Kristina Rueter

Anti-bacterial IgE in the antibody responses of house dust mite allergic children convalescent from asthma exacerbation

Background Atopic sensitization to the house dust mite (HDM) is associated with altered antibody responses to the nasopharyngeal colonizing bacterium Haemophilus influenzae and children admitted to the emergency department for asthma exacerbation have reduced IgG responses to HDM allergens.

Vitamin D and Allergic Disease: Sunlight at the End of the Tunnel?

A role for vitamin D in the regulation of immune function was first proposed after the identification of Vitamin D Receptors in lymphocytes. It has since been recognized that the active form of vitamin D, 1α,25(OH)2D3, has direct affects on naïve and activated helper T cells, regulatory T cells, activated B cells and dendritic cells. There is a growing body of literature linking vitamin D (serum 25(OH)D, oral intake and surrogate indicators such as latitude) to various immune-related conditions, including allergy, although the nature of this relationship is still unclear. This review explores the findings of epidemiological, clinical and laboratory research, and the potential role of vitamin D in promoting the inappropriate immune responses which underpin the rise in a broad range of immune diseases.

β2-Adrenoceptor Polymorphisms Predict Response to β2-Agonists in Children with Acute Asthma

The aim of this study was to determine the influence of single nucleotide polymorphisms in the β2-adrenoceptor gene, on the response to inhaled β2-agonists in children with acute asthma. We hypothesised that children with polymorphisms that generate enhanced receptor downregulation in vitro, Gly16 and Gln27, would have a slower response to β2-agonist therapy during acute asthma. One hundred and forty-eight children with acute asthma were recruited and genotyped for β2Arg16Gly and β2Gln27Glu. For Gln27Glu, individuals Gln27Gln took longest to stretch out to 1, 2 and 4 hourly β2-agonists, followed by heterozygotes who were intermediate and Glu27Glu who responded most rapidly (1hourly: 2.6hr vs. 2.0 vs. 1.4, p = 0.02; 2 hourly: 10.6hr vs. 10.7 vs. 6.8, p = 0.07; 4 hourly: 29.8hr vs. 28.5 vs. 24.3, p = 0.30). The ability to prospectively identify children who respond less effectively to β 2-agonists during an acute asthma attack has the potential to allow the generation of genotype-specific treatment pathways.

Symptomatic Viral Infection is Associated with Impaired Response to Treatment in Children with Acute Asthma

OBJECTIVE To examine the influence of viral respiratory infection (VRI) on treatment response in acute asthma in children. STUDY DESIGN A total of 218 children (mean age, 6.6 years) with acute asthma were recruited. Symptoms were recorded, an asthma severity score was determined, and whenever possible, a per-nasal aspirate was obtained for detection of viruses. Each childs response to inhaled β(2)-agonists was assessed after 6, 12, and 24 hours. RESULTS The 168 children with VRI symptoms received more treatment with inhaled β(2)-agonists after 6 hours (P = .010), 12 hours (P = .002), and 24 hours (P = .0005) compared with the 50 children without such symptoms. Asthma severity did not differ between the 2 groups. A per-nasal aspirate was obtained from 77% of the children. The most frequently identified virus was rhinovirus (61.4%). Among children with symptoms of a VRI, those with rhinovirus had an impaired response to β(2)-agonists at 6 hours (P = .032). CONCLUSION Children with acute asthma and symptoms of VRI respond less effectively to β(2)-agonists after 6, 12, or 24 hours and thus may benefit from more intense therapy and monitoring.

Leukotriene pathway polymorphisms are associated with altered cysteinyl leukotriene production in children with acute asthma

Cysteinyl leukotrienes (cysLTs) are pro-inflammatory mediators with increasing evidence for a role in childhood acute asthma. This study examined the influence of polymorphisms in cysLT pathway genes on urinary leukotriene E(4) (uLTE(4)) levels and clinical status in acute asthmatic children. Children aged 2-16 years were recruited during an asthma attack (n=205). Where possible, asthma severity scores were assigned, ALOX5AP G-336A, ALOX5 G-1708A, LTC4S A-444C and G-1072A, GPX4 C718T, and CYSTLTR1 T927C genotypes were determined and uLTE(4) was measured in acute and convalescent samples. uLTE(4) levels were higher acutely compared with convalescence (acute GM: 115.7pg/mg creatinine; 95% CI 88.6-151.1, convalescence GM: 66.4pg/mg creatinine; 95% CI 51.5-85.6; n=50 paired samples, p=0.003) and paired sample analysis showed genotype-specific effects with significantly increased uLTE(4) for LTC(4)S-444AA (acute GM: 127.9pg/mg creatinine; 95% CI 91.8-178.3, convalescence GM: 68.2pg/mg creatinine; 95% CI 50.5-92.0; n=32, p=0.002), LTC(4)S-1072 GG (acute GM: 126.7pg/mg creatinine; 95% CI 95.4-168.3, convalescence GM: 78.9pg/mg creatinine; 95% CI 59.7-104.1; n=39, p=0.019) and CYSLTR1 927 TT/T_ (acute GM: 96.8pg/mg creatinine; 95% CI 73.8-126.9, convalescence GM: 62.4pg/mg creatinine; 95% CI 46.8-83.3; n=28, p=0.036) but not AC/CC, GA/AA, or TC/CC/C_, respectively. When we compared the allele frequencies of the CYSLTR1 SNP between asthmatics and non-asthmatics, the 927C allele was found to be a risk allele for asthma (OR=2.13, 95% CI: 1.06-4.26, p=0.033). Genotypes were not associated with acute or convalescent uLTE(4) levels alone and neither the SNPs nor uLTE(4) correlated with acute asthma severity. Leukotriene pathway gene polymorphisms may influence the magnitude of cysLT production during an attack, yet their influence alone may not be substantial enough to alter the severity of exacerbations.

In utero and postnatal vitamin D exposure and allergy risk.

Introduction: The epidemic of allergic disease is a public health crisis, particularly for children in developed countries. Recognized effects of vitamin D in immune development have given credence to the hypothesis that changing patterns of human behavior associated with declining sunlight exposure may be linked to the rising immune and inflammatory diseases. Although data to support this are still limited and heterogeneous, vitamin D supplementation in early life is recommended to prevent vitamin D deficiency in many countries, raising important questions around safety and benefit for immune development and implications for allergic risk. Areas covered: This review article examines the evidence of the impact of in utero and postnatal vitamin D exposure on allergy risk in childhood. Evaluated are relevant studies from 2007 to June 2014. Expert opinion: Information on the impact of vitamin D on rising rates of allergic diseases is largely based on observational studies with conflicting results. There is an urgent need to conduct well-designed randomized controlled trials to address the significant uncertainty in this field. Additionally, the effects of other potential immunomodulatory factors associated with sun exposure (such as UV light) need to be examined further.

Nutritional approaches for the primary prevention of allergic disease: An update

The dramatic rise in early childhood allergic diseases indicates the specific vulnerability of the immune system to early life environmental changes. Dietary changes are at the centre of lifestyle changes that underpin many modern inflammatory and metabolic diseases, and therefore are an essential element of prevention strategies. Although modern dietary changes are complex and involve changing patterns of many nutrients, there is also an interest in the early life effects of specific nutrients including polyunsaturated fatty acids, oligosaccharides (soluble fibre), antioxidants, folate and other vitamins that have documented effects on immune function as well as metabolism. A better understanding of nutritional programming of immune health, nutritional epigenetics and the biological processes sensitive to nutritional exposures in early life may lead to dietary strategies that provide more tolerogenic conditions during early immune programming and reduce the burden of many inflammatory diseases, not just allergy.

Consensus of stakeholders on precautionary allergen labelling: A report from the Centre for Food and Allergy Research

Consensus of stakeholders on precautionary allergen labelling: A report from the Centre for Food and Allergy Research Giovanni A Zurzolo, Jennifer J Koplin, Anne-Louise Ponsonby, Vicki McWilliam, Shyamali Dharmage, Ralf G Heine, Mimi LK Tang, Susan Prescott, Dianne E Campbell, Richard Loh, Kristina Rueter, Merryn Netting, Katie Frith, Wendy Norton, Maria Said, Michael Gold, N Alicec Lee, Michael Mathai, Maximilian deCourten and Katrina J Allen Murdoch Children’s Research Institute, Centre for Food and Allergy Research, Centre for Chronic Disease, College of Health and Biomedicine, Victoria University, Department of Paediatrics and Melbourne School of Population and Global Health, University of Melbourne, Department of Allergy and Immunology, Royal Children’s Hospital, Melbourne, Victoria School of Paediatrics and Child Health, University of Western Australia, Princess Margaret Hospital for Children, Perth, Western Australia, The Children’s Hospital at Westmead, Department of Immunology and Infectious Diseases, Sydney Children’s Hospital, Allergy and Anaphylaxis, ARC Training Centre for Advanced Technologies in FoodManufacture, The University of New SouthWales, Sydney, New SouthWales, Women’s and Children’s Health Research Institute and Discipline of Paediatrics, School of Medicine, The University of Adelaide, Adelaide, South Australia, Australia

Physician training programs significantly improve diagnosis in cases coded as anaphylaxis over time: A major factor compounding time-trend data?

Allergy training programs have improved physician recognition and correct coding of anaphylaxis. This may be a confounding factor in studies relying on coding data to assess time trends in anaphylaxis presentation.

Kawasaki disease: An ongoing challenge

Kawasaki disease: An ongoing challenge Chui Han Chong, Senq-J Lee, Andrew Bullock, Linda Harris, Richard Loh, Geoff Knight and Kristina Rueter Departments of Paediatrics and Adolescent Medicine, Paediatric Rheumatology, Paediatric Cardiology, Paediatric Immunology, Paediatric Emergency Medicine, and Paediatric Intensive Care Unit, Princess Margaret Hospital for Children and School of Paediatrics and Child Health, University of Western Australia, Perth, Western Australia, Australia