The University of Newcastle, Australia

A breath of fresh air

Professor Jodie Simpson's pioneering research has changed the focus of asthma treatment and promises new relief for many who suffer from the disease.

Jodie Simpson near some trees

Making the transition from pure science to medical research involved a leap of faith for Professor Jodie Simpson, but the accomplished asthma researcher has not looked back since joining the University of Newcastle's leading respiratory group. The chemistry graduate's science background prompted her to approach research questions with a different perspective and subsequently led to a breakthrough finding about asthma subtypes that has brought her international recognition in the field.

Simpson was appointed as a research assistant with the respiratory team, based at the Hunter Medical Research Institute (HMRI), in 1997 after completing her Honours in chemistry. When she began studying asthma, the accepted treatment paradigm was using steroid-based medications to target inflammation in the airways caused by increased levels of eosinophils (a type of white blood cell). However, Simpson was puzzled by the fact that some asthma sufferers had normal levels of eosinophils, which led her to question whether there could be more than one type of the disease.

"I could never understand why it was assumed that all asthma was due to increased eosinophils when only about half of the patient studies we saw had that characterisation," Jodie reflects.

Encouraged by a small number of scholarly reports advocating a similar theory, Jodie embarked in 2002 on an ambitious PhD project investigating the inflammatory pathways of asthma, counting cells in sputum samples and analysing levels of enzymes and proteins. Simpson concluded that there were four subtypes of asthma and, significantly, identified a non-eosinophilic category common among people who did not respond well to conventional, steroid-based treatments. This subtype is characterised by higher levels of a different white blood cell, called the neutrophil.

Jodie's research led to a randomised control trial, conducted in Newcastle, which produced another breakthrough finding, published in 2008 in the American Journal of Critical and Respiratory Care Medicine. The study established that treating people who suffered from non-eosinophilic asthma with macrolide antibiotics successfully reduced their neutrophil levels and resulted in a clinical improvement in their condition. "It was a small study, but novel at the time, and it showed that identifying the inflammatory phenotype was important for the effective management of asthma," Simpson explains.

That original eight-week, 45-person study has since evolved into a four-year, 420-person national trial led by Professor Peter Gibson, with whom Simpson has worked closely, and funded by the National Health and Medical Research Council. The $2.9 million AMAZES trial (Asthma and Macrolides: the Azithromycin Efficacy and Safety Study) seeks to determine whether treating asthmatics with macrolides in addition to their normal medication can reduce the incidence of severe attacks, known as exacerbations, and ease their general symptoms.

"The focus of the AMAZES study is treatment but it has all developed from the original idea of characterising subtypes of asthma," Jodie says. "Instead of a blanket treatment for everyone who has asthma, we can now move towards a more individualised approach, drawing from a range of effective treatments."

As well as working on the AMAZES trial, Simpson has instigated a series of peripheral studies aimed at increasing understanding of non-eosinophilic asthma. One project is testing the extent to which sufferers can reduce their steroid medication without a detrimental impact on their health; another is testing alternatives to macrolide antibiotics for reducing inflammation; and a third is investigating possible triggers for the condition, such as reflux and cough. She is also working with colleague Dr Katie Baines to advance the characterisation of asthma subtypes through gene expression.

"Substantial progress has been made in understanding non-eosinophilic asthma but there is far more that we need to know," Jodie acknowledges.  "We want to attack it from all angles."

Off to a flying start

How does a chemistry graduate come to supervise a medical trial for her first postdoctoral project? For Dr Jodie Simpson, the encouragement of her supervisor and mentor Professor Peter Gibson was critical to her rapid and successful induction to the field of asthma research.Professor Gibson is co-director of the HMRI Viruses, Infections/Immunity, Vaccines and Asthma (VIVA) Program and has been an influential figure in Simpson's career.

"What he did from the beginning was provide opportunity," Jodie says. "I came to the team with an Honours degree in chemistry and he gave me the chance to learn about the clinical side of research and participate in it. To be able to lead a clinical trial for my first project after my PhD was such a wonderful opportunity."

The insight into clinical issues that Jodie gained from working with Professor Gibson has greatly enhanced her work. "When you are in the lab counting cells and measuring proteins, you can lose the sight of the fact that this is all about a person out there who is struggling to breathe and function," she advises. "Working in this team, where we can combine basic science and clinical work, has given me a more rounded perspective."

The mother of young children acknowledges that the supportive environment at the University and HMRI for researchers with young families has been critical to her work. "As researchers we are passionate about what we do and it is important to have the support to remain productive during periods where we might have to modify our working commitments."

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