Chronic airflow obstruction attributable to poverty in the multinational Burden of Obstructive Lung Disease (BOLD) study.

Poverty is strongly associated with all-cause and chronic obstructive pulmonary disease (COPD) mortality. Less is known about the contribution of poverty to spirometrically defined chronic airflow obstruction (CAO)-a key characteristic of COPD. Using cross-sectional data from an asset-based questionnaire to define poverty in 21 sites of the Burden of Obstructive Lung Disease study, we estimated the risk of CAO attributable to poverty. Up to 6% of the population over 40 years had CAO attributable to poverty. Understanding the relationship between poverty and CAO might suggest ways to improve lung health, especially in low-income and middle-income countries.

Proposal of 0.5 mg of protein/100 g of processed food as threshold for voluntary declaration of food allergen traces in processed food-A first step in an initiative to better inform patients and avoid fatal allergic reactions: A GA²LEN position paper.

BACKGROUND: Food anaphylaxis is commonly elicited by unintentional ingestion of foods containing the allergen above the tolerance threshold level of the individual. While labeling the 14 main allergens used as ingredients in food products is mandatory in the EU, there is no legal definition of declaring potential contaminants. Precautionary allergen labeling such as "may contain traces of" is often used. However, this is unsatisfactory for consumers as they get no information if the contamination is below their personal threshold. In discussions with the food industry and technologists, it was suggested to use a voluntary declaration indicating that all declared contaminants are below a threshold of 0.5 mg protein per 100 g of food. This concentration is known to be below the threshold of most patients, and it can be technically guaranteed in most food production. However, it was also important to assess that in case of accidental ingestion of contaminants below this threshold by highly allergic patients, no fatal anaphylactic reaction could occur. Therefore, we performed a systematic review to assess whether a fatal reaction to 5mg of protein or less has been reported, assuming that a maximum portion size of 1kg of a processed food exceeds any meal and thus gives a sufficient safety margin. METHODS: MEDLINE and EMBASE were searched until 24 January 2021 for provocation studies and case reports in which one of the 14 major food allergens was reported to elicit fatal or life-threatening anaphylactic reactions and assessed if these occurred below the ingestion of 5mg of protein. A Delphi process was performed to obtain an expert consensus on the results. RESULTS: In the 210 studies included, in our search, no reports of fatal anaphylactic reactions reported below 5 mg protein ingested were identified. However, in provocation studies and case reports, severe reactions below 5 mg were reported for the following allergens: eggs, fish, lupin, milk, nuts, peanuts, soy, and sesame seeds. CONCLUSION: Based on the literature studied for this review, it can be stated that cross-contamination of the 14 major food allergens below 0.5 mg/100 g is likely not to endanger most food allergic patients when a standard portion of food is consumed. We propose to use the statement "this product contains the named allergens in the list of ingredients, it may contain traces of other contaminations (to be named, e.g. nut) at concentrations less than 0.5 mg per 100 g of this product" for a voluntary declaration on processed food packages. This level of avoidance of cross-contaminations can be achieved technically for most processed foods, and the statement would be a clear and helpful message to the consumers. However, it is clearly acknowledged that a voluntary declaration is only a first step to a legally binding solution. For this, further research on threshold levels is encouraged.

Prevention and management of allergic reactions to food in child care centers and schools: Practice guidelines.

Food allergy management in child care centers and schools is a controversial topic, for which evidence-based guidance is needed. Following the Grading of Recommendations Assessment, Development, and Evaluation approach, we conducted systematic literature reviews of the anticipated health effects of selected interventions for managing food allergy in child care centers and schools; we compiled data about the costs, feasibility, acceptability, and effects on health equity of the selected interventions; and we developed the following conditional recommendations: we suggest that child care centers and schools implement allergy training and action plans; we suggest that they use epinephrine (adrenaline) to treat suspected anaphylaxis; we suggest that they stock unassigned epinephrine autoinjectors, instead of requiring students to supply their own personal autoinjectors to be stored on site for designated at-school use; and we suggest that they do not implement site-wide food prohibitions (eg, "nut-free" schools) or allergen-restricted zones (eg, "milk-free" tables), except in the special circumstances identified in this document. The recommendations are labeled "conditional" due to the low quality of available evidence. More research is needed to determine with greater certainty which interventions are likely to be the most beneficial. Policymakers might need to adapt the recommendations to fit local circumstances.

Children with nut allergies have impaired gene expression of Toll-like receptors pathway.

BACKGROUND: Trends in food allergies prompted investigation into the underlying mechanisms. Genetic and epigenetic factors are of high interest, and, in particular, the interplay between genes relating to immune factors directly and indirectly involved in food allergy pathogenesis. We sought to determine potential links between gene expression and epigenetic factors relating to Toll-like receptor (TLR) pathways and childhood food allergies. METHODS: In a cross-sectional study, samples from 80 children with and without food allergies were analysed for gene expression, DNA methylation and a range of immune factors relating to TLR pathways. TLR2, TLR4, CD14, IL5, IL13 and vitamin D were explored. RESULTS: The importance of these immune factors appeared to vary between the different types of food allergies. Expression of TLR2 (P < .001), TLR4 (P = .014) and CD14 (P = .028) varied significantly between children with no food allergy, allergy to nuts and peanuts, and allergy to eggs. DNA methylation in the promoter regions of these genes had a significant association with gene expression. These trends persisted when subjects were stratified by nut allergy vs no nut allergy. Furthermore, TLR2 (P = .001) and CD14 (P = .007) expressions were significantly lower in children with food allergies when compared to those without. CONCLUSION: Gene expression of TLR pathway genes was directly related to food allergy type, and DNA methylation had an indirect effect. TLR2 pathways are of significant interest in nut allergies.

SmartStartAllergy: a novel tool for monitoring food allergen introduction in infants.

OBJECTIVES: To estimate the proportion of infants introduced to peanut and other common food allergens by 12 months of age; to collect information about parent-reported reactions to food. DESIGN, SETTING: Observational cohort study, applying the SmartStartAllergy SMS protocol and online questionnaire to parents of 12-month-old infants attending 69 Australian general practices between 21 September 2018 and 3 May 2019. PARTICIPANTS: 3374 parents recruited via the 69 participating general practices. MAIN OUTCOME MEASURES: Proportions of infants who had eaten peanut and other common food allergens; proportions with parent-reported reactions to food. RESULTS: 1940 of 3374 invited parents participated in the study (response rate, 57%), of whom 836 (46%) completed the online questionnaire. At 12 months of age, 1673 of 1940 infants had eaten peanut-including foods (86.2%; 95% confidence interval [CI], 84.6-87.7%); 235 of 1831 parents (12.8%; 95% CI, 11.3-14.5%) reported food-related reactions. Questionnaire responses indicated that dairy was the food type most frequently reported to cause a food-related reaction (72 of 835 exposed infants, 8.6%; 95% CI, 6.8-11%); peanut-related reactions were reported for 20 of 764 exposed children (2.6%; 95% CI, 1.6-4.0%). 97 of 250 parent-reported reactions to food (39%) did not include symptoms that suggested an IgE-mediated allergic reaction. CONCLUSION: Infant feeding practices in Australia have changed over the past decade; a large majority of infants are now fed peanut before 12 months of age. The SmartStartAllergy program allows monitoring of infant feeding practices in primary care, as well as of parent-reported reactions to food in infants.

Diagnosis and management of severe combined immunodeficiency in Australia and New Zealand.

This consensus document outlines the recommendations from the Australasian Society of Clinical Immunology and Allergy Transplantation and Primary Immunodeficiency group for the diagnosis and management of patients with severe combined immunodeficiency. It also provides a proposed framework for the early investigation, management and supportive care prior to haematopoietic stem cell transplantation.

The Implications of DNA Methylation on Food Allergy.

Food allergy is a major clinical and public health concern worldwide. The risk factors are well defined, however, the mechanisms by which they affect immune development remain largely unknown, and unfortunately the effective treatment or prevention of food allergy is still being researched. Recent studies show that the genes that are critical for the development of food allergy are regulated through DNA methylation. Environmental factors can affect host DNA methylation status and subsequently predispose people to food allergy. DNA methylation is therefore an important mediator of gene-environment interactions in food allergy and key to understanding the mechanisms underlying the allergic development. Indeed, the modification and identification of the methylation levels of specific genetic loci have gained increasing attention for therapeutic and diagnostic application in combating food allergy. In this review, we summarize and discuss the recent developments of DNA methylation in food allergy, including the pathogenesis, therapy, and diagnosis. This review will also summarize and discuss the environmental factors that affect DNA methylation levels in food allergy.

Atopic dermatitis in children.

BACKGROUND: Atopic dermatitis is a frequent reason for presentation to general practice. A large number of children are affected by this condition and its treatment can cause significant anxiety for parents. The role of the general practitioner (GP) is to provide advice and allay concerns regarding conventional and alternative treatments. OBJECTIVE: The aim of this article is to provide an overview of atopic dermatitis management in children in the general practice setting. This article also reviews when it is necessary to refer to specialists, the evidence for management and the link to allergies. DISCUSSION: Prescribing topical steroids to young children with atopic dermatitis involves a thorough understanding of this condition. Achieving treatment compliance partly involves providing adequate explanation to parents in order to reduce their concerns regarding the long-term side effects of topical corticosteroids. Making GPs confident and knowledgeable about atopic dermatitis will make the interaction between the practitioner, families and children more rewarding.

ASCIA guidelines for prevention of anaphylaxis in schools, pre-schools and childcare: 2015 update.

The aim of these guidelines is to assist staff in school and childcare settings to plan and implement appropriate risk minimisation strategies, taking into consideration the needs of the allergic child, the likely effectiveness of measures and the practicality of implementation. Although these guidelines include risk minimisation strategies for allergic reactions to insect stings or bites, latex and medication, the major focus relates to food allergy. This is due to the higher relative prevalence of food allergy in childhood (compared with other allergic triggers) and the higher likelihood of accidental exposure in these settings. Care of the allergic child in the school, pre-school or childcare settings requires accurate information obtained from parents and carers, staff training in the recognition and management of acute allergic reactions, planning for unexpected reactions (including in those not previously identified as being at risk), age appropriate education of children with severe allergies and their peers, and implementation of practical strategies to reduce the risk of accidental exposure to known allergic triggers. Strategy development also needs to take into account local or regional established legislative or procedural guidelines and the possibility that the first episode of anaphylaxis may occur outside the home. Food bans are not recommended as the primary risk minimisation strategy due to difficulties in implementation and lack of proven effectiveness.

Molecular pathogenesis of EBV susceptibility in XLP as revealed by analysis of female carriers with heterozygous expression of SAP.

X-linked lymphoproliferative disease (XLP) is a primary immunodeficiency caused by mutations in SH2D1A which encodes SAP. SAP functions in signalling pathways elicited by the SLAM family of leukocyte receptors. A defining feature of XLP is exquisite sensitivity to infection with EBV, a B-lymphotropic virus, but not other viruses. Although previous studies have identified defects in lymphocytes from XLP patients, the unique role of SAP in controlling EBV infection remains unresolved. We describe a novel approach to this question using female XLP carriers who, due to random X-inactivation, contain both SAP(+) and SAP(-) cells. This represents the human equivalent of a mixed bone marrow chimera in mice. While memory CD8(+) T cells specific for CMV and influenza were distributed across SAP(+) and SAP(-) populations, EBV-specific cells were exclusively SAP(+). The preferential recruitment of SAP(+) cells by EBV reflected the tropism of EBV for B cells, and the requirement for SAP expression in CD8(+) T cells for them to respond to Ag-presentation by B cells, but not other cell types. The inability of SAP(-) clones to respond to Ag-presenting B cells was overcome by blocking the SLAM receptors NTB-A and 2B4, while ectopic expression of NTB-A on fibroblasts inhibited cytotoxicity of SAP(-) CD8(+) T cells, thereby demonstrating that SLAM receptors acquire inhibitory function in the absence of SAP. The innovative XLP carrier model allowed us to unravel the mechanisms underlying the unique susceptibility of XLP patients to EBV infection in the absence of a relevant animal model. We found that this reflected the nature of the Ag-presenting cell, rather than EBV itself. Our data also identified a pathological signalling pathway that could be targeted to treat patients with severe EBV infection. This system may allow the study of other human diseases where heterozygous gene expression from random X-chromosome inactivation can be exploited.

Early regular egg exposure in infants with eczema: A randomized controlled trial.

BACKGROUND: Observational studies suggest that early regular ingestion of allergenic foods might reduce the risk of food allergy. OBJECTIVE: We sought to determine whether early regular oral egg exposure will reduce subsequent IgE-mediated egg allergy in infants with moderate-to-severe eczema. METHODS: In a double-blind, randomized controlled trial infants were allocated to 1 teaspoon of pasteurized raw whole egg powder (n = 49) or rice powder (n = 37) daily from 4 to 8 months of age. Cooked egg was introduced to both groups after an observed feed at 8 months. The primary outcome was IgE-mediated egg allergy at 12 months, as defined based on the results of an observed pasteurized raw egg challenge and skin prick tests. RESULTS: A high proportion (31% [15/49]) of infants randomized to receive egg had an allergic reaction to the egg powder and did not continue powder ingestion. At 4 months of age, before any known egg ingestion, 36% (24/67) of infants already had egg-specific IgE levels of greater than 0.35 kilounits of antibody (kUA)/L. At 12 months, a lower (but not significant) proportion of infants in the egg group (33%) were given a diagnosis of IgE-mediated egg allergy compared with the control group (51%; relative risk, 0.65; 95% CI, 0.38-1.11; P = .11). Egg-specific IgG4 levels were significantly (P < .001) greater in the egg group at both 8 and 12 months. CONCLUSION: Induction of immune tolerance pathways and reduction in egg allergy incidence can be achieved by early regular oral egg exposure in infants with eczema. Caution needs to be taken when these high-risk infants are first exposed to egg because many have sensitization already by 4 months of age.

ASCIA guidelines for prevention of anaphylaxis in schools, pre-schools and childcare: 2012 update.

Appropriate management and prevention of anaphylaxis in the school, pre-school and childcare settings requires advanced planning and communication. The Australasian Society of Clinical Immunology and Allergy has developed Guidelines for Prevention of Anaphylaxis in Schools, Pre-schools and Childcare to assist school, pre-school and childcare staff in appropriate implementation of risk-minimisation strategies. Risk-minimisation strategies recommended take into consideration the needs of the allergic child; effectiveness of measures; stresses on parents and staff, the allergic child and their peers; and the implications of the recommended risk-minimisation strategies. These Guidelines address risk-minimisation strategies for food, insect and medication allergies; however, the majority of strategies relate to food allergy due to the higher risk of exposure in these settings. Training in recognition of allergic symptoms (including anaphylaxis), appropriate response and treatment, as well as how to prevent exposure to known allergens are essential for effective anaphylaxis management in the school, pre-school and childcare settings.

Quantitative serum immunoglobulin tests.

What is the test? Immunoglobulins are protein molecules. They contain antibody activity and are produced by the terminal cells of B-cell differentiation known as 'plasma cells'. There are five classes of immunoglobulin (Ig): IgG, IgM, IgA, IgD and IgE. In normal serum, about 80% is IgG, 15% is IgA, 5% is IgM, 0.2% is IgD and a trace is IgE. Quantitative serum immunoglobulin tests are used to detect abnormal levels of the three major classes (IgG, IgA and IgM). Testing is used to help diagnose various conditions and diseases that affect the levels of one or more of these immunoglobulin classes. Some conditions cause excess levels, some cause deficiencies, and others cause a combination of increased and decreased levels. IgD and IgE will not be discussed in this article.

Antinuclear antibody test.

The antinuclear antibody (ANA) test is widely used as a serological marker of autoimmune disease. Antinuclear antibodies are immunoglobulins or antibodies that bind to one or more antigens expressed within the nucleus of human cells. Used selectively, the ANA test can be a useful laboratory tool to help confirm or exclude the diagnosis of systemic rheumatic disease. However, the relatively high prevalence of ANAs in other inflammatory conditions, as well as healthy individuals, can make a positive result difficult to interpret.

Contemporary trends in anaphylaxis burden and healthcare utilisation in Western Australia: A linked data study.

Background: Anaphylaxis is a growing public health problem in Australia. To determine the extent of the problem, we linked multiple health datasets to examine temporal trends in anaphylaxis events across the health system in Western Australia (WA). Methods: We identified an anaphylaxis cohort from 1980 to 2020 using linked datasets from ambulance, emergency departments, hospital inpatients and deaths. Age-standardised anaphylaxis event rates were calculated from 2010 to 2020. Dataset-specific rates for anaphylaxis were also examined, to show differences in health care utilisation. Annual percent change in rates (2010-2019) were estimated using age-adjusted Poisson regression models. Results: A total of 19 140 individuals (mean age 31 years; 51% female) experienced 24 239 anaphylaxis events between 2010 and 2020. From 2010 to 2019, the average annual percent increase (95% CI) in rates was 5.3% (4.8-5.8%), from 70.3 to 113.9, with rates reducing to 76.5/100 000 population in 2020. Adolescents and young adults aged 5-14 years and 15-24 years had the greatest increase of 6.9% (5.6-8.1%) and 6.8% (5.6-8.0) respectively, with those over 25 years increasing by approximately 5% per year and children 1-4 years showing the lowest annual increase of 2.6% (1.1-4.2%). The highest absolute rates were seen in under 1 year (269.7/100 000; 2019). There has been an acceleration of trends from 2015 to 2019, underpinned by large increases in 15-24 and 25-34 years. All databases, show similar increasing trends, with ambulance attendance (33.7 per 100 000), emergency presentation (89.8 per 100 000) and hospital admissions (46.2 per 100 000), for anaphylaxis highest in 2019. However, whilst ambulance and emergency presentations have grown by 8.9% (95%CI 7.9-9.8%) and 6.6% per year (95%CI 6.0-7.2%), respectively, hospitalisations appear to be steadying with only a 0.9% (95%CI 0.2-1.6%) yearly rise. Conclusion: Rates of anaphylaxis continue to increase, with WA having higher rates than previous estimates for Australia. Whilst rates are still high in infants, lower trends in children compared to older ages may indicate better prevention of allergy. Results show more people experiencing anaphylaxis now receive care in emergency and ambulance, rather than hospital. Further exploration of the patient care journey through prehospital and inpatient care is required, to understand the changing health demands of people who experience anaphylaxis.

Welcome back Kotter-Developing a National Allergy strategy for Australia.

Background: Allergic diseases have become an increasing health issue worldwide, being one of the fastest growing chronic diseases in Australia and other westernized countries. In 2013, allergic diseases were reported to affect 20% of the Australian population. Despite the high prevalence there was no national strategy to address these complex health issues, to enable the health system to manage the increasing number of patients. This project aimed to develop and implement a national strategy to improve allergy management in Australia, with a view of improving the quality of life of people living with or caring for someone with allergic diseases. Methods: The need for a national strategy to improve allergy management was identified. The Australasian Society of Clinical Immunology and Allergy (ASCIA) and Allergy & Anaphylaxis Australia (A&AA) worked together as partners to progress a national strategy using a theoretical model to underpin its development. Unrestricted education grants were sought to fund engagement with stakeholder organizations for both development and implementation summits. Several stages of advocacy were undertaken. Results: The National Allergy Strategy was developed as a partnership between ASCIA and A&AA. The Kotter's Change Management Model provided the basis for the steps undertaken to develop and implement the National Allergy Strategy. Two Allergy Summits, one for development and the other for implementation, were held. Several events were held to advocate for federal government funding. Five individual funding grants were achieved to implement National Allergy Strategy projects addressing the most urgent issues. Conclusion: The development of the National Allergy Strategy, a partnership between ASCIA and A&AA, was important in enabling successful advocacy for funding and implementation of important Australia-wide projects. The partnership has also helped facilitate engagement with key stakeholders to help advocate for funding and provide guidance and expertise in project implementation and resource development. The National Allergy Strategy has been successful in attracting funding to implement projects and develop resources urgently needed. The National Allergy Strategy has also provided a framework and a collaborative approach, for advocacy for further funding and future work to be undertaken.

Overview of registries for anaphylaxis: a scoping review.

OBJECTIVE: This review aimed to describe the scope and operational features of anaphylaxis registries, and to assess their contribution to improving knowledge of anaphylaxis and care of patients who experience anaphylaxis by measuring their research output. INTRODUCTION: Structured data collection and reporting systems, such as registries, are needed to better understand the burden of anaphylaxis and to protect the growing number of patients with severe allergy. There is a need to characterize current anaphylaxis registries to identify their value in anaphylaxis surveillance, management, and research. Information synthesized in this review will provide knowledge on benefits and gaps in current registries, which may inform the implementation and global standardization of future anaphylaxis reporting systems. INCLUSION CRITERIA: This scoping review considered literature describing registries worldwide that enroll patients who have experienced anaphylaxis. Published and gray literature sources were included if they described the scope and operational features of anaphylaxis registries. METHODS: This review followed the JBI methodology for scoping reviews. Embase, MEDLINE, Scopus, and CINAHL were searched for relevant articles. Identified keywords and index terms were adapted for searches of gray literature sources, using Google advanced search functions. Only full-text studies in English were considered for inclusion. Two independent reviewers conducted title and abstract screening and those that did not meet the inclusion criteria were excluded. The full text of potentially relevant articles were retrieved; full-text screening and data extraction were also conducted by two independent reviewers. Any discrepancies were resolved through discussion or with a third reviewer. Tables and a narrative summary were used to describe and compare the scope and features (eg, inclusion criteria, patient demographics, clinical symptoms) of the identified anaphylaxis registries, and to outline their output to assess their contribution to research and clinical practice for anaphylaxis. RESULTS: A total of 77 full-text publications and eight gray literature sources were used to extract data. The literature search identified 19 anaphylaxis registries, with sites in 28 countries including Europe, the United Kingdom, Canada, the United States, Korea, and Australia. The main purposes of the identified registries were to collect clinical data for research; provide clinical support tools to improve patient care; and operate as allergen surveillance systems to protect the wider community with allergies. Differences in inclusion and health care settings exist, with 11 collecting data on anaphylaxis of any cause, two on food reactions alone, three on fatal anaphylaxis, one on perioperative anaphylaxis, and two on allergic reactions (including anaphylaxis). Five registries enroll cases in allergy centers, five in hospital settings, one in schools, and others target a combination of general practitioners, specialists in emergency departments, and other relevant hospital departments and allergy outpatient clinics. Only three registries operate under a mandatory framework. A total of 57 publications were considered research outputs from registries. All registries except two have published studies from collected data, with the greatest number of articles published from 2019 to the present. Publications mostly addressed questions regarding demographic profile, causes and cofactors, severity, fatal reactions, and gaps in management. CONCLUSIONS: This review demonstrated that anaphylaxis registries differ in their scope and operation, having been established for different purposes. Importantly, registries have contributed significantly to research, which has highlighted gaps in anaphylaxis management, provoking allergens, and informed targets for prevention for severe and fatal events. Beyond this, registries relay information about anaphylaxis to clinicians and regulatory bodies to improve patient care and protect the community. The ability to link registry data with other health datasets, standardization of data across registries, and incorporation of clinical care indicators to promote quality health care across the health system represent important targets for future systems.

Identifying gene network patterns and associated cellular immune responses in children with or without nut allergy.

BACKGROUND: Although evidence suggests that the immune system plays a key role in the pathophysiology of nut allergy, the precise immunological mechanisms of nut allergy have not been systematically investigated. The aim of the present study was to identify gene network patterns and associated cellular immune responses in children with or without nut allergy. METHODS: Transcriptome profiling of whole blood cells was compared between children with and without nut allergy. Three genes were selected to be validated on a larger cohort of samples (n = 86) by reverse transcription-polymerase chain reactions (RT-qPCR). The composition of immune cells was inferred from the transcriptomic data using the CIBERSORTx algorithm. A co-expression network was constructed employing weighted gene co-expression network analysis (WGCNA) on the top 5000 most variable transcripts. The modules were interrogated with pathway analysis tools (InnateDB) and correlated with clinical phenotypes and cellular immune responses. RESULTS: Proportions of neutrophils were positively correlated and CD4+ T-cells and regulatory T-cells (Tregs) were negatively correlated with modules of nut allergy. We also identified 2 upregulated genes, namely Interferon Induced With Helicase C Domain 1 (IFIH1), DNA damage-regulated autophagy modulator 1 (DRAM1) and a downregulated gene Zinc Finger Protein 512B (ZNF512B) as hub genes for nut allergy. Further pathway analysis showed enrichment of type 1 interferon signalling in nut allergy. CONCLUSIONS: Our findings suggest that upregulation of type 1 interferon signalling and neutrophil responses and downregulation of CD4+ T-cells and Tregs are features of the pathogenesis of nut allergy.