surface tension of upper airway mucosal lining liquid in obstructive sleep apnea/hypopnea syndrome. Sleep. 2005; 28:457-63 [Abstract]

2004

  • Madronio, M, Di Somma, E, Stavrinou, R, Kirkness, J, Goldfinch, E, Wheatley, J, Amis, T. Older individuals have increased oro-nasal breathing during sleep. The European respiratory journal : official journal of the European Society for Clinical Respiratory Physiology. 2004; 24:71-7 [Abstract]
  • Wheatley, J, Flemons, W, Douglas, N, Kuna, S, Rodenstein, D. Access in Diagnosis and Treatment of Patients with Suspected Sleep Apnea. American Journal of Respiratory Critical Care Medicine. 2004; 169:668-672.

Understanding the Mechanisms that lead to Stroke in Snoring and Sleep Apnoea Patients

Primary supervisor: John Wheatley

Heavy snoring and obstructive sleep apnoea syndrome (OSAS) are associated with the development of cerebral vascular disease and stroke. The mechanisms of this association are unclear but likely involve the development of specific stroke promoting vascular pathologies. Retinal photography provides a direct window to assess for cerebral microvascular disease, while carotid artery ultrasound is an established indicator of carotid atherosclerosis (and stroke risk). We have previously shown that heavy snoring is a risk factor for carotid atherosclerosis.
 Aims:
 In patients with severe snoring and OSAS demonstrate:
 1) An increased prevalence of retinal microvascular abnormalities
 2) Increased prevalence of retinal micro-emboli following a heavy night of snoring, consistent with carotid plaque rupture
 
 Project 1: In patients with snoring and OSAS, we will: 1) undertake polysomnography (PSG); 2) take retinal photographs before (pm) and after (am) sleep to quantify retinal microvascular lesions including retinal emboli; 3) quantify carotid artery intima-media thickness, and atheromatous plaque using ultrasound.
 This study will establish the prevalence of retinal microvascular abnormalities (including retinal emboli) and carotid atherosclerosis in untreated severe snoring and OSAS.
 
 The use of retinal photography may provide a clinical tool to target reduction of both overall vascular risk and stroke risk in snoring and OSAS.


Discipline: Physiology
Co-supervisors: Terry Amis, Kristina Kairaitis
Keywords: Obstructive Sleep Apnoea, Retina, Stroke
Contact: