Respiratory, Immunology and Inflammation
- A/Prof Graham Hall, Telethon Kids institute (firstname.lastname@example.org)
- Dr Elysia Hollams, Telethon Kids Institute (email@example.com)
List of local Investigators (name and affiliation)
- Sunil Bhat, University of Western Australia
- Prof Peter Eastwood, University of Western Australia
- Prof Mark Everard, University of Western Australia
- Dr Peter Franklin, University of Western Australia
- A/Prof Graham Hall, Telethon Kids Institute
- Dr Elysia Hollams, Telethon Kids Institute
- Prof Patrick Holt, Telethon Kids Institute
- Prof Jeffrey Keelan, University of Western Australia
- A/Prof Anthony Kicic, Telethon Kids Institute
- A/Prof Alexander Larcombe, Telethon Kids Institute
- Prof Peter le Souef, University of Western Australia
- Dr Ashleigh Lin, Telethon Kids Institute
- Prof Peter Sly, University of Queensland
- A/Prof Deb Strickland, Telethon Kids Institute
- Dr Phil Stumbles, Murdoch University
- Dr Kimberley Wang, Telethon Kids Institute
- Ms Elisha White, Telethon Kids Institute
Overview of the current data resources available in the SIG area
Overview of current/recent SIG activity
Outline of SIG plans for next 5 years
- Promote the use of existing under-utilised Raine Study data by new research projects
- Promote co-operative efforts to undertake a new Raine Study follow-up focussing on respiratory health, immune function and/or inflammation, in collaboration with other SIGs
Brief list of potential student/early career researcher projects
Please contact the Respiratory, Immunology and Inflammation SIG Leaders if you are interested in a research project incorporating Respiratory, Immunology and Inflammation data and they will coordinate whom to contact within the group.
List of National/International Collaborating Investigators (name and affiliation)
- Prof Peter Sly, University of Queensland
- Prof Zoltan Hantos, University of Szeged, Hungary
- Prof Adnan Custovic, Imperial College, United Kingdom
- Prof Shyamali Dharmage, University of Melbourne, Canada
- Prof Fernando Martinez, University of Arizona, U.S.A.
- A/Prof Padmaja Subbarao, University of Toronto, Canada
- Prof John Henderson, University of Bristol, United Kingdom
Top 5-10 key findings (with reference)
- Examination of newborn participants of the Raine Study demonstrated that in utero smoke exposure, a family history of asthma, and maternal hypertension during pregnancy were associated with reduced respiratory function after birth. It was speculated that these factors adversely affect lung development in utero. Stick, S. M., P. R. Burton, L. Gurrin, P. D. Sly and P. N. LeSouëf (1996). “Effects of maternal smoking during pregnancy and a family history of asthma on respiratory function in newborn infants.” The Lancet 348(9034): 1060-1064.
- Introduction of milk other than breast milk before 4 months of age was found to be a risk factor for asthma and allergy at age 6 years. Oddy WH, Holt PG, Sly PD, Read AW, Landau LI, Stanley FJ, Kendall GE, Burton PR. Association between breast feeding and asthma in 6 year old children: findings of a prospective birth cohort study. BMJ. 1999;319(7213):815-9.
- Concentrations of a panel of immunological messengers known as cytokines were measured in umbilical cord blood. Low concentrations of the cytokines interleukin-4 and interferon-gamma at birth were linked to increased risk for asthma, wheeze or allergy at age 6 years. Levels of these two cytokines appeared to be reduced by maternal smoking in pregnancy. Macaubas C, de Klerk NH, Holt BJ, Wee C, Kendall G, Firth M, Sly PD, Holt PG. Association between antenatal cytokine production and the development of atopy and asthma at age 6 years. Lancet. 2003;362(9391):1192-7.
- Comprehensive immune function profiling of Raine Study participants was performed at age 14, yielding the largest such dataset published to date. 10% of the 1380 children studied were asthmatic, and 81% of asthmatics had one or more allergies, with house dust mite allergy the most common. This study demonstrated for the first time that normal pro-inflammatory mechanisms unrelated to allergy appear to heighten risk for asthma only in children with allergy, and suggested that prevention of allergy may reduce asthma rates in childhood. Hollams EM, Deverell M, Serralha M, Suriyaarachchi D, Parsons F, Zhang G, de Klerk N, Holt BJ, et al. Elucidation of asthma phenotypes in atopic teenagers through parallel immunophenotypic and clinical profiling. Journal of Allergy & Clinical Immunology. 2009;124(3):463-70, 70.e1-16.
- Measurement of the storage form of vitamin D, from serum collected during the 6y and 14y follow-ups, showed that vitamin D deficiency was common amongst Raine Study children during the winter months (9%). Low vitamin D at age 6y was linked with allergy at age 6y, predominantly in boys, and this relationship remained at age 14y. Furthermore, low vitamin D at age 6y was linked to an increased risk of asthma at age 14y, supporting evidence from other studies suggesting that a lack of vitamin D may promote asthma development. Hollams EM, Hart PH, Holt BJ, Serralha M, Parsons F, De Klerk NH, Zhang G, Sly PD, Holt PG. Vitamin D and atopy and asthma phenotypes in children: a longitudinal cohort study. European Respiratory Journal. 2011;38:1320-7.
- Analysis of data from the age 14 follow-up found that maternal smoking during pregnancy increases the risk for asthma that persists into adolescence, even in adolescents with normal lung function. In contrast, maternal smoking in pregnancy was not associated with diminished immune function or risk for allergy in adolescence. Hollams EM, de Klerk NH, Holt PG, Sly PD. Persistent effects of maternal smoking during pregnancy on lung function and asthma in adolescents. American Journal of Respiratory & Critical Care Medicine. 2014;189(4):401-7.
- A machine learning approach was used to identify distinct patterns of cytokine (immunological messenger) expression in response to house dust mite, which were consistent between children with house dust mite allergy from the Raine Study (age 14) and the Manchester Asthma and Allergy cohort (10y, UK). Six classes of cytokine response were identified, and risk for asthma differed according to response class. This study suggests that the use of cytokine-targeted approaches for asthma prevention or treatment is more likely to be effective if a “personalized medicine” approach is utilised. Wu J, Prosperi MC, Simpson A, Hollams EM, Sly PD, Custovic A, Holt PG. Relationship between cytokine expression patterns and clinical outcomes: two population-based birth cohorts. Clinical & Experimental Allergy. 2015;45(12):1801-11.
- To determine how networks of genes are differentially expressed in immune cells from healthy adolescents versus those with allergy or allergic asthma, this study combined the cutting edge techniques of transcriptome profiling and a systems biology analytical approach. This approach identified “hub” genes, which appear to control expression of other genes to either protect against or promote disease, and which are logical targets for new asthma therapies. Troy NM, Hollams EM, Holt PG, Bosco A. Differential gene network analysis for the identification of asthma-associated therapeutic targets in allergen-specific T-helper memory responses. BMC Medical Genomics. 2016;9(1):9.
- This study aimed to quantify the diagnostic utility of mannitol challenge testing for asthma within the 22-year Raine Study follow-up. We found that when the mannitol test is applied to groups with symptoms suggestive of asthma, it is a useful tool with a high correlation between positive test and a diagnosis of asthma. However, when used in non-clinical groups (those who have no symptoms of asthma), a positive mannitol test is no longer correlated very highly at all with an asthma diagnosis. White EC, de Klerk NH, Hantos Z, Priston M, Hollams EM, James A, Sly PD, Holt PG, Hall GL. “Mannitol challenge testing for asthma in a community cohort of young adults.” Respirology, In Press: available online November 2016.
Additional recent publications
- Jones AC, Troy NM, White E, Hollams EM, Gout AM, Ling KM, Kicic A, Sly PD, Holt PG, Hall GL, Bosco A. Persistent activation of interlinked Th2-airway epithelial gene networks in sputum-derived cells from aeroallergen-sensitized symptomatic atopic asthmatics. bioRxiv. 2016 Jan 1:063602.
- Holt PG, Strickland D, Bosco A, Belgrave D, Hales B, Simpson A, Hollams E, Holt B, Kusel M, Ahlstedt S, Sly PD. Distinguishing benign from pathologic TH2 immunity in atopic children. Journal of Allergy and Clinical Immunology. 2016;137:379-87.
- Collins RA, Parsons F, Deverell M, Hollams EM, Holt PG, Sly PD. Risk factors for bronchial hyperresponsiveness in teenagers differ with sex and atopic status. Journal of Allergy and Clinical Immunology. 2011 Aug 31;128(2):301-7.
- Hollams EM, Hales BJ, Bachert C, Huvenne W, Parsons F, de Klerk NH, Serralha M, Holt BJ, Ahlstedt S, Thomas WR, Sly PD. Th2-associated immunity to bacteria in teenagers and susceptibility to asthma. European Respiratory Journal. 2010 Sep 1;36(3):509-16.
- Roponen M, Yerkovich ST, Hollams E, Sly PD, Holt PG, Upham JW. Toll-like receptor 7 function is reduced in adolescents with asthma. European Respiratory Journal. 2010 Jan 1;35(1):64-71.
List of current/recent grants for Raine Study projects
- National Health and Medical Research Council of Australia (NHMRC) Project Grant #1080492: 2015-2017 $713,813 – Professor Patrick Holt, Dr Elysia Hollams, Dr Anthony Bosco. “Waxing and waning of asthma during transition from the teens to adulthood: identification of immunophenotypic markers to predict disease trajectory and guide development of treatment strategies to prevent progression to chronicity.”
- NHMRC Project Grant 1021858: 2012-2015 $984,248 – A/Prof Graham Hall, Professor Patrick Holt, Dr Elysia Hollams, Professor Zoltan Hantos. “Predicting asthma in young adults.”
Examples of recent media