Asthma and Allergy Lay Summaries

2014

The effect of maternal smoking during pregnancy on asthma and lung function in teenagers

Keywords: immune function, asthma, wheeze, maternal smoking during pregnancy

What is already known about this subject:

  • Nicotine has detrimental effects on airway development.
  • Children born to mothers who smoked during pregnancy have reduced lung function at birth and up to at least 6 years of age. They also have an increased risk of asthma and wheeze, though it is not known whether the risks persist into later life.
  • Development and maturation of the immune system starts in utero and continues after birth, it has been suggested that maternal smoking can interfere with this process and increase the risk of respiratory problems later in life.

What this Raine study adds:

  • Adolescents born to mothers who smoked during pregnancy had lower lung function and were more likely to have asthma and wheeze.
  • Persistent changes in respiratory health due to maternal smoking during pregnancy are not due to changes in immune function and are due to more than just reduced lung function.

Hollams, Elysia M EM, Nicholas H de Klerk, Patrick G Holt, and Peter D Sly. 2014. “Persistent Effects of Maternal Smoking during Pregnancy on Lung Function and Asthma in Adolescents.” American Journal of Respiratory and Critical Care Medicine (November 19): 1-36.
doi:10.1164/rccm.201302-0323OC. [publink]

Identification of genetic risk factors for having both asthma and hay fever

Keywords: asthma, hay fever, allergy, genome-wide association study, genetic inheritance

What is already known about this subject:

  • Individuals with asthma often also have hay fever.
  • Genetics plays a large part in an individual’s susceptibility to asthma and hay fever. A number of variations in genes have been identified that increase the risk of both conditions, but it is likely that many other (as yet unknown) genes are also involved.
  • Evidence suggests that having both asthma and hay fever has a stronger genetic cause than asthma without hay fever. It may be easier to identify causative genes if only the condition with the strongest genetic influence is studied.

What this Raine study adds:

  • Genome-wide screening of DNA data from over 20,000 individuals (including Raine participants) identified 11 gene variants associated with an increased risk of having both asthma and hay fever.
  • The gene variants identified were all also associated with risk of asthma and hay fever when they were considered separately, but these associations were not as strong.
  • This approach enabled the identification of genetic risk factors for two important conditions using a smaller number of participants that may otherwise be needed. This has implications for future genome-wide association studies.

Ferreira MA, et al. (2014). “Genome-wide association analysis identifies 11 risk variants associated with the asthma with hay fever phenotype.” Journal of Allergy and Clinical Immunology 133(6): 1564-1571. [publink]

Stress during pregnancy increases the risk of allergic disease in children

Keywords: allergic disease, asthma, pregnancy, stress, child

What is already known about this subject:

  • Asthma and allergies are becoming increasingly common and affect up to one third of children.
  • It is becoming increasingly clear that environmental factors are important in the development of asthma and allergies, particularly exposures occurring before birth.
  • Parental stress may be a risk factor for asthma and allergic disease, but this has not been well studied.

What this Raine study adds:

  • Analysis of data describing asthma, allergies, eczema and allergic rhinitis in Raine participants at 6 and 14 years of age, together with assessment of stressful life events during pregnancy in the parents showed that children of mothers who had experienced adverse life events during pregnancy had a greater likelihood of developing asthma and eczema as teenagers.
  • Children whose mothers did not have asthma were at greater risk of developing asthma in response to stressful life events during pregnancy.
  • Early life exposures are an important area for further research into the developmental origins of asthma and allergic disease.

Hartwig, I. R. V, Sly, P. D., Schmidt, L. A., van Lieshout, R. J., Bienenstock, J., Holt, P. G., & Arck, P. C. (2014). Prenatal adverse life events increase the risk for atopic diseases in children, which is enhanced in the absence of a maternal atopic predisposition. The Journal of Allergy and Clinical Immunology, 134(1), 160-9. doi:10.1016/j.jaci.2014.01.033. [publink]

2013

The impact of asthma on mental health – the role of asthma severity and persistence

Keywords: mental health, anxiety, asthma, depression, youth

What is already known about this subject:

  • Asthma and respiratory symptoms have consistently been linked with anxiety disorders in young people.
  • Well-controlled asthma is associated with fewer mental health problems than uncontrolled asthma in adults.
  • The degree to which asthma affects mental health may be influenced by its severity and whether it persists from childhood into later life.

What this Raine study adds:

  • Children with more severe and/or persistent asthma are more vulnerable to mental health problems.
  • The likelihood of mental health problems among youth with asthma increases as the severity of asthma increases.
  • Mild asthma and having had asthma (that has resolved) are not associated with mental health problems.

Goodwin, R D, M Robinson, P D Sly, I W McKeague, E S Susser, S R Zubrick, F J Stanley, and E Mattes. 2013. “Severity and Persistence of Asthma and Mental Health: A Birth Cohort Study.” Psychological
Medicine 43 (6) (June): 1313-22. doi:10.1017/S0033291712001754. [publink]

International collaborative genetic study finds ten new gene variants that contribute to allergic sensitisation

Keywords: allergic sensitisation, atopic disease, genetic predisposition, genome-wide association study

What is already known about this subject:

  • Asthma, eczema and rhinitis are atopic (allergy-associated) diseases caused by sensitisation to common environmental allergens.
  • Allergic sensitisation means that the body releases allergen-specific antibodies that bind to environmental allergens when they enter the body, triggering an inflammatory response.
  • A predisposition to allergic sensitisation can be inherited, and identifying the genes responsible will help in the understanding of how allergic diseases occur.

What this Raine study adds:

  • Ten susceptibility genes for allergic sensitisation were identified by genome-wide analysis of over 50,000 individuals from population-based cohorts (including DNA data from the Raine participants at 14 years of age, and allergy data at 6 and 14 years of age).
  • All of the 10 gene variants identified were significantly associated with self-reported allergy symptoms in an independent companion study (Hinds et al., 2013) of more than 53,000 individuals.
  • It is estimated that at least 25% of allergic sensitisation and allergic rhinitis may be caused by these gene variants, and further investigation may lead to a better understanding of how allergic diseases occur.

Bønnelykke, Klaus, MC Melanie C Matheson, Tune H TH Pers, Raquel Granell, David P Strachan, Alexessander Couto Alves, Allan Linneberg, et al. 2013. “Meta-Analysis of Genome-Wide Association Studies Identifies Ten Loci Influencing Allergic Sensitization.” Nature Genetics 45 (8) (August): 902-6. doi:10.1038/ng.2694. [publink]

2012

Identification of three new genetic risk factors for eczema

Keywords: genetic predisposition, dermatitis, atopic disease, genome-wide association study, eczema

What is already known about this subject:

  • Eczema is a common inflammatory skin condition associated with allergic diseases (particularly asthma, rhinitis and food allergy).
  • The development and severity of eczema are thought to be influenced by problems with the barrier function of the skin, and also abnormalities of the immune system.
  • A genetic predisposition is thought to be important in eczema; however the exact mechanisms are unclear.

What this Raine study adds:

  • Genome-wide analysis in over 50,000 individuals from population-based cohorts (including data from the Raine participants: DNA 14 years of age, allergy data at 6 and 14 years of age) identified three new gene variants increasing the risk of eczema.
  • Two of these gene variants are associated with abnormalities in
    skin barrier function, and one with altered immune function, suggesting these may be important mechanisms for eczema.

Paternoster, L, Marie Standl, Chen CM, Ramasamy A, Bønnelykke K, Duijts L, Ferreira MA, et al. 2012. “Meta-Analysis of Genome-Wide Association Studies Identifies Three New Risk Loci for Atopic Dermatitis.” Nature Genetics 44 (2) (February): 187-92. doi:10.1038/ng.1017. [publink]

2011

Adolescent girls have more reactive airways than boys

Keywords: asthma, allergy, lung function, sex differences

What is already known about this subject:

  • One of the most noticeable features of asthma is airways that are ‘hyper-responsive’; that is, affected individuals have airways that narrow  (get smaller) more easily and to a greater extent, resulting in wheezing, chest tightness, shortness of breath and coughing.
  • Even though airway hyper-responsiveness is traditionally thought of as being a marker for asthma, it may in fact be a separate process with different causes and may be more related to growth and development of the airways.
  • Little is known about how early life exposures influence the risk of airway hyper-responsiveness, and how these may differ from the risk factors for asthma.

What this Raine study adds:

  • Data from lung function and allergy tests in Raine participants at 14 years of age revealed that airway hyper-responsiveness was more common and more severe in girls, and that risk factors for airway responsiveness differed between adolescent girls and boys.
  • In both boys and girls, better lung function was protective against airway hyper-responsiveness, whereas being allergic was a risk factor. Asthma was a risk factor for hyper-responsiveness in boys but not in girls. None of these factors was sufficient to explain the differences in hyper-responsiveness between boys and girls.
  • Understanding the factors involved in the development of airway responsiveness may help in the development of preventative strategies in the future.

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. J Allergy Clin Immunol. 2011 Apr 15. [publink]

Discovery of two new genes for asthma

Keywords: asthma, genome-wide association study, genetic inheritance, risk factors

What is already known about this subject:

  • Asthma is a long-term lung condition in which the airways react easily to triggers (such as dust, pet hair or mould), making it difficult to breathe.
  • Around one in ten Australians have asthma (2.3 million people).
  • It is known that genetic inheritance is important in determining a person’s risk of asthma, but only a small number of asthma genes have been identified.

What this Raine study adds:

  • Genome-wide analysis of DNA and asthma data from over 7,000 Australians (including Raine participants) in combination with existing DNA data from another 50,000 participants of European descent (nearly 58,000 participants in total) identified two new asthma genes, and confirmed four previously identified genes.
  • One of these genes (IL6R) is known to be involved in causing inflammation. The other gene has not previously been identified, but is thought to be associated with allergic disease and Crohn’s disease.
  • The identification of new genes affecting the risk of asthma will help us to understand the mechanisms underlying the disease, potentially leading to new prevention and treatment strategies.

Ferreira MA, Matheson MC, Duffy DL, Marks GB, Hui J, Le Souef P, Danoy P, Baltic S, Nyholt DR, Jenkins M, Hayden C, Willemsen G, Ang W, Kuokkanen M, Beilby J, Cheah F, de Geus EJ, Ramasamy A, Vedantam S, Salomaa V, Madden PA, Heath AC, Hopper JL, Visscher PM, Musk B, Leeder SR, Jarvelin MR, Pennell C, Boomsma DI, Hirschhorn JN, Walters H, Martin NG, James A, Jones G, Abramson MJ, Robertson CF, Dharmage SC, Brown MA, Montgomery GW, Thompson PJ. Identification of IL6R and chromosome 11q13.5 as risk loci for asthma. Lancet. 2011 Sep 10;378(9795):1006-14. [publink]

Adolescent girls have more reactive airways than boys

Keywords: asthma, allergy, lung function, sex differences

What is already known about this subject:

  • One of the most noticeable features of asthma is airways that are ‘hyper-responsive’; that is, affected individuals have airways that narrow  (get smaller) more easily and to a greater extent, resulting in wheezing, chest tightness, shortness of breath and coughing.
  • Even though airway hyper-responsiveness is traditionally thought of as being a marker for asthma, it may in fact be a separate process with different causes and may be more related to growth and development of the airways.
  • Little is known about how early life exposures influence the risk of airway hyper-responsiveness, and how these may differ from the risk factors for asthma.

What this Raine study adds:

  • Data from lung function and allergy tests in Raine participants at 14 years of age revealed that airway hyper-responsiveness was more common and more severe in girls, and that risk factors for airway responsiveness differed between adolescent girls and boys.
  • In both boys and girls, better lung function was protective against airway hyper-responsiveness, whereas being allergic was a risk factor. Asthma was a risk factor for hyper-responsiveness in boys but not in girls. None of these factors was sufficient to explain the differences in hyper-responsiveness between boys and girls.
  • Understanding the factors involved in the development of airway responsiveness may help in the development of preventative strategies in the future.

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. J Allergy Clin Immunol. 2011 Apr 15. [publink]

International collaborative study finds 16 new gene variants affecting lung function

Keywords: genetic predisposition to disease, pulmonary function, genome-wide association study, respiratory health

What is already known about this subject:

  • Pulmonary function tests measure how well the airways and lungs work, and can be used to detect lung disease.
  • Pulmonary function is at least partly inherited genetically.
  • Identifying genes that affect lung function may help develop new therapies for lung disease.

What this Raine study adds:

  • 16 new gene variants associated with lung function were discovered, more than doubling the number that were previously known, and the 10 previously identified gene variants were confirmed as being associated with lung function.
  • A number of the newly identified gene variants were found to be important in the regulation of pulmonary function in both adults and children (including lung function data from Raine participants at 6 and 14 years of age).

Soler Artigas, MS, DW Loth, LV Wain, and SA Gharib. 2011. “Genome-Wide Association and Large-Scale Follow up Identifies 16 New Loci Influencing Lung Function.” Nature Genetics 43 (11): 1082-1090. doi:10.1038/ng.941.Genome-wide. [publink]

The influence of Vitamin D on asthma and allergies in children and teenagers

Keywords: asthma, atopy, bronchial hyperresponsiveness, vitamin D

What is already known about this subject:

  • Vitamin D is important for healthy immune and respiratory systems.
  • Inadequate childhood vitamin D may be a risk factor for asthma and allergy.

What this Raine study adds:

  • Low levels of vitamin D were common during the winter months (49% of children tested had low vitamin D, 9% very low).
  • Asthma and allergies were more common in children, particularly boys, with low or very low levels of vitamin D.
  • Low vitamin D at 6 years of age was a predictor of asthma and allergy at 14 years of age.
  • Vitamin D status may influence the risk of asthma and allergies during early life.

Hollams, E M, P H Hart, B J Holt, M Serralha, F Parsons, N H de Klerk, G Zhang, P D Sly, and P G Holt. 2011. “Vitamin D and Atopy and Asthma Phenotypes in Children: A Longitudinal Cohort Study.” The European Respiratory Journal 38 (6) (December): 1320-7. doi:10.1183/09031936.00029011. [publink]

The role of socioeconomic status in the development of asthma

Keywords: socioeconomic status, asthma, stress, poverty

What is already known about this subject:

  • Chronic poverty puts children at risk of poor health, including an increased risk of asthma.
  • Low-income households and neighbourhoods typically have high levels of chronic stress.
  • The relationship between chronic poverty, chronic stress and asthma development is uncertain.

What this Raine study adds:

  • Chronic exposure to a low-income environment from birth is associated with asthma that persists throughout childhood and into adolescence.
  • Children whose families had moved out of poverty were less likely to have asthma.
  • Chronic stress plays a role in the pathway between poverty and childhood asthma.

Kozyrskyj, AL, and GE Kendall. 2010. “Association between Socioeconomic Status and the Development of Asthma: Analyses of Income Trajectories.” American Journal of Public Health 100 (3) (March): 540-6. doi:10.2105/AJPH.2008.150771. [publink]

Adolescents with asthma have impaired anti-viral immunity

Keywords:  viruses, respiratory infections, asthma, immune response

What is already known about this subject:

  • Viral respiratory infections are a major cause of asthma exacerbations in adults and children.
  • Children with asthma are more susceptible to respiratory viruses than children without asthma.
  • People with asthma may have a less effective immune response to viral infections, although how the anti-viral immune response differs in asthmatics is not yet known.

What this Raine study adds:

  • Adolescents with asthma had an impaired anti-viral immune response.
  • Receptors that sense the presence of viral genetic matter within cells (particularly respiratory viruses) functioned abnormally in blood cells taken from asthmatic adolescents.
  • Impaired anti-viral immune responses may increase susceptibility to viral respiratory infections in people with asthma.

Roponen, M, ST T Yerkovich, E Hollams, P D Sly, P G Holt, and J W Upham. 2010. “Toll-like Receptor 7 Function Is Reduced in Adolescents with Asthma.” European Respiratory Journal 35 (1) (January): 64-71. doi:10.1183/09031936.00172008. [publink]

A new approach to understanding the genes that cause allergic disease

Keywords: gene expression profiling, immunology, atopy, allergic disease

What is already known about this subject:

  • Atopy/allergy is a complex immunological disease that is thought to be caused by a large number of genes.
  • Current therapies target single genes, and these have had little success in the clinic.
  • Network theory provides a new approach to understanding the development of disease; not only does it consider the multiple genes involved, but also how they interact.
  • Using a network modelling approach may help to identify and target multiple genes for treating atopic disease.

What this Raine study adds:

  • The atopic response is orchestrated by an interconnected network of genes, some of which have not previously been identified as being involved with atopy.
  • Genes with the highest level of overall connectivity in the network called “hubs” were shown to be essential to the function of the network, blocking their signalling disrupted the entire network.
  • Targeting entire networks of genes via their hubs may be a successful strategy in designing new therapies for atopic disease.

Bosco, Anthony, Kathy L Mckenna, Martin J Firth, D Peter, Patrick G Holt, and Peter D Sly. 2009. “A Network Modeling Approach to Analysis of the Th2 Memory Responses Underlying Human Atopic Disease.” Journal of Immunology 182 (10) (May 15): 6011-21. doi:10.4049/jimmunol.0804125. [publink]

How does the immune system generate allergic responses to inhaled allergens?

Keywords: asthma, dendritic cells, gene expression, inflammation, aeroallergens, allergy

What is already known about this subject:

  • Aeroallergens are tiny particles present in the air, that when breathed in may trigger an immune response. This is the body’s way of removing foreign material from the lungs.
  • People with allergic asthma are the most sensitive to aeroallergens, and their immune response is harmful compared to the immune response in someone without allergies or asthma.
  • It is thought that dendritic cells (a specialised type of cell that controls immune responses) help the body to decide how to respond to aeroallergens, and dendritic cells from people with asthma and allergies may be able to trigger an allergic-type immune response.

What this Raine study adds:

  • Increased thrombomodulin production by dendritic cells was found in blood samples from three different subsets of individuals: in adult volunteers with allergies; in children having acute asthma attacks; and 14-year-old Raine participants with asthma and allergies.
  • Thrombomodulin-positive dendritic cells were able to cause an allergic-type immune response.
  • Thrombomodulin is better known as an anti-coagulant and has not previously been shown to be important in allergic disease. Further investigation may reveal an important role for thrombomodulin in asthma and allergies.

Yerkovich, Stephanie T, Marjut Roponen, Miranda E Smith, Kathy McKenna, Anthony Bosco, Lily S Subrata, Emilie Mamessier, et al.
2009. “Allergen-Enhanced Thrombomodulin (blood Dendritic Cell Antigen 3, CD141) Expression on Dendritic Cells Is Associated with a TH2-Skewed Immune Response.” The Journal of Allergy and Clinical Immunology 123 (1) (January): 209-216.e4. doi:10.1016/j.jaci.2008.09.009. [publink]

Risk of asthma in breast-fed children of mothers with asthma

Keywords: asthma, atopy, maternal asthma, breast-feeding, childhood

What is already known about this subject:

  • Exclusive breast-feeding is associated with a lower risk of childhood asthma, allergy and wheeze.
  • However it has been suggested that this may not be the case in children who have both allergies and a mother with asthma.
  • Conflicting information exists about whether children of mothers with asthma should be breast-fed.

What this Raine study adds:

  • Exclusive breast-feeding for 4 months or longer was protective against asthma at 6 years of age, and this protective effect was the same in children with allergies and in children whose mothers had asthma.
  • No increased risk of asthma was found in breast-fed children of mothers with asthma, regardless of whether the child had allergies or not.

Oddy, Wendy H., Jennifer K. Peat, and Nicholas H. de Klerk. 2002. “Maternal Asthma, Infant Feeding, and the Risk of Asthma in Childhood.” Journal of Allergy and Clinical Immunology 110 (1) (July): 65-67. doi:10.1067/mai.2002.125296. [publink]