Prof Nick Freezer - Researcher Profile

Nick Freezer

Address

Department of Paediatrics, Level Three
Southern Clinical School, Clayton

Contact Details

Tel: +61 3 9594 3633

Email: Nick.Freezer@monash.edu


Biography

Making it easier and safer for children to breathe

Our first breaths are our most important, but for the growing number of children with asthma, they can also be the most traumatic, especially when the best asthma treatment can damage their health. Professor Nick Freezer was among the first group of researchers to alert the world to the dangers of overdosing asthmatic children with inhaled corticosteroids.

Nothing quite shows how finely-tuned we are to our environment as the research Professor Nick Freezer has done into children with asthma, the most common reason for child hospital admissions.

As children, our sensitive, undeveloped immune system and small airways encounter new infections constantly and, sometimes, powerful medications, intended to help us.

Nick was a member of the first team of researchers to show that high doses of our best asthma treatment – corticosteroids, inhaled through a puffer – were affecting children’s ability to fight disease.

“We were seeing higher and higher doses of corticosteroids and starting to see side effects,” he says. “These children were very unwell and needed intensive care as they became lethargic and comatose.”

The work of his team at Southampton University in the early 1990s was confirmed by other researchers and led to a complete overhaul of corticosteroid use.

The research showed that high doses of corticosteroids tricked the body’s adrenal system, which produces natural steroids to help fight infections, into thinking it didn’t need to add to the steroid load, leaving children unable to fight infections properly. 

The researchers also found restricted growth in highly dosed children, and later research by Nick at Monash showed enough reduction in bone density to increase the risk of fractures.

Children overcome these side effects when their doses of corticosteroids are reduced.

In his battle against the overuse of corticosteroids, Nick and his team at Monash also found that children who had infrequent asthma attacks didn’t need to be on the treatment all the time – as thought by some European doctors.   

Thanks to the work of Nick and researchers like him, national guidelines in the UK, Australia and elsewhere now ask doctors to consider non-steroid asthma treatments before trying corticosteroids.

But as corticosteroids are so effective – they’ve “revolutionised” asthma treatment, Nick says – the guidelines also suggest that doctors lower the dose once they’ve controlled asthma using them until they find a minimum effective amount.

Packaging instructions now recommend mouth-rinsing after inhaling corticosteroids to get rid of any excess that would otherwise enter the bloodstream.

Nick says the most likely cause of the growing incidence of asthma in children in the developed world is our success at fighting bacterial infections, which has left us more vulnerable to virus infections – the main cause of asthma attacks.

“If you grow up in a first world country, you have ready access to antibiotics and don’t get the chronic bacterial infections found in the developing world,” he says. “But your immune system is skewed toward the allergic spectrum of reactions, especially to virus infections, which cause 85 per cent of asthma attacks.”

Nick says we’ll continue to rely on corticosteroids because our best virus vaccines only protect against influenza and not rhinovirus – the common cold – which is the most common asthma trigger, especially in winter and spring.

When infected by a virus, asthma sufferers have an allergic reaction as their airways become inflamed and narrow and their mucous production increases.

Attacks can occur often and prove very distressing in children, which is why they’re the main cause of child hospital admissions. But they become less frequent for most children as they mature.

“About 70 per cent of children have infrequent, episodic asthma, so aren’t on regular treatment,” Nick says. “About 20 per cent have frequent, episodic asthma and about five per cent have persistent asthma with symptoms most days.”

So, about 25 per cent of children need a corticosteroid preventer, particularly in winter, exposing them to possible side effects without a proper asthma management plan.

As Professor and Head of Paediatrics at Monash University, the Medical Director of the Women’s and Children’s Program for Southern Health, where he’s also Medical Director of Monash Children’s, and as a practising respiratory physician, Nick continues to research the dangers of corticosteroid use in children, especially children aged under six.

“That age group hasn’t really been studied much in the world literature, and their immune system is so undeveloped and sensitive that even if we give them the lowest possible dosage we don’t know if that’s causing side effects.”

Qualifications

DOCTOR OF MEDICINE
Institution: The University of Melbourne
Year awarded: 1994
MBBS
Institution: The University of Tasmainia
Year awarded: 1981
BACEHLOR OF MEDICAL SCIENCE
Institution: University of Tasmainia
Year awarded: 1978

Publications

Journal Articles

King, P.T., Holdsworth, S.R., Farmer, M., Freezer, N., Holmes, P., 2012, Chest pain and exacerbations of bronchiectasis, International Journal of General Medicine [E], vol 5, Dove Medical Press Ltd, United Kingdom, pp. 1019-1024.

Tan, J.Z.Y., Ditchfield, M., Freezer, N., 2012, Tracheobronchomalacia in children: review of diagnosis and definition, Pediatric Radiology [P], vol 42, issue 8, Springer, Germany, pp. 906-915.

King, P., Holdsworth, S., Freezer, N., Villanueva, E.V., Farmer, M., Guy, P., Holmes, P., 2010, Lung diffusing capacity in adult bronchiectasis: A longitudinal study, Respiratory Care [P], vol 55, issue 12, Daedalus Enterprises, Inc., United States, pp. 1686-1692.

Stockx, E.M., Camilleri, P., Skuza, E.M., Churchward, T., Howes, J., Ho, M., McDonald, T., Freezer, N., Hamilton, G.S., Wilkinson, M.H., Berger, P.J., 2010, New acoustic method for detecting upper airway obstruction in patients with sleep apnoea, Respirology [E], vol 15, issue 2, Wiley-Blackwell Publishing Asia, Australia, Japan, pp. 326-335.

King, P.T., Bennett-Wood, V.R., Hutchinson, P.E., Robins-Browne, R.M., Holmes, P., Freezer, N., Holdsworth, S.R., 2009, Bactericidal activity of neutrophils with reduced oxidative burst from adults with bronchiectasis, APMIS : acta pathologica, microbiologica, et immuno..., vol 117, issue 2, Wiley-Blackwell Munksgaard, Denmark, pp. 133-139.

King, P.T., Holdsworth, S.R., Farmer, M., Freezer, N., Villanueva, E.V., Holmes, P., 2009, Phenotypes of adult bronchiectasis: Onset of productive cough in childhood and adulthood, C O P D: Journal of Chronic Obstructive Pulmonary, vol 6, issue 2, Informa Healthcare, United States, pp. 130-136.

Calderon, C.A., Rivera, L., Hutchinson, P.E., Dagher, H., Villanueva, E.V., Ghildyal, R., Bardin, P.G., Freezer, N., 2009, T-cell cytokine profiles are altered in childhood asthma exacerbation, Respirology [P], vol 14, issue 2, Wiley-Blackwell Publishing Asia, Australia, pp. 264-269.

Thomas, B., Lindsay, M., Dagher, H., Freezer, N., Li, D., Ghildyal, R., Bardin, P., 2009, Transforming growth factor-beta enhances rhinovirus infection by diminishing early innate responses, American Journal Of Respiratory Cell And Molecular Biology [P], vol 41, issue 3, American Thoracic Society, USA, pp. 339-347.

King, P.T., Holdsworth, S.R., Freezer, N., Villanueva, E.V., Holmes, P.W., 2007, Microbiologic follow-up study in adult bronchiectasis, Respiratory Medicine, vol 101, issue 8, WB Saunders Co Ltd, UK, pp. 1633-1638.

Maclennan, C., Hutchinson, P.E., Holdsworth, S.R., Bardin, P., Freezer, N., 2006, Airway inflammation in asymptomatic children with episodic wheeze, Pediatric Pulmonology, vol 41, issue 6, John Wiley & Sons, Inc., Hoboken USA, pp. 577-583.

King, P.T., Hutchinson, P.E., Holmes, P., Freezer, N., Bennett-Wood, V.R., Robins-Browne, R.M., Holdsworth, S.R., 2006, Assessing immune function in adult bronchiectasis, Clinical and Experimental Immunology, vol 144, issue 3, Blackwell Publishing, Oxford England, pp. 440-446.

King, P.T., Holdsworth, S.R., Freezer, N., Holmes, P., 2006, Bronchiectasis, Internal Medicine Journal, vol 36, issue 11, Blackwell Science Asia, Australia, pp. 729-737.

Doyle, L., Faber, B., Callanan, C., Freezer, N., Ford, G., Davis, N., 2006, Bronchopulmonary dysplasia in very low birth weight subjects and lung function in late adolescence, Pediatrics [P], vol 118, issue 1, American Academy of Pediatrics, USA, pp. 108-113.

King, P.T., Holdsworth, S.R., Freezer, N., Villanueva, E.V., Holmes, P., 2006, Characterisation of the onset and presenting clinical features of adult bronchiectasis, Respiratory Medicine, vol 100, issue 12, W B Saunders, UK, pp. 2183-2189.

Dharmage, S.C., Walters, E.H., Thien, F., Bailey, M., Raven, J., Wharton, C., Rolland, J.M., Light, L., Freezer, N., Abramson, M.J., 2006, Encasement of bedding does not improve asthma in atopic adult asthmatics, International Archives of Allergy and Immunology, vol 139, issue 2, Karger, Basil Switzerland, pp. 132-138.

Doyle, L., Anderson, P., Callanan, C., Carse, E.A., Casalaz, D., Charlton, M., Davis, N., Duff, J., Ford, G., Fraser, S., Freezer, N., Hayes, M., Kaimakamis, M.A., Kelly, E., Opie, G., Watkins, A., Woods, H., Yu, V.Y.H., 2006, Respiratory function at age 8-9 years in extremely low birthweight/very preterm children born in Victoria in 1991-1992, Pediatric Pulmonology, vol 41, Wiley-Liss, Inc, Hoboken USA, pp. 570-576.

De Silva, D., Dagher, H., Ghildyal, R., Lindsay, M.L., Li, X., Freezer, N., Wilson, J.W., Bardin, P., 2006, Vascular endothelial growth factor induction by rhinovirus infection, Journal of Medical Virology, vol 78, issue 5, John wiley & Sons, Inc, Hoboken USA, pp. 666-672.

Hughes, A.J., Hutchinson, P.E., Gooding, T., Freezer, N.J., Holdsworth, S.R., Johnson, P.D.R., 2005, Diagnosis of Mycobacterium tuberculosis infection using ESAT-6 and intracellular cytokine cytometry, Clinical and Experimental Immunology, vol 142, issue 1, Blackwell Publishing Ltd, UK, pp. 132-139.

King, P.T., Holdsworth, S.R., Freezer, N.J., Villanueva, E.V., Gallagher, M., Holmes, P., 2005, Outcome in adult bronchiectasis, COPD: Journal of Chronic Obstructive Pulmonary Disease, vol 2, issue 1, Informa Healthcare, London UK, pp. 27-34.

Ghildyal, R., Dagher, H., Donninger, H.M., De Silva, D.G., Xun, L., Freezer, N., Wilson, J.W., Bardin, P.G., 2005, Rhinovirus infects primary human airway fibroblasts and induces a neutrophil chemokine and a permeability factor, Journal of Medical Virology, vol 75, issue 4, John Wiley & Sons, Inc., USA, pp. 608-615.

Lyell, P.J., Villanueva, E.V., Burton, D., Freezer, N.J., Bardin, P.G., 2005, Risk factors for intensive care in children with acute asthma, Respirology, vol 10, issue 4, Blackwell Publishing Asia, Australia, pp. 436-441.

Holmes, P., Armstrong, D., Freezer, N., 2005, Smoothing the transition to adult care [3], Medical Journal Of Australia [P], vol 183, issue 3, Australasian Medical Publishing Company Pty. Ltd., LEVEL 2, 26-32 PYRMONT BRIDGE RD, PYRMONT, NSW 2009, AUSTRALIA, p. 164.

Griffiths, A.L., Sim, D., Strauss, B.J.G., Rodda, C.P., Armstrong, D., Freezer, N., 2004, Effect of high-dose fluticasone propionate on bone density and metabolism in children with asthma, Pediatric Pulmonology, vol 37, Wiley-Liss, Div. John Wiley & Sons Inc., Hoboken USA, pp. 116-121.

Sim, D., Griffiths, A., Armstrong, D., Clarke, C.F., Rodda, C.P., Freezer, N., 2003, Adrenal suppression from high-dose inhaled fluticasone propionate in children with asthma, European Respiratory Journal, vol 21, issue 4, European Respiratory Society, Sheffield UK, pp. 633-636.

King, P.T., Hutchinson, P., Johnson, P.D., Freezer, N., Holdsworth, S.R., 2002, Adaptive Immunity to Nontypeable Haemophilus influenzae, American Journal of Respiratory and Critical Care Medicine, vol Online, American Thoracic Society, New York NY USA, pp. 1-45.

Frey, B., Freezer, N., 2001, Diagnostic value and pathophysiologic basis of pulsus paradoxus in infants and children with respiratory disease, Paediatric Pulmonology, vol 31, issue 2, Wiley-Liss, USA, pp. 138-143.

Postgraduate Research Supervisions

Completed Supervision

Student:
King, P.
Program of Study:
ADULT BRONCHIECTASIS: CLINICAL FEATURES, PATHOGENESIS AND TREATMENT. (PHD) 2003.
Supervisors:
Holdsworth, S (Main), Freezer, N (Associate).