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pISSN 2092-7355   eISSN 2092-7363
    Allergy Asthma Immunol Res. 2023 May;15(3):290-302. English.
    Published online May 08, 2023.
    https://doi.org/10.4168/aair.2023.15.3.290
    Copyright © 2023 The Korean Academy of Asthma, Allergy and Clinical Immunology • The Korean Academy of Pediatric Allergy and Respiratory Disease
    Review

    The Concept of One Health for Allergic Diseases and Asthma

    Ioana Agache, Alexandru Laculiceanu, Daniela Spanu and Dan Grigorescu
      • Faculty of Medicine, Transylvania University, Brasov, Romania.
    • Correspondence to Ioana Agache, MD. Faculty of Medicine, Transylvania University; 2A Pictor Ion Andreescu Brasov, Romania. Tel: +40-727-849-321; Fax: +40-268-516688; Email: ibrumaru@unitbv.ro
    Received January 19, 2023; Revised April 05, 2023; Accepted April 05, 2023.

    This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

    Abstract

    The worldwide prevalence of allergic disease is rising as a result of complex gene-environment interactions that shape the immune system and host response. Climate change and loss of biodiversity are existential threats to humans, animals, plants, and ecosystems. While there is significant progress in the development of targeted therapeutic options to treat allergies and asthma, these approaches are inadequate to meet the challenges faced by climate change. The exposomic approach is needed with the recognition of the bidirectional effect between human beings and the environment. All stakeholders need to work together toward mitigating the effects of climate change and promoting a One Health concept in order to decrease the burden of asthma and allergy and to improve immune health. Healthcare professionals should strive to incorporate One Health counseling, environmental health precepts, and advocacy into their practice.

    Keywords
    Allergy; asthma; biodiversity; climate; exposome; gene; environment; One Health

    INTRODUCTION

    The global challenge

    The Anthropocene Epoch is an unofficial unit of geologic time and is used to describe the most recent period in Earth’s history when human activity started to have a significant impact on the planet’s climate and ecosystems. The Anthropocene is debated to be situated either after or within the Holocene, the current epoch, which began approximately 10,000 years ago with the end of the last glacial period.1, 2 Although not yet accepted by all scientists, there is now overwhelming global evidence that human activity profoundly impacts atmospheric, geologic, hydrologic, biospheric, and other earth system processes.1, 2, 3 Planet Earth will be conquered by the man with 10 billion inhabitants by 2050 and with a global human-made mass exceeding all living biomass.4

    The Planetary Boundaries concept describes 9 processes and systems based on the interactions between land, ocean, atmosphere, and life that regulate the stability and resilience of the Earth System.5, 6, 7 Four of these boundaries have now been crossed as a result of human activity: climate change, loss of biosphere integrity, land-system change, and altered biogeochemical cycles (phosphorus and nitrogen). Climate change and biosphere integrity are “core boundaries,” as they can significantly drive the Earth System into a new state. In 2015, the International Geosphere-Biosphere Programme reassessed and updated its “Planetary Dashboard,” first published in 2004.8 A combination of 12 earth system trends and 12 socio-economic indicators forms the “Planetary Dashboard,” depicting the “Great Acceleration” in human imprint from 1950 onward. The global water cycle is continuously altered through damming, agriculture, and carbon emissions, plastic waste has exploded, and concentrations of carbon dioxide (CO2) in the atmosphere have risen from 280 parts per million (ppm) in pre-industrial times to 400 ppm in 2014 while “novel entities” created entirely by humans (detergents, emulsifiers, radioactive materials, genetically modified organisms, nanomaterials, micro-plastics and many more) can persist in the environment for a very long time, and their effects are potentially irreversible.9, 10, 11, 12, 13, 14, 15 The State of Food Security and Nutrition in the World 2022 report reinforces the doubts that the world is moving backward to end hunger, food insecurity, and malnutrition.16 Political unrest, economic shocks, and growing inequalities will continue challenging the Earth System.

    Pollution caused by increased human activity is a major concern. Key air pollutants designated by the World Health Organization (WHO) are particulate matter (PM), ozone, nitrogen dioxide (NO2), and sulfur dioxide. Besides these, other air pollutants such as gases (benzene, toluene, and xylenes), liquid aerosols (perchloroethylene and methylene chloride), and inhalable particles (polycyclic aromatic hydrocarbons, cadmium, chromium, lead, and mercury) have been categorized as hazardous or toxic air pollutants.17 The burning of fossil fuels, which include CO2, methane, nitrous oxides, and other fluorinated gases, has increased greenhouse gas (GHG) concentrations.18 The global food system, including its production, manufacturing, and transportation, is responsible for nearly one-third of anthropogenic GHG emissions.19, 20 The healthcare system is also a big contributor to GHG.21, 22 By trapping heat GHG has raised global temperatures, the main driver of climate change.23, 24 Deforestation reduces nature’s ability to remove CO2.25 Rising atmospheric CO2 levels have also been shown to decrease concentrations of plant carotenoids, antioxidants that are essential to human health.26

    Global plastic pollution is a growing threat to planetary health. Less than 10% of the world's plastic is actually recycled with the majority of the plastic waste being incinerated (increasing air pollution and release of more GHG together with airborne toxins) or ending up in landfills (polluting soil and water sources), or in rivers and oceans, with threatened marine ecosystems and the ubiquitous ingestion of microplastics.11, 27 Mosquitoes and other vectors that breed in plastic waste contribute to outbreaks of deadly infections.28

    Resilience and human health

    Whereas homeostasis refers to stability through constancy, allostasis refers to stability through variation.29 Resilience is the capacity of a system to buffer the aggression and reorganize while undergoing changes to preserve its identity, structure and function, and regulatory feedback. Crucial for building resilience in ecosystems is maintaining diversity and redundancy while acknowledging the complex and unpredictable web of connections and interdependencies.30, 31, 32

    The level of resilience is key to maintaining health by keeping the balance between the impact and response.32 The key aggression pathways (binding to macromolecules, DNA mutation, adducts, epigenetic modifications, disruption of enzyme function, and damage via reactive oxygen or nitrogen species) are continuously being counteracted by DNA repair systems, ubiquitination, autophagy and proteolysis, antioxidant systems, chaperone proteins and many more. However, the impact of the repair process, coined as allostatic load, especially if overloaded, might have long-term consequences on health.33, 34, 35, 36, 37

    Nature provides us with exquisite resilience models. An interesting example is the forest living lab where leaves slow rainwater to protect the soil, mulch protects and feeds the soil, worms and fungi degrade the leaves and enrich the soil with precious nutrients, the soil cleans the water, stores and provides minerals, nutrients, and water supporting the tree growth.38 Plants and microbes coinhabit the earth and have coevolved during environmental changes over time. Root metabolites are the key to mediating the dynamic association between plants and microbes during environmental stress.39 In the human resilience model, the genome is continuously shaped by biodiversity and other protective exposure to a protective epigenome supporting resilience to all the exposome challenges.40

    Recent decades have seen a rapid increase in chronic inflammatory disorders due to inappropriate or misdirected immune responses accompanied by insufficient development of immune regulatory networks. Diet, microbiome, and the epithelial barrier are key regulators of the crosstalk to ensure that the immune system adapts to challenges by establishing, maintaining, and regulating an appropriate immune response.9, 40, 41

    Biodiversity and human health

    Biodiversity refers to the variety of life on Earth, from genes to ecosystems, including plants, animals, bacteria, and fungi. While Earth’s biodiversity is so rich that many species have yet to be discovered, many species are being threatened with extinction due to pollution, climate change, and population growth with unsustainable resource use.42, 43, 44 Climate change alone threatens with the extinction of approximately one-quarter or more of all species on land by the year 2050, surpassing habitat loss as the biggest threat to life on land. Humans are part of biodiversity. Many basic human needs depend on biodiversity such as food, fuel, shelter, and medicine. Ecosystems further contribute to pollination, seed dispersal, climate regulation, water purification, nutrient cycling, and control of agricultural pests.45

    The holobiont includes all resident bacteria, archaea, viruses, fungi, and their genes that are essential to our body. These microbiomes exist in all our organ systems including the skin, gut, airways, urogenital tract, breast tissue, and breast milk. All species involved in the holobiont form discrete ecological units called bionts. The combined genome of all bionts is referred to as a hologenome.46, 47 Ecological relationships are well established with the human body, but also with species residing close enough to modify shared biological matrices, such as air or water, through the release of metabolites.48 This interaction is of paramount for achieving and maintaining human health, as it can lead to the generation of symbiotic structures.

    Changes in biodiversity can greatly affect the holobiont. Urban environments are characterized by a dramatic decrease in biodiversity, which is only partially mitigated by the existence of green spaces or by pet-keeping behaviors. In addition, modern humans spend an average of 22 hours a day indoors, which profoundly limits opportunities to interact with most animal and vegetal species naturally populating the ecological niche.49, 50

    Losses of biodiversity impact human health in numerous ways such as the emergence, transmission, and spread of many human infectious diseases (the pathogens for 60 percent of human infectious diseases are zoonotic), or impaired resilience with chronic inflammation.51, 52, 53, 54

    The exposomic science

    Exposomics is particularly applicable to the study of environmental causes of chronic disease as it offers risk profiles instead of single predictors, while concomitant access to biological data, exposure data, and health outcomes evaluates the biological plausibility of the hypothesis.32 Real-time analysis of geospatial, environmental, and health data as well as the application of computer-learning techniques for a better understanding of environment-human interactions are currently some of the most important challenges in understanding the impact of global change on human health and disease. Big data analyses and artificial intelligence can be used to decipher the complex, multidimensional relationships of diverse parameters in the cause of diseases, with special attention to vulnerable populations, chronicity of cumulative effects over a lifetime, and multiple exposures at once.32, 55, 56

    The bidirectional effect of the environment on human subjects and the human influence on all living systems and their genomes is called the metaexposome. The metaexposome starts building the allostasis during early-life immune maturation, with efficient regulation of the human host response requiring: 1) anticipation of the changing environment through metaexposome interactions and 2) subsequent implementation of the epigenetic changes supporting an adequate response to further external threats.57, 58

    ALLERGY IS A TYPICAL ONE HEALTH ISSUE

    Asthma and allergy are proto-types of One Health diseases, as they are directly and indirectly influenced by the health status of the environment (water, soil, and air), plants, and companion and wild animals.59 Environmental stress following climate change and global warming with extreme storms, floods, wildfires, droughts, melting ice caps, sea level rise, and heatwaves directly impacts patients with allergic diseases and asthma.9, 60 Heavy rainfalls, high humidity, and thunderstorms might occur more frequently due to climate change. Especially thunderstorms have been shown to go along with atmospheric peaks in highly respirable sub-pollen particles and fungal spores, which are linked to thunderstorm asthma.61 The rise in sea level would expose a sizable percentage of the population who live in coastal and wetland areas to additional wet housing conditions, posing an increased risk of indoor mold contamination and resultant sensitization.62, 63 The frequency and intensity of heatwaves will likely increase over the coming century as world temperatures rise. The impact of heatwaves on mortality is typically greatest in urban areas, mainly due to the “heat island” effect. Vulnerable populations include the elderly and those with co-morbidities, such as respiratory diseases.64 Major cellular mechanisms of tolerance, which employ ion transporters, proteins, osmoprotectants, antioxidants, and other factors involved in signaling cascades and transcriptional control, are activated to offset stress-induced biochemical and physiological alterations. At the molecular level, heat stress causes alterations in the expression of genes involved in direct protection from high-temperature stress. These include genes responsible for expressing osmoprotectants, detoxifying enzymes, transporters, and regulatory proteins. Modifying physiological and biochemical processes by gene expression changes gradually leads to the development of heat tolerance in the form of acclimation, or in the ideal case, to adaptation.65, 66, 67 These mechanisms are highly conserved in plants and animal and human cells; however, when overridden might lead to chronic inflammation, pathologic apoptosis, and the generation of allergenic proteins in plants or animals.68, 69, 70, 71

    Climate change and global warming also lead to the migration of plants, prolonged flowering seasons, and increased allergenicity, thus enhancing the risk for allergy development and symptoms in animals and people. Allergenic plants (e.g., Ambrosia in South-East Europe or pollen grains at high altitudes) and animals (e.g., insects like Polistes spp. in arctic regions) are reported in geographical regions where they have not been resident before. Allergens are environmental antigens and are as such subject to modification by environmental factors. Pollen-producing plants, in specific, react to biotic and abiotic stressors by inducing secondary metabolites, such as lipid mediators and host-defense proteins, some of which are allergenic. The earlier and prolonged blooming season due to increased temperature leads to higher and prolonged allergen exposure, while the allergenicity of molecules becomes more potent in combination with CO2, ozone, or fine and ultrafine particles.72, 73, 74 The diversity of pollen-associated microbiota was found to be reduced in association with elevated NO2 levels.75

    A shift away from traditional diets rich in plant-based foods with dietary fiber and micronutrients to highly processed foods loaded with additives, such as preservatives and emulsifiers, is thought to be particularly important for negatively affecting the epithelial barriers, microbiome diversity and metabolism, and immunological tolerance.41, 54, 76, 77, 78 Processing changes the allergenicity of food by influencing protein structure and ligand loading. Cow’s milk can be allergenic, while raw milk was shown to protect against allergies.79 The major whey protein beta-lactoglobulin (BLG), a lipocalin, is a typical milk allergen (Bos d 5), but can also be tolerogenic under certain conditions. Proteins of the lipocalin family are carrier molecules for iron-siderophore complexes, vitamins A and D, and zinc. BLG coupled with vitamins and iron is tolerogenic, while its uptake without ligands evokes a type 2 (T2) immune response.80, 81

    Breeding conditions and feed of pets and farm animals shape their microbiome and may modulate the allergenicity of tolerogenic properties of their products like proteins in milk or dander.82, 83, 84, 85 Pollution of water, soil, or air and/or depletion of nutrients/nutrient diversity in the soil can increase the allergenicity of proteins from plants and animals used as sources of food for humans.85, 86, 87, 88

    Environmental exposure to some microbes, parasites, green spaces, and dirty soil can protect against allergy, while excessive body hygiene (shampoos, shaving, deodorants, perfumes, disinfectants, etc.) and use of detergents and cleaning agents damage the epithelial barriers even in infinitesimal amounts and thus favor the initiation of a T2-immune response instead of a tolerogenic response.41, 54, 88, 89

    HOW CAN WE INTERVENE?

    Several holistic and interdisciplinary approaches to safeguard health have developed in the last decades: One Health, EcoHealth, and Planetary Health.90 One Health is an interdisciplinary approach focusing on the interconnectedness of the health of humans, animals, and the environment. It is an “umbrella” depiction including environmental health, ecology, veterinary medicine, public health, human medicine, molecular, and microbiology as well as health economics, focused on the scientific multidisciplinary approach.90, 91 EcoHealth is committed to fostering the health of humans, animals, and ecosystems and conducting research that recognizes the inextricable linkages between the health of all species and their environments.90, 92 Planetary Health aims at achieving the highest attainable standard of health, well-being, and equity worldwide through judicious attention to the human systems—political, economic, and social—that shape the future of humanity and Earth’s natural systems that define the safe environmental limits within which humanity can flourish.90, 93 Both the Planetary and the EcoHealth concepts focus mainly on sustainability and equity by better balancing human needs with the preservation of Earth’s ecosystems in an effort to protect the health and well-being of future generations.

    Replacing planetary degradation and achieving sustainability will require a multidisciplinary, cross-sector, and transborder approach to change practices and policies at every level, from global to local.9, 91 The exposome concept helps frame solutions related to mitigation and adaptation to address the complex environmental exposures faced today by individuals with asthma and allergy.32 Mitigation refers to primary prevention intended to cut or prevent the emission of GHG, thus limiting the magnitude of future warming, whereas adaptation is secondary prevention intended to reduce vulnerability to climate change impacts.

    The Circular Bioeconomy Alliance, established in 2020, is building a global network of Living Labs for Nature, People, and Planet, empowering nature and people in a concrete territorial context, integrating traditional knowledge, capitalizing on new research and innovation based on public-private partnerships that place local communities at their center. Each Living Lab uses a landscape restoration project as the starting point to catalyze the development of circular bioeconomy value chains while restoring biodiversity and local livelihoods.94

    Diversity in dietary proteins early in life has been shown to reduce the risk of allergy and asthma. In addition to their nutritive value, fatty acids, and dietary fibers have important immunoregulatory effects. However, the lack of standardized formats (i.e., food versus supplement) and standardized doses significantly limit the ability to correctly assess outcomes across studies and to provide clear recommendations at this time.77, 78 The EAT-Lancet Commission recommends a healthy, plant-rich diet, high in whole grains, legumes, vegetables, fruits, and healthy fats.95 By including a wide variety of plant-based proteins in early life, allergies can be prevented by developing immune tolerance. Understanding how these dietary interventions can enable better control of an immune system biased to chronic inflammation, improve microbiota, and enhance health will be important for the future.

    Sustainable food systems with minimal climate impact while ensuring food security and diversity of food choices together with access to healthy food, are all important measures for allergy and asthma prevention. The EAT-Lancet Commission on healthy diets from sustainable food systems established a target of 5 billion tons of CO2 equivalent from food systems by 2050.95 Agricultural practices need to become more sustainable as well. Regenerative agriculture is a holistic land-management practice that aims to sequester carbon in the soil while improving soil health, crop yields, water resilience, and nutrient density. It advocates for the use of cover crops, reducing tilling, rotating crops, and spreading compost while moving away from synthetic fertilizers, pesticides, herbicides, and factory farming.85, 96

    Exposure to a biodiverse environment, especially in early life, has been found to be one of the strongest and most consistent protective factors against the development of asthma and related atopic conditions. A greater diversity of microbes is thought to be one of the key drivers of the early immune system away from developing asthma and allergies, while green spaces may protect against asthma development or symptoms.54, 57, 88, 89, 97 Many greening practices are currently being implemented in big cities around the world to mitigate the impact of climate change by sequestering CO2 and reducing temperature. However, plants can be allergenic, and thus allergists and asthma experts should be included in policy discussions and city planning to promote biodiversity while reducing allergenicity. For example, native species of heterosexual plants reduce allergen spread and promote natural growth for mitigation against climate change.98

    The One Health medical professional connects traditional healthcare with a holistic approach to improving diet, physical exercise/mobility of citizens, housing and working environment, and connectivity with nature. Allergy and asthma specialists can play a vital role in education, communication, and advocacy on climate change mitigation and adaptation measures. For example, climate change was emphasized during the recent Finnish Allergy Program 2008–2018.99 In the City of Lahti, the EU Green Capital 2021, Natural Step to Health—a Regional Health and Environment Programme 2022–2032—is using asthma and allergy as one of the main focus areas. The goals also include the mitigation of climate change and biodiversity loss.100

    More collaborative research on the effect of climate change and the impact on allergies and asthma is needed together with an integrated approach to environmental and health policies based on high-quality evidence (ideally in the format of guidelines) in order to implement appropriate measures. The advanced methodological approach to proving causality instead of associations together with an integrated surveillance network for the environmental impact on allergies and asthma is key to moving the field forward. It is important to tackle the challenges of the climate crisis, pollution, energy, and biodiversity from both ends, top-down and bottom-up, meaning that policymakers have to implement and control sustainable strategies, but also individuals need to contribute with appropriate measures in their personal and professional life.

    OPEN QUESTIONS

    Many questions remain to be solved on how the multiple concomitant environmental stressors continuously shape the allostatic load and what is the role of the immune system, microbiota, epithelial barrier, and diet in promoting resilience. In addition, what is the population of interest (“the model”), what is the nature (duration, frequency, timing) and magnitude (concentration and dose) of relevant exposures, which associations are relevant for a particular allergic disease, what are the mechanisms driving the environmental endotypes, and what is the value of population-level interventions versus the personalized medicine approach.

    CONCLUSION

    Asthma and allergic diseases, as environment-driven entities with life-long impacts, are very suitable for One Health policy implementation, knowing that the environment can support health through key pillars of resilience like diet, microbiome, and the epithelial barrier. In line with the concept of One Health, an interdisciplinary and holistic approach from a broad range of fields of expertise (healthcare professionals, ecology, biology, agriculture, veterinary medicine, aerobiology, microplastics, water ecology, etc.) is required to prevent diseases, like the chronic disease, epidemic (including allergies and asthma), and the catastrophic impact of climate change on human health and planet Earth.

    Notes

    Disclosure:There are no financial or other issues that might lead to conflicts of interest.

    References

      1. Waters CN, Turner SD. Defining the onset of the Anthropocene. Science 2022;378:706–708.
      1. Bauer AM, Edgeworth M, Edwards LE, Ellis EC, Gibbard P, Merritts DJ. Anthropocene: event or epoch? Nature 2021;597:332.
      1. Moysés SJ, Soares RC. Planetary health in the Anthropocene. Health Promot Int 2019;34:i28–i36.
      1. UN Department of Economic and Social Affairs. Growing at a slower pace, world population is expected to reach 9.7 billion in 2050 and could peak at nearly 11 billion around 2100 [Internet]. Paris: United Nations; 2019 [cited 2023 Jan 18].
        Available from: https://www.un.org/development/desa/en/news/population/world-population-prospects-2019.html.
      1. Galaz V. Environment: planetary boundaries concept is valuable. Nature 2012;486:191.
      1. Nash KL, Cvitanovic C, Fulton EA, Halpern BS, Milner-Gulland EJ, Watson RA, et al. Planetary boundaries for a blue planet. Nat Ecol Evol 2017;1:1625–1634.
      1. Stockholm Resilience Centre. Stockholm Resilience Centre Annual Report 2015 [Internet]. Stockholm: Stockholm Resilience Centre; 2016 [cited 2023 Jan 18].
        Available from: https://www.stockholmresilience.org/download/18.1939e4a15356be76ad1bfd/1459560386557/Annual_2015_webb.pdf.
      1. International Geosphere-Biosphere Programme. Planetary dashboard shows “Great Acceleration” in human activity since 1950 [Internet]. Stockholm: International Geosphere-Biosphere Programme; 2015 [cited 2023 Jan 18].
        Available from: http://www.igbp.net/news/pressreleases/pressreleases/planetarydashboardshowsgreataccelerationinhumanactivitysince1950.5.950c2fa1495db7081eb42.html.
      1. Agache I, Sampath V, Aguilera J, Akdis CA, Akdis M, Barry M, et al. Climate change and global health: a call to more research and more action. Allergy 2022;77:1389–1407.
      1. Kåresdotter E, Destouni G, Ghajarnia N, Lammers RB, Kalantari Z. Distinguishing direct human-driven effects on the global terrestrial water cycle. Earths Futur 2022;10:EF002848
      1. Rhodes CJ. Plastic pollution and potential solutions. Sci Prog 2018;101:207–260.
      1. United States Environmental Protection Agency. Climate change indicators: atmospheric concentrations of greenhouse gases [Internet]. Washington, D.C.: United States Environmental Protection Agency; 2022 [cited 2023 Jan 18].
        Available from: https://www.epa.gov/climate-indicators/climate-change-indicators-atmospheric-concentrations-greenhouse-gases.
      1. Celebi Sozener Z, Ozdel Ozturk B, Cerci P, Turk M, Gorgulu Akin B, Akdis M, et al. Epithelial barrier hypothesis: effect of the external exposome on the microbiome and epithelial barriers in allergic disease. Allergy 2022;77:1418–1449.
      1. Schirinzi GF, Pérez-Pomeda I, Sanchís J, Rossini C, Farré M, Barceló D. Cytotoxic effects of commonly used nanomaterials and microplastics on cerebral and epithelial human cells. Environ Res 2017;159:579–587.
      1. Długosz-Lisiecka M, Tyborowski D, Krystek M. Radioactive fossils: the uranium anomaly and its paleobiological implications. Chemosphere 2021;285:131444
      1. Food and Agriculture Organization. The state of food security and nutrition in the world 2022 [Internet]. Rome: Food and Agriculture Organization; 2022 [cited 2023 Jan 18].
        Available from: https://www.fao.org/3/cc0639en/online/sofi-2022/about.html.
      1. World Health Organization. WHO global air quality guidelines: particulate matter (PM2.5 and PM10), ozone, nitrogen dioxide, sulfur dioxide and carbon monoxide [Internet]. Geneva: World Health Organization; 2021 [cited 2023 Jan 18].
        Available from: https://www.who.int/publications/i/item/9789240034228.
      1. Martins T, Barreto AC, Souza FM, Souza AM. Fossil fuels consumption and carbon dioxide emissions in G7 countries: Empirical evidence from ARDL bounds testing approach. Environ Pollut 2021;291:118093
      1. Bellarby J, Tirado R, Leip A, Weiss F, Lesschen JP, Smith P. Livestock greenhouse gas emissions and mitigation potential in Europe. Glob Change Biol 2013;19:3–18.
      1. Ghosh A, Misra S, Bhattacharyya R, Sarkar A, Singh AK, Tyagi VC, et al. Agriculture, dairy and fishery farming practices and greenhouse gas emission footprint: a strategic appraisal for mitigation. Environ Sci Pollut Res Int 2020;27:10160–10184.
      1. MacNeill AJ, Lillywhite R, Brown CJ. The impact of surgery on global climate: a carbon footprinting study of operating theatres in three health systems. Lancet Planet Health 2017;1:e381–e388.
      1. Schmidt L, Bohnet-Joschko S. Planetary health and hospitals’ contribution-a scoping review. Int J Environ Res Public Health 2022;19:13536.
      1. Montzka SA. The NOAA Annual Greenhouse Gas Index (AGGI) [Internet]. Boulder (CO): NOAA Global Monitoring Laboratory; 2022 [cited 2023 Jan 18].
        Available from: https://gml.noaa.gov/aggi/aggi.html.
      1. UCAR Center for Science Education. The greenhouse effect [Internet]. Boulder (CO): UCAR Center for Science Education; 2023 [cited 2023 Jan 18].
        Available from: https://scied.ucar.edu/learning-zone/how-climate-works/greenhouse-effect.
      1. Longobardi P, Montenegro A, Beltrami H, Eby M. Deforestation Induced Climate Change: Effects of Spatial Scale. PLoS One 2016;11:e0153357
      1. Loladze I, Nolan JM, Ziska LH, Knobbe AR. Rising atmospheric CO2 lowers concentrations of plant carotenoids essential to human health: a meta-analysis. Mol Nutr Food Res 2019;63:e1801047
      1. Rillig MC, Lehmann A. Microplastic in terrestrial ecosystems. Science 2020;368:1430–1431.
      1. Banerjee S, Aditya G, Saha GK. Household disposables as breeding habitats of dengue vectors: linking wastes and public health. Waste Manag 2013;33:233–239.
      1. McEwen BS, Wingfield JC. What is in a name? Integrating homeostasis, allostasis and stress. Horm Behav 2010;57:105–111.
      1. Moore JW, Schindler DE. Getting ahead of climate change for ecological adaptation and resilience. Science 2022;376:1421–1426.
      1. Malhi Y, Franklin J, Seddon N, Solan M, Turner MG, Field CB, Knowlton N. Climate change and ecosystems: threats, opportunities and solutions. Philos Trans R Soc Lond B Biol Sci 2020;375:20190104
      1. Agache I, Miller R, Gern JE, Hellings PW, Jutel M, Muraro A, et al. Emerging concepts and challenges in implementing the exposome paradigm in allergic diseases and asthma: a Practall document. Allergy 2019;74:449–463.
      1. Shiels PG, Buchanan S, Selman C, Stenvinkel P. Allostatic load and ageing: linking the microbiome and nutrition with age-related health. Biochem Soc Trans 2019;47:1165–1172.
      1. Logan JG, Barksdale DJ. Allostasis and allostatic load: expanding the discourse on stress and cardiovascular disease. J Clin Nurs 2008;17:201–208.
      1. Juster RP, McEwen BS, Lupien SJ. Allostatic load biomarkers of chronic stress and impact on health and cognition. Neurosci Biobehav Rev 2010;35:2–16.
      1. Barry LE, O’Neill S, Heaney LG, O’Neill C. Stress-related health depreciation: using allostatic load to predict self-rated health. Soc Sci Med 2021;283:114170
      1. Barry LE, O’Neill C, Heaney LG. Association between asthma, corticosteroids and allostatic load biomarkers: a cross-sectional study. Thorax 2020;75:835–841.
      1. Wall DH, Nielsen UN, Six J. Soil biodiversity and human health. Nature 2015;528:69–76.
      1. Hong Y, Zhou Q, Hao Y, Huang AC. Crafting the plant root metabolome for improved microbe-assisted stress resilience. New Phytol 2022;234:1945–1950.
      1. Haahtela T, Alenius H, Lehtimäki J, Sinkkonen A, Fyhrquist N, Hyöty H, et al. Immunological resilience and biodiversity for prevention of allergic diseases and asthma. Allergy 2021;76:3613–3626.
      1. Akdis CA. Does the epithelial barrier hypothesis explain the increase in allergy, autoimmunity and other chronic conditions? Nat Rev Immunol 2021;21:739–751.
      1. Goymer P. Biodiversity: leaping lizards. Nature 2014;513:492.
      1. Seddon N, Mace GM, Naeem S, Tobias JA, Pigot AL, Cavanagh R, et al. Biodiversity in the Anthropocene: prospects and policy. Proc Biol Sci 2016;283:20162094
      1. Reijenga BR, Murrell DJ, Pigot AL. Priority effects and the macroevolutionary dynamics of biodiversity. Ecol Lett 2021;24:1455–1466.
      1. Marton-Lefèvre J. Biodiversity is our life. Science 2010;327:1179.
      1. Collier RJ, Casadevall A. The holobiont/hologenome concept series. MBio 2016;7:e00605-16
      1. Richardson LA. Evolving as a holobiont. PLoS Biol 2017;15:e2002168
      1. Postler TS, Ghosh S. Understanding the holobiont: how microbial metabolites affect human health and shape the immune system. Cell Metab 2017;26:110–130.
      1. Mills JG, Brookes JD, Gellie NJ, Liddicoat C, Lowe AJ, Sydnor HR, et al. Relating urban biodiversity to human health with the ‘holobiont’ concept. Front Microbiol 2019;10:550.
      1. Simon JC, Marchesi JR, Mougel C, Selosse MA. Host-microbiota interactions: from holobiont theory to analysis. Microbiome 2019;7:5.
      1. Korath AD, Janda J, Untersmayr E, Sokolowska M, Feleszko W, Agache I, et al. One Health: EAACI Position Paper on coronaviruses at the human-animal interface, with a specific focus on comparative and zoonotic aspects of SARS-CoV-2. Allergy 2022;77:55–71.
      1. Moore A. Getting fat from an inflamed relationship? The revenge of the holobiont. BioEssays 2016;38:119.
      1. Castillo-Álvarez F, Marzo-Sola ME. Disease of the holobiont, the example of multiple sclerosis. Med Clin (Barc) 2019;152:147–153.
      1. Haahtela T. A biodiversity hypothesis. Allergy 2019;74:1445–1456.
      1. Vermeulen R, Schymanski EL, Barabási AL, Miller GW. The exposome and health: where chemistry meets biology. Science 2020;367:392–396.
      1. Chung MK, Rappaport SM, Wheelock CE, Nguyen VK, van der Meer TP, Miller GW, et al. Utilizing a biology-driven approach to map the exposome in health and disease: an essential investment to drive the next generation of environmental discovery. Environ Health Perspect 2021;129:85001.
      1. Renz H, Holt PG, Inouye M, Logan AC, Prescott SL, Sly PD. An exposome perspective: early-life events and immune development in a changing world. J Allergy Clin Immunol 2017;140:24–40.
      1. Lindley SJ, Cook PA, Dennis M, Gilchrist A. Biodiversity, physical health and climate change: a synthesis of recent evidence. In: Marselle M, Stadler J, Korn H, Irvine K, Bonn A, editors. Biodiversity and Health in the Face of Climate Change. Cham: Springer; 2019. pp. 17-46.
      1. Pali-Schöll I, Roth-Walter F, Jensen-Jarolim E. One Health in allergology: a concept that connects humans, animals, plants, and the environment. Allergy 2021;76:2630–2633.
      1. D’Amato G, Akdis CA. Global warming, climate change, air pollution and allergies. Allergy 2020;75:2158–2160.
      1. D’Amato G, Annesi-Maesano I, Urrutia-Pereira M, Del Giacco S, Rosario Filho NA, Chong-Neto HJ, et al. Thunderstorm allergy and asthma: state of the art. Multidiscip Respir Med 2021;16:806.
      1. D’Amato G, Chong-Neto HJ, Monge Ortega OP, Vitale C, Ansotegui I, Rosario N, et al. The effects of climate change on respiratory allergy and asthma induced by pollen and mold allergens. Allergy 2020;75:2219–2228.
      1. Rorie A, Poole JA. The role of extreme weather and climate-related events on asthma outcomes. Immunol Allergy Clin North Am 2021;41:73–84.
      1. Romaszko J, Dragańska E, Jalali R, Cymes I, Glińska-Lewczuk K. Universal Climate Thermal Index as a prognostic tool in medical science in the context of climate change: a systematic review. Sci Total Environ 2022;828:154492
      1. Richter K, Haslbeck M, Buchner J. The heat shock response: life on the verge of death. Mol Cell 2010;40:253–266.
      1. Qu AL, Ding YF, Jiang Q, Zhu C. Molecular mechanisms of the plant heat stress response. Biochem Biophys Res Commun 2013;432:203–207.
      1. Dos Santos MM, Souza-Junior JB, Dantas MR, de Macedo Costa LL. An updated review on cattle thermoregulation: physiological responses, biophysical mechanisms, and heat stress alleviation pathways. Environ Sci Pollut Res Int 2021;28:30471–30485.
      1. Petrova NV, Velichko AK, Razin SV, Kantidze OL. Early S-phase cell hypersensitivity to heat stress. Cell Cycle 2016;15:337–344.
      1. Koch F, Thom U, Albrecht E, Weikard R, Nolte W, Kuhla B, et al. Heat stress directly impairs gut integrity and recruits distinct immune cell populations into the bovine intestine. Proc Natl Acad Sci U S A 2019;116:10333–10338.
      1. Ikwegbue PC, Masamba P, Oyinloye BE, Kappo AP. Roles of heat shock proteins in apoptosis, oxidative stress, human inflammatory diseases, and cancer. Pharmaceuticals (Basel) 2017;11:2.
      1. Niu D, Zhao Y, Gong X, Yang R, Hu L, Zhang W. Stress response and silencing verification of heat shock proteins in Dermatophagoides farinae under temperature stress. Int J Biol Macromol 2020;144:351–361.
      1. Rauer D, Gilles S, Wimmer M, Frank U, Mueller C, Musiol S, et al. Ragweed plants grown under elevated CO2 levels produce pollen which elicit stronger allergic lung inflammation. Allergy 2021;76:1718–1730.
      1. Beck I, Jochner S, Gilles S, McIntyre M, Buters JT, Schmidt-Weber C, et al. High environmental ozone levels lead to enhanced allergenicity of birch pollen. PLoS One 2013;8:e80147
      1. Carlsen HK, Haga SL, Olsson D, Behndig AF, Modig L, Meister K, et al. Birch pollen, air pollution and their interactive effects on airway symptoms and peak expiratory flow in allergic asthma during pollen season - a panel study in Northern and Southern Sweden. Environ Health 2022;21:63.
      1. Obersteiner A, Gilles S, Frank U, Beck I, Häring F, Ernst D, et al. Pollen-associated microbiome correlates with pollution parameters and the allergenicity of pollen. PLoS One 2016;11:e0149545
      1. Sonnenburg ED, Smits SA, Tikhonov M, Higginbottom SK, Wingreen NS, Sonnenburg JL. Diet-induced extinctions in the gut microbiota compound over generations. Nature 2016;529:212–215.
      1. Venter C, Meyer RW, Nwaru BI, Roduit C, Untersmayr E, Adel-Patient K, et al. EAACI position paper: Influence of dietary fatty acids on asthma, food allergy, and atopic dermatitis. Allergy 2019;74:1429–1444.
      1. Venter C, Meyer RW, Greenhawt M, Pali-Schöll I, Nwaru B, Roduit C, et al. Role of dietary fiber in promoting immune health-An EAACI position paper. Allergy 2022;77:3185–3198.
      1. Brick T, Hettinga K, Kirchner B, Pfaffl MW, Ege MJ. The beneficial effect of farm milk consumption on asthma, allergies, and infections: from meta-analysis of evidence to clinical trial. J Allergy Clin Immunol Pract 2020;8:878–889.e3.
      1. Hufnagl K, Ghosh D, Wagner S, Fiocchi A, Dahdah L, Bianchini R, et al. Retinoic acid prevents immunogenicity of milk lipocalin Bos d 5 through binding to its immunodominant T-cell epitope. Sci Rep 2018;8:1598.
      1. Roth-Walter F, Afify SM, Pacios LF, Blokhuis BR, Redegeld F, Regner A, et al. Cow’s milk protein β-lactoglobulin confers resilience against allergy by targeting complexed iron into immune cells. J Allergy Clin Immunol 2021;147:321–334.e4.
      1. Lopes DR, La Reau AJ, Duarte MS, Detmann E, Bento CB, Mercadante ME, et al. The bacterial and fungal microbiota of Nelore steers is dynamic across the gastrointestinal tract and its fecal-associated microbiota is correlated to feed efficiency. Front Microbiol 2019;10:1263.
      1. Lehtimäki J, Sinkko H, Hielm-Björkman A, Salmela E, Tiira K, Laatikainen T, et al. Skin microbiota and allergic symptoms associate with exposure to environmental microbes. Proc Natl Acad Sci U S A 2018;115:4897–4902.
      1. Lehtimäki J, Sinkko H, Hielm-Björkman A, Laatikainen T, Ruokolainen L, Lohi H. Simultaneous allergic traits in dogs and their owners are associated with living environment, lifestyle and microbial exposures. Sci Rep 2020;10:21954.
      1. Montgomery DR, Biklé A, Archuleta R, Brown P, Jordan J. Soil health and nutrient density: preliminary comparison of regenerative and conventional farming. PeerJ 2022;10:e12848
      1. Delerue F, Scattolin M, Atteia O, Cohen GJ, Franceschi M, Mench M. Biomass partitioning of plants under soil pollution stress. Commun Biol 2022;5:365.
      1. Stefanovic N, Flohr C, Irvine AD. The exposome in atopic dermatitis. Allergy 2020;75:63–74.
      1. Ruokolainen L, Fyhrquist N, Laatikainen T, Auvinen P, Fortino V, Scala G, et al. Immune-microbiota interaction in Finnish and Russian Karelia young people with high and low allergy prevalence. Clin Exp Allergy 2020;50:1148–1158.
      1. Aerts R, Honnay O, Van Nieuwenhuyse A. Biodiversity and human health: mechanisms and evidence of the positive health effects of diversity in nature and green spaces. Br Med Bull 2018;127:5–22.
      1. Lerner H, Berg C. A comparison of three holistic approaches to health: One Health, EcoHealth, and Planetary Health. Front Vet Sci 2017;4:163.
      1. World Health Organization. One Health [Internet]. Geneva: World Health Organization; 2023 [cited 2023 Jan 18].
        Available from: https://www.who.int/health-topics/one-health#tab=tab_1.
      1. Harrison S, Kivuti-Bitok L, Macmillan A, Priest P. EcoHealth and One Health: a theory-focused review in response to calls for convergence. Environ Int 2019;132:105058
      1. Whitmee S, Haines A, Beyrer C, Boltz F, Capon AG, de Souza Dias BF, et al. Safeguarding human health in the Anthropocene epoch: report of The Rockefeller Foundation-Lancet Commission on planetary health. Lancet 2015;386:1973–2028.
      1. Circular Bioeconomy Alliance. Living Labs [Internet]. place unknown: Circular Bioeconomy Alliance; 2023 [cited 2023 Jan 18].
        Available from: https://circularbioeconomyalliance.org/living-labs.
      1. Willett W, Rockström J, Loken B, Springmann M, Lang T, Vermeulen S, et al. Food in the Anthropocene: the EAT-Lancet Commission on healthy diets from sustainable food systems. Lancet 2019;393:447–492.
      1. Movilla-Pateiro L, Mahou-Lago XM, Doval MI, Simal-Gandara J. Toward a sustainable metric and indicators for the goal of sustainability in agricultural and food production. Crit Rev Food Sci Nutr 2021;61:1108–1129.
      1. Soyiri IN, Alcock I. Green spaces could reduce asthma admissions. Lancet Respir Med 2018;6:e1
      1. Cariñanos P, Grilo F, Pinho P, Casares-Porcel M, Branquinho C, Acil N, et al. Estimation of the allergenic potential of urban trees and urban parks: towards the healthy design of urban green spaces of the future. Int J Environ Res Public Health 2019;16:1357.
      1. Haahtela T, Valovirta E, Bousquet J, Mäkelä M. Allergy Programme Steering Group. The Finnish Allergy Programme 2008-2018 works. Eur Respir J 2017;49:1700470
      1. Hämäläinen RM, Halonen JI, Haveri H, Prass M, Virtanen SM, Salomaa MM, et al. Nature step to health 2022-2032: interorganizational collaboration to prevent human disease, nature loss, and climate crisis. J Clim Chang Health 2023;10:100194
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    MeSH Terms
    Animals
    Asthma*
    Biodiversity
    Climate
    Climate Change
    Counseling
    Delivery of Health Care
    Ecosystem
    Environmental Health
    Exposome
    Gene-Environment Interaction
    Humans
    Hypersensitivity
    Immune System
    One Health*
    Prevalence
    Metrics
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