Research Report 2010
Thoracic Medicine
Adult Cystic Fibrosis Centre
Name of Program
has been developed based on the concept of
examining ways to improve the quality of life
of adults with cystic fibrosis and how care is
delivered. Research laboratories are based at
the Sir Albert Sakzewski Research Institute
at Herston, following the establishment of
the Brisbane Cystic Fibrosis Pseudomonas
Research group (Leader: SC Bell), which
includes a multi-disciplinary team of clinicians
and scientists from RCH and TPCH. The
arrival of Dr David Reid from the University of
Tasmania and provided a great opportunity to
expand the research direction of the group.
The Centre is currently collaborating with
a number of research centres in Australia
including:
Thoracic Medicine
Name of Research Unit
Adult Cystic Fibrosis Centre
Program Medical Director
Associate Professor Scott Bell
T: 07 3139 5407
E: [email protected] or bells@
uq.edu.au
Program Nursing Director
Toni Ferguson (Acting)
T: 07 3139 5407
E: [email protected]
1.
Director Research Unit
Associate Professor Scott Bell
Contact details as above
Address Adult Cystic Fibrosis Centre
The Prince Charles Hospital
Rode Road
Chermside Qld 4032
Affiliations
Queensland Children’s Medical Research
Institute (Bell)
Queensland Institute of Medical Research
(Reid)
International Professional Linkages
Professor Stuart Elborn, Belfast, UK
Professor Kevin Webb, Manchester, UK
Associate Professor Shawn Aaron, Ottawa,
Canada
Professor Michael Knowles, North Carolina,
USA
Professor Gary Cutting, Maryland, USA
Professor Paul Rainey, Auckland, NZ
Professor Ian Paulson, Sydney, NSW
The Royal Children’s Cystic Fibrosis
Service
2. Queensland Health Pathology Services
Associate Professor Scott Bell
Senior Research Clinicians and
Personnel
Dr David Reid
Dr Philip Masel
Dr Megan France Lisel Robbins
Michelle Wood Timothy Kidd (PhD Student) Kay Ramsay
Dr Daniel Smith (PhD Student)
Dr Anna Tai (PhD Student) Dr Alison Badrick (Post doc Fellow)
Neroli Houston
Dr Claire Butler (CF Fellow)
Administrative Staff
Jean Hawker
History
The Adult Cystic Fibrosis Centre was
established in 1998 following funding from
the Queensland Government. The core multidisciplinary team was appointed and over
the past ten years patient population has
increased from ~100 to >270 patients. During
this time of growth a large research program
3. The Department of Infectious Diseases,
University of Sydney
4. The Department of Medicine, Mater
Adults Hospital
5.
Royal Prince Alfred Cystic Fibrosis Unit,
Sydney
6. Institute of Molecular Bioscience, UQ
7.
Queensland Institute of Medical Research
8. Menzies Research Institute, Hobart
9. Department of Chemistry and
Biomolecular Sciences, Macquarie
University
10. School of Chemistry and Biomolecular
Science, UQ
11. International Laboratory of Air Quality
and Health, QUT
Major Research Highlights
1.
Description of the role of a novel therapy
for the treatment of post-transplant
lymphoproliferative disorders including
the demonstration for the first time
the therapeutic role of allo-specific
T-lymphocytes in patients with post
transplantation lymphoproliferative
disease.
2. Pioneered work on establishing the role
of macrolides in patients with CF.
3. Established linkages between
chronic inflammation and metabolic
74
Research Report 2010
Research Report 2010
Thoracic Medicine
Adult Cystic Fibrosis Centre
consequences of cystic fibrosis (including
nutrition and bone disease of CF).
4. The recognition of the changing
epidemiology of Burkholderia cepacia
complex infection in clinical settings
outside the environment of major
epidemic sites of cross infection.
5.
Over $7.2million raised in peer reviewed
research grants, representing >40 grants.
6. Identification of relationship between
environmental Pseudomonas aeruginosa
and clinical isolates.
7.
Identification of potential non-CF genes
involved in the development in CF-related
liver disease.
8. Identification of common environmental
Pseudomonas aeruginosa isolates in
small groups or isolated patients with
CF yet no evidence of the major clonal
strains in the environment.
9. First description of cyanogenesis
occurring in the lungs of Pseudomonas
aeruginosa infected CF patients.
10. First description of a relationship
between airway iron content and infection
load with Pseudomonas aeruginosa in CF.
Current Research Projects
1.
The epidemiology and clinical
consequences of clonal Pseudomonas
aeruginosa infection in children and
adults with cystic fibrosis (support from
NHMRC Project grant, TPCH Foundation,
Australian CF Research Trust, Rotary
Australia).
2. The molecular epidemiology and clinical
consequences of Burkholderia cepacia
complex in Australian cystic fibrosis
children and adults.
3. Mechanisms of antibiotic resistance
in bacteria derived from cystic fibrosis
patients.
4. The role of inhaled mannitol in patients
with cystic fibrosis.
5.
7.
Relationship between clinical
and environmental Pseudomonas
aeruginosa.
8. The role of ventilation in the prevention
of airborne transmission of infection in
a hospital environment.
9. Comprehensive study of the long term
effect of liver disease in CF.
Dr Daniel Smith
Dr Anna Tai
Clinical/Research Fellows 12 Clinical and Research Fellows since 2000
Current Fellow Dr Claire Butler and Dr Suzanne
Poole (2011 – six months’ rotation each).
10. Decision making in CF patients with
advanced lung disease.
Scientists
Neroli Houston
Kay Ramsay
11. Development of molecular tools
to determine the mechanisms of
exacerbation in CF.
Publications
12. Improving self-efficacy in adolescents
and adults with CF using behavioural
techniques and web-based support.
1.
13. Development of novel strategies to
disrupt bacterial biofilms.
14. Development of a new CF mouse model.
In addition to these formal areas of
research, a number of audit projects are
being undertaken to examine delivery of
care of people with cystic fibrosis.
Outcomes
1.
Progress to improved understanding of
the risks of cross infection of bacterial
infections in CF and the clinical impact.
2. Establishment of the first national study
of Pseudomonas aeruginosa in patients
with CF in Australia with a very large
organism bank.
3. Establishment of a Pseudomonas
aeruginosa bank from different
ecological niches.
4. Improved understanding of bacterial
virulence in vivo in CF.
5.
Progress toward new anti-microbial
strategies to disrupt bacterial biofilms.
Post-Doctorial Appointments
Alison Badrick (QIMR)
The role of viruses in causing respiratory
exacerbations of patients with cystic
fibrosis and non-CF bronchiectasis.
PhD supervision Completed
Two PhD completions (UQ, QUT)
6. The effect of aging on people with cystic
fibrosis.
PhD Supervision – Ongoing
Timothy Kidd (submission 2011)
Knibbs LD, Morawska L, Bell SC,
Grzybowski P. Room ventilation and the
risk of airborne infection transmission
in three health care settings in a large
teaching hospital. Am J Infect Contr. (in
press date of acceptance 11th February
2011)
2. Smith D, Reid D, Slaughter R, Masel
P, Tai A, Bell SC. Superior vena cava
obstruction due to total implantable
venous access devices in cystic fibrosis:
case series and review. Respiratory
Medicine – CME (in press, date of
acceptance 22nd December 2010).
3. Anuj SN, Whiley DM, Kidd TJ, Ramsay
KA, Bell SC, Syrmis MW, Grimwood K,
Wainwright CE, Nissen MD, Sloots TP.
Rapid SNP-based identification of clonal
Pseudomonas aeruginosa isolates from
patients with cystic fibrosis using realtime PCR and high resolution melting
curve analysis. Clinical Microbiology and
Infection (in press acceptance date 29th
November 2010, doi: 10.1111/j.14690691.2010.03439.x)
4. Kidd TJ, Gibson JM, Cobbold RN, Greer
RM, Moss S, Ramsay KA, Wright R,
Grimwood K, Bell SC. Clonal complex
Pseudomonas aeruginosa in horses,
Australia. Vet Microbiology (in press
acceptance date 23rd November 2010,
doi: 10.1016/j.vetmicro.2010.11.030)
5.
Bradbury R, Inglis TJJ, DW Reid, AC
Champion. A comparison of three
methods for antimicrobial sensitivity
testing of cystic fibrosis and non-CF
clinical isolates of P. aeruginosa. British J
of Biomedial Science. In Press, accepted
Nov., 2010.
75
Research Report 2010
Thoracic Medicine
Adult Cystic Fibrosis Centre
6. Bradbury R, Reid DW, Inglis T, Champion
AC. Decreased virulence of P. aeruginosa
in Dictyliostellium discoideum.
Microbiol Immunol, 2011 Jan 28. doi:
10.1111/j.1348-0421.2011.00314.x. Epub
ahead of print.
7.
O’Grady K, Maguire G, Reid DW Chang
A. Lung health care for Aboriginal and
Torres Strait Islander Queenslanders:
breathing easy is not so easy. Australian
Health Review, In Press, accepted Feb.,
2011.
8. Reid DW, Blizzard L, Shugg D, Flowers
C, Cash C, Greville H. Changes in cystic
fibrosis mortality and gender inequalities
in Australia, 1979–2005. Med J Aust.,
provisionally accepted Feb., 2011,
pending revision.
9. Kuys SS, Hall K, Peasey M, Wood M,
Cobb R, Bell SC. Ninendo-Wii is a feasible
model of aerobic exercise in adults with
cystic fibrosis: a randomised cross-over
trial. J Physiotherapy 2011; 51(1): 35-40.
10. Lewindon PJ, Shepherd RW, Walsh
MJ, Greer R, Williamson R, Pereira TN,
Frawley K, Bell SC, Smith J, Ramm GA.
Importance of hepatic fibrosis in cystic
fibrosis and the predictive value of liver
biopsy. Hepatology 2011; 53(1): 193-201.
receptor beta variable repertoire during
symptomatic herpesvirus infection in
transplant patients. Immunology and Cell
Biology 2010, 88(2): 125-35.
14. France MW, Tai SZ, Masel PJ, Moore VL,
McMahon TL, Ritchie AJ. Bell SC. The
month of July: an early experience with
pandemic influenza A (H1N1) in adults
with cystic fibrosis. BMC Pulmonary
Medicine 2010, 10:8.
15. Tiller RV, Gee JE, Lonsway DR, Gribble S,
Bell SC, Jennison A, Bates J, Coulter C,
Hoffmaster AR, De BK. Identification of
an unusual Brucella strain (BO2) from a
lung biopsy in a 52-year old patient with
chronic destructive pneumonia. BMC
Microbiology 2010, 10:23.
16. DW Reid. Bong lung in Cystic Fibrosis. J of
Case Reports: 2010, 19(4):371.
17. R Bradbury, L Roddam, DW Reid, AC
Champion. Virulence gene distribution
in P. aeruginosa in nosocomial,
environmental strains. J of Medical
Microbiology, 2010: 59(Pt 8 ); 881-90.
18. U Pratap, S Quinn, L Blizzard, DW
Reid. A population based study of
haemochromatosis as a disease modifier
in cystic fibrosis. Respirology, 2010;
15(1):141-9.
11. Kidd TJ, Grimwood K, Ramsay KA,
Rainey PB, Bell SC. Comparison of
three molecular techniques for typing
of Pseudomonas aeruginosa isolates in
cystic fibrosis sputum. J Clin Micro 2011;
46(1):263-8.
19. Wen Y, Reid DW, Zhang D, Ward, C, WoodBaker R, Walters EH. Assessment of
airway inflammation using sputum, BAL
and endobronchial biopsies in current
and ex-smokers with established COPD.
International J of COPD. 2010; (5): 327-34.
12. Chang AB, Bell SC, Byrnes CA, Grimwood
K, Holmes P, King PT, Kolbe J, Landau
LI, Maguire G, McDonald M, Reid D,
Thien F, Torzillo PJ. Thoracic Society of
Australia and New Zealand (TSANZ) and
Australian Lung Foundation (ALF) position
statement Bronchiectasis and chronic
suppurative lung disease in Australia and
New Zealand. Medical Journal of Australia
2010; 193(6): 356-65.
20. Soltani A, Reid DW, Sohal SS, Weston
S, Muller HK, WoodBaker R, Walters
EH. Basement membrane and vascular
remodelling in smokers and COPD; a
cross-sectional study. Respir Research
2010; 11:105.
13. Wynn KK, Crough T, Campbell S, McNeil
K, Galbraith A, Moss DJ, Silins SL,
Bell SC, Khanna R. Narrowing of T-cell
76
21. Sohal SS, Reid DW, Soltani A, WoodBaker
R, Walters EH. Reticular basement
membrane fragmentation and potential
epithelial mesenchymal transition (EMT)
in the airways of smokers is exaggerated
in COPD. Respirology, 2010; 15(6): 930-8.
22. M Turner, R Bohmer, H Jackson, R Harle,
DW Reid. Atypical presentation of acute
pancreatitis in Cystic Fibrosis. J of Case
M. Wood
Reports, 2010: 18(4): 275.
23. Wainwright CE, France MW, O’Rourke
P, Anuj S, Kidd TJ, Nissen M, Sloots T,
Coulter C, Ristovski Z, Hargreaves M,
Rose BR, Harbour C, Bell SC, Fennelly
K. Cough-generated Aerosols of
Pseudomonas aeruginosa and other
Bacteria from Patients with Cystic
Fibrosis. (SCB and KF contributed equally
to this work). Thorax 2009: 64:926-931.
24. Vandemheen KL, O’Connor A, Bell SC,
Freitag A, Bye P, Jeanneret A, Berthiaume
Y, Brown N, Wilcox P, Ryan G, Brager
N, Rabin H, Morrison N, Gibson P,
Jackson M, Paterson N, Middleton P,
Aaron SD. Randomized Controlled Trial
Of A Decision Aid For Cystic Fibrosis
Patients Considering Referral For Lung
Transplantation. Am J Resp Crit Care Med
2009 180: 761-768.
25. Bartlett JR, Friedman KJ, Ling SC, Pace RG,
Bell SC, Bourke B, Castaldo G, Castellani
C, Cippolli M, Colombo C, Colombo JL,
Debray D, Ferdandez A, Lacaiile F, Macek
Jr M, Rowland M, Salvatore F, Taylor CJ,
Wainwright C, Wilschanski M, Zemkova D,
Handler AJ, Phillips MJ, Corey M, Zielenski
Research Report 2010
Research Report 2010
Thoracic Medicine
Adult Cystic Fibrosis Centre
J, Dorfman R, Wang Y, Zou F, Silverman
LM, Drumm M, Wright FA, Lange EM,
Durie PR, Knowles MR for the Gene
Modifier Study Group. Genetic modifiers
of liver disease in cystic fibrosis. JAMA
2009: 302:1076-83.
26. Kidd TJ, Marks GB, Bye PTP, Wainwright
CE, Robinson PJ, Rose BR, Harbour C, Bell
SC and the ACPinCF Investigators. Multicentre Research – Analysis of a recent
NHMRC funded Project. Respirology
2009; 14:1051-5.
27. Soulsby N, Bell SC, Greville H, Doeke C.
Intravenous aminoglycoside usage and
monitoring of patients with cystic fibrosis
in Australia – what’s new? Intern Med J.
2009; 39: 527-31.
28. Sawyer SM, Farrant B, Wilson J, Ryan
G, O’Carroll M, Bye P, Bell S. Sexual
and reproductive health in men with
cystic fibrosis: Consistent preferences,
inconsistent practices, J Cyst Fibr 2009;
8: 264-9.
29. Kidd TJ, Ramsay KA, Hu H, Bye PTP,
Elkins MR, Grimwood K, Harbour C,
Marks GB, Nissen MD, Robinson PJ,
Rose BR, Sloots TP, Wainwright CE,
Bell SC and The ACPinCF Investigators.
Low rates of Pseudomonas aeruginosa
misidentification in cystic fibrosis
patients. J Clin Micro 2009: 47: 1503-9.
30. Manos J, Arthur J, Rose B, Bell S, Webb J,
Kjelleberg S, Bye P, Harbour C. Increased
expression of attachment, motility and
anaerobic respiration genes in clonal
Pseudomonas aeruginosa from the CF
lung. FEMS Letters 2009; 292: 107-114.
31. Anuj SN, Whiley DM, Kidd TJ, Bell SC,
Wainwright CE, Nissen MD, Sloots
TP. Identification of Pseudomonas
aeruginosa by a duplex real-time PCR
assay targeting the ecfX and the gyrB
genes. Diagnostic Microbiology and
Infectious Disease 2009: 63: 127-131.
32. Kapur N, Bell S, Kolbe J, Chang AB.
Inhaled steroids for bronchiectasis.
Cochrane Database of Systematic
Reviews 2009, Issue 1. Art.
No.:CD000996.DOI: 10.1002/14651858.
CD000996.pub2.
33. N Dwyer, DW Reid, R Smith, D Challis, D
Kilpatrick. Acute pulmonary oedema with
Bosentan in the setting of pulmonary
veno-occlusive disease secondary to
granulomatous venulitis. Eur Respir J,
2009; 33(3): 666-9.
34. C O’May, L Roddam, K Sanderson, SM
Kirov, DW Reid. Anti-biofilm effects of
iron-chelation therapy especially under
anaerobic conditions. J of Medical
Microbiology 2009;58(Pt 6):765-73.
35. S Pant, EH Walters, A Griffiths, DP
Johns, R Wood-Baker, DW Reid. Airway
inflammation and anti-protease defences
recover rapidly during treatment of an
acute exacerbation of COPD. Respirology,
2009; 14(4):495-503.
36. Y Khor, DW Reid, EH Walters. Increased
vascular permeability precedes cellular
inflammation as asthma control
deteriorates. Clin and Exp Allergy, 2009;
39(11):1659-67.
43. DW Reid, IL Lamont, G Anderson. The role
of lung iron in determining the bacterial
and host bacterial struggle in Cystic
Fibrosis. American Journal of Physiology;
Lung Cellular and Molecular Physiology.
Nov, 2009; 97(5):L795-802.
Book Chapters and Monographs
44. Smith DJ, Chang AB, Bell SC. Antiinflammatory therapies in bronchiectasis.
European Respiratory Monograph (in
press date of acceptance 16th October
2010).
45. Kidd TJ, Whiley DM, Bell SC, Grimwood K.
Chapter 85. Pseudomonas. In: Molecular
Detection of Human Bacterial Pathogens.
Editor: Dongyou Liu. Taylor and Francis
CRS Press, Florida, USA. 2010. pp 100719.
37. R Bradbury, AC Champion, DW Reid.
Epidemiology of P. aeruginosa infection
in a tertiary referral teaching hospital. J of
Hospital Infection, 2009; 73(2):151-6.
46. Kidd TJ. Chapter 11; Burkholderia cepacia
Complex and Burkholderia gladioli, PCR
for Clinical Microbiology – An Australian
and International Perspective. Book
Chapter. Springer Netherlands, 2010. pp
133-136.
Reviews and Editorials
Published Guidelines
38. Towns SJ, Bell SC. Transition in
adolescents with cystic fibrosis from
paediatric to adult care. Clinical
Respiratory Journal (in press date of
acceptance 18th September 2010).
47. Chang AB, Bell SC, Byrnes CA, Grimwood
K, Holmes P, King PT, Kolbe J, Landau
LI, Maguire G, McDonald M, Reid D,
Thien F, Torzillo PJ. Thoracic Society of
Australia and New Zealand (TSANZ) and
Australian Lung Foundation (ALF) position
statement. Bronchiectasis and chronic
suppurative lung disease in Australia
and New Zealand. TSANZ and Australian
Lung Foundation. Published 26th October
2010.
39. Bell SC, Morris NR. Exercise testing in
patients with cystic Fibrosis: why and
which? Editorial. Journal of Cystic Fibrosis
2010; 9(5): 299-301.
40. R Anderson, K Sanderson, L Roddam,
DW Reid. Biosignificance of bacterial
cyanogenesis in the CF lung. J of Cystic
Fibrosis 2010; 9(3): 158-64.
41. Downey DG, Bell SC, Elborn JS.
Neutrophils in cystic fibrosis (review).
Thorax 2009; 64: 81-89.
48. http://www.lungfoundation.
com.au/professional-resources/
guidelines/chronic-suppurative-lungdiseaseanz-2010
42. IL Lamont, AF Konings, DW Reid. Iron
acquisition by P. aeruginosa in the lungs
of patients with cystic fibrosis. Biometals
2009;22(1):53-60.
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Research Report 2010
Thoracic Medicine
Adult Cystic Fibrosis Centre
Letters to Editor
Clinical Trials Program
49. Chang AB, Bell SC, Byrnes CA, Grimwood
K, Holmes P, King PT, Kolbe J, Landau LI,
Maguire G, McDonald M, Reid D, Thien F,
Torzillo PJ. Reply to Letter to the Editor.
MJA 2010 in press.
Clinical trials are an expanding area within
the Adult Cystic Fibrosis Centre. A number
of pharmaceutical studies ranging from
symptomatic therapies to novel treatments
targeting the cystic fibrosis gating defect are
currently being conducted:
These include:
1. The role of Tiotropium Bromide in
children and adults with cystic fibrosis
50. DW Reid, C O’May, L Roddam, IL Lamont.
Chelated iron as an anti-P. aeruginosa
biofilm therapeutic strategy. J of Applied
Microbiology 2009;106(3):1058.
51. DW Reid, C O’May, L Roddam, IL Lamont,
SM Kirov, K Sanderson. Iron chelation as
an adjunct to conventional antibiotics as
anti-biofilm agents. American Journal of
Physiology; Lung Cellular and Molecular
Physiology 2009; 296(5):L857-8.
52. Reid DEC, Bell SC. Sugar sweet and
deadly? Microbiology 2009:155: 665-6.
53. Hopkins PM, Kidd TJ, Coulter C, Feather
IH, Derrington P, Bell SC. Death after lung
transplantation in CF patients infected
with Burkholderia cepacia. Am J Resp Crit
Care Med 2009; 279: 257-8.
Submissions
Several applications to NHMRC and Australian
Cystic Fibrosis Research Trust for peer review
grants.
Awards
1.
Excellence in Clinical Research, The
Prince Charles Hospital 2007 – SC Bell
2. Health Research Fellowships ($150k per
annum for five years) awarded by the
Office of Health and Medical Research,
Qld Health – Dr Scott Bell and Dr David
Reid (2011-2015)
3. NHMRC Practitioner Fellowship 2010-2015
($300,000 total) for Dr David Reid.
2. The safety profile and role of Vertex
770 (chloride channel potentiator) and
Vertex 809 (chloride channel corrector)
in people with cystic fibrosis and specific
gene mutations
3. The role of inhaled Levofloxacin and
inhaled Ciprofloxacin in stable cystic
fibrosis patients
4. The effect of Denufosol Tetrasodium
inhaled solution in cystic fibrosis patients
with mild lung disease
The centre is also currently collaborating
with US based CF centres investigating gene
modifiers in Cystic Fibrosis Liver Disease and
the genetic and environmental influences in
Siblings with Cystic Fibrosis.
Current Research Grant Funding
1.
NHMRC Project Grant (2011-3) – Novel
Therapies for bronchiectasis (Bell)
2. TPCH Foundation (2010-11) (Bell and Reid,
Bell)
3. Queensland Children’s Medical Research
Institute (2010-15) – Program Grant (Sly,
Wainwright, Bell)
4. Australian Cystic Fibrosis Research Trust
(2011) (Reid, Bell)
5.
Perpetual Philanthropy and Colliers
Charitable Fund (2010-2011) - equipment
(Bell, Reid)
6. Office of Health and Medical Research
(2010-2015)
78
a. Health Research Fellowships (Bell,
Reid)
b. Near Miss Project Grant Support (Bell)
c. Queensland Children’s Medical
Research Institute
7.
a. Near Miss Project Grant Support (Bell)
Research Report 2010
Research Report 2010
Thoracic Medicine
Core Thoracic Medicine
Name of Program
Thoracic Medicine
Name of Research Unit
Core Thoracic Medicine
Program Medical Director
Associate Professor Scott Bell
T: 07 3139 5407
F: 07 3139 5630
E: [email protected]
Program Nursing Director
Toni Ferguson
T: 07 3130 5407
F: 07 3139 5630
E: [email protected]
Director Research Unit
Dr Philip Masel
T: 07 3139 4408
F: 07 3139 5630
E: [email protected]
Research Personnel
The program is involved with various research
projects and the keys researchers are:
Professor Kwun Fong, Associate Professor
Ian Yang and Associate Professor Rayleen
Bowman, Associate Scott Bell, Dr Philip
Masel, Dr James Douglas.
Administrative Staff
Jan Harris
T: 07 3139 4042
F: 07 3139 5630
E: Jan_Harris @health.qld.gov.au
Address
Thoracic Medicine
Administration Building
The Prince Charles Hospital
Rode Road
Chermside Q 4032
History
This program commenced in 2009.
Previously much research was undertaken by
members of the program but with no overall
coordination of activities. The program’s main
interests are Asthmas, COPD, Pneumonia,
Pneumothorax, Cystic Fibrosis, Lung Cancers
and Bronchiectasis.
Affiliations
We have a strong collaboration with Professor
Kwun Fong, Associate Professor Ian Yang
and Associate Professor Rayleen Bowman.
We plan to do a study on Pneumonia in
collaboration with the internal medicine
program.
Research Projects
Current Research Projects
P. Masel
Review of Pneumothorax
Community acquired Pneumonia: An audit
of Current Assessment and Management
Practice.
Treatment Adherence Workshops
Major Research Highlights
Poster presentation accepted for TSANZ 2011.
Financial Details
The program will be applying for a Novice
Researcher Grant through TPCH Foundation in
2011.
Publications
Med J Aust. 2009 Nov 16;191(10):549-53.
Variability in the rate of prescription and cost
of domiciliary oxygen therapy in Australia.
Serginson JG, Yang IA, Armstrong JG, Cooper
DM, Matthiesson AM, Morrison SC, Gair JM,
Cooper B, Zimmerman PV.
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Research Report 2010
Thoracic Medicine
Queensland Centre for Pulmonary Transplantation
& Vascular Disease
Name of Program
Social Worker
Name of Research Unit
Occupational Therapist
Thoracic Medicine
Queensland Centre for Pulmonary
Transplantation & Vascular Disease
Program Medical Director
Peter Hopkins
T: 07 3139 4000
F: 07 3139 5696
E: [email protected]
Program Nursing Director
Trish Leisfield
T: 07 3139 5561
F: 07 3139 5696
E: [email protected]
Director Research Unit
Daniel Chambers
T: 07 3139 4000
F: 07 3139 5696
E: [email protected]
Clinical Research Co-ordinators
Kay Wiggins
Tracey Tse
The Queensland Centre for Pulmonary
Transplantation & Vascular Disease
(QCPTVD) Research Program was formed
at the beginning of 2008 initially with four
staff members. Since then we have grown
to include an onsite laboratory dedicated to
research in the fields of lung transplantation
and pulmonary vascular disease, 14 staff
members and a large program of research
supported by considerable grant success.
Administrative Staff
Affiliations
Address
The program has strong collaborations
with the Royal Adelaide Hospital, the South
Australian, Victorian and West Australian Lung
Transplant Programs, as well as the Mater
Medical Research Institute, Cell & Tissue
Therapies WA, Dept of Physiotherapy Griffith
University and the Australian Centre for
Metagenomics, UQ.
Jessica Hopper
Dietician
jennifer McMillan
Pharmacist
Mary-Ellen Bilby
T: 07 3139 4511
F: 07 3139 5696
E [email protected]
Queensland Centre for Pulmonary
Transplantation & Vascular Disease
Level 1, Administration Building
The Prince Charles Hospital
Rode Road
Chermside Q 4032
Anne Carle
Sandra Bancroft
Debra Enever
Nicole Ostenfeld
Kathy O’Brien
Anna Larsson
Paula Quantrill
Peter McLeod
PhD Supervision or Other Items of
Notable Academic Merit
The program currently has two PhD students
enrolled.
Research Projects
Current Research Projects
A new and better way to check your new
lung(s) – assessment of the lung allograft
using bronchial brushings. Dr Dan Chambers,
Dr Peter Hopkins and Dr Fiona Kermeen.
Research Scientists
Stephanie Yerkovich
Maxine Tan
Will Dodt
Microbial Diversity in Chronic Allograft
Dysfunction following Lung Transplantation.
Daniel Chambers, Fiona Kermeen, Kevin
Matar, Morgan Windsor, Stephanie Yerkovich,
Nicole Ostenfeld, Debra Enever, Edwina Duhig
and Peter Hopkins.
Physiotherapists
James Walsh
Helen Seale
Michael Tuppin
P. Hopkins
80
History
The role of circulating cells in heart and lung
transplantation. Daniel Chambers, Peter
Hopkins, George Javorsky, Fiona Kermeen,
Debra Enever, Nicole Ostenfeld and Stephanie
Yerkovich.
Research Report 2010
Research Report 2010
Thoracic Medicine
Queensland Centre for Pulmonary Transplantation
& Vascular Disease
Mesenchymal Stem Cells in Idiopathic
Pulmonary Fibrosis. Daniel Chambers, Lisa
Sparks and Peter Hopkins.
A Phase 1 Study to Evaluate the Potential
of Mesenchymal Stromal Cells to Treat
Obliterative Bronchiolitis After Lung
Transplantation. Daniel Chambers, Lisa
Sparks and, Peter Hopkins
Assessment of the number of progenitor cells
in the lung epithelium post-transplant.
Daniel Chambers, Peter Hopkins, Fiona
Kermeen, Edwina Duhig, Sandra Bancroft,
Debra Enever, Nicole Ostenfeld and Stephanie
Yerkovich.
Does papilloma virus cause skin cancer?
Daniel Chambers, Peter Hopkins, Fiona
Kermeen, Robert Franz, Edwina Duhig, Andrew
Dettrick, Debra Enever, Nicole Ostenfeld and
Stephanie Yerkovich.
Exploring Mechanisms of Exercise Intolerance
in Adult Survivors of Extreme Preterm Birth.
Dan Chambers, James Walsh, Debra Enever,
Annette Dent, Peter Hopkins, Fiona Kermeen,
David Platts and Richard Slaughter.
A double-blind, randomised, placebocontrolled, multicentre, parallel group
study to evaluate the efficacy, safety, and
tolerability of macitentan in patients with
idiopathic pulmonary fibrosis (MUSIC:
Macitentan Use in an Idiopathic pulmonary
fibrosis Clinical study). Dr Peter Hopkins, Dr
Daniel Chambers.
A Phase III multi-centre, randomized, parallel
group, controlled, double-blinded study to
investigate the safety and efficacy of inhaled
mannitol over 12 months in the treatment
of bronchiectasis (DPM-B-305). Dr Daniel
Chambers, Dr Philip Masel, Dr Fiona Kermeen,
Helen Seale and Dr Peter Hopkins.
A 3-Year Randomized, Open Label, MultiCentre Investigator Driven Study Comparing
de Novo Enteric Coated Mycophenolate
Sodium with Delayed Onset Everolimus,
Both Arms in Combination with Cyclosporin
(using C2 monitoring) and Corticosteroids
for the Prevention of Bronchiolitis Obliterans
Syndrome in Heart-Lung, Bilateral Lung
and Single Lung Transplant Recipients. Dr
Peter Hopkins, Dr Keith McNeil and Dr Fiona
Kermeen.
ARTEMIS-PH: A Phase 3, Randomized, DoubleBlind, Placebo-Controlled, Multi-Center,
Parallel-Group Study to Evaluate the Efficacy
and Safety of Ambrisentan in Subjects with
Idiopathic Pulmonary Fibrosis and Pulmonary
Hypertension. Dr Peter Hopkins, Dr Daniel
Chambers and Dr Fiona Kermeen.
A multicenter, double-blind, placebocontrolled Phase 3 study to demonstrate the
efficacy and safety of ACT-293987 in patients
with Pulmonary Arterial Hypertension. Dr
Fiona Kermeen, Dr Peter Hopkins and Dr
Daniel Chambers.
Prostacyclin (PGI2) Receptor agonist In
Pulmonary arterial HypertensiON
AC-065A303: Long-term single-arm openlabel study, to assess the safety and
tolerability of ACT 293987 in patients with
pulmonary arterial hypertension. Dr Fiona
Kermeen, Dr Peter Hopkins and Dr Daniel
Chambers.
An Open-Label Extension Trial of UT-15C
SR in Subjects with Pulmonary Arterial
Hypertension. Dr Fiona Kermeen, Professor
Keith McNeil and Dr Peter Hopkins.
A 16-Week, International, Multicenter,
Double-Blind, Randomized, PlaceboControlled Study of the Efficacy and
Safety of Oral UT-15C Sustained Release
Tablets in Subjects with Pulmonary Arterial
Hypertension. Dr Fiona Kermeen and Dr Peter
Hopkins.
A randomized, double-blind, placebocontrolled, multi-centre and multi-national
study to assess the efficacy and safety of
different doses of a new drug, riociguat
(BAY 63 2521), given orally to patients with
Pulmonary Arterial Hypertension.
(PATENT 1) Dr Fiona Kermeen, Dr Peter
Hopkins, Dr Daniel Chambers, Dr George
Javorsky and Professor Keith McNeil.
Long-term extension, multi-centre, multinational study to evaluate the safety and
tolerability of oral BAY 63 2521 in patients
with Pulmonary Arterial Hypertension (PAH).
(PATENT 2) Dr Fiona Kermeen, Dr Peter
Hopkins, Dr Daniel Chambers, Dr George
Javorsky and Professor Keith McNeil.
The efficacy and safety of proliferation signal/
mTOR inhibitor everolimus, in combination
with a statin in patients with pulmonary
arterial hypertension. Dr F. Kermeen, Dr P
Hopkins, Dr D Chambers, Dr G Javorsky, C
Franks and Dr K McNeil.
A randomised, double-blind, placebocontrolled, multi-centre and multi-national
study to assess the efficacy and safety of
different doses of a new drug riociguat (BAY
63 2521), given orally to patients with Chronic
Thromboembolic Pulmonary Hypertension.
(CHEST 1- 11348) Dr Fiona Kermeen, Dr Peter
Hopkins, Dr Daniel Chambers, Dr George
Javorsky and Professor Keith McNeil.
Long-term extension, multi-centre, multinational study to evaluate the safety and
tolerability of oral BAY 63 2521 in patients
with Chronic Thromboembolic Pulmonary
Hypertension (CTEPH). CHEST 2 (Extension)
Dr Fiona Kermeen, Dr Peter Hopkins, Dr Daniel
Chambers, Dr George Javorsky and Professor
Keith McNeil.
Major Research Highlights
The program has been in the top three in
the world for the last two years in terms of
research output at the International Society
for Heart & Lung Transplantation Annual
Scientific Meeting. One of our PhD students,
Balarka Banerjee, won the UWA three
minute thesis competition in 2010 for his
presentation entitled, ‘Lung transplantation
– making the second chance count’, and then
went on to win the trans-Tasman finals.
The program has recently commenced the first
trials of stem cell therapy for lung disease
ever to be conducted in Australia, using bone
marrow derived mesenchymal stromal cells
81
Research Report 2010
Thoracic Medicine
Queensland Centre for Pulmonary Transplantation
& Vascular Disease
(MSC) to treat obliterative bronchiolitis, in a
collaboration between ourselves, the West
Australian Lung Transplant Program and Cell
& Tissue Therapies WA, and placental derived
MSC to treat idiopathic pulmonary fibrosis
in collaboration with the Mater Medical
Research Institute.
Chambers D., Hodge S., Hodge G., Yerkovich
S., Kermeen F., Reynolds P., Holmes M.
and Hopkins P. A Novel Approach to the
Assessment of Lymphocytic Bronchiolitis after
Lung Transplantation – Transbronchial Brush.
J Heart Lung Transplant Accepted 21st Oct
2010.
Our clinical trials program has recruited the
largest number of patients in the world to
recent trials in idiopathic pulmonary fibrosis,
and was the first in the world to treat patients
with emphysema with steam therapy –
endobronchial thermal vapour ablation.
Kermeen F.D., Franks C., O’Brien K., Seale H.,
Hall K., McNeil K. and Radford D.
Endothelin receptor antagonists are an
effective long term treatment option in
pulmonary arterial hypertension associated
with congenital heart disease with or
without trisomy 21. Heart Lung Circ. 2010.
Oct;19(10):595-600.
Grants (See table on opp. page)
With Helen Seale’s grant money, she has
purchased a portable metabolic carte and in
conjunction with the Pre term birth study, and
had a bike prototype manufactured through
the School of I.T and Electrical engineering
at the University of Queensland. This is
used during right heart catheters and MRI to
see the effects of exercise in these patient
cohorts.
James Walsh has presented his research
findings at many conferences nationally and
internationally. In addition to his research,
James is currently completing his PhD in
“Predictive Factors in Success of Pulmonary
Rehabilitation”.
Stephanie Yerkovich is the chief scientist in
the now fully established QCPTVD Research
Laboratory. Several projects are now up
and running with the assistance of several
research assistants. The results of these
projects are starting to be compiled and will
be presented at national and international
conferences in 2011.
S. Yerkovich
Where are they now?
Balarka Banerjee returned to Perth in January
2010 after working in our research facility
for several months to finish the laboratory
component of his PhD. Balarka’s work on the
role of epithelial repair in the pathogenesis
of obliterative bronchiolitis will continue this
year with the assistance of the Prince Charles
Hospital Foundation.
Awards
Dan Chambers received a Health Research
Fellowship in 2010 worth $750 000 over five
years.
Publications
Manuscripts
Ng B., Glanville A., Snell G., Musk M., Holmes
M., Chambers D.C. and Hopkins P.M.A. The
impact of pandemic influenza A H1N1 2009
on Australian Lung Transplant Recipients. In
Press. American Journal of Transplantation.
Accepted 19th Dec 2010.
Keogh A., Strange G., Kotlyar E., Williams
T., Kilpatrick D., Macdonald P., Brown K.,
Pidoux A., Kermeen F., Steele P., Dalton B.
and Gabbay E. Survival After the Initiation
of Combination Therapy in Patients With
Pulmonary Arterial Hypertension - An
Australian Collaborative Report. Intern Med J.
2010 Dec 1.
82
Yerkovich S., Hopkins P. and Chambers
D. Survival after Bronchiolitis Obliterans
Syndrome. Am J Resp Crit Care Med. Accepted
14th Oct 2010.
D. Chambers
Tsang B.K., Kermeen F.D., Hopkins P.M.
and Chambers D.C. Reversible posterior
leukoencephalopathy syndrome: diagnosis
and management in the setting of lung
transplantation. Intern Med J. 2010
Oct;40(10):716
Chambers D. and Sole A. Mold Infections
In Cardiothoracic Transplantation. Invited
Review for J Heart Lung Transplant In press 5th
August 2010. IF=3.09 (0)
Research Report 2010
Research Report 2010
Thoracic Medicine
Queensland Centre for Pulmonary Transplantation
& Vascular Disease
Grants
International
2010
ROTRF
Hopkins P, Bruce K
‘Microbial diversity in chronic allograft
dysfunction’
CHF 167,192 2 years
2009
Cellcept Australia Research
Grants
Chambers D
‘Assessment of airway rejection in lung
transplantation – no longer B grade?’
$40,000 1 year
2009
Research Infrastructure
Support Services (Riss Ltd)
NCRIS 5.5
Marian Sturm (Manufacturing
Facility Investigator), Daniel
Chambers (Principal Clinical
Investigator)
A phase I study to evaluate the potential of
mesenchymal stromal cells to treat obliterative
bronchiolitis after lung transplant
$100,000
1 year
2008
Cellcept Australia Research
Grant
Fraser J, Nataatmadja M,
Passmore M, Chambers D,
Konstantinov I, Fung L, Barnett A
‘The implications of brain death in donor
lung injury: investigation and blockade of the
endothelin axis’
$40,000 1 year
2007
NHMRC Project Grant
Reynolds P, Holmes M, Hodge G,
Hodge S, Chambers D
‘Monitoring of leucocyte cytokine/chemokines
to improve morbidity and rejection rates in
lung transplant patients’
$358,950 3 years
2010
TPCH Foundation
Chambers D, Musk M, Herrmann
R, Hopkins P
A Phase I Study to Evaluate the Potential
of Mesenchymal Stromal Cells to Treat
Obliterative Bronchiolitis After Lung
Transplantation
$86,285 1 year
2010
TPCH Foundation
Yerkovich S, Chambers D,
Hopkins P
Mechanisms of epithelial-mesenchymal
transition post-lung transplantation
$84,250 1 year
2010
TPCH Foundation
Chambers D
Small equipment grant SEQ2010-03
$5,000
2010
Qld Health
Helen Seale, Dr Dan Chambers,
Kathleen Hall, Julie Harris, Dr
Fiona Kermeen, A/Prof Norm
Morris. Dr Peter Hopkins, Dr
George Javorsky, Dr David
Platts, Dr Richard Slaughter,
Rebecca Davis, Wendy Stugwell,
Cherie Franks
Evaluation of haemodynamic responses during
incremental exercise in trained and untrained
pulmonary arterial hypertension (PAH) in
different subclasses of PAH disease
$67 600
2010
Qld Health
Walsh J, Paratz J, McKeough Z,
Morris N
Identifying Responders to Pulmonary
Rehabilitation
$30 000
2010
TPCH Foundation
Hopper J
Return to work after a lung transplant
$5500 1 year
2010
TPCH Foundation
Yerkovich, S
Large equipment grant LEQ2010-02
$6750
National
Regional
83
Research Report 2010
Thoracic Medicine
Queensland Centre for Pulmonary Transplantation
& Vascular Disease
Hopkins P.M., Kermeen F., Duhig E., Fletcher
L., Gradwell J., Whitfield L., Godinez C., Musk
M., Chambers D., Gotley D. and McNeil K. Oil
red O stain of alveolar macrophages is an
effective screening test for gastroesophageal
reflux disease in lung transplant recipients. J
Heart Lung Transplant. 2010 Aug;29(8):85964. IF=3.09 (0)
Hodge G, Hodge S, Liew C, Chambers D,
Hopkins P, Reynolds P, Holmes, M. Time postlung transplant correlates with increasing
peripheral blood T-cell granzyme B and proinflammatory cytokines. Clin Exp Immunol.
2010 May 28. [Epub ahead of print]
IF=3.009 (0)
Hodge G, Hodge S, Li-Liew C, Hopkins P,
Chambers DC, Reynolds PN, Holmes M.
Lymphocytic bronchiolitis is associated
with inadequate suppression of peripheral
blood T-cell granzyme B, IFNγ and TNFα.
Transplantation 2010 May 27;89(10):1283-9.
IF=3.64 (1)
K Shekar, C Foot, J Fraser, M Ziegenfuss, P
Hopkins, M Windsor Bronchopleural Fistula –
an Update for Intensivists. Journal of Critical
Care, 2010 Mar; 25:47-55.
G Snell, P Hopkins, G Westall, L Holsworth,
A Carle, T Williams A Feasibility and Safety
Study of Bronchoscopic Thermal Vapour
Ablation: A Novel Emphysema Therapy. Ann
Thorac Surg. 2009 Dec;88(6): 1993-8.
S Hodge, G Hodge, J Ahern, C Liew, P Hopkins,
D Chambers, P Reynolds, M Holmes Increased
Levels of T Cell Granzyme B in Bronchiolitis
Obliterans Syndrome are not Suppressed
Adequately by Current Immunosuppressive
Regimens. Clin Exp Immunol. 2009
Nov;158(2): 230-6. Epub 2-009 Aug 3.
P Hopkins, T Kidd, C Coulter, I Feather,
P Derrington, S Bell Death After Lung
Transplantation in Cystic Fibrosis Patients
Infected with Burkholderia cepacia. Am J
Respir Crit Care Med. 2009 Feb 1;179(3):257-8.
Hodge G, Hodge S, Li-Liew C, Chambers
D, Hopkins P, Reynolds PN, Holmes M.
Time post-lung transplant correlates with
increasing peripheral blood T cell granzyme
B and proinflammatory cytokines. Clinic Exp
Immunol 2010, Sep;161(3):584-90
Wurzel D, Marchant JM, Yerkovich ST, Upham
JW, Masters IBrent & Chang AB (2010)
Short courses of antibiotics for children
and adults with bronchiectasis. Cochrane
Database of Systematic Reviews, Issue 9 .
Art. No.: CD008695. DOI: 10.1002/14651858.
CD008695.
Carroll ML, Yerkovich ST, Pritchard AL, Davies
JM & Upham JW (2010) Adaptive immunity to
rhinoviruses: Sex and age matter Respiratory
Research Accepted 8th December 2010.
Smith MD, Chang AT, Seale HE, Walsh JR,
Hodges PW (2010): Balance is impaired in
people with chronic obstructive pulmonary
disease. Gait & posture, 31(4):456-460.
Smith DJ*, Yerkovich ST*, Towers MA, Carroll
ML, Thomas R & Upham JW (2010) Reduced
soluble receptor for advanced glycation end
products in chronic obstructive pulmonary
disease. European Respiratory Journal
Accepted 16th June 2010
* Joint first author.
Pizzutto SJ, Upham JW, Yerkovich ST &
Chang AB (2010) Inhaled non-steroid antiinflammatories for children and adults
with bronchiectasis. Cochrane Database of
Systematic Reviews 2010, Issue 4. Art. No.:
CD007525. DOI:10.1002/14651858.CD007525.
pub2.
Roponen M*, Yerkovich ST*, Hollams E, Sly
PD, Holt PG & Upham JU (2010) Toll-like
receptor 7 function is reduced in adolescents
with asthma. European Respiratory Journal
35:64-71.
* Joint first author.
Upham JW, Zhang G, Rate A, Yerkovich
ST, Kusel M, Sly PD & Holt PG (2009)
Plasmacytoid dendritic cells during infancy
are inversely associated with childhood
respiratory infections and wheezing. Journal
of Allergy and Clinical Immunology 124:707713.
Yerkovich ST & Upham JW (2009) Reply to
Bratke et al. Thrombomodulin: a novel player
in allergic asthma. Journal of Allergy and
Clinical Immunology 123:1192-1193.
Yerkovich ST and Upham JU (2009) Regulation
of urokinase receptor expression: Interpreting
data in the absence of statistics. American
Journal of Respiratory and Critical Care
Medicine 180:583.
Yerkovich ST, Roponen M, Smith ME,
McKenna K, Bosco A, Subrata LS, Mamessier
E, Wikström ME, Le Souef P, Sly PD, Holt
PG & Upham JW (2009) Allergen enhances
thrombomodulin expression on dendritic cells
and is associated with a Th2 skewed immune
response. Journal of Allergy and Clinical
Immunology 123:209-216.
Abstracts
Andreas Fiene, Daniel Chambers, Graeme
Heart, John F. Fraser, Andrew Dettrick, Fiona
Kermeen, Peter Hopkins, and Daniel Mullany.
Successful Treatment Of Hyperacute Lung
Transplant Rejection With Plasma Exchange
And Veno-venous Extra-corporeal Membrane
Oxygenation (VV ECMO). Am J Resp Crit Care
Med May 2010; 181: A3069.
Greg L. Hodge, Sandy J. Hodge, Chien-Li Liew,
Paul N. Reynolds, Daniel Chambers, Peter
Hopkins, and Mark Holmes. Lymphocytic
Bronchiolitis Is Associated With Inadequate
Suppression Of Peripheral Blood T-cell
Granzyme B, IFNγ And TNFα – Possible Link
With Obliterative Bronchiolitis? Am. J. Respir.
Crit. Care Med., May 2010; 181: A1096.
Maria Nataatmadja, Margaret Passmore,
Fraser Russell, Amanda Corley, Peter Hopkins,
Daniel Chambers, Fiona Kermeen, and John
F. Fraser. Systemic And Local Upregulation Of
The Angiotensin II System Is Associated With
Lung Transplant Injury. Am. J. Respir. Crit.
Care Med., May 2010; 181: A2565.
*†D.C. Chambers, B. Davies, S. Yerkovich,
P.M. Hopkins. Serum IgA Deficiency is
84
Research Report 2010
Research Report 2010
Thoracic Medicine
Queensland Centre for Pulmonary Transplantation
& Vascular Disease
Common in Lung Transplantation and is
Independently Associated with Bronchiolitis
Obliterans Syndrome (BOS). The Journal of
Heart and Lung Transplantation, February
2010 (Vol. 29, Issue 2, Supplement, Pages
S118-S119).
*D.C. Chambers, S. Hodge, G. Hodge, F.
Kermeen, P. Reynolds, M. Holmes, P. Hopkins.
A Novel Approach to the Assessment of
Lymphocytic Bronchiolitis – The ‘B Score’.
The Journal of Heart and Lung Transplantation
February 2010 (Vol. 29, Issue 2, Supplement,
Page S102).
C.A. Beck, D.C. Chambers, F.D. Kermeen, T.
Tse, P.M.A. Hopkins Significant Side Effect
Burden of Voriconazole Curtails Clinical Utility
in Lung Transplantation. The Journal of Heart
and Lung Transplantation February 2010 (Vol.
29, Issue 2, Supplement, Pages S138-S139).
P.M.A. Hopkins, F.D. Kermeen, H. Seale, T.M.
Leisfield, S.T. Yerkovich, D.C. Chambers.
RSV and Human Metapneumovirus Are Not
Associated with Obliterative Bronchiolitis or
Inferior Survival Post Lung Transplantation.
The Journal of Heart and Lung Transplantation
February 2010 (Vol. 29, Issue 2, Supplement,
Page S67).
B. Banerjee, A. Kicic, M.M. Musk, S.M. Stick,
D.C. Chambers. Explaining the Bronchiolitis
Obliterans Syndrome (BOS) Phenotype –
Epithelial-Mesenchymal Transition (EMT)
Occurs More Readily in Small Airway
Epithelium The Journal of Heart and Lung
Transplantation February 2010 (Vol. 29, Issue
2, Supplement, Pages S114-S115).
Heart and Lung Transplantation February 2010
(Vol. 29, Issue 2, Supplement, Page S56).
B. Levvey, M. Harkess, D. Chambers, E.
Granger, I. Ahmed, P. Hopkins, A. Glanville,
G. Snell. Are DCD Lungs Superior? Excellent
Intermediate Results from a Donation after
Cardiac Death Lung Transplant National
Collaborative. The Journal of Heart and Lung
Transplantation February 2010 (Vol. 29, Issue
2, Supplement, Pages S117-S118).
Granzyme B, IFNγ and TNFα.The Journal of Heart
and Lung Transplantation February 2010 (Vol.
29, Issue 2, Supplement, Page S101).
A. Fiene, K.D. McNeil, F.D. Kermeen, D.C.
Chambers, K. Stuart, J. Fawcett, R. Tam,
G.J. Hart, P.M.A. Hopkins. The Australian
Experience with Combined Heart-Lung-Liver
Transplantation. The Journal of Heart and
Lung Transplantation February 2010 (Vol. 29,
Issue 2, Supplement, Page S18).
B.J.H. Ng, P.M.A. Hopkins, F.D. Kermeen, D.C.
Chambers. A Single-Centre Experience with
the Use of Posaconazole for Invasive Fungal
Infections in Lung and Heart-Lung Transplant
Recipients. The Journal of Heart and Lung
Transplantation February 2010 (Vol. 29, Issue
2, Supplement, Page S17).
T. Tse, P.M.A. Hopkins, M.W. France,
P.J. Masel, S.C. Bell, F.D. Kermeen, D.C.
Chambers. Antibiotic Desensitisation in
Cystic Fibrosis Patients with a History
of Hypersensitivity Undergoing Lung
Transplantation Is Not Mandatory. The Journal
of Heart and Lung Transplantation February
2010 (Vol. 29, Issue 2, Supplement, Page
S136).
B.J.H. Ng, A.R. Glanville, J. D’Costa, G. Snell,
M. Musk, M. Holmes, D.C. Chambers, P.M.A.
Hopkins. The Combined Australian Experience
with Human Swine Influenza H1N1 in Lung
Transplant Recipients The Journal of Heart and
Lung Transplantation February 2010 (Vol. 29,
Issue 2, Supplement, Page S141).
J.L. McMillan, P.M.A. Hopkins, S.T. Yerkovich,
K.M. Herd, D.C. Chambers. First Year Body
Mass Index Trajectory Predicts Subsequent
Survival in Lung Transplant Recipients. The
Journal of Heart and Lung Transplantation
February 2010 (Vol. 29, Issue 2, Supplement,
Pages S139-S140).
J.R. Walsh, D.C. Chambers, R.J. Davis, H.E.
Seale, N.R. Morris, F.D. Kermeen, P.M.A.
Hopkins. Ambulatory Muscle Strength
Recovery Is Significantly Delayed When
Compared to Improvements in Lung Function
and Six Minute Walk Distance after Lung
Transplantation. The Journal of Heart and Lung
Transplantation February 2010 (Vol. 29, Issue
2, Supplement, Page S122).
S.C. Leong, D.C. Chambers, F.D. Kermeen,
P.M.A. Hopkins. Achieving Therapeutic Levels
of Cyclosporin C2 Early Post Transplant Has
No Impact on Rejection Burden The Journal of
C.-L. Liew, G. Hodge, S. Hodge, D. Chambers,
P. Hopkins, P.N. Reynolds, M.D. Holmes
Lymphocytic Bronchiolitis Is Associated
with Inadequate Suppression of Blood T-Cell
From left to right: N. Ostenfield, D. Enever, S. Bancroft
and A. Carle
T. Tse, D.C. Chambers, P.M.A. Hopkins.
Retinoid Therapy Is Ineffective in Preventing
Cutaneous Malignancy Complicating Lung
Transplantation. The Journal of Heart and
Lung Transplantation February 2010 (Vol. 29,
Issue 2, Supplement, Page S121)
Hamilton-Craig C., Kermeen F., Dunning J.J.
and Slaughter R.E. Eur Heart J. 2010 Jan 6
Cardiovascular magnetic resonance prior to
surgical treatment of chronic
thrombo-embolic pulmonary hypertension.
Eur Heart J. 2010 Jan 6.
D. Enever, S. Yerkovich, P. Gray and D.
Chambers. Reported respiratory symptoms
in young adult survivors of extreme preterm
birth. Respirology (2010) 15 (Suppl. 1), A11.
A. Wilson, D. Chambers, P. Wong, J. Louw,
K. Gain. C. Murray. High resolution CT chest
findings in young adults with a history of
bronchopulmonary dysplasia. Respirology
(2010) 15 (Suppl. 1), A39.
B. Ng, P. Hopkins, K. McNeil, D. Chambers,
R. Slaughter, J. Dunning. Chronic
thromboembolic pulmonary hypertension:
85
Research Report 2010
Thoracic Medicine
Queensland Centre for Pulmonary Transplantation
& Vascular Disease
assessing pulmonary endarterectomy
outcomes with MRI. Respirology (2010) 15
(Suppl. 1), A15.
epithelium is more susceptible to epithelialmesenchymal transition. Respirology (2010)
15 (Suppl. 1), A23.
A. Jaffe, A. Laverty, D. Chambers, M. Wilsher,
J. Twiss, E. Gabbay, I. Glaspole. Report of
the Australasian registry network for orphan
lung disease (ARNOLD) – the first quarter.
Respirology (2010) 15 (Suppl. 1), A21.
J.R. Walsh, D.C. Chambers, R.J. Davis, H.E.
Seale, N.R. Morris, F.D. Kermeen, P.M.A.
Hopkins. Ambulatory Muscle Strength
Recovery Is Significantly Delayed When
Compared to Improvements in Lung Function
and Six Minute Walk Distance after Lung
Transplantation. Respirology (2010) 15 (Suppl.
1), A27.
S. Yerkovich, P.M.A. Hopkins, D.C. Chambers.
Tacrolimus delays progression of bronchiolitis
obliterans syndrome (BOS) in lung
transplantation. Respirology (2010) 15 (Suppl.
1), A16.
B.J.H. Ng, A.R. Glanville, J. D’Costa, G. Snell,
M. Musk, M. Holmes, D.C. Chambers, P.M.A.
Hopkins. The Combined Australian Experience
with Human Swine Influenza H1N1 in Lung
Transplant Recipients Respirology (2010) 15
(Suppl. 1), A22.
A. Fiene, K.D. McNeil, F.D. Kermeen, D.C.
Chambers, K. Stuart, J. Fawcett, R. Tam,
G.J. Hart, P.M.A. Hopkins. The Australian
Experience with Combined Heart-Lung-Liver
Transplantation. Respirology (2010) 15 (Suppl.
1), A78.
Greg L. Hodge, Sandy J. Hodge, Chien-Li Liew,
Paul N. Reynolds, Daniel Chambers, Peter
Hopkins, and Mark Holmes. Lymphocytic
Bronchiolitis Is Associated With Inadequate
Suppression Of Peripheral Blood T-cell
Granzyme B, IFNγ And TNFα - Possible Link With
Obliterative Bronchiolitis? Respirology (2010)
15 (Suppl. 1), A77.
S. Yerkovich, B. Davies, P.M. Hopkins, D.C.
Chambers. Serum IgA Deficiency Is Common
in Lung Transplantation and Is Independently
Associated with Bronchiolitis Obliterans
Syndrome (BOS). Respirology (2010) 15
(Suppl. 1), A22.
B. Banerjee, A. Kicic, M.M. Musk, S.M. Stick,
D.C. Chambers Lung allograft small airway
86
T. Tse, P.M.A. Hopkins, M.W. France,
P.J. Masel, S.C. Bell, F.D. Kermeen, D.C.
Chambers. Antibiotic Desensitisation in
Cystic Fibrosis Patients with a History
of Hypersensitivity Undergoing Lung
Transplantation Is Not Mandatory. Respirology
(2010) 15 (Suppl. 1), A15.
*D.C. Chambers, S. Hodge, G. Hodge, F.
Kermeen, P. Reynolds, M. Holmes, P. Hopkins.
A Novel Approach to the Assessment of
Lymphocytic Bronchiolitis – The ‘B Score’.
Respirology (2010) 15 (Suppl. 1), A76.
P.M.A. Hopkins, F.D. Kermeen, H. Seale, T.M.
Leisfield, S.T. Yerkovich, D.C. Chambers.
RSV and Human Metapneumovirus Are Not
Associated with Obliterative Bronchiolitis or
Inferior Survival Post Lung Transplantation.
Respirology (2010) 15 (Suppl. 1), A21.
G. Hodge, S. Hodge, C. Li-Liew, D. Chambers,
P. Hopkins, P.N. Reynolds, M. Holmes. Time
post-transplant correlates with increasing
peripheral blood T-cell granzyme B and proinflammatory cytokines. Respirology (2010) 15
(Suppl. 1), A77.
J.L. McMillan, P.M.A. Hopkins, S.T. Yerkovich,
K.M. Herd, D.C. Chambers. First Year Body
Mass Index Trajectory Predicts Subsequent
Survival in Lung Transplant Recipients.
Respirology (2010) 15 (Suppl. 1), A78.
Ng, P. Hopkins, F. Kermeen, D. Chambers,
K. McNeil. A single centre experience with
the use of posaconazole for invasive fungal
infection in lung/heart-lung transplants.
Respirology (2010) 15 (Suppl. 1), A79.
S. Yerkovich, D. Enever, F. Lee, N. French, P.
Gray, D.C. Chambers. Perinatal predictors of
respiratory symptoms in young adult survivors
of extreme preterm birth. Respirology (2010)
15 (Suppl. 1), A45.
T. Tse, D.C. Chambers, P.M.A. Hopkins.
Retinoid Therapy Is Ineffective in Preventing
Cutaneous Malignancy Complicating Lung
Transplantation. Respirology (2010) 15 (Suppl.
1), A80.
Banerjee B, Kicic A, Musk M, Sutanto E, Stick
S Chambers DC. Successful establishment of
primary small airway cell cultures in human
lung transplantation. Accepted for publication
in Resp Res 18th Sep 2009.
Chambers DC. Adverse outcomes of labour
in public and private hospitals in Australia: a
population-based descriptive study. Accepted
for publication in Med J Aus 8th Sep 2009.
Tsang B, Kermeen F, Hopkins P, Chambers D.
Reversible Posterior Leukoencephalopathy
Syndrome – Diagnosis and Management in
the Setting of Lung Transplantation. In Press.
Accepted for publication in Internal Medicine
Journal 3rd November 2009. IF=2.03 (0)
Chambers DC. Adverse outcomes of labour
in public and private hospitals in Australia:
a population-based descriptive study. Med J
Aus 2009 Nov 16;191(10);578. IF=2.58 (0)
Hodge S, Hodge G, Ahern J, Liew C, Hopkins
P, Chambers D, Reynolds P, Holmes M.
Increased levels of T-cell granzyme b in
bronchiolitis obliterans syndrome are
not adequately suppressed by current
immunosuppressive regimens. Accepted
for publication in Clin Exp Immunol 2009
Nov;158(2):230-6IF 2.85.
Banerjee B, Kicic A, Musk M, Sutanto E, Stick
S, Chambers DC. Successful establishment of
primary small airway cell cultures in human
lung transplantation. Respiratory Research
2009 Oct 26;10(1):99. IF=3.13 (1)
Hodge G, Hodge S, Chambers D, Reynolds PN,
Holmes M. Bronchiolitis obliterans syndrome
is associated with absence of suppression
of peripheral blood Th1 pro-inflammatory
cytokines. Transplantation 2009 Jul 27;88(2).
IF=3.64 (3)
Research Report 2010
Research Report 2010
Thoracic Medicine
Queensland Centre for Pulmonary Transplantation
& Vascular Disease
May L, Rigby P, Charles A, Kicic A, Stick S,
Chambers DC. Cells of epithelial lineage are
detectable in peripheral blood and engraft
the bronchial epithelium after human lung
transplantation. Journal of Heart and Lung
Transplantation 2009 Jun;28(6):550-7. Cited
0; IF 3.09.
P.M.A. Hopkins, F.D. Kermeen, B. Tsang,
T.W.V. Daniels, J. Walsh, T.M. Leisfield, D.C.
Chambers. Intragam Use for Severe Refractory
Paramyxoviral Infection in Lung Transplant
Recipients. The Journal of Heart and Lung
Transplantation February 2009 (Vol. 28, Issue
2, Supplement, Page S161).
Hodge S, Holmes M, Banerjee B, Musk
M, Kicic A, Waterer G, Reynolds P, Hodge
G & Chambers DC. Post-transplant
bronchiolitis obliterans syndrome is
associated with bronchial epithelial to
mesenchymal transition. American Journal of
Transplantation 2009 Apr;9(4):727-33. Cited
1; IF 6.32.
P.M.A. Hopkins, F.D. Kermeen, B. Tsang,
T.W.V. Daniels, H. Seale, C. Bec, D.C.
Chambers. Preceeding Respiratory Viral
Infection Is a Strong Risk Factor for Fungal
Infection in Lung Transplant Recipients. The
Journal of Heart and Lung Transplantation
February 2009 (Vol. 28, Issue 2, Supplement,
Page S160).
Hodge G, Hodge S, Chambers D, Reynolds PN,
Holmes M. Bronchiolitis obliterans syndrome
is associated with absence of suppression
of peripheral blood Th1 pro-in GL Hodge, SJ
Hodge, D Chambers, PN Reynolds, and M
Holmes.
B.K.T. Tsang, F. Kermeen, P.M.A. Hopkins,
D.C. Chambers. Calcineurin Inhibition Can Be
Safely Maintained in Lung Transplantation
Complicated by Reversible Posterior
Leukoencephalopathy Syndrome. The Journal
of Heart and Lung Transplantation February
2009 (Vol. 28, Issue 2, Supplement, Pages
S290-S291).
Bronchiolitis Obliterans Syndrome Is
Associated with Absence of Suppression
of Peripheral Blood Th1 Pro-Inflammatory
Cytokines. Am. J. Respir. Crit. Care Med., Apr
2009; 179: A4302.
CI Whale, J McMorrow, A Higton, N Fernandez,
S Lawrence, C Jary, D Chambers, E Gabbay,
and M Musk. Pleural Cavity Irrigation with
Taurolidine during Lung Transplant May
Reduce the Risk of Post-Operative Pleural
Infection. Am. J. Respir. Crit. Care Med.,
Apr 2009; 179: A4611flammatory cytokines.
Transplantation 2009 Jul 27;88(2). IF 3.64.
Chambers D. Lung function in ex-preterm
adults. American Journal of Respiratory &
Critical Care Medicine 2009 Mar 15;179(6):517.
Cited 0; IF 9.1
Hodge G, Hodge S, Reynolds P, Chambers D,
Holmes M. Leucocyte intracellular cytokines in
lung transplant patients- a more physiological
indicator of immunosuppression than plasma
drug levels. In Immunosuppression: New
Research, Nova Publishers, 2009, Chapter 3,
91-115.
D.C. Chambers, M. Musk, S. Wong, S.
Temple, T.M. Liesfield, F. Kermeen, P.M.A.
Hopkins A Polymorphism in the Hepatocyte
Growth Factor (HGF) Gene Is Associated with
Bronchiolitis Obliterans Syndrome (BOS)Free Survival after Lung Transplantation. The
Journal of Heart and Lung Transplantation
February 2009 (Vol. 28, Issue 2, Supplement,
Pages S172-S173).
T.W.V. Daniels, D.C. Chambers, B.K.-T.
Tsang, H.E. Seale, T.M. Leishfield, F.D.
Kermeen, P.M.A. Hopkins Adenovirus Is Not
Associated with Graft Dysfunction Post Lung
Transplantation and Does Not Warrant AntiViral Therapy. The Journal of Heart and Lung
Transplantation February 2009 (Vol. 28, Issue
2, Supplement, Page S287).
D.C. Chambers, P.M.A. Hopkins, F. Kermeen,
J. Ahern, G. Hodge, P. Reynolds, M. Holmes,
S. Hodge. Mucosal Integrin Expressing CD8
Lymphocytes Infiltrate Small Airways during
Episodes of Acute Lung Allograft Rejection –
Link between Rejection and BOS? The Journal
of Heart and Lung Transplantation February
2009 (Vol. 28, Issue 2, Supplement, Pages
S138-S139).
D. Chambers, S. Hodge, G. Hodge, J. Ahern,
J. Nairn, C.-L. Liew, P.N. Reynolds, P.
Hopkins, M. Holmes. Increased Levels of
T-Cell Granzyme b in Bronchiolitis Obliterans
Syndrome (BOS) Are Not Adequately
Suppressed by Current Immunosuppressive
Regimens. The Journal of Heart and Lung
Transplantation February 2009 (Vol. 28, Issue
2, Supplement, Page S172).
T.W.V. Daniels, B.K.-T. Tsang, D.C. Chambers,
F.D. Kermeen, J.R. Walsh, C. Beck, P.M.
Hopkins. Parainfluenza Infection after Lung
Transplantation Is a Strong Predictor for
Obliterative Bronchiolitis The Journal of Heart
and Lung Transplantation February 2009 (Vol.
28, Issue 2, Supplement, Page S287).
T.W.V. Daniels, G.B. Rogers, B. Banarjee, J.F.
Fraser, P.M.A. Hopkins, F.D. Kermeen, M.
Musk, A. Corley, K.D. Bruce, D.C. Chambers.
Bronchiolitis Obliterans Syndrome: Do
Uncultured Bacterial Species Play a Role? The
Journal of Heart and Lung Transplantation
February 2009 (Vol. 28, Issue 2, Supplement,
Pages S118-S119).
L.A. May, A. Kicic, K. Heel, B. Banerjee, M.
Musk, P.M.A. Hopkins, D.C. Chambers
Cells of Epithelial Lineage Are Detectable in
Peripheral Blood and Are Increased in Lung
Transplantation. The Journal of Heart and Lung
Transplantation February 2009 (Vol. 28, Issue
2, Supplement, Pages S247-S248).
D.C. Chambers, B. Banerjee, G. Hodge,
P. Hopkins, A. Kicic, M. Musk, S. Stick, P.
Reynolds, M. Holmes, S. Hodge. Epithelial
Mesenchymal Transition (EMT) in Bronchiolitis
Obliterans Syndrome (BOS) Is Not Restricted
to Small Airways. The Journal of Heart and
Lung Transplantation February 2009 (Vol. 28,
Issue 2, Supplement, Pages S246-S247).
G. Hodge, S. Hodge, D. Chambers, P.N.
Reynolds, M. Holmes. Bronchiolitis obliterans
syndrome is associated with absence of
suppression of peripheral blood TH1 proinlfammatory cytokines. Respirology (2009)
14, (Suppl. 1) A24.
87
Research Report 2010
Thoracic Medicine
Queensland Centre for Pulmonary Transplantation
& Vascular Disease
P.M.A. Hopkins, F.D. Kermeen, B. Tsang,
T.W.V. Daniels, J. Walsh, T.M. Leisfield, D.C.
Chambers. Intragam Use for Severe Refractory
Paramyxoviral Infection in Lung Transplant
Recipients. Respirology (2009) 14, (Suppl. 1)
A24.
J. Walsh, D. Chambers, T. Daniels, S.
Leong, H. Seale, F. Kermeen, P. Hopkins.
Exercise induced desaturation is related
to primary graft dysfunction after bilateral
lung transplantation. Respirology (2009) 14,
(Suppl. 1) A73.
A. Jaffe, A. Laverty, D. Chambers, M. Wilsher,
J. Twiss, I. Glaspole, E. Gabbay. Establishment
of a web-based registry for orphan lung
diseases in Australia and New Zealand.
Respirology (2009) 14, (Suppl. 1) A67.
J. Walsh, H. Seale, D. Chambers, T. Daniels,
F. Kermeen, P. Hopkins. The change in
lung function and exercise capacity in the
first six months after lung transplantation.
Respirology (2009) 14, (Suppl. 1) A74.
CI Whale, J McMorrow, A Higton, N Fernandez,
S Lawrence, C Jary, D Chambers, E Gabbay,
and M Musk. Pleural Cavity Irrigation with
Taurolidine during Lung Transplant May
Reduce the Risk of Post-Operative Pleural
Infection. Respirology (2009) 14, (Suppl. 1)
A71.
P.M.A. Hopkins, F.D. Kermeen, B. Tsang,
T.W.V. Daniels, H. Seale, C. Bec, D.C.
Chambers. Preceeding Respiratory Viral
Infection Is a Strong Risk Factor for Fungal
Infection in Lung Transplant Recipients.
Respirology (2009) 14, (Suppl. 1) A75.
P Hopkins, K McNeil. Evidence for
Immunosuppression in Lung Transplantation.
Current Opinion Organ Transplant 2008 Oct
13;477-483.
D.C. Chambers, P.M.A. Hopkins, F. Kermeen,
J. Ahern, G. Hodge, P. Reynolds, M. Holmes,
S. Hodge. Mucosal Integrin Expressing CD8
Lymphocytes Infiltrate Small Airways during
Episodes of Acute Lung Allograft Rejection –
Link between Rejection and BOS? Respirology
(2009) 14, (Suppl. 1) A71.
B.K.T. Tsang, F. Kermeen, P.M.A. Hopkins,
D.C. Chambers. Calcineurin Inhibition Can Be
Safely Maintained in Lung Transplantation
Complicated by Reversible Posterior
Leukoencephalopathy Syndrome. Respirology
(2009) 14, (Suppl. 1) A71.
C. Beck, D. Chambers, P. Hopkins, F. Kermeen,
T. Tse. Significant side effect burden of
voriconazole curtails clinical utility in lung
transplantation. Respirology (2009) 14,
(Suppl. 1) A71.
88
Research Report 2010
Thoracic Medicine
Sleep Disorders Centre Research Group
Name of Program
Thoracic Medicine
Name of Research Unit
Sleep Disorders Centre Research Group
Program Medical Director
Dr James Douglas
T: 07 3139 5786
F: 07 3139 4510
E: [email protected]
Head of Sleep Sciences
Greg Jorgensen
T: 07 3139 6175
E: [email protected]
Nicola Dunn and Andrea Beevers, SAVE study
coordinators, TPCH SDC
Nicola Dunn, Andrea Beevers, Jennie Fry and
Brenda Modina MINT study coordinators,
TPCH SDC
Network (ASTN) endorsed multicentre trials:
ASTN Concordance Study: Does external
proficiency testing and method intervention
improve inter-scorer and inter-laboratory PSG
scoring reliability? and the SAVE Study.
Lynn Hoey, TPCH SDC
Masters in Science in Medicine (Sleep
Medicine)
University of Sydney
PhD Supervision or Other Items of
Notable Academic Merit
Address
Sleep Disorders Centre
The Prince Charles Hospital
Rode Road
Chermside Q 4032
Jan Robinson
T: 07 3139 5623
E: [email protected]
Research Group Coordinator
Geoff Doyle
T: 07 3139 4804
E: [email protected]
Dr Simon Smith
Research Fellow
Centre for Accident Research & Road Safety Queensland
Queensland University of Technology
Sara Olsen
Postdoctoral Research Fellow, School of
Psychology, University of Queensland
Jacqui Blake
PhD Candidate
Faculty of Business, University of Sunshine
Coast
Chris Watling
PhD Candidate
Centre for Accident Research and Road Safety
– Queensland (CARRS-Q)
Queensland University of Technology (QUT)
Research Projects
Current Research Projects
1. Sleep Apnoea CardioVascular Endpoints
(SAVE) Study. This is the largest ever
intervention study conducted in patients with
Obstructive Sleep Apnoea. This world wide
study aims to determine if treatment of OSA
with CPAP reduces secondary cardiovascular
events. There is close collaboration with
cardiology, general medicine, cardiac surgery
and rehabilitation services at TPCH in the
recruitment of patients.
Head of Nursing
Research Personnel
Sara Olsen was awarded her PhD in 2010.
Jacqui Blake & Chris Watling are undertaking
their PhDs with the Sleep Disorders Centre
Research Group.
J. Douglas
History
The Sleep Disorders Centre originated in 1982.
Investigations were performed by Respiratory
Investigation Unit staff. The unit was under
the direction of Dr Paul Zimmerman. Later
in 1982; an 8 Channel chart polygraph was
acquired and it interfaced to sensors largely
designed and built in house. A permanent
site was allocated in 1988 and a four bed unit
was established in 1992. The current six bed
centre laboratory was established in the new
main acute hospital building in 1998. Dr James
Douglas was appointed the Director of the
Unit since 2002.
Affiliations
The research group has a broad range
of collaborations with the University of
Queensland, Queensland University of
Technology and University of Sunshine Coast.
The group has also participated in two NH&
MRC supported Australasian Sleep Trials
2. Screening questionnaire for sleep
disorders. This ARC Funded project that is
examining the feasibility of a web based
screening questionnaire and a decision
support analysis tool for sleep disorders. It
forms the major part of Jacqui Blake’s PhD.
3. Predicting sleepiness whilst driving in shift
workers – This work has been undertaken
by Geoff Doyle and Dr Simon Smith. It is
examining TPCH nursing staff’s risk of fall
asleep driving accidents and the impact of
shift work on this risk.
4. Assessment of countermeasures to improve
driving ability. Chris Watling & Dr Simon
Smith are examining the role of scheduled
rest breaks versus other countermeasures
on subsequent driver simulator performance.
Extension of this work to look at patients with
OSA.
5. UQ Hons student projects done with Dr
Simon Smith as mentor included: “Diet
intention and Sleep, sleep alters food
preference and relationship to consumption”
and “Executive Cognitive Function –
Survival curve analysis, quality of sleep and
disruption”.
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Research Report 2010
Thoracic Medicine
Sleep Disorders Centre Research Group
6. Phil Terrill from MedTech at UQ and Greg
Jorgensen. This research is looking at whether
more accurate measures of leg and body
movements via accelerometry have advantage
over current methods.
7. Dr Suvenesh Prasad in collaboration with
the Advanced Heart Failure Team investigated
The Prevalence of Sleep Disordered Breathing
in Heart Failure Patients at a Tertiary Centre.
8. Jessica Mayrseidl. Alison Mudge, James
Douglas, Greg Jorgensen, Simon Smith are
investigating The Effect of a Supervised
Hospital Based Exercise Program on Sleep
Quality in Recently Discharged Heart Failure
Patients. This is part of a wider NH&MRC
funded study.
Major Research Highlights
1. The Research highlight for the Sleep
Disorders Centre is a series of projects that
started in the Centre in 2003 involving various
people but primarily Simon Smith and Sara
Olsen. A health beliefs model was created that
predicts patient’s adherence to Continuous
Positive Airway Pressure (CPAP) and from
this an educational intervention delivered by
nursing staff using motivational interviewing
was developed. The subsequent randomized
control clinical trial (MINT Study) was funded
by the Prince Charles Hospital Foundation. The
12 month data revealed that the intervention
arm were more likely to take up CPAP,
commenced CPAP therapy in a significantly
shorter time frame and had a substantially
better objective adherence to CPAP. A manual
on the MINT education intervention has been
created so other centres can benefit from our
research.
2. Nurse Led Discharge Clinics – Data on the
success of this initiative have been presented
at the Australian Sleep association national
meeting in 2009. This is a very successful
nursing intervention which has achieved
high patient and staff satisfaction and
increases capacity to undertake new cases
consultations within the Sleep Disorders
Centre.
3. The Effect of Insomnia on Adherence to
CPAP for Obstructive Sleep Apnoea., Simon
Smith, Nicola Dunn and James Douglas. We
extended our work from 2004 which identified
the high prevalence of concomitant insomnia
and OSA. We demonstrated that patients who
report initial insomnia were less likely to take
up CPAP.
Financial Details
NRMA Road Safety Trust. The effect of rest
breaks on driver fatigue. Dr Simon Smith
$51,514. July 2009.
Awards
1. TPCH Foundation 2009 Grant Project Grants
(NoviceResearcher) Dr Daniel Smith.
2.TPCH Foundation 2010 Project Grants
(Novice Researcher) Jessica Mayrseidl.
3. Olsen S, Smith S, Oei TPS & Douglas J.
Motivational intervention improves CPAP
acceptance and adherence. Sleep and
Biological Rhythms 2009; 7 (s1), A20.
[Abstract].
4. Smith D, Douglas J, Jorgensen G and Smith S.
Prevalence and causes of residual sleepiness
12-months after CPAP treatment for obstructive
sleep apnoea. Sleep and Biological Rhythms
2009; 7 (s1), A52. [Abstract].
5. N Dunn N, Beevers A, Douglas J
Nurse led discharge clinics – Improve access
to sleep service. Sleep and Biological Rhythms
2009; 7 (s1), A42 [Abstract].
6. Smith S.
Testing the effectiveness of sleepiness
countermeasures in the driving simulator.
Sleep and Biological Rhythms 2010; 8 (s1) A5.
[Invited speaker].
(Also presented at 27th International Congress
of Applied Psychology 2010 in Melbourne.)
From left to right: G. Jorgensen, G. Doyle, J. Robinson, J.
Douglas and S. Smith
Publications
1. Olsen, S., Smith, S., Oei, TPS., & Douglas, J.
Cues to Starting CPAP in Obstructive Sleep
Apnoea: Development and Validation of the
Cues to CPAP Use Questionnaire. Journal of
Clinical Sleep Medicine, 2010; 6(3):229-237.
2. Jacqueline Blake, J., Kerr, D. Development
of an Online Sleep Diary for Physician and
Patient Use. Knowledge Management &
E-Learning: An International Journal, 2010;
2(2):188-202.
Published Abstracts
1. Smith S and Doyle G.
Sleepiness while driving in shift-workers.
90
Sleep and Biological Rhythms 2009; 7 (s1)
A35-A36. [Abstract].
2. Smith S, Dunn N, Douglas J & Jorgensen G.
Sleep onset insomnia reduces adherence to
CPAP therapy. Sleep and Biological Rhythms
2009; 7 (s1), A74. [Abstract].
7. Prasad, S,. Smith, D., Douglas, J., Brown,
M., Javorsky, G., Galbraith, A. Prevalence and
Predictors of excessive
sleepiness in attendees to a Tertiary Heart
Failure
Clinic. Sleep and Biological Rhythms 2010; 8
(s1) A31. [Abstract].
8. Terrill, P., Jorgensen, G., Wilson, S.,
Douglas, J.
A Continuous Multisite Accelerometry System
(CMAS) to Investigate Periodic Leg Movements:
Comparison with Tibialis Anterior EMG. Sleep
and Biological Rhythms 2010; 8 (s1) A68.
[Abstract].
9. Douglas, J., Smith, D., Jorgensen, G.
Prevalence and causes of residual sleepiness
(RS) 12 months after continuous positive airway
pressure (CPAP) treatment for obstructive sleep
apnoea syndrome (OSAS)
European Respiratory Society Annual Congress
– Barcelona 2010 [Abstract].
Research Report 2010
Research Report 2010
Thoracic Medicine
University of Queensland Thoracic Research Centre
Name of Program
Thoracic Medicine
Name of Research Unit
University of Queensland (UQ) Thoracic
Research Centre
Director of Research Unit
Professor Kwun Fong
T: 07 3139 4314
F: 07 3139 4510
E: [email protected]
Research Personnel
The Thoracic Research Laboratory is a core
part of the Thoracic Program of The Prince
Charles Hospital, and the Northside Clinical
School, School of Medicine, The University of
Queensland (UQ).
The research team consists of:
• Director (Professor Kwun Fong)
• Senior Investigators (Associate Professor
Rayleen Bowman, Associate Professor
Ian Yang, Associate Professor Paul
Zimmerman, Dr Edwina Duhig, Dr Belinda
Clarke and Consultants in the Thoracic
Medicine Program)
• Post-doctoral Fellows (one full time, one
part time)
• Higher degree students (six PhD, one
Masters, one BSc Honours and two MBBS
Honours)
• Research scientists (two full time, one part
time, six casual)
• Research nurses (two full time, four part
time)
• Administration assistant (one full time)
• Collaborators
Address
Thoracic Research Laboratory
Level 1, Clinical Sciences Building
The Prince Charles Hospital
Rode Road
Chermside Q 4032
History
The Prince Charles Hospital has had a
long history of research in lung health,
in collaboration with the University of
Queensland. The Thoracic Research
Laboratory was initially established in 1998
by Associate Professor Paul Zimmerman
(Director of Thoracic Medicine 1981-2009) and
Dr Kwun Fong (Director of the Laboratory), as
a translational clinical research laboratory
of the Department of Thoracic Medicine, The
Prince Charles Hospital, Queensland Health.
Since its inception, the Thoracic Research
Laboratory has worked in partnership
with the patients and staff of The Prince
Charles Hospital to improve lung health
through research. With development of the
laboratory’s research program over time,
we have partnered with The University of
Queensland to undertake significant training
and mentoring of higher degree students
(Honours, Masters and PhD), enrolled in UQ,
in biomedical research into chronic lung
diseases.
As the UQ Thoracic Research Centre in
the School of Medicine, Faculty of Health
Sciences, The University of Queensland,
since September 2009, we are continuing to
build our national and international profile,
with a training of early career researchers,
higher degree students, publications, national
and international grants and fellowships,
invitations to present at scientific meetings,
and representation on clinical and scientific
committees.
Our mission is to improve lung health of
patients through high quality translational
clinical research.
Our vision is to translate lung health research
with cutting edge technology and innovation
to improve outcomes in the diagnosis,
prevention and treatment of chronic lung
diseases for patients.
Our clinical research program is focused
on translational research for patients with
chronic lung disease, including lung cancer,
asthma, chronic obstructive pulmonary
disease (COPD), and mesothelioma.
We are studying the effects of geneenvironment interaction, especially in relation
to exposure to cigarette smoke, respiratory
infection, asbestos and air pollution. Our
aim is to better understand how chronic lung
diseases develop and progress, in order to
improve diagnosis, prevention and treatment
for people with lung conditions.
Affiliations
We have been fortunate to develop
enduring local, national and international
collaborations with biomedical researchers,
in order to synergise and optimise outcomes
from strong partnerships.
Within our Department, we work on joint
projects with Assoc Prof Scott Bell, Dr Daniel
Chambers and Assoc Prof Paul Zimmerman, in
various fields including bronchiectasis, cystic
fibrosis, airways disease, lung transplant
biology, and lung nodule detection in at-risk
smokers.
Within our institution, we have strong
partnerships with the clinicians, surgeons,
pathologists, radiologists, radiographers and
scientific staff of The Prince Charles Hospital.
Collaborators include:
• Dr Edwina Duhig, Dr Belinda Clarke and the
Anatomical Pathology Department
• Dr Morgan Windsor, Dr Kevin Matar and the
Thoracic Surgery Department
• Dr Richard Slaughter, Dr Melanie Fuentes,
Dr Jane Crossin, Stanley Redmond, and the
Department of Medical Imaging
• Staff of the Respiratory Investigations Unit
• Staff of Phlebotomy.
We have a strong collaboration with Professor
Nick Hayward, Oncogenomics Laboratory,
Queensland Institute of Medical Research
(QIMR) for use of microarray technology.
This has enabled all of our PhD students
to undertake microarray experiments in
Professor Hayward’s laboratory, as part of
their PhD programs.
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Research Report 2010
Thoracic Medicine
University of Queensland Thoracic Research Centre
We collaborate with School of Medicine
groups and have enduring international
collaborations (Prof Minna and Prof Gazdar,
UTSouthwestern, Dallas, USA; Prof Holgate, Dr
Holloway, University of Southampton, UK).
Current collaborations include:
National collaborations
• Queensland Institute of Medical Research
(Prof Nick Hayward): We have a current
collaboration with QIMR in microarray
studies in lung cancer and COPD.
• The National Centre for Asbestos Related
Diseases (NCARD) is a research centre
funded by the federal government as part
of the Government’s Strengthening Cancer
Care package with measures aimed at
prevention, treatment and support for
cancer patients and their families.
• The Australasian Lung Cancer Trials Group
(ALTG) is Australia and New Zealand’s
lung and thoracic cancer clinical research
group. The ALTG is a multi-disciplinary
organization dedicated to reducing the
incidence, morbidity and mortality of lung
and thoracic cancer and improving the
quality of life of lung and thoracic cancer
patients in Australia and New Zealand
through the coordination and facilitation of
high quality clinical research.
• Professor Alexander Dobrovic. Head,
Molecular Pathology Research &
Development, Department of Pathology,
Peter MacCallum Cancer Centre.
• Division of Physiotherapy (The University
of Queensland): This collaboration is
undertaking a randomised controlled trial
of chronic disease self-management and
pulmonary rehabilitation in COPD patients.
• International Air Quality Laboratory
(Queensland University of Technology): Air
pollution collaboration with Professor Lidia
Morawska and Dr Zoran Ristovski.
• Asthma Research Laboratory (The
University of Queensland, Princess
Alexandra Hospital): Collaboration with
Professor John Upham.
92
• Asthma Research Centre (Royal Children’s
Hospital): Professor Anne Chang.
sequencing, to detect mutations in the
lung cancer genome.
• Bronchology and volatile organic
compounds (Royal Brisbane and Women’s
Hospital): Dr David Fielding.
• Michael R. Green, M.D., Ph.D.Investigator,
HHMI Programs in Gene Function and
Expression and Molecular Medicine,
University of Massachusetts Medical
School, Worcester, MA.
• Professor Nico Van Zandwjck, Asbestos
Diseases Research Institute, Bernie Banton
Centre. Concord NSW.
• Experimental Therapeutics Program;
Professor Michelle Haber AM, Children’s
Cancer Institute Australia, Randwick NSW
2031.
• Professor Sunil Lahkani, Professor of
Pathology, UQCCR – collaboration on
tissue microarrays.
• Gerwin Heller, Ph.D. and Professor
Sabine Zöchbauer-Müller, M.D., Medical
University of Vienna, Department of
Medicine I, Clinical Division of Oncology,
Comprehensive Cancer Center, Währinger
Gürtel, Vienna, Austria.
Financial Details
International collaborations
NHMRC
• University of Southampton, UK (Professor
Stephen Holgate and Dr John Holloway:
Asthma Genetics Laboratory): A series
of genetic association studies were
performed using cohorts recruited by these
groups. The close partnership continues
in the field of asthma genetics and COPD
genetics, as well as cell biology.
NHMRC. 440800. NHMRC Practitioner
Fellowship. Fong. $404,250. 2007-2011. 5 yr.
• University of Texas Southwestern Medical
Center, Professor John Minna, Professor
Adi Gazdar): A post-doctoral fellowship
(Kwun Fong) and post-doctoral study leave
(Ian Yang) have been undertaken at this
international lung cancer centre, to learn
techniques in molecular genetics and
primary bronchial epithelial cell culture. To
further extend our existing collaboration
in the lung cancer field, Dr Jill Larsen from
our laboratory is currently undertaking her
post-doctoral fellowship in this NIH-funded
laboratory (NHMRC CJ Martin Fellowship).
• US National Cancer Institutes, National
Institutes of Health: The Cancer Genome
Atlas Project (TCGA): The Cancer Genome
Atlas (TCGA) is a comprehensive and
global coordinated effort to accelerate
understanding of the molecular basis
of cancer through the application of
genome analysis technologies, including
large-scale genome sequencing. With
Queensland Health and ethics approval,
DNA of non-small cell lung cancer
specimens will be provided to the TCGA for
NHMRC. 456158. NHMRC Career
Development Award: Preventing progression
of COPD. Yang. $316,750. 2007-2011. 5 yr.
NHMRC. 569246. The AMAZES Study:
Asthma and Macrolides: the AZithromycin
Efficacy and Safety study. Gibson, Simpson,
Upham, Reynolds, Yang, Hodge, James.
$2,991,000. 2009-2013. 5 yr.
NHMRC. Project grant APP1006695.
Prospective methylation biomarker
validation study in lung cancer. Fong,
Dobrovic, Duhig. $510,048. 2011-2013. 3 yr.
NHMRC Biomedical Scholarship. 511255.
Genomic characterisation of Asbestos
Related Lung Cancer. Wright. $66,771. 20092011. 3 yr.
NHMRC Postgraduate Medical Scholarship.
569762. Identification, validation and
functional analysis of genes and miRNAs
involved in recurrent non-small cell lung
cancer. Sriram. $97,884. 2009-2011. 3 yr.
NHMRC Biomedical Scholarship - Medical
1. 631306. Low-Dose Computerised
Tomography Screening for Lung Cancer in
Queensland. Marshall. $89,875. 2010-2012.
2.5 yr.
Research Report 2010
Research Report 2010
Thoracic Medicine
University of Queensland Thoracic Research Centre
Other funding bodies
Cancer Australia. 550600. Individualising
treatment for mesothelioma. Bowman, Fong,
Clarke, Relan, Gazdar. $349,500. 2009-2010.
2 yr.
Cancer Council Queensland. 550608.
Genome-wide association study of protective
alleles in lung cancer and COPD. Yang, Fong,
Bowman, Zimmerman, Holloway. $162,750.
2009-2010. 2 yr.
Cancer Council Queensland. 550605. Novel
microRNAs in pulmonary neoplasia. Fong,
Bowman, Yang, Zimmerman, Clarke, Relan,
Minna. $164,000. 2009-2010. 2 yr.
Dust Diseases Board. Fast-track testing of
existing drugs for malignant mesothelioma
chemoprevention. Bowman, Yang,
The Prince Charles Hospital Foundation
Novice Researcher Grant. NR2010-109.
Clinical Utility of High Resolution Melt
Analysis in Detecting EGFR Mutations in the
Serum of NSCLC Patients. Martins. $9,675.
2010. 1 yr.
University of Queensland. 2010003154. UQ
NHMRC equipment - tissue culture facility.
Yang. $33,048. 2011. 1 yr.
University of Queensland. UQ MEI equipment
– Roche light cycler. Fong. $69,000. 2011.
1 yr.
Pfizer Australia Cancer Research Grant. no
number. The clinical utility of high resolution
melt analysis in detecting EGFR mutations in
the serum of NSCLC patients. Sriram, Fong,
Bowman, Yang. $55,000. 2011. 1 yr.
The Prince Charles Hospital Foundation
Novice Researcher Grant. NR2010208. Biomarkers of severity of COPD
exacerbations. Goh. $10,000. 2011. 1 yr.
The Prince Charles Hospital Foundation
Novice Researcher Grant. NR2010-228.
Tumour suppressor functions of miR-218.
Parsonson. $9,913. 2011. 1 yr.
Research staff
Zimmerman, Fong, van Zandwijk, Robinson,
Creaney. $260,000. 2009-2010. 2 yr.
University of Queensland Early Career
Researcher grant. no number. Novel
microRNAs in malignant mesothelioma. Relan.
$25,000. 2010. 1 yr.
The Prince Charles Hospital Foundation
Novice Researcher Grant. NR2010-105. Effect
of AGER gene polymorphisms on lung function
and sRAGE levels in subjects with COPD.
Smith. $10,000. 2010. 1 yr.
The Prince Charles Hospital Foundation
Novice Researcher Grant. NR2010-107.
Biomarkers in the Diagnosis of Malignant
Pleural Mesothelioma (MPM) and Lung
Cancer. Sriram. $9,586. 2010. 1 yr.
The Prince Charles Hospital Foundation
Major Strategic Grant. MS2010-15.
Interventions to reduce pulmonary toxicity of
ultrafine particles. Yang. $107,941. 2011. 1 yr.
The Prince Charles Hospital Foundation
Major Strategic Grant. MS2010-30. Early
detection of life-threatening lung diseases
by breath analysis . Dent, Yang, Fong,
Zimmerman, Bowman, Chambers. $86,475.
2011. 1 yr.
Cote ML, Chen W, Smith DW, Benhamou S,
Bouchardy C, Butkiewicz D, Fong KM, Gene
M, Hirvonen A, Kiyohara C, Larsen JE, Lin P,
Raaschou-Nielsen O, Povey AC, Reszka E,
Risch A, Schneider J, Schwartz AG, Sorensen
M, To-Figueras J, Tokudome S, Pu Y, Yang P,
Wenzlaff AS, Wikman H, Taioli E. Meta- and
pooled analysis of GSTP1 polymorphism
and lung cancer: a HuGE-GSEC review. Am J
Epidemiol 2009;169:802-14.
Fong KM, Berend N, Nana A. Optimal Use of
Technology: 13th Congress of the Asian Pacific
Society of Respirology. Expert Review of
Respiratory Medicine 2009;3:9-11.
Kolb MR, Yang I. Respirology year-inreview 2008: basic science. Respirology
2009;14:318-26.
Savarimuthu Francis SM, Larsen JE, Pavey SJ,
Bowman RV, Hayward NK, Fong KM, Yang IA.
Expression profiling identifies genes involved
in emphysema severity. Respiratory research
2009;10:81.
Serginson JG, Yang IA, Armstrong JG, Cooper
DM, Matthiesson AM, Morrison SC, Gair JM,
Cooper B, Zimmerman PV. Variability in the
rate of prescription and cost of domiciliary
oxygen therapy in Australia. Med J Aust
2009;191:549-53.
Yang IA, Fong KM, Zimmerman PV, Holgate
ST, Holloway JW. Genetic susceptibility to the
respiratory effects of air pollution (Reprinted
from Thorax, vol 63, pg 555-63, 2008).
Postgrad Med J 2009;85:428-36.
Yang IA, Francis SM. Deconstructing
COPD using genomic tools. Respirology
2009;14:313-7.
Publications
Clarke MS, Wills RA, Bowman RV, Zimmerman
PV, Fong KM, Coory MD, Yang IA. Exploratory
study of the ‘weekend effect’ for acute medical
admissions to public hospitals in Queensland,
Australia. Intern Med J 2010;40:777-83.
Bowman RV, Wright CM, Davidson MR,
Francis SM, Yang IA, Fong KM. Epigenomic
targets for the treatment of respiratory
disease. Expert Opin Ther Targets
2009;13:625-40.
Davidson MR, Larsen JE, Yang IA, Hayward NK,
Clarke BE, Duhig EE, Passmore LH, Bowman
RV, Fong KM. MicroRNA-218 is deleted
and downregulated in lung squamous cell
carcinoma. PLoS ONE 2010;5:e12560.
Rebecca Cooper Medical Research
Foundation. COPD exacerbations. Yang.
$11,200. 2011. 1 yr.
93
Research Report 2010
Thoracic Medicine
University of Queensland Thoracic Research Centre
Fong KM, Shim Y, Park SH. 14th congress of
the APSR and 3rd Joint Congress of the APSR/
ACCP. Expert Rev Respir Med 2010;4:21-3.
Holloway JW, Yang IA, Holgate ST. Genetics
of allergic disease. J Allergy Clin Immunol
2010;125:S81-94.
Holloway JW, Yang IA, Holgate ST. The
potential of genetics in allergic diseases.
In: Pawankar R CG, Holgate ST, Lockey RF,
ed. WAO White Book on Allergy 2011-2012:
World Allergy Organization; 2011:Accepted
23/12/2010.
Nguyen AN, Lawley MJ, Hansen DP, Bowman
RV, Clarke BE, Duhig EE, Colquist S. Symbolic
rule-based classification of lung cancer stages
from free-text pathology reports. J Am Med
Inform Assoc 2010;17:440-5.
Yang IA, Relan V, Wright CM, Davidson MR,
Sriram BK, Savarimuthu Francis SM, Clarke
BE, Duhig EE, Bowman RV, Fong KM. Common
pathogenic mechanisms and pathways in
the development of COPD and lung cancer.
Expert Opinion On Therapeutic Targets 2011:
Accepted 13/1/2011.
Reddel HK, Upham JW, Salvi SS, Yang IA. Yearin-review 2009: Asthma, COPD and airway
biology. Respirology 2010;15:365-76.
Selected publication highlights
Samardhi H, Radford DJ, Fong KM.
Leeuwenhoek’s disease: diaphragmatic
flutter in a cardiac patient. Cardiol Young
2010;20:334-6.
Sriram KB, Larsen JE, Yang IA, Bowman RV,
Fong KM. Genomic Medicine in Non-Small Cell
Lung Cancer: Paving the Path to Personalised
Care. Respirology 2010:doi 10.1111/j.440843.2010.01892.x.
Sriram KB, Savarimuthu Francis SM, Tan ME,
Bowman RV, Yang IA, Fong KM. EGFR mutation
testing in non-small cell lung cancer. Current
Respiratory Medicine Reviews 2010:Accepted
6/7/2010. Manuscript number CRMR-6-4-1.
Wright CM, Larsen JE, Colosimo ML, Barr JJ,
Chen L, McLachlan RE, Yang IA, Bowman RV,
Fong KM. Genetic association study of CYP1A1
polymorphisms identifies risk haplotypes
in nonsmall cell lung cancer. Eur Respir J
2010;35:152-9.
Wright CM, Larsen JE, Hayward NK, Martins
MU, Tan ME, Davidson MR, Savarimuthu
SM, McLachlan RE, Passmore LH, Windsor
MN, Clarke BE, Duhig EE, Yang IA, Bowman
RV, Fong KM. ADAM28: a potential
oncogene involved in asbestos-related lung
adenocarcinomas. Genes Chromosomes
Cancer 2010;49:688-98.
94
ADAM28, PPP1CA, IRF6, RAB3D, and PRDX1.
Expression of these six genes was technically
and biologically replicated by qRT-PCR in the
training set and biologically validated in three
independent test sets. ADAM28, encoding
a disintegrin and metalloproteinase domain
protein that interacts with integrins, was
consistently upregulated in ARLC across all
four datasets.
Lung cancer
Wright CM, Larsen JE, Hayward NK, Martins
MU, Tan ME, Davidson MR, Savarimuthu
SM, McLachlan RE, Passmore LH, Windsor
MN, Clarke BE, Duhig EE, Yang IA, Bowman
RV, Fong KM. ADAM28: a potential
oncogene involved in asbestos-related lung
adenocarcinomas. Genes Chromosomes
Cancer 2010;49:688-98.
Genes involved in lung cancer related to
asbestos exposure
Asbestos-related lung cancer accounts for 4%
to 12% of all lung cancers worldwide. Since
putative mechanisms of carcinogenesis differ
between asbestos and tobacco induced lung
cancers, tumors induced by the two agents
may be genetically distinct.
To identify gene expression biomarkers
associated with asbestos-related lung
tumorigenicity we performed gene expression
array analysis on tumors of 36 patients with
primary lung adenocarcinoma, comparing
12 patients with lung asbestos body counts
above levels associated with urban dwelling
(ARLC-AC: asbestos-related lung canceradenocarcinoma) with 24 patients with no
asbestos bodies (NARLC-AC: non-asbestos
related lung cancer-adenocarcinoma). Genes
differentially expressed between ARLC-AC
and NARLC-AC were identified on fold change
and P value, and then prioritized using
gene ontology. Candidates included ZNRF3,
M. Martins
Further studies are being designed to
investigate the possible role of this gene in
asbestos lung tumorigenicity, its potential
utility as a marker of asbestos related lung
cancer for purposes of causal attribution, and
its potential as a treatment target for lung
cancers arising in asbestos exposed persons.
Davidson MR, Larsen JE, Yang IA, Hayward NK,
Clarke BE, Duhig EE, Passmore LH, Bowman
RV, Fong KM. MicroRNA-218 is deleted
and downregulated in lung squamous cell
carcinoma. PLoS ONE 2010;5:e12560.
Small molecules involved in lung cancer
MicroRNAs (miRNAs) are a family of small,
non-coding RNA species functioning as
negative regulators of multiple target genes
including tumour suppressor genes and
oncogenes. Many miRNA gene loci are located
within cancer-associated genomic regions.
To identify potential new amplified oncogenic
and/or deleted tumour suppressing miRNAs in
lung cancer, we inferred miRNA gene dosage
from high dimensional arrayCGH data. From
Research Report 2010
Thoracic Medicine
University of Queensland Thoracic Research Centre
miRBase v9.0, 474 human miRNA genes were
physically mapped to regions of chromosomal
loss or gain identified from a high-resolution
genome-wide arrayCGH study of 132 primary
non-small cell lung cancers (NSCLCs) (a
training set of 60 squamous cell carcinomas
and 72 adenocarcinomas). MiRNAs were
selected as candidates if their immediately
flanking probes or host gene were deleted or
amplified in at least 25% of primary tumours
using both Analysis of Copy Errors algorithm
and fold change (> +1.2) analyses. Using
these criteria, 97 miRNAs mapped to regions
of aberrant copy number. Analysis of three
independent published lung cancer arrayCGH
datasets confirmed that 22 of these miRNA
loci showed directionally concordant copy
number variation. MiR-218, encoded on
4p15.31 and 5q35.1 within two host genes
(SLIT2 and SLIT3), in a region of copy number
loss, was selected as a priority candidate for
follow-up as it is reported as underexpressed
in lung cancer. We confirmed decreased
expression of mature miR-218 and its host
genes by qRT-PCR in 39 NSCLCs relative to
normal lung tissue. This downregulation of
miR-218 was found to be associated with a
history of cigarette smoking, but not human
papilloma virus.
Thus, we show for the first time that putative
lung cancer-associated miRNAs can be
identified from genome-wide arrayCGH
datasets using a bioinformatics mapping
approach, and report that miR-218 is a
strong candidate tumour suppressing miRNA
potentially involved in lung cancer.
COPD
Savarimuthu Francis SM, Larsen JE, Pavey SJ,
Bowman RV, Hayward NK, Fong KM, Yang IA.
Expression profiling identifies genes involved
in emphysema severity. Respiratory research
2009;10:81.
What determines progression of chronic lung
disease?
Chronic obstructive pulmonary disease (COPD)
is a major public health problem. The aim of
this study was to identify genes involved in
emphysema severity in COPD patients.
Gene expression profiling was performed
on total RNA extracted from non-tumor lung
tissue from 30 smokers with emphysema.
Class comparison analysis based on gas
transfer measurement was performed to
identify differentially expressed genes. Genes
were then selected for technical validation
by quantitative reverse transcriptase-PCR
(qRT-PCR) if also represented on microarray
platforms used in previously published
emphysema studies. Genes technically
validated advanced to tests of biological
replication by qRT-PCR using an independent
test set of 62 lung samples. Class comparison
identified 98 differentially expressed genes
(p<0.01). Fifty-one of those genes had been
previously evaluated in differentiation
between normal and severe emphysema
lung. qRT-PCR confirmed the direction
of change in expression in 29 of the 51
genes and 11 of those validated, remaining
significant at p<0.05. Biological replication
in an independent cohort confirmed the
altered expression of eight genes, with seven
genes differentially expressed by greater
than 1.3 fold, identifying these as candidate
determinants of emphysema severity.
Controlling genes through modifying DNA
‘Epigenomic modifications’ are heritable
changes that do not require changes in DNA
sequence. A number of processes lead to
epigenetic and epigenomic modifications,
including DNA methylation, histone
modification and gene silencing by noncoding RNAs.
In lung cancer and mesothelioma, a number
of genes in biological pathways involved in
carcinogenesis have been demonstrated to
be hypermethylated, implicating epigenomic
changes in the aetiology of these cancers.
Hypermethylated genes have also been
associated with lung cancer recurrence,
pointing to epigenomic mechanisms of
regulation of metastasis. In airway diseases,
modulation of histone function may activate
inflammatory mechanisms in COPD patients
and lead to relative steroid resistance.
There is emerging evidence for the role of
epigenetic changes in chronic lung diseases
such as asthma, including responses to
environmental exposures in utero and to
the effects of air pollution. Insight into
epigenomics will lead to the development of
novel biomarkers and treatment targets in
respiratory diseases.
Gene expression profiling of lung from
emphysema patients identified seven
candidate genes associated with emphysema
severity including COL6A3, SERPINF1, ZNHIT6,
NEDD4, CDKN2A, NRN1 and GSTM3
Genomics
Bowman RV, Wright CM, Davidson MR, Francis
SM, Yang IA, Fong KM. Epigenomic targets for
the treatment of respiratory disease. Expert
Opin Ther Targets 2009;13:625-40.
95
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