Inquiry into allergies and anaphylaxis The House of Representatives Standing Committee on Health, Aged Care and Sport. This submission addresses two of the specific terms of reference (number 4 and 5) for this parliamentary inquiry. 4. Access to and cost of services, including diagnosis, testing, management, treatment and support; Current knowledge and practice Diagnosis for allergy relies on clinical history and evidence of allergen-specific sensitisation. Allergic sensitisation is usually measured with a skin prick test requiring training and consistency of practice. Skin prick test accuracy has a dependence on quality of allergen extracts. This method is performed by nurses or doctors in clinical immunology specialist or hospital outpatient clinics limiting access for patients in rural and remote areas. It requires patients to withdraw anti-histamine treatment for three days prior to testing. Allergen sensitisation can also be measured by immunopathology tests reported as concentrations of specific IgE. Whole blood basophil activation tests can be performed in a specialised immunopathology setting but this is not routinely offered and is time dependent in terms of duration since the blood was sampled and time since the anaphylactic event occurred. Most of allergen sensitisation tests are based on aqueous extracts of whole allergen sources. The extracts contain a mixture of allergenic and not allergenic material. As complex biological sources, the content of allergen and non-allergenic matter within aqueous extracts will vary from batch to batch affecting the consistency and efficacy of products for diagnosis and allergen-specific immunotherapy. Over 100 standardized allergen component resolved diagnostic tests for common food, animal dander and aeroallergen sources are available as single point high-throughput testing and/or multi-allergen arrays by pathology services. The principles and clinical utility of molecular allergen component resolved testing is described for an array of allergen components in the world first guidelines produced by The European Academy of Allergy and Clinical Immunology Task Force on Component Resolved Diagnosis. https://www.eaaci.org/resources/3873-eaaci-molecular-allergology-user-s-guide.html Gaps in knowledge and unmet clinical needs The diagnostic precision that allergen component testing can offer has not been widely adopted in Australian clinical practice. The reasons for low clinical use in Australia of this technology include cost, reimbursement and fee structures, accessibility to a laboratory equipped to perform allergen component testing, the relevance of allergen components to local Australian environments, knowledge and experience of clinicians with using and interpreting outcomes for clinical decision support. Allergic sensitisation tests are reported as dichotomous outcome; sensitisation or not. Thresholds of allergic sensitisation; as millimetre diameter skin prick test wheel response or concentration of specific IgE to major allergens, that are associated with clinical symptoms are not well understood. Thresholds of sensitisations can vary between geographic regions and with levels and routes of exposure to particular allergen sources. Local Australian research is needed to ascertain the prevalence of allergic sensitisation to common allergen sources and the levels of sensitisation that are associated with clinical symptoms, disease persistence and progression. Relevance of available tests and treatment options to local allergen sources Skin prick test and allergen immunotherapy materials used clinically have been developed based on sources of allergens in Europe and North America. Australia has diverse environment and biodiversity that are not fully represented in materials for clinical allergy testing and treatments. Although not considered to be allergenically important in most cases, certain allergen sources such as pollen from Prof. Davies QUT Inquiry into Allergy and Anaphylaxis 1 native Australian shrubs and trees (Mellaluca; tea tree, Eucalyptus; gum tree, Casuarina; sheoak tree and Acacia; wattle) have been implicated as allergy triggers for some people. However, there are no standardized and registered diagnostic tests or therapeutic options for pollen of native Australian plants. This limits the reliability of testing for individual patients and at a population level, valid evaluation of their allergenic potential. Furthermore, other clinically important pollens from species of grass of subtropical families, insects including various species of stinging ants and wasps as well as seafood allergens for fish or shellfish sources common in Australian waters or species imported from Asia. Whilst Australia has a strong track record of research in allergy including allergen characterisation of subtropical grass pollen and seafood allergen components by a number of research teams, these innovations, many protected by patents, have not been commercially developed and registered as products for translation into clinical use. Possible barriers to realisation of this opportunity include that the local Australian relevance of any newly developed products may limit the perceived commercial return on investment. Thus despite the clinical importance and socioeconomic impact of allergic disease in our community, we have not to date attracted sufficient development funds to successfully translate innovations in the allergy area. Diagnostic and prognostic biomarkers of allergic disease Specific IgE concentrations to particular allergen components could serve as diagnostic and prognostic immunological biomarkers for clinically important allergic disease and prognostic biomarkers for risk of disease progression. For instance, the concentration of serum specific IgE to peanut allergen extract or certain major allergen components (e.g. Ara h 2) may serve as useful diagnostic tools for identifying clinically relevant food allergy and likelihood of allergic reaction in a child upon exposure to peanut. It has been proposed and some research suggests that the concentration of specific IgE to whole ryegrass pollen extract and/or major allergen components (for instance Lol p1 and Lol p 5) may serve to identify patients with hayfever who are more at risk of season allergic asthma or incidence of thunderstorm asthma. https://www.bmj.com/content/360/bmj.k432 Further research is needed to investigate, in real world Australian settings, the clinical applicability and utility of serology and allergen component testing for clinical decision support. Real-world clinical research is needed to ascertain the clinical value and provide education for clinicians on the interpretation of serological sensitisation tests. Further innovative point of care test platforms could transform allergy testing in future and make sensitisation tests more accessible for Australians in rural and remote setting as well as those urban patients not able to see a specialist. 5. Developments in research into allergy and anaphylaxis including prevention, causes, treatment and emerging treatments (such as oral immunotherapy); Allergic respiratory diseases including allergic rhinoconjunctivitis (or hayfever) affects approximately 20% of Australian population causing significant adverse impacts on health, quality of life and performance at school or work. Hayfever is the most common allergic disease. It is associated with important comorbid conditions including asthma, sinusitis, dental malformation and sleep aponia. Whilst often dismissed as a trivial condition, hayfever per se is associated with considerable ill health. People with hayfever often suffer from additional allergic diseases including food allergies and asthma. The harm that allergy to grass pollen can cause became tragically apparent by the thunderstorm asthma epidemic that occurred on 21 November 2016. https://www.thelancet.com/journals/lanplh/article/PIIS2542-5196(18)30120-7/fulltext Epidemic thunderstorm asthma; mechanisms and who is at risk Thunderstorm asthma is caused by a combination of environmental, meteorological and individual susceptibility factors. These factors include exposure to high to extreme levels of airborne grass pollen on days with particular types of severe thunderstorms that can be associated with a rapidly moving cold front Prof. Davies QUT Inquiry into Allergy and Anaphylaxis 2 that “sweeps up” into the advancing clouds, vast quantities of allergen sources including fungal spores and grass pollen from rural source land areas. It is proposed that during these types of thunderstorms pollen entrapped in the clouds can burst open due to osmotic shock releasing from each grass pollen grain hundreds of allergen-containing, small breathable starch granules. As the storm passes, a downdraft delivers the allergen particles overpopulated areas leading to allergic reactions in the lungs of people sensitized to grass pollen. All people affected by thunderstorm asthma have hayfever whilst only 40% of patients had previously been diagnosed with asthma. Notably, those who were more severely affected by thunderstorm asthma and required admission to respiratory wards or care in intensive care units, were those patients with known uncontrolled asthma. Additional to those who presented to hospital emergency departments, it is estimated based on the frequency of allergic rhinitis in the Melbourne population that tens of thousands of people in the community were affected by the thunderstorm asthma epidemic. The broad array of interacting factors associated