External exposome and allergic respiratory and skin diseases
2018; Elsevier BV; Volume: 141; Issue: 3 Linguagem: Inglês
10.1016/j.jaci.2018.01.016
ISSN1097-6825
AutoresLorenzo Cecchi, Gennaro D’Amato, Isabella Annesi‐Maesano,
Tópico(s)Indoor Air Quality and Microbial Exposure
ResumoAllergies are complex diseases that result from interactions between multiple genetic and environmental factors. However, the increase in allergies observed in the past decades is explained exclusively by environmental changes occurring in the same period. Presently, the exposome, the totality of specific and nonspecific external environmental exposures (external exposome) to which a subject is exposed from preconception onward and their consequences at the organ and cell levels (internal exposome), is being considered to explain the inception, development, and exacerbations of allergic diseases. Among the best-studied environmental factors of the specific external exposome, indoor and outdoor aeroallergens and air pollutants play a key role in the etiopathogenesis of the inflammatory response to allergens and in clinical manifestations of allergic disease. Climate change, urbanization, and loss of biodiversity affect sources, emissions, and concentrations of main aeroallergens and air pollutants and are among the most critical challenges facing the health and quality of life of the still increasing number of allergic patients today and in the coming decades. Thunderstorm-related asthma is a dramatic example of the effects of combined environmental factors and an in vivo model for understanding the mechanisms at work in respiratory allergy. Environment- or lifestyle-driven aberrancies in the gut and skin microbiome composition represent key mediators of allergic diseases. A better knowledge of the effect of the external exposome on allergy development is crucial for urging patients, health professionals, and policymakers to take actions to mitigate the effect of environmental changes and to adapt to them. Allergies are complex diseases that result from interactions between multiple genetic and environmental factors. However, the increase in allergies observed in the past decades is explained exclusively by environmental changes occurring in the same period. Presently, the exposome, the totality of specific and nonspecific external environmental exposures (external exposome) to which a subject is exposed from preconception onward and their consequences at the organ and cell levels (internal exposome), is being considered to explain the inception, development, and exacerbations of allergic diseases. Among the best-studied environmental factors of the specific external exposome, indoor and outdoor aeroallergens and air pollutants play a key role in the etiopathogenesis of the inflammatory response to allergens and in clinical manifestations of allergic disease. Climate change, urbanization, and loss of biodiversity affect sources, emissions, and concentrations of main aeroallergens and air pollutants and are among the most critical challenges facing the health and quality of life of the still increasing number of allergic patients today and in the coming decades. Thunderstorm-related asthma is a dramatic example of the effects of combined environmental factors and an in vivo model for understanding the mechanisms at work in respiratory allergy. Environment- or lifestyle-driven aberrancies in the gut and skin microbiome composition represent key mediators of allergic diseases. A better knowledge of the effect of the external exposome on allergy development is crucial for urging patients, health professionals, and policymakers to take actions to mitigate the effect of environmental changes and to adapt to them. GlossaryGREENHOUSE GASESGases that trap heat in the atmosphere. The major contributor to this group is carbon dioxide (CO2), but others include methane, nitrous oxide, and fluorinated gases.HEAT WAVESThe World Meteorological Organization is specific in its definition by stating that a heat wave occurs when the daily maximum temperature for more than 5 consecutive days exceeds the average maximum temperature by 9°. Per the National Weather Service, a heat wave is a period of abnormally and uncomfortably hot and unusually humid weather. Typically, a heat wave lasts 2 or more days.LAG EFFECTTemporal effect estimated by an analysis that correlates exposures occurring at different time points with an outcome (eg, asthma exacerbation). Lagged exposure can be analyzed often as either the amount of exposure on a certain day preceding the outcome or a cumulative exposure for a number of days preceding the outcome (ie, spore counts on one day 3 days before the admission or cumulative spore counts in the 3 days leading up to admission). This analysis allows multiple different correlations to be looked at for a given exposure/outcome relationship.NANOTECHNOLOGYThe study and manipulation of matter at dimensions between approximately 1 and 100 nm for the purposes of building microscopic devices, such as computer chips.NITROGEN DIOXIDE (NO2)Outdoors, NO2 forms from fuel burning emissions from automobiles, power plants, and off-road equipment. A highly reactive gas, it contributes to both ozone and particulate matter pollution, as well as acid rain.OZONEA gas composed of 3 oxygen atoms. Ground-level ozone (smog) is formed when volatile organic compounds combine with nitrogen oxides in the presence of heat and sunlight.PARTICULATE MATTER (PM)PM is the sum of all solid and liquid particles suspended in air many of which are hazardous. This complex mixture includes both organic and inorganic particles, such as dust, pollen, molds, soot, smoke, and liquid droplets. Created by both natural (volcanoes, dust storm, dryness, etc) and man-made causes (combustion, traffic, industries, etc), particulates impact the earth's climate, precipitation levels and can have (those of less than 2.5 mm in diameters [PM2.5]) substantial negative effects on human health (allergies included).PHENOLOGYA branch of science dealing with the relation between climate and periodic biological phenomena (eg, bird migration or plant flowering).POLYCYCLIC AROMATIC HYDROCARBONS (PAHs)Also known as polyaromatic hydrocarbons, these are volatile substances produced by combustion. Traffic vehicles are a main source of PAH emission in urban areas.URBANIZATIONThe process of a population becoming more urban. The definition of urban varies by country. In the United States the Census Bureau identifies 2 types of urban areas: urbanized areas of 50,000 or more persons and urban clusters of at least 2,500 and less than 50,000 persons. The United States contains 486 urbanized areas and 3,087 urban clusters.VOLATILE ORGANIC COMPOUNDS (VOCs)Emitted gases from solids or liquids that contain chemicals that might have health effects. Concentrations are higher indoors than outdoors. Household products that are sources of volatile organic compounds include paints, wood preservatives, aerosol sprays, disinfectants, air fresheners, dry-cleaned clothing, and pesticides. Volatile organic compounds are also released from burning fuel and are emitted from diesel exhaust. VOCs exposure has been associated with allergies.The Editors wish to acknowledge Daniel Searing, MD, for preparing this glossary. Gases that trap heat in the atmosphere. The major contributor to this group is carbon dioxide (CO2), but others include methane, nitrous oxide, and fluorinated gases. The World Meteorological Organization is specific in its definition by stating that a heat wave occurs when the daily maximum temperature for more than 5 consecutive days exceeds the average maximum temperature by 9°. Per the National Weather Service, a heat wave is a period of abnormally and uncomfortably hot and unusually humid weather. Typically, a heat wave lasts 2 or more days. Temporal effect estimated by an analysis that correlates exposures occurring at different time points with an outcome (eg, asthma exacerbation). Lagged exposure can be analyzed often as either the amount of exposure on a certain day preceding the outcome or a cumulative exposure for a number of days preceding the outcome (ie, spore counts on one day 3 days before the admission or cumulative spore counts in the 3 days leading up to admission). This analysis allows multiple different correlations to be looked at for a given exposure/outcome relationship. The study and manipulation of matter at dimensions between approximately 1 and 100 nm for the purposes of building microscopic devices, such as computer chips. Outdoors, NO2 forms from fuel burning emissions from automobiles, power plants, and off-road equipment. A highly reactive gas, it contributes to both ozone and particulate matter pollution, as well as acid rain. A gas composed of 3 oxygen atoms. Ground-level ozone (smog) is formed when volatile organic compounds combine with nitrogen oxides in the presence of heat and sunlight. PM is the sum of all solid and liquid particles suspended in air many of which are hazardous. This complex mixture includes both organic and inorganic particles, such as dust, pollen, molds, soot, smoke, and liquid droplets. Created by both natural (volcanoes, dust storm, dryness, etc) and man-made causes (combustion, traffic, industries, etc), particulates impact the earth's climate, precipitation levels and can have (those of less than 2.5 mm in diameters [PM2.5]) substantial negative effects on human health (allergies included). A branch of science dealing with the relation between climate and periodic biological phenomena (eg, bird migration or plant flowering). Also known as polyaromatic hydrocarbons, these are volatile substances produced by combustion. Traffic vehicles are a main source of PAH emission in urban areas. The process of a population becoming more urban. The definition of urban varies by country. In the United States the Census Bureau identifies 2 types of urban areas: urbanized areas of 50,000 or more persons and urban clusters of at least 2,500 and less than 50,000 persons. The United States contains 486 urbanized areas and 3,087 urban clusters. Emitted gases from solids or liquids that contain chemicals that might have health effects. Concentrations are higher indoors than outdoors. Household products that are sources of volatile organic compounds include paints, wood preservatives, aerosol sprays, disinfectants, air fresheners, dry-cleaned clothing, and pesticides. Volatile organic compounds are also released from burning fuel and are emitted from diesel exhaust. VOCs exposure has been associated with allergies. The Editors wish to acknowledge Daniel Searing, MD, for preparing this glossary. Allergic diseases affect a considerable segment of the population, resulting in significant socioeconomic burden, and their prevalence has been increasing in the past decades. As shown below, this is due to environmental changes, although their precise role is not yet established. Worldwide, according to the World Health Organization (WHO), there are now at least 300 million persons with asthma and more than 300 million persons with allergic rhinitis, and half of the global population will have had an allergic disease by 2050.1Pawankar R, Canonica GW, Holgate ST, Lockey RF; World Allergy Organization. White book on allergy 2011-2012 executive summary. http://www.worldallergy.org/UserFiles/file/WAO-White-Book-on-Allergy_web.pdf. Accessed February 11, 2018.Google Scholar Up to 50% of the general population already presents with allergic sensitization to at least 1 allergen, as defined by skin prick test response positivity or positive specific IgE levels. In terms of annual mortality, globally, there are almost 300,000 avoidable allergy-related deaths caused by asthma, food allergy, or anaphylaxis.1Pawankar R, Canonica GW, Holgate ST, Lockey RF; World Allergy Organization. White book on allergy 2011-2012 executive summary. http://www.worldallergy.org/UserFiles/file/WAO-White-Book-on-Allergy_web.pdf. Accessed February 11, 2018.Google Scholar Although recognized as the result of an interaction between multiple genetic and environmental factors,2Holloway J.W. Yang I.A. Holgate S.T. Genetics of allergic diseases.J Allergy Clin Immunol. 2010; 125: S81-S94Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar allergies are mainly considered an environmental disease. Indeed, as suggested in a recent review published in this Journal,3Renz H. Holt P.G. Inouye M. Logan A.C. Prescott S.L. Sly P.D. An exposome perspective: early-life events and immune development in a changing world.J Allergy Clin Immunol. 2017; 140: 24-40Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar pure genetic factors are unable to explain the dramatic increase in allergy-related diseases observed in the past decades. Various environmental factors have been involved in exacerbations (eg, viruses, tobacco smoking, air pollutants, and allergens) and development (eg, allergens, in utero tobacco smoking, air pollutants, and dietary factors) of allergic diseases.4Burbank A.J. Sood A.K. Kesic M.J. Peden D.B. Hernandez M.L. Environmental determinants of allergy and asthma in early life.J Allergy Clin Immunol. 2017; 140: 1-12Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar However, the initiation and development of allergic diseases result from the interplay, duration, and timing of several environmental exposures. In the context of allergic diseases, it has become apparent that the period of early life is of the most importance for inception. This is referred to as the developmental origins of health and disease hypothesis according to which intergenerational vulnerability for disease is established before and in the first 1000 days after conception.5Chavatte-Palmer P. Tarrade A. Rousseau-Ralliard D. Diet before and during Pregnancy and Offspring Health: the importance of animal models and what can be learned from them.Int J Environ Res Public Health. 2016; 13Crossref PubMed Scopus (9) Google Scholar Recently, it has become evident that the exposome (ie, the totality of the external and internal environment from preconception onward, complementing the genome to which the subject is exposed) needs to be considered to fully explain development and thus allergy epidemics. The exposome includes 3 broad domains: specific external, nonspecific external, and internal domains. The external exposome encompasses exposures to specific external environmental factors (namely chemical, biological, occupational, and physical exposures, including diet, drug, and consumer products), as well as nonspecific general exposures (eg, climate, biodiversity, and socioeconomic factors; Fig 1). However, an informative assessment of a subject's exposure might need the combination of aspects of the 2 domains because these can be viewed as both overlapping and intertwining, and it is sometimes difficult to place a particular exposure into one domain or another. The internal exposome includes internal chemical environments determined by internal processes (eg, metabolic and inflammatory), as assessed through evaluation of proteins, lipid mediators, xenobiotics, and their metabolites through ad hoc omics tools (Fig 1). The internal exposome is specific to each subject because it depends on age, physiology, body morphology, health status, and the genome among others. There is also evidence that various environmental factors can influence the epigenome thus promoting changes in a chromosome that affect gene activity and expression, and thus modifying the risk of allergic diseases.6Yang I.V. Lozupone C.A. Schwartz D.A. The environment, epigenome, and asthma.J Allergy Clin Immunol. 2017; 140: 14-23Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar Recent data have shown that air pollution is able to change the epigenome in peripheral blood in prenatal life.7Gruzieva O. Xu C.J. Breton C.V. Annesi-Maesano I. Antó J.M. Auffray C. et al.Epigenome-wide meta-analysis of methylation in children related to prenatal NO2 air pollution exposure.Environ Health Perspect. 2017; 125: 104-110Crossref PubMed Scopus (0) Google Scholar However, very few data are available on the effects of the relationship between allergen exposure and allergic sensitization and changes of the epigenome.6Yang I.V. Lozupone C.A. Schwartz D.A. The environment, epigenome, and asthma.J Allergy Clin Immunol. 2017; 140: 14-23Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar These changes might have a transgenerational effect, like those caused by prenatal exposure to tobacco smoke.8Breton C.V. Siegmund K.D. Joubert B.R. Wang X. Qui W. Carey V. et al.Prenatal tobacco smoke exposure is associated with childhood DNA CpG methylation.PLoS One. 2014; 9: e99716Crossref PubMed Scopus (0) Google Scholar Finally, it is widely accepted that both host microbiome and external microbial exposure are critical in increasing susceptibility to allergic diseases, especially during early life, as reviewed recently by Burbank et al.4Burbank A.J. Sood A.K. Kesic M.J. Peden D.B. Hernandez M.L. Environmental determinants of allergy and asthma in early life.J Allergy Clin Immunol. 2017; 140: 1-12Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar Here we review recent advances in the macromechanisms and micromechanisms underlying the effects of the external specific exposome on allergic diseases, with specific emphasis on fresh data on aeroallergens and air pollutants and their effects on respiratory and skin allergies. Successively, we will stress the part played by the nonspecific external exposome by detailing the role of climate change, urbanization, and loss of biodiversity, which act indirectly on allergies by increasing their risk factors. These constitute the most critical challenges to be faced in the near future because of their dramatic progression observed in the past decades (Table I). Unless we act now to reduce greenhouse gas (GHG) emissions and air pollution, climate change, urbanization, and biodiversity loss will get worse, and the burden of allergies will increase.9Barry M. Annesi-Maesano I. Ten principle for climate, environment and respiratory health.Eur Respir J. 2017; 50Crossref PubMed Scopus (0) Google ScholarTable IKey factors for climate change, urbanization, and biodiversity lossSituationRemediation/challenges of the 21st centuryClimate changeOccurrence, duration, and intensity of extreme weather events, such as heat waves or flooding, are increasing and will continue to increase in the near future under current climate change scenarios. Similarly, air pollutant concentrations and pollen and mold levels will increase.Mitigation and adaptation measures. Mitigation (reducing climate change) involves reducing greenhouse gases into the atmosphere, either by reducing sources of these gases or by enhancing the sinks (oceans, forests, soils) that store these gases. Adaptation (adapting to life in a changing climate) involves adjusting to new climate by reducing indiviudual vulnerability to the harmful effects of climate change.UrbanizationThe urban population in 2014 accounted for 54% of the total global population, up from 34% in 1960, and continues to grow. The world's urban population is expected to surpass six billion by 2045. Much of the expected urban growth will take place in countries of developing regions, particularly Africa. Already in 2016, the World Health Organization reported that 92% of the world's population lives in places where air quality levels exceed the WHO's ambient air quality guidelines for annual mean PM2.5. This is going to increase.Managing urban areas (“smart cities”)Biodiversity lossDecreasing biodiversity in terms of species as a consequence of industrialization, air pollution, and use of chemicals that have affected the environment and microorganisms with which human subjects have lived since time immemorial is occurring.Protect biodiversity by reducing its causes. Mobilize knowledge. Ensure that the available knowledge is presented in ways that can be used by decision makers. Open table in a new tab Allergens and air pollutants are well-established ubiquitous risk factors for allergic diseases. Everyone is exposed to a mixture of allergens and air pollutants, which changes many times a day, moving between indoor and outdoor spaces and urban and rural areas during different seasons of the year (Fig 2). Indoor environments are usually not hermetically sealed, and outdoor air and its content “contaminate” indoor spaces10Lai A.C. Thatcher T.L. Nazaroff W.W. Inhalation transfer factors for air pollution health risk assessment.J Air Waste Manag Assoc. 2000; 50: 1688-1699Crossref PubMed Scopus (73) Google Scholar; in addition, meteorological and indoor conditions affect concentrations and the exchange of these factors in and between the 2 environments.11D'Amato G. Holgate S.T. Pawankar R. Ledford D.K. Cecchi L. Al-Ahmad M. et al.Meteorological conditions, climate change, new emerging factors, and asthma and related allergic disorders. A statement of the World Allergy Organization.World Allergy Organ J. 2015; 8: 25Crossref PubMed Scopus (0) Google Scholar To make it more complicated, all these factors can interact before coming into contact with human beings or synergistically on the mucosa.11D'Amato G. Holgate S.T. Pawankar R. Ledford D.K. Cecchi L. Al-Ahmad M. et al.Meteorological conditions, climate change, new emerging factors, and asthma and related allergic disorders. A statement of the World Allergy Organization.World Allergy Organ J. 2015; 8: 25Crossref PubMed Scopus (0) Google Scholar Among the environmental changes suspected to be major drivers of the increasing trend of allergic diseases, there are chemical air pollutants with levels that are still of concern, even in industrialized countries.12Annesi-Maesano I. The air of Europe: where are we going?.Eur Respir Rev. 2017; 26Crossref PubMed Scopus (0) Google Scholar These air pollutants are produced by both natural and human sources and include nitrogen dioxide (NO2), ozone (O3), volatile organic compounds, and especially particulate matter (PM), which is heterogeneous in size and composition. For instance, fine PM from diesel exhaust contains polycyclic aromatic hydrocarbons (PAHs). Today there is sufficient evidence that various indoor and outdoor air pollutants are not only exacerbating but also causing an increase in allergic diseases. Exposure to particulate matter of less than 2.5 μm in diameter (PM2.5) (called fine particles) and 10 μm in diameter, O3, or NO2 is associated consistently with increased asthma exacerbations and higher medication use,13Guarnieri M. Balmes J.R. Outdoor air pollution and asthma.Lancet. 2014; 383: 1581-1592Abstract Full Text Full Text PDF PubMed Scopus (176) Google Scholar as well as aggravation of atopic dermatitis (AD).14Ahn K. The role of air pollutants in atopic dermatitis.J Allergy Clin Immunol. 2014; 134: 993-999Abstract Full Text Full Text PDF PubMed Google Scholar Several studies have also suggested a contribution of air pollutants to new-onset asthma.13Guarnieri M. Balmes J.R. Outdoor air pollution and asthma.Lancet. 2014; 383: 1581-1592Abstract Full Text Full Text PDF PubMed Scopus (176) Google Scholar The strength of the evidence is variable and depends on the pollutant. However, the most recent systematic reviews on cross-sectional and prospective studies reported an increased risk of traffic-related air pollution to asthma and allergic outcomes, including sensitization.15Anderson H.R. Favarato G. Atkinson R.W. Long-term exposure to air pollution and the incidence of asthma: meta-analysis of cohort studies.Air Qual Atmos Health. 2013; 6: 541-542Crossref Scopus (3) Google Scholar, 16Bowatte G. Lodge C. Lowe A.J. Erbas B. Perret J. Abramson M.J. et al.The influence of childhood traffic-related air pollution exposure on asthma, allergy and sensitization: a systematic review and a meta-analysis of birth cohort studies.Allergy. 2015; 70: 245-256Crossref PubMed Scopus (58) Google Scholar Moreover, a very recent review summarizing the state of the art from birth cohort studies, the most informative studies for establishing causation, indicated an increased risk between early-life traffic-related air pollution (mostly PM2.5 or NO2) exposure and incident asthma.17Heinrich J. Guo F. Fuertes E. Traffic-related air pollution exposure and asthma, hayfever, and allergic sensitisation in birth cohorts: a systematic review and meta-analysis.Geoinfor Geostat. 2016; 4: 4Google Scholar Only a trend was found for hay fever.17Heinrich J. Guo F. Fuertes E. Traffic-related air pollution exposure and asthma, hayfever, and allergic sensitisation in birth cohorts: a systematic review and meta-analysis.Geoinfor Geostat. 2016; 4: 4Google Scholar However, a significant positive association was observed for sensitization to aeroallergens in the case of PM2.5 in birth cohort studies.17Heinrich J. Guo F. Fuertes E. Traffic-related air pollution exposure and asthma, hayfever, and allergic sensitisation in birth cohorts: a systematic review and meta-analysis.Geoinfor Geostat. 2016; 4: 4Google Scholar The existence of a causal association is strongly supported by the results of laboratory studies and human exposure experiments for PM, in particular PM2.5, whereas it is weaker for NO2, possibly because it has been less investigated.13Guarnieri M. Balmes J.R. Outdoor air pollution and asthma.Lancet. 2014; 383: 1581-1592Abstract Full Text Full Text PDF PubMed Scopus (176) Google Scholar The involved mechanisms include oxidative injury to the airways, leading to inflammation, remodeling, and increased risk of sensitization. A detailed review,14Ahn K. The role of air pollutants in atopic dermatitis.J Allergy Clin Immunol. 2014; 134: 993-999Abstract Full Text Full Text PDF PubMed Google Scholar as well as data from 3 birth cohorts,18Huang C.C. Wen H.J. Chen P.C. Chiang T.L. Lin S.J. Guo Y.L. Prenatal air pollutant exposure and occurrence of atopic dermatitis.Br J Dermatol. 2015; 173: 981-988Crossref PubMed Scopus (11) Google Scholar, 19Kramer U. Sugiri D. Ranft U. Krutmann J. von Berg A. Berder D. et al.Eczema, respiratory allergies, and traffic-related air pollution in birth cohorts from small-town areas.J Dermatol Sci. 2009; 56: 99-105Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar, 20Gehring U. Wijga A.H. Brauer M. Fischer P. de Jonqste J.C. Kerkhof M. et al.Traffic-related air pollution and the development of asthma and allergies during the first 8 years of life.Am J Respir Crit Care Med. 2010; 181: 596-603Crossref PubMed Scopus (226) Google Scholar indicated that a variety of air pollutants (environmental tobacco smoke, volatile organic compounds, formaldehyde, toluene, NO2, and PM) act as risk factors for the development of AD. These air pollutants can induce oxidative stress in the skin, leading to skin barrier dysfunction or immune dysregulation.14Ahn K. The role of air pollutants in atopic dermatitis.J Allergy Clin Immunol. 2014; 134: 993-999Abstract Full Text Full Text PDF PubMed Google Scholar However, these results need to be confirmed because of the low number of studies and limitations in methods. Recently, concerns have been raised about the detrimental effects of nanomaterials, including ultrafine particles, which were defined as having at least 1 dimension less than 100 nm, from diesel exhaust, cooking, heating, and wood burning and from increasing use of nanotechnology,21Li N. Georas S. Alexis N. Fritz P. Xia T. Williams M.A. Horner E. et al.A work group report on ultrafine particles (American Academy of Allergy, Asthma & Immunology): why ambient ultrafine and engineered nanoparticles should receive special attention for possible adverse health outcomes in human subjects.J Allergy Clin Immunol. 2016; 138: 386-396Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar which possess not only chemical but also physical characteristics with the potential to modify disease risk and outcome. Although some toxicological studies on animals and experimental in vitro tests on lung cells are available, exhaustive data on the effects of nanoparticles and nanomaterials on allergies are still lacking.22Geary S.M. Morris A.S. Salem A.K. Assessing the effect of engineered nanomaterials on the environment and human health.J Allergy Clin Immunol. 2016; 138: 405-408Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar Lastly, environmental chemicals, such as phthalate esters, which are commonly used as plasticizers, or persistent organic pollutants have also been related to asthma and allergy.23Li M.C. Chen C.H. Guo Y.L. Phthalate esters and childhood asthma: a systematic review and congener-specific meta-analysis.Environ Pollut. 2017; 229: 655-660Crossref PubMed Scopus (1) Google Scholar, 24Vernet C. Pin I. Giorgis-Allemand L. Philippat C. Benmerad M. Quentin J. et al.In utero exposure to select phenols and phthalates and respiratory health in five-year-old boys: a prospective study.Environ Health Perspect. 2017; 125: 097006Crossref PubMed Scopus (0) Google Scholar, 25Soomro M.H. Baiz N. Philippat C. Vernet C. Siroux V. Maesano C.N. et al.Prenatal exposure to phthalates and the development of eczema phenotypes in male children: results from the EDEN mother-child Cohort study.Environ Health Perspect. 2018; 126: 027002Crossref PubMed Scopus (0) Google Scholar Overall, all these effects happen at even low doses of air pollutants, sometimes at much lower levels than air quality standards, and are stronger in subjects who are highly sensitive to allergies.12Annesi-Maesano I. The air of Europe: where are we going?.Eur Respir Rev. 2017; 26Crossref PubMed Scopus (0) Google Scholar It is generally accepted that aeroallergen exposure is associated with exacerbations and development of clinical allergy. In general, indoor allergens are linked more strongly to the development of asthma than outdoor allergen sensitization related to hay fever. The understanding of the skin immune response to allergens has started only recently. Several
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