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

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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 with thunderstorm asthma has been reviewed (link below) and the Victorian government agency reports provide further information on the 2016 thunderstorm asthma event. The Victorian Department of Health and Human Services rapidly implemented a substantial three-year public health program of response to improve preparedness of emergency services, educate clinicians; nurses, pharmacists, general practitioners, and community, and establish a regional Victorian pollen monitoring and thunderstorm asthma forecasting program. https://www2.health.vic.gov.au/about/publications/researchandreports/thunderstorm-asthma-literature- review-may-2107 https://www.igem.vic.gov.au/our-workevaluation-and-review/review-of-the-thunderstorm-asthma- emergency-response https://www2.health.vic.gov.au/public-health/environmental-health/climate-weather-and-public- health/thunderstorm-asthma

Since the 1980s, 10 of the 23 episodes of thunderstorm asthma that have been documented globally have happened in Australia. With the climate change the distribution of grasses and frequency of extreme weather events including severe thunderstorms are predicted to increase. Whilst the recent focus has been on Victorian thunderstorm asthma response, thunderstorm asthma has been observed throughout temperate parts of New South Wales and Victoria. Epidemic level events of thunderstorm asthma may increase in frequency and change their biogeographical distribution.

The scope of the response to thunderstorm asthma focused on reduction of the risk of epidemic level thunderstorm asthma and its impact on emergency and public hospital services. Allergic rhinitis is a factor in susceptibility to thunderstorm and seasonal allergic asthma. However, the vast majority of patients with allergic rhinitis manage their condition without medical support. There would be health, social and economic benefit of addressing the issue of allergic rhinitis in our community. There is a need for integrated care pathways involving allergy and respiratory specialists to manage people with allergic rhinitis who may have known asthma or latent, undiagnosed asthma. Better control of allergic rhinitis in patients with moderate to severe disease, that is not well controlled by pharmacotherapy, may be achieved by allergen specific immunotherapy. Research has demonstrated in multiple systematic reviews and meta-analyses that allergen specific immunotherapy benefits patients with allergic rhinitis in terms of symptom reduction and disease control.

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Dhami et al., Allergy 2019 “Allergen immunotherapy for allergic rhinoconjunctivitis: A systematic review and meta-analysis” https://onlinelibrary.wiley.com/doi/full/10.1111/all.13201

Evidence gaps and research needs for the value of grass pollen allergen immunotherapy to reduce seasonal allergic asthma There are opportunities for research to identify and treat those patients with allergic rhinitis who are at risk of seasonal asthma in order to improve the management patients with allergic rhinitis and reduce risk of asthma. There is evidence from a small-scale open label mechanistic study of grass pollen allergen immunotherapy to indicate that patients with allergic rhinitis due to grass pollen allergy who were receiving grass pollen allergen specific immunotherapy were protected from severe effects of thunderstorm asthma. O’Hehir et al., 2018 https://www.atsjournals.org/doi/full/10.1164/rccm.201711-2337LE?url_ver=Z39.88- 2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub%3Dpubmed

There is need for additional research with larger sample sizes to investigate the efficacy and health economic benefit of grass pollen allergen immunotherapy for reducing the risk of thunderstorm, and indeed seasonal allergic asthma, in patients with moderate to severe allergic rhinitis.

Research is need to develop and test the utility of immunological and other (e.g. genetic or epigenetic) biomarkers of risk of seasonal asthma in patients with hayfever to identify those allergic rhinitis patients who need clinical support with managing their rhinitis and reduce their risk of experiencing asthma during the pollen season on high pollen days with and without thunderstorms.

Further research is needed to address gaps in knowledge of the natural history of allergic rhinitis and asthma including the influence and intersection of social determinants and factors such as age, ethnicity and gender. AusPollen aeroallergen monitoring network Australian has one of the highest frequencies of allergy respiratory disease worldwide. Understanding exposure to aeroallergen sources in people’s local environment helps inform patients of their allergen triggers and enables them to modify behaviour to reduce exposure. Local exposure to an allergen source assists medical teams to understand clinical history of patients and identify individual causes of allergic disease. Knowing both local current pollen exposure and evidence of sensitisation patterns, can be used by clinicians to better diagnose allergy and when indicated, inform choice of allergen-specific immunotherapy treatment for their patients.

Until recently, Australia has not been well served with accurate local current information on daily airborne pollen and spore levels. Since inception in September 2016, the NHMRC funded AusPollen Partnership has been establishing the inaugural national standardized pollen monitoring program. This project is also using an implementation science framework to evaluate the need and benefit of providing pollen information and how this helps people to better self-manage pollen allergies to improve quality of life. The overarching goal is to lower the medical and socio-economic burden of the prevalent chronic inflammatory diseases of hay fever and allergic asthma. Some of the interim project outcomes include the following.

Milic et al., Aerobiologia 2019 “Quality control of pollen identification and quantification exercise for the AusPollen Aerobiology Collaboration Network: a pilot study” https://link.springer.com/article/10.1007%2Fs10453-019-09580-4 Medek et al., Aerobiologia 2019 “Enabling self-management of pollen allergies: a pre-season questionnaire evaluating the perceived benefit of providing local pollen information” https://link.springer.com/article/10.1007/s10453-019-09602-1 Australian Airborne Pollen and Spore Monitoring Network Interim Standard and Protocols Version 2, 14 September 2018 https://www.allergy.org.au/hp/papers/australian-airborne-pollen-and-spore- monitoring-network-interim-standard-and-protocols

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Whilst the AusPollen Aerobiology Collaboration Network has implemented a standardized pollen monitoring network across Australia through the efforts of dedicated academic researchers supported by various current NHMRC, ARC, student stipends and other short-term competitive grants, the funding to support these services will cease in 2020. Projects contributing to the AusPollen Aerobiology Collaboration Network include the NHMRC AusPollen Partnership (led by Queensland University of Technology), the ARC Discovery Grass pollen Health Threats (led by University of Technology Sydney), the Victorian thunderstorm asthma Pollen Surveillance (led by Bureau of Meteorology), AirRater (led by University of Tasmania) and Deakin AirWatch (Deakin University). NHMRC AusPollen Partners include the Australian Society for Clinical Immunology and Allergy, Asthma Australia, Bureau of Meteorology, CSIRO, Meteorology Switzerland, and Stallergenes Australia. There is no further state or federal government funding, including direct or competitive grant support, or other resources to continue this pollen monitoring service.

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It would be useful to establish a national inter-agency scoping study to address this need and develop strategies to sustain pollen monitoring services for patients in the community who experience hayfever. Currently, state Health Departments tend to focus on risk and preparedness for epidemic level thunderstorm asthma events including ambulatory service and public hospital emergency department capabilities. Health service units that have responsibility for environmental health, disease prevention, health and wellness, or chronic disease management, have not to date been engaged in consideration of this need. As well as academic research partners, stakeholders should include the Bureau of Meteorology who are engaged currently with the NHMRC AusPollen Partnership and the Victorian Thunderstorm Asthma Pollen Surveillance projects. Whilst pollen is a natural bioaerosol rather than an anthropogenically produced particle, agencies that are responsible for other forms (particulate and gaseous) air quality monitoring would make a valuable contribution to this discussion. Indeed in some states Departments of Environment and Science with responsibility or air quality monitoring are engaged in or affiliated with pollen monitoring research.

Evidence gaps and research needs in relation to monitoring and disseminating airborne pollen levels locally  Continued research on short-term, local daily pollen forecasting algorithms and seasonal severity forecasting  Innovation to transform and automate pollen monitoring so the network does not depend on antiquated technology of impaction samplers and labour-intensive microscopy identification and enumeration processes.  Better evidence of the direct and indirect health and social impacts of pollen exposure including allergic rhinitis and seasonal allergic asthma in different age, gender and socioeconomic and ethnic communities.  Health economic research and evaluation of the socio-economic impact of allergic rhinitis per se and co-morbidities including asthma, sleep apnoea, sinusitis, cardiovascular and mental health condition.  The efficacy, utility and benefit of well-designed mobile health technologies to assist patients in managing their exposure to airborne pollen. mHealth technologies may assist with communicating with patient communities about pollen exposure and medication use as well as for monitoring and reporting symptoms experienced. Follow up Should this need be recognised as a priority, I would be happy to be approached to consider this issue further and assist in establishing a multi-disciplinary interagency working party to facility this body of work.

Additionally, I would be happy to be consulted further in relation to the other points raised in this submission should this be of use.

Author Professor Janet Davies,

Head of Allergy Research Group,

School of Biomedical Science and Institute of Health and Biomedical Innovation,

Queensland University of Technology [email protected]

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About this submission  Professor Janet Davies is a biomedical scientist who leads the multidisciplinary Allergy Research Group at Queensland University of Technology. She also has a position as the Assistant Director of Research with the Metro North Hospital and Health Service. After graduating with a PhD from Murdoch University in the School of Biological and Environmental Science, Western Australia, in August 1994, Professor Davies completed post-doctoral research training with AgResearch New Zealand and Monash University, Department of Biochemistry and Molecular Biology. She has worked in the field of allergy research since 1999 including 10 years as a research fellow with Allergy Immunology and Respiratory Medicine at The Alfred Hospital and 7 years as Deputy Director of the Lung and Allergy Research Centre, School of Medicine, The University of Queensland. At QUT, she leads the NHMRC AusPollen Partnership (2016-2020) with eight academic and six government, peak body or industry organisations to establish Australia’s national standardized pollen monitoring and forecast network. Her research team is supported by multiple grants from the NHMRC, ARC, Emergency Medicine Foundation, Bureau of Meteorology, Victorian Department of Health and Human Services and the National Foundation for Medical Research Innovation. She is an inventor of patents granted in Australia and USA that underpin more specific immunodiagnosis and treatment for subtropical grass pollen allergy. Professor Davies has contributed to multiple global position papers such as the Global Atlas of Allergy (2014) and the Molecular Allergology User’s Guide (2016) and serves as Vice Chair of the WHO IUIS Allergen Nomenclature Sub-Committee. Through various roles and engagements with diverse stakeholders, Prof Davies is actively involved and experienced in translating and implementing research outcomes into policy and procedures to deliver improvements in patient health and wellbeing.

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