Is there an allergy epidemic and what are the possible causes?

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1 Is there an allergy epidemic and what are the possible causes? Professor Michael Gold Department of Allergy and Immunology Women s and Children s Health Network Discipline of Paediatrics University of Adelaide

2 Outline Allergic diseases Allergy Epidemics Hay fever and hygiene Asthma and indoor environment Food allergy and microbiome

3 What are the allergic diseases?

4 Allergic Disease Chronic Inflammatory conditions that effect the epithelial and endothelial barrier; Skin Eczema (Atopic dermatitis) Respiratory tract Allergic rhinitis (Hay fever), Asthma Gastrointestinal tract Enteropathy, Eosinophilic Esophagitis, FPIES Colitis

5 Allergic Disease Acute hypersensitivity conditions; Food, drug, insect venom allergy

6 New manifestations of allergic disease last decade Food Protein Induced Enterocolitis Syndrome Eosinophilic Esophagitis Multiple Food Protein Allergy Allergic gastroenteritis hospital admissions Time trends in Australia

7 Epidemic The occurrence in a community or region of cases of an illness, specific health-related behaviour, or other health-related events clearly in excess of normal expectancy ; Late Latin Greek epidēmía staying in one place, among the people

8 History A dissertation on the cause of the coryza which occurs in the spring when the roses give forth their scent Rhazes 865 AD

9 Why did the hay fever epidemic start in the mid 1800 s? Post industrial revolution epidemic ( ) He developed symptoms of hay fever in June of 1875 but after several years of symptoms he could not find a physician who was aware of the condition. By 1890, he knew a group of sufferers but none of them had had symptoms before sites existed where hay fever sufferers could go during the season to avoid exposure to pollen: North Sea Island was kept free of grass pollen 1911 First pollen immunotherapy studies Emanuel MB. Clin Allergy 1988 Noon L. Prophylactic innoculation for hay fever. Lancet. 1911; i:1572 Platts-Mills T. JACI July ; 136(1): 3 13.

10 Prevalence of HF in previous year Hay fever, hygiene and household size Hygiene hypothesis Age 23 be explained if allergic disease were prevented by infection in early childhood, transmitted by unhygienic contact with older siblings,. Number of children in house at 11 years of age Strachan D. BMJ 1989

11 The Hay Fever Epidemic Clean drinking water established after the relationship between sewage (Broad Street Pump) and enteric disease (Cholera) was established by John Snow in Pollen exposure - Corn laws of 1878 allowed importation of cheap wheat into the UK and Italian Rye grass (Lolium perene) was introduced which pollinated more heavily. Platts-Mills T. JACI July ; 136(1): 3 13.

12 The Asthma Epidemic 1960 to 1990 Prior to 1960, most text books of paediatrics did not regard asthma as common let alone epidemic. The first publication came in Change in hay-fever prevalence Australian adults Male Female Hopper et al. Australian J Pub Health 1995

13 The Asthma Epidemic Indoor environment, etc Given that the major changes in hygiene had occurred by 1920, it is difficult to ascribe the massive changes in prevalence of asthma between 1960 and 2000 to the minor changes in hygiene that occurred, over that period. Changes that occurred to promote indoor activity; Television in 1950 s Increase comfort carpeting and heating Effect of increased indoor exposure Increased exposure to indoor allergens Reduced exercise - Changes in breathing patterns sigh rates Progressive increase in BMI Progressive increase in broad spectrum antibiotics Use of paracetamol to treat fever in childhood that replaced Aspirin Increased exposure to vaccines and change in type of vaccines Platts-Mills T. JACI July ; 136(1): 3 13.

14 The Food Allergy Epidemic 1990 to current Poulos et al JACI Oct;120(4): Osborne et al al JACI 2007 Oct;120(4):878-84

15 The Food Allergy Epidemic the exposome Daily Telegraph10 September 2005 Weekend Australian: September 2005

16 The Exposome Total environmental exposure affecting all living systems and their genome Renz H. An exposome perspective: Early-life events and immune development in a changing world. JACI2017;140:24-40

17 The microbiome and evolution of the immune system Homo Sapiens evolved together with viruses, bacteria, fungi, archaea, Collectively know as the human microbiome Relationship is synbiotic benefits human health and vice versa Protection against pathogens Maintain skin/mucosal barrier function Nutrient extraction Vitamin production Lipid metabolism Provision of bioactive metabolites (SCFA) Synbiosis confers an evolutionary advantage This evolution could not have occurred without the development of adaptive immunity

18 Innate and adaptive immunity Invertebrates INNATE IMMUNITY RAG 1 and RAG 2 Genes Responsible for construction of the antigen receptors through RNA splicing, to a constant (C) region to produce a functional receptor. Because each loci comprises numerous copies of each V, D or J segment, random joining of these different regions of DNA can produce in excess of possible receptor combinations which are capable or recognizing the array of antigens encountered. 100,000,000,000,000

19 Importance of adaptive immunity Invertebrates Vertebrates INNATE IMMUNITY ADAPTIVE IMMUNITY 500 million years ago Microbial DNA infecting marine animals early RAG genes

20 Allergic disease an evolutionary mismatch between our immune systems and our exposome Dysbiosis Changes to the structure of complex commensal microbial communities resulting in changes that may threaten symbiosis loss of beneficial effects Both an absence of factors that may prevent allergic disease but also a presence of factors that may contribute Overall degree of microbiome diversity is reduced

21 A unifying hypothesis for Non Communicable Disease Chronic inflammation

22

23 Conclusion Understanding allergic diseases Multiple allergy epidemics Hay fever and hygiene Asthma and indoor environment Food allergy and microbiome

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