Airways

Role

The role of the Airways Group is to foster productive interaction between each of its member groups.

The Airways Group consists of the research groups within the Woolcock working on some aspect of asthma research. The Group includes representatives from:

• Epidemiology
• Cell Biology & Molecular Medicine
• Allergen
• Clinical Management
• Airways Physiology and Clinical Trials Groups.

The leaders of each group meet weekly to plan and co-ordinate research activities and directions. These meetings provide a forum for discussion between the research leaders and foster a cooperative approach to research. They also create an opportunity to strengthen research capabilities through visitors, meetings, resource provision, training and education opportunities.

Research

The Airway Physiology Group has been studying the relationship between variability in ventilation and airway hyperresponsiveness, the cardinal clinical abnormality of the airway smooth muscle in people with asthma, and a testimony to their progress is the award of a new NHMRC grant, begun in 2007, titled “Does the pattern of ventilation distribution predict airway hyperresponsiveness?”

The Airways Physiology Group is working on the development of a simple physiological marker of airway remodelling, using the Forced Oscillation Technique (FOT) to measure the distensibility of the airways. The measurement of airway inflammation to assess asthma control and the effectiveness of treatment is becoming widely accepted but reliable, portable and affordable devices are needed for primary care use of this test, and for their use in children.

This research is part of the range of work being undertaken by the Airways Group’s within the CRC for Asthma and Airways. The group is also continuing to refine and validate the FOT and to compare it with spirometry for measuring airway calibre changes. This technique is simpler to perform but many issues have yet to be addressed regarding its applicability in day to day clinical practice.

In the Allergen Group, stand-out achievements in the last year include the development of a method for measurement of exhaled respiratory viruses, currently part of a project funded through the Commonwealth’s influenza pandemic planning initiative.

The Allergen Group continues its commitment to the development of nasal devices for sampling and prophylactic protection from allergen exposure.

The Epidemiology Group continues its wide array of activities, which encompass population respiratory health, particularly in asthma, documenting the national patterns of asthma prevalence and impact through ACAM, and this year in COPD, with the completion of the BOLD study in Sydney. BOLD (Burden of Obstructive Lung Disease) is a global project to describe the prevalence and morbidity from COPD, using a standardised protocol for data collection.

This will enable comparisons of COPD impact between countries and regions, and is likely to make a huge contribution to our understanding of the causes and consequences of COPD. With this awareness is likely to come a vision for change to address the root causes of this devastating lung disease which is still on the rise globally, and even in Australia.

Funding from the pharmaceutical industry enabled the Sydney BOLD study to take place and this provided the basis on which the application to the NHMRC to conduct BOLD in other regions, namely Melbourne, Busselton, Tasmania and the Kimberly, could be made.

The Epidemiology Group has also notched up another success in the last year with the publication of the main outcomes of the Childhood Asthma Prevention Study (CAPS).

The Imaging Group’s highlight included the microCT work on measuring airways from high-resolution 3-D CT images of inflation-fixed lung. This work made the cover of the European Respiratory Journal! At RNSH, Ben Harris and Dale Bailey have developed a novel method of quantifying ventilation and V/Q ratios using SPECT/CT. This should prove to have multiple clinical applications in pulmonary vascular disease, airways disease and lung cancer.

At a more than micro level, the Molecular Biology Group has continued to define the features of airway smooth muscle cells that regulate responses to corticosteroids. In COPD patients they observed that the expression and activation of another steroid receptor, a C/EBP-isoform is deregulated compared to healthy control and asthma patients’ cells. This particular receptor is a major regulator for extra-cellular matrix turnover is over-expressed in cells of COPD and emphysema patients. This observation offers important insights in relation to the genetic influences on airway smooth muscle and risk of asthma.

Another new observation from this group concerns the interaction between house dust mite and the corticosteroid binding receptor, C/EBP-α, which may shed light on the mechanisms by which allergen causes cell proliferation and inflammatory changes in asthmatic airways.

The Clinical Trials Group has continued to run early phase and Phase 3 multi-centre studies, but has encountered increasing difficulty in recruiting in the last year. For a variety of reasons, attracting people into clinical trials is becoming very hard work. People are too busy, not suitable for the studies because of the highly defined eligibility criteria, or very satisfied with their treatment, and therefore studies are taking longer to complete and are not cost effective.