Research at Lung and Allergy Research Centre

This past year has seen further growth in the Centre, and has been highly productive for all concerned with success in attracting research funding, multiple publications in peer-reviewed journals and book chapters, and a successful patent application.

The research of the group is well supported with grants from NH&MRC, and the Asthma Foundation of Queensland.

Key achievements have included:

  • Investigating the importance of antigen presenting dendritic cells (DC) in the pathogenesis of human allergic disease, confirming the importance of DC in asthma.
  • Describing the key determinants of host defence against viral infections in chronic respiratory disease, with particular emphasis on the function of plasmacytoid dendritic cells innate interferon production, interleukin 33 and understanding how this varies in people with severe asthma
  • Showing that that low doses of the macrolide antibiotic azithromycin over 48 weeks reduce severe asthma exacerbations by 41% compared with placebo.

Recent publications

  1. Taylor SL, Leong L, Choo JM, Wesselingh S, Yang IA, Upham JW, Reynolds PN, et al. Inflammatory phenotypes in severe asthma are associated with distinct airway microbiology. J Allergy Clin Immunol 2018 Jan; 141: 94-103. PubMed PMID: 28479329
  2. Revez JA, Killian K, O’Byrne PM, Boulet L-P, Upham JW, Gauvreau GM, Ferreira MA. Sputum cytology during late phase responses to inhalation challenge with different allergens. Allergy 2018; 73 (7): 1470-1478. doi.org/10.1111/all.13415 PubMed PMID: 29337345.
  3. Chen AC-H, Tran H, Xi Y, Yerkovich ST, Baines K, Pizzutto S, Carroll M, Robertson A, Cooper M, Schroder K, Simpson J, Gibson PG, Hodge G, Masters IB, Buntain H, Petsky H, Gardiner S, Chang AB, Hodge S, Upham JW. Multiple inflammasomes may regulate the IL-1-driven inflammation in protracted bacterial bronchitis. ERJ Open Research 2018 Mar 23;4(1). pii: 00130-2017. doi:10.1183/23120541.00130-2017. eCollection 2018 Jan. PubMed PMID: 29594175
  4. Chen AC-H, Pena OM, Nel HJ, Yerkovich ST, Chang AB, Baines KJ, Gibson PG, Petsky HL,Pizzutto SJ, Hodge S, Masters IB, Buntain HL, Upham JW. Airway cells from protracted bacterial bronchitis and bronchiectasis share similar gene expression profiles. Pediatric Pulmonology 2018 May;53(5):575-582. doi: 10.1002/ppul.23984. PMID: 29575797
  5. Werder RB, Zhang V, Lynch JP, Snape N, Upham JW, Spann K, Phipps S. Chronic IL-33 expression predisposes to viral-induced exacerbations of asthma by increasing type-2 inflammation and dampening antiviral immunity. J Allergy Clin Immunol 2018 May;141(5):1607-1619.e9. doi: 10.1016/j.jaci.2017.07.051. PMID: 28947081
  6. Werder RB, Lynch JP, Simpson JC, Zhang V, Hodge NH, Poh M, Forbes-Blom E, Kulis C, Smythe ML, Upham JW, Spann K, Everard ML, Phipps S. PGD2/DP2 receptor activation promotes severe viral bronchiolitis by suppressing IFN-λ production. Science Translational Medicine 2018 May; Vol. 10, Issue 440, eaao0052. DOI: 10.1126/scitranslmed.aao0052
  7. Hiles S, Harvey E, McDonald V, Peters M, Bardin P, Reynolds P, Upham JW, Baraket M, et al, Working while unwell: Workplace impairment in people with severe asthma. Clin Exp Allergy 2018 Vol. 48 (6):650-662. doi: 10.1111/cea.13153. PMID: 29676834
  8. Upham JW, Chung LP. Optimising treatment for severe asthma. Med J Aust 2018; 209 (2 Suppl): S22-S27. || doi: 10.5694/mja18.00175
  9. Upham JW. The Bronchial Epithelial IgE Secretory IgA System in Asthma. Amer J Resp Crit Care Med 2018 Nov 1;198(9):1236. PMID: 30059233
  10. Jurak LM, Xi Y, Landgraf M, Carroll M, Murray L, Upham JW. Interleukin 33 selectively augments rhinovirus-induced type 2 immune responses in asthmatic but not healthy people. Frontiers in Immunology 2018 Aug 16;9:1895. doi:10.3389/fimmu.2018.01895. PMID: 30174671
  11. V. M. McDonald, S. A. Hiles, K. Godbout, E. S. Harvey, G. B. Marks, M. Hew, M. Peters, P. Bardin, P. N. Reynolds, JW Upham, et al. Treatable traits can be identified in a severe asthma registry and predict future exacerbation. Respirology (in press; accepted 1st August 2018).
  12. Chung LP, Hew M, Bardin P, McDonald VM, Upham JW Managing patients with severe asthma in Australia: current challenges with the existing models of care. Intern Med J 2018 (in press; accepted 29 July 2018)
  13. Menzies-Gow A, Canonica GW, Winders T, Correia de Sousa J, Upham JW, Fink-Wagner AH. A Charter to Improve Patient Care in Severe Asthma. Adv Ther 2018; Oct;35(10):1485-1496 https://doi.org/10.1007/s12325-018-0777-y. PMID: 30182174
  14. Fanning M, Upham J. Reducing the burden of severe asthma. Respiratory Medicine Today 2018; 3(2): 10-14.
  15. Murray L, Xi Y, Upham JW. CLEC4C gene expression can be used to quantify circulating plasmacytoid dendritic cells. J Immunol Methods 2018 (in press; accepted 1/11/2018).

Student projects

Quality, innovative research is a major component of the UQ Medicine's commitment to world-class education and health outcomes. The Faculty of Medicine offers the postgraduate research degrees of Doctor of Philosophy (PhD) and Master of Philosophy (MPhil).

Visit our Research Higher Degrees page for more information.

The Lung and Allergy Research Centre is actively involved in postgraduate supervision, and has numerous student research projects underway.

1. Protection against respiratory virus infections.

Supervisor: Prof John Upham
Contact: j.upham@uq.edu.au +61 7 3443 8024

Immune cells and structural cells in the lungs combine to provide protection against virus infections in healthy people. The project will examine how dendritic cells interact with the epithelial cells that line the airways to provide optimal immunity against respiratory viruses. 

2. Asthma, common cold viruses and the immune system.
Supervisor: Prof John Upham
Contact: j.upham@uq.edu.au +61 7 3443 8024

The common cold virus (human rhinovirus) is the most common trigger for flare-ups of asthma, but why an innocuous virus should cause major problems has long been a puzzle. The project will examine the function of various immune cells and regulation of interferon in people with asthma.

3.  Understanding how azithromycin prevents exacerbations in severe asthma. Supervisor: Prof John Upham
Contact: j.upham@uq.edu.au +61 7 3443 8024

There is an important need for new interventions in asthma, especially for those whose disease remains poorly controlled despite conventional treatments such as inhaled steroids and long acting bronchodilators. We recently completed the NHMRC funded AMAZES study: this randomised control trial enrolled 420 participants, showing that low doses of the macrolide antibiotic azithromycin over 48 weeks reduce severe asthma exacerbations by 41% compared with placebo (p=0·002). Azithromycin appears therefore to be a highly effective ‘add-on’ treatment in this population, however the mechanisms of action of azithromycin are not well understood, and there is a need to better identify which people with severe asthma are most likely to respond.

4. How efficiently does influenza vaccination work in people with chronic lung disease, and can this be improved through lifestyle interventions?
Supervisor: Prof John Upham
Contact: j.upham@uq.edu.au +61 7 3443 8024

People with chronic lung disease are at increased risk of serious complications following influenza infection. The project will improve understanding of influenza vaccination and examine ways to make vaccination more effective.

Giving

Funds received through donations, gifts and bequests will help us stay at the cutting edge of research, and directly benefit our research programs which are to improve the health outcomes for people with asthma, allergies and chronic lung diseases, as well as benefit the general community.

If you would like to show your support, you can direct your donation to the Lung and Allergy Research Centre by completing The University of Queensland online donation form

To ensure your gift is directed towards the research programs within this Centre, please select "Other" on the online donation from and specify the Lung and Allergy Research Centre, under the Area of Funding.

The Lung and Allergy Research Centre team would like to thank the members of the public and organisations that have recognised our research efforts and continue to support our endeavours.