Respiratory, Immunology and Inflammation

Our Respiratory, Immunology and Inflammation Special Interest Group is able to investigate areas of research relating to respiratory health and immune function and/or inflammation. The group has a range of measures on our participants relating to history of asthma and allergy, respiratory function, markers of inflammation and immune response, across different ages within the Raine Study.

SIG Leaders:

Dr Rachel Foong, Telethon Kids Institute

Dr John Blakey, Curtin University

Key findings over the last 30 years have included:

Using information collected from the Raine Study participants, researchers found that different factors during pregnancy, such as maternal smoking, hypertension and family history of asthma where associated with reduced respiratory function in newborn babies. Maternal smoking during pregnancy also seems to increase the risk for asthma that persists into adolescence, but was not associated with worse immune function or risk of allergy in adolescence. A comprehensive assessment of Raine Study participants’ immune function was done at age 14, the largest such dataset published to date, which suggested that prevention of allergy may reduce asthma rates in childhood. Additionally, researchers showed that the mannitol challenge test is an useful tool to help diagnose asthma in people who have symptoms suggestive of asthma. Raine Study data was also used to identify genes that appear to control expression of other genes to either protect against or promote disease, which are logical targets for new asthma therapies, as well as contributed to international collaboration that identified new genetic locations related to asthma.

Maternal smoking, a family history of asthma, and maternal hypertension during pregnancy were associated with reduced respiratory function after birth, which could be due to these factors adversely affecting lung development in utero.  

  • Stick SM, Burton PR, Gurrin L, Sly PD,  LeSouëf PN.Effects of maternal smoking during pregnancy and a family history of asthma on respiratory function in newborn infants. The Lancet. 1996;348(9034):1060-64.

Maternal smoking during pregnancy increases the risk for asthma that persists into adolescence, even in adolescents with normal lung function, but not associated with reduced 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.
  • 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.

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.

Comprehensive immune function profiling of Raine Study participants was performed at age 14, demonstrating for the first time that normal pro-inflammatory mechanisms unrelated to allergy appear to heighten risk for asthma only in children with allergy.  

  • 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.

The mannitol test, when 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.

  • 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. 2017;22(4):678-683.

Networks of genes are differentially expressed in immune cells from healthy adolescents versus those with allergy or allergic asthma.

  • 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.

Raine Study data contributed to international collaboration that identified new genetic locations related to asthma.

  • Demenais  F, Margaritte-Jeannin P, Barnes KC, Cookson WOC, Altmüller J, Ang W et al. Multiancestry association study identifies new asthma risk loci that colocalize with immune-cell enhancer marks. Nature Genetics. 2018;50:42-53.

 

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