Patella et al. Clin Mol Allergy (2018) 16:20 https://doi.org/10.1186/s12948-018-0098-3 Clinical and Molecular Allergy

REVIEW Open Access Urban and change: “The Decalogue: Allergy Safe Tree” for allergic and respiratory diseases care Vincenzo Patella1,2,3*† , Giovanni Florio1,2†, Diomira Magliacane1†, Ada Giuliano4†, Maria Angiola Crivellaro3,5†, Daniela Di Bartolomeo3,6†, Arturo Genovese2,3†, Mario Palmieri3,7†, Amedeo Postiglione3,8†, Erminia Ridolo3,9†, Cristina Scaletti3,10†, Maria Teresa Ventura3,11†, Anna Zollo3,12† and Air Pollution and Climate Change Task Force of the Italian Society of Allergology, Asthma and Clinical Immunology (SIAAIC)

Abstract Background: According to the World Health Organization, air pollution is closely associated with climate change and, in particular, with global warming. In addition to melting of ice and , rising sea level, and fooding of coastal areas, global warming is leading to a tropicalization of temperate marine ecosystems. Moreover, the efects of air pol- lution on airway and lung diseases are well documented as reported by the World Allergy Organization. Methods: Scientifc literature was searched for studies investigating the efect of the interaction between air pollu- tion and climate change on allergic and respiratory diseases. Results: Since 1990s, a multitude of articles and reviews have been published on this topic, with many studies con- frming that the warming of our planet is caused by the “greenhouse efect” as a result of increased emission of “green- house” gases. Air pollution is also closely linked to global warming: the emission of hydrocarbon combustion products leads to increased concentrations of biological allergens such as pollens, generating a mixture of these particles called particulate matter (PM). The concept is that global warming is linked to the emission of hydrocarbon combustion products, since both carbon dioxide and heat increase pollen emission into the atmosphere, and all these particles make up PM10. However, the understanding of the mechanisms by which PM afects human health is still limited. Therefore, several studies are trying to determine the causes of global warming. There is also evidence that increased concentrations of air pollutants and pollens can activate infammatory mediators in the airways. Our Task Force has prepared a Decalogue of rules addressing public administrators, which aims to limit the amount of allergenic pollen in the air without sacrifcing public green areas. Conclusions: Several studies underscore the signifcant risks of global warming on human health due to increas- ing levels of air pollution. The impact of climate change on respiratory diseases appears well documented. The last decades have seen a rise in the concentrations of pollens and pollutants in the air. This rise parallels the increase in the number of people presenting with allergic symptoms (e.g., allergic rhinitis, conjunctivitis, and asthma), who often require emergency medical care. Our hope is that scientists from diferent disciplines will work together with institu- tions, pharmaceutical companies and lay organizations to limit the adverse health efects of air pollution and global warming.

*Correspondence: [email protected] †All authors contributed equally to this manuscript 1 Division Allergy and Clinical Immunology, Department of Medicine ASL Salerno, “Santa Maria della Speranza” Hospital, Battipaglia, Salerno, Italy Full list of author information is available at the end of the article

© The Author(s) 2018. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creat​iveco​mmons​.org/licen​ses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creat​iveco​mmons​.org/ publi​cdoma​in/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Patella et al. Clin Mol Allergy (2018) 16:20 Page 2 of 11

Background decrease during spring and summer when pollen concen- Climate change is already underway and is expected to trations are typically highest [13]. continue in the next decades: temperatures are increas- Some particulates are naturally occurring and originate ing, global precipitation patterns are changing, ice and from volcanoes, dust storms, forest and grassland fres, snow are melting, and global average sea level is ris- living vegetation, and sea spray. Although most aerosols ing. Moreover, the impact of global warming on human remain suspended in the atmosphere for short periods health has been documented by several reports from (typically between 4 days and a week), they can travel the World Health Organization (WHO) [1], which illus- vast distances. Dust plumes from the Sahara often cross trate that a major concern about this phenomenon is the Atlantic and reach the Caribbean. Winds sweep a the increase in air pollution levels. In this respect, the mixture of Asian aerosols, including dust from the Gobi last report of the European Environment Agency (EEA) desert and pollution from China, to the east over Japan indicates that up to 96% of the urban population in the and toward the central Pacifc Ocean. Smoke from wild- European Union are exposed to particulate and fne dust fres in Siberia and Canada can go as far as the Arctic ice levels in excess of threshold values [2]. In addition to air cap [11]. Sea spray from the Mediterranean Sea and min- pollution produced by hydrocarbon combustion emis- eral dust from Sahara in North Africa can contribute to sions, there is another issue: the formation of particles the chemical composition of PM in Southern Europe [14, related to global warming, and the presence of gases, 15]. such as ozone, with generation of a mixture of particles Human activities, including the combustion of fos- in the atmosphere, called particulate matter (PM) or sil fuels in vehicles, power plants, and many industrial particle pollution. Environmental PM is a heterogene- processes [10], can also generate signifcant amounts of ous mixture of particles produced by various processes, particulates. Coal combustion in developing countries is whose size ranges from 2.5 to 10 μm. Te fne particulate the primary means to generate energy and heat homes. fraction (PM2.5) (also known as “fne particles”) consists Although salt spray is the most common form of partic- of particles with a size of 2.5 microns (or smaller), while ulate in the atmosphere over the oceans, anthropogenic the ultrafne particulate fraction (also known as “ultrafne aerosols, i.e. those that are generated by human activities, particles”) consists of particles with a size smaller than currently account for about 10% of the total mass of aero- 0.1 μm. Te latter has a variable chemical composition, sols in the atmosphere [11]. with the highest volatility, which is obviously due to its In recent years, air quality has improved in industrial- smaller size. It should also be noted that, although the ized Western countries, while it has worsened in devel- ultrafne fraction represents less than 1% of the particu- oping countries. In Asia, for example, anthropogenic late mass, it is suspected of causing the greatest harm to emissions have increased in recent decades with the the exposed population [3–6]. Importantly, this particu- rapid development of and industrializa- late fraction can reach the deepest parts of the bronchial tion. On the contrary, aerosol emissions have declined tree, leading to major infammatory and procarcinogenic in North America and Europe with the relocation of fac- efects on the bronchial mucosa [6]. Of note, PM is also tories to developing countries and with the adoption of involved in other diseases, including cardiovascular dis- more stringent clean air regulations in Western coun- orders such as coronary heart disease and heart failure. tries. However, it may be difcult to defne the amount Tese conditions are mainly due to the oxidative stress of air pollution in diferent areas of the world, since most generated by the infammatory response, with both short- aerosols remain suspended in the atmosphere for short and long-term adverse efects on human health through periods, typically between 4 days and a week. PM parti- a variety of mechanisms [7–11]. In addition, it has been cles in the atmosphere can move at 5 m (16.4 ft) per sec- demonstrated that exposure to ozone and PM2.5 induces ond, and may travel thousands of kilometres in a week, adverse health efects, including various pulmonary dis- making it difcult to accurately measure pollution levels; eases and lung cancer. Overall, air pollution-related consequently, any predictions about the deterioration of global mortality has been associated with several emis- air quality can be distorted by this initial bias, especially sion sources; therefore, air pollution control can be an with regard to time. efective strategy to reduce mortality [12]. Both concen- trations and chemical composition of PM show a large Air pollution and climate change‑related health impacts variability not only geographic, but also seasonal. PM Global warming is a major public health emergency. concentrations are usually higher in urban areas than in Global temperature has risen markedly over the last rural areas. With regard to seasonal variability, PM levels 50 years and is still rising, as demonstrated by warm- increase signifcantly during the winter due to increased ing of the oceans, rising sea levels, melting of glaciers, emissions from road trafc and residential heating, and retreating of Arctic sea ice, and diminishing snow cover Patella et al. Clin Mol Allergy (2018) 16:20 Page 3 of 11

in the Northern Hemisphere. Climate change is also claim that can concentrate pollen grains associated with extreme weather events such as heat at ground level which rupture due to osmotic shock and waves, droughts, foods, and hurricanes. Tese changes release allergenic particles of respirable size into the are probably due to increased emissions of greenhouse atmosphere [19]. gases (namely, carbon dioxide, methane and nitrous Rising temperatures, a higher concentration of carbon oxide), largely from anthropogenic sources. Projections dioxide in the atmosphere, heavier rainfalls, and higher of future greenhouse gas emissions indicate a worsening humidity induce faster proliferation of pollens, moulds, of the situation with further increase in average tempera- and fungi [20]. In addition, increases in humidity asso- tures and temperature extremes by the end of the twenty- ciated with higher temperatures may encourage the frst century [16]. growth of cockroaches, house dust mites, and moulds, A large body of evidence suggests that climate change and, thus, allergen load [17]. Higher temperatures can have signifcant health impacts, both direct and indirect. also induce the migration of stinging and biting insects Direct health impacts include morbidity and mortality into new environments, as well as increasing the pop- associated with direct exposure to hazardous weather ulation of existing insect species [19]. Indeed, climate conditions such as heat waves, foods, cyclones, etc. Indi- changes and globalization are altering the distribution rect health impacts, which include the majority of climate and consistency of allergenic species including venom- change-related diseases, are mediated by environmental ous insects. In particular, given the expansion of native conditions which afect the spatial and temporal distri- species and the colonization of invasive ones, one can bution of aeroallergens, the generation and dispersion of predict, despite the uncertainty of current models, that air pollutants, and the population of disease-transmitting stinging Hymenoptera will pose new challenges in the vectors like mosquitoes and ticks. future [21]. Several epidemiological studies have demonstrated Many studies have reported the impact of climatic a close association between global warming, air pollu- changes on the spatial and temporal distribution of tion and respiratory allergic diseases, such as bronchial infectious diseases such as vector-borne, rodent-borne, asthma and rhinitis. Climate changes afect the quantity, food-borne and water-borne diseases, including in par- quality, timing and distribution of aeroallergens [17]. ticular malaria, tick-borne diseases, cholera and other Te increased atmospheric carbon dioxide concentra- diarrhoeal diseases. Importantly, several vector-borne tions due to fossil fuel burning stimulate the growth diseases have emerged in Europe in recent years; these of plants, including allergenic species. On top of that, include vivax malaria, West Nile fever, dengue fever, Chi- higher temperatures can lead to earlier and longer polli- kungunya fever, Leishmaniasis, Lyme disease, and tick- nation seasons, leading to increased pollen sensitization borne encephalitis [22, 23]. rate and symptom duration. Individuals with asthma are Chronic exposure to air pollution is also associated at increased risk of developing obstructive airway attacks with pulmonary infammation, chronic obstructive pul- when exposed to gaseous and particulate components of monary disease (COPD), and lung cancer. Several stud- air pollution [17]. In addition, air pollution can modify ies suggest that chronic exposure to outdoor air pollution the allergenic potential of pollens, especially in the pres- increases the prevalence and incidence of COPD [24]. ence of favourable weather conditions. Air pollution— Moreover, among individuals with COPD, air pollution is in particular PM, diesel exhaust particles (DEP), ozone, associated with increased respiratory symptoms, loss of nitrogen dioxide, and sulfur dioxide—have been shown to lung function, COPD exacerbations and higher mortality have an infammatory efect on the airways of susceptible [24]. Air pollution is also linked to lung cancer, and the subjects, causing increased mucosal permeability, facili- International Agency for Research on Cancer (IARC) has tating the penetration and access of inhaled allergens to classifed the particulate matter in outdoor air pollution the cells of the immune system [18]. Tere are also data as carcinogenic to humans [25]. suggesting that air pollution can lead to the development Studies from across the world have consistently dem- of asthma. Terefore, climate change combined with air onstrated that exposure to particulate air pollution is pollution may have severe impacts on respiratory health, associated with a host of cardiovascular diseases, includ- especially in children. ing myocardial ischaemia and infarctions, heart failure, Tunderstorms occurring during the pollen season arrhythmias, strokes and increased cardiovascular mor- have been shown to induce severe asthma attacks in tality [26]. Acute exposure may contribute to plaque pollinosis patients [18, 19]. Te -related instability and trigger acute cardiovascular events, epidemics are limited to late spring and summer when including myocardial ischaemia and infarction, stroke, there are high levels of pollen grains in the atmosphere. heart failure, arrhythmias, and sudden death, particularly Te main hypotheses for thunderstorm-related asthma in high-risk subjects, while chronic exposure may favour Patella et al. Clin Mol Allergy (2018) 16:20 Page 4 of 11

the development and progression of atherosclerosis and pollutants can activate diferent epithelial and immune possibly of hypertension in the long term [27]. cells in the airways, leading to the release of infamma- Finally, a number of studies have reported an asso- tory mediators [35]. However, the specifc components ciation between air pollution and higher risk of neuroin- and the mechanisms responsible for oxidative stress fol- fammation and neurodegeneration [28, 29]. In particular, lowing exposure to PM are not fully understood. Direct there is some evidence that chronic exposure to airborne oxidant production by air pollution particles in epithelial pollutants in the early years of life may contribute to neu- cells of the respiratory mucosa has been reported. Tis rodegenerative disease processes including Alzheimer’s efect has been attributed to both organic components disease and Parkinson’s disease [30]. and a number of heavy metals (e.g., arsenic, cadmium, In summary, air pollution and climate change-related chromium, mercury, nickel, lead, and thallium). Tese health impacts are enormous and are expected to increase metals have a wide distribution in the environment as a during the next decades. As a result, also the social and result of their multiple industrial, domestic, agricultural, economic costs of climate change are enormous and will medical, and technological applications, which raises increase in the future. Nevertheless, there is a relative many concerns about their potential efects on human scarcity of economic studies on the health impacts of cli- health and the environment. Te main consequences of mate change. Most studies have estimated the economic oxidative stress include the activation of specifc cellular costs of extreme weather events or the impacts of climate reactions (including activation of kinases and transcrip- change on respiratory diseases and infectious diseases tion factors), the release of infammatory mediators, and (vector borne, water related, and food borne). However, eventually cell damage or apoptosis [36]. All this pro- these economic studies are heterogeneous in terms of motes bronchial hyperreactivity as well as a decline in objectives and methodology. To this end, a review has pulmonary function, increasing the risk of allergic sensi- pointed out the need for climate change-specifc health tisation, asthma, chronic obstructive pulmonary disease, economic guidelines to provide a standardized approach and cancer. Recent epigenetic studies have shown that a and stimulate economic research [31]. A more recent number of genes controlling immune and infammatory review, conducted to evaluate the health costs result- responses are sensitive to tropospheric ozone. Indeed, ing from human exposure to weather-related extreme atmospheric pollutants like diesel exhaust particles events such as heat waves, droughts, foods, storms and [particulate] (DEPs) and ozone are directly involved in hurricanes, has highlighted a lack of evidence about the asthma pathogenesis [37]. Importantly, DEPs are a major potential cost-efectiveness of interventions that exploits component of trafc-related particulate air pollution in the capacity of natural ecosystems to reduce exposure to most urban areas. In addition, a number of evidence indi- extreme events, despite the observations that evidence cates that DEPs may facilitate entry of allergens into the that poor land management increases the vulnerability to airways eliciting immunopathological response, and can these events [32]. However, all studies identifed in this also bind pollen, dog, cat, and house dust mite allergens review indicate that the health costs associated with the [38–40]. Due to their very fne size, DEPs can facilitate impacts of extreme events are substantial. For example, the penetration of these allergens into the lungs, thereby six climate change-related events that struck the United increasing the amount of allergens interacting with the States between 2000 and 2009, accounted for about $14 airway epithelium. It has also been demonstrated that billion in lost lives and health costs [33]. DEPs can disrupt pollen particles causing the release of allergenic sub-pollen particles. Interestingly, a detailed Mechanisms responsible for allergic and respiratory analysis of pollen taken from air-polluted areas showed diseases an increased amount of allergenic proteins with higher Te mechanisms by which PM afects human health are allergenic potential. In another study, comparing recent still debated [34]. Te atmosphere is the medium of tran- and decade-old pollen extracts, the recent pollen extract sit not only for pollutant gases and particles, but also for showed higher allergenic potency. In addition, the recent a wide variety of biogenic materials of plant and animal pollen extract obtained from the had a higher origin. Among biogenic materials, there is the bioaero- allergenic potency than the recent pollen extract from the sol, which consists of diferent kinds of airborne particles suburban area [39]. More recently, the same authors of such as viruses, bacteria, moulds, plant fbres, and also the above study demonstrated that a recent pollen extract pollen with variable sizes, ranging from tens of nanom- from an urban area signifcantly exposed to pollution eters to a few hundreds of micrometers. Tese biological and climate change was more efective at inducing tran- substances are involved in allergic and respiratory dis- sepithelial permeability and ROS production in cultured eases, and act both directly and indirectly on airway epi- airway epithelial cells [41]. Tis DEPs ability seems to thelial cells. Te increased concentration of pollen and air be strongly dependent on a range of variables. However, Patella et al. Clin Mol Allergy (2018) 16:20 Page 5 of 11

the latest scientifc fndings indicate that DEPs are likely patients compared to non-asthmatic individuals. How- involved in exacerbations of already existing disease pro- ever, experimental and clinical studies have demonstrated cesses, and not in the development of new diseases. Te that asthmatic patients have an increased infammatory latter hypothesis is based on the enhancement of T2- response to air pollutants like PM2.5-10 [48] and espe- dependent responses induced by DEPs [42]. Nonetheless, cially ozone [49]. Several factors may contribute to the there are a variety of mechanisms involved in exposure adverse efects of ozone in asthmatic patients by impair- to asthma triggers that do not depend on IgE-medi- ing innate immune responses [50]. ated responses. Tese observations have been partially Epidemiological studies indicate that older people are confrmed by epigenetic studies. Epigenetics refers to at higher risk of hospitalisation. In particular, increased changes in gene expression that are not caused by altera- exposure to air pollution has been linked to increased tions in DNA sequences; these changes can be associated mortality, hospital admissions and emergency-room with environmental factors such road trafc and smoke visits in the elderly [51]. Tese efects are mainly due to pollution [43]. With regard to this issue, recent stud- exacerbations of chronic diseases or to respiratory tract ies have been focused on mutation hotspots and DNA infections (e.g., pneumonia), and may be modulated by methylation, involving the so called CpG islands, which ambient temperature as demonstrated by several stud- are located near the promoter region of many genes. In ies showing that the elderly are particularly vulnerable particular, one of these studies showed signifcant difer- to heat waves. In general, it seems that elderly subjects ences in methylation levels of CpG islands in eosinophils are more vulnerable to PM than to other pollutants, with from asthmatic patients compared with non-asthmatic greater efects on cardiorespiratory mortality and acute individuals, with the lowest levels of methylation in the hospital admissions [51]. Te elderly are at greater risk subjects with asthma. Tis study also showed signif- than other age groups due to their enhanced suscepti- cant associations between IgE and low methylation at bility to air pollutants as a result of normal and patho- 36 loci concentrated in CpG islands [44]. In addition logical ageing and related processes. In fact, ageing has to the above, changes in histone acetyltransferase and been associated with a decline in immune defences and deacetylase activity have been observed in cells from respiratory function, resulting in a higher predisposition patients with lung disorders such as severe asthma and to respiratory infections. Moreover, among the chronic chronic obstructive pulmonary disease (COPD) [45]. diseases that afect the elderly population, COPD and Considering that the anti-infammatory efects of gluco- asthma can accelerate pulmonary function decline and corticoids are dependent on histone deacetylase activ- increase the risk of mortality [52]. ity, this fnding may be relevant for patients with severe Te relationship between short-term exposure to air asthma and COPD who are insensitive to glucocorticoid pollution and cardiorespiratory morbidity and mortality therapy. Indeed, it has been shown that glucocorticoid- in the elderly is well-documented. A systematic review insensitive asthmatics have an increased activation of p38 and meta-analysis conducted by Bell et al. [53] found mitogen-activated protein kinase (MAPK), which can strong, consistent evidence of a higher risk of PM-asso- reduce the ligand-binding afnity of the glucocorticoid ciated hospitalisation and death in the elderly. Te results receptor (GR) leading to impaired corticosteroid sensi- of this meta-analysis showed that a 10 μg/m3 increase tivity [46]. Tis can contribute to poor disease control in in PM10 exposure was associated with a higher risk of patients with chronic asthma and COPD. In this respect, death of 0.64% (95% confdence interval (CI) 0.50, 0.78) it is worth mentioning that also disruption of circadian for older populations compared with 0.34% (95% CI 0.25, rhythms may impair asthma control. For example, the 0.42) for younger populations. In another systematic degree of asthma control has been shown to strongly review by Bell et al. [54], regarding sensitivity to mortality correlate with sleep quality. In fact, individuals whose or hospital admission from short-term ozone exposure, asthma is not well controlled take longer to fall asleep, mortality risk was also higher for older persons (1.27%; awake more often, and spend more time awake during 95% CI 0.76–1.78) than for younger persons (0.60%; 95% the night compared to those with well controlled asthma CI 0.40–0.80). [47]. Interestingly, many other immunological and aller- Further evidence of an association between air pollu- gic diseases, including allergic rhinitis, atopic eczema, tion and mortality in the elderly was provided by another chronic urticaria, and rheumatoid arthritis, show a cir- study, which showed that a 3–4% increase in daily deaths cadian rhythm in the intensity of symptoms and disease for all causes and for cardiovascular disease in the elderly severity, which suggests the importance of chronotherapy was associated with an increase in fne particulate mat- as a strategy to achieve symptoms control [47]. ter and sulfur dioxide from the 10th to the 90th percen- Of note, not all studies support the hypothesis that air tile [55]. Te increase in mortality was even higher (6%) pollution has a greater deleterious efect on asthmatic for respiratory deaths. Cardiovascular deaths were also Patella et al. Clin Mol Allergy (2018) 16:20 Page 6 of 11

associated with levels of carbon monoxide (4% increase senescence of the immune system [57–61]. To this regard, in daily deaths). On the contrary, the associations outdoor trafc pollution exposure is the most impor- between air pollution and mortality were not statistically tant predictive factor for asthma in the elderly [62–66]. signifcant in children under 5 years. In summary, there Indeed, higher levels of outdoor and indoor exposures to was a signifcant trend of increased risk of death based DEPs, combined with obesity and atopic state, are associ- on age, with efects more evident for individuals over ated with inadequate asthma control in the elderly [67]. 65 years old. Te efect of air pollution was even larger in Tere is also evidence that heat waves are associated with areas with higher socioeconomic level [55]. an increased risk of hospitalisation and higher mortality With regard to the efects of socioeconomic vulner- in the elderly [68]. In particular, two studies have shown ability on the risk of mortality in populations exposed that severe cardiovascular and respiratory diseases can to high PM concentrations, an Asian study showed that be induced by the elevated air pollution associated with economic inactivity had the greatest infuence on the risk heat waves, especially in the elderly [69, 70]. of mortality (Table 1) [56]. People who were economi- Environmental pollution exposure signifcantly cally inactive had a 5.5% higher risk of all-cause mortal- increases the risk of respiratory diseases, particularly ity and a 5.6% higher risk of cardiorespiratory mortality asthma. Both adult and young patients, smokers or non- from a 10 μg/m3 increase in PM10–2.5 compared with smokers, are prone to acute asthma attacks as a result of those who were employed during a day with an extreme greater exposure to air pollution. In particular, children dust event. Also, the elderly and non-married people had from low-income backgrounds have been found to be higher risks of mortality during days with extreme dust more susceptible to acute asthma attacks due to air pollu- events. People aged 65 years and older had a 4.4% higher tion. However, larger studies are required to confrm the risk of all-cause mortality and a 5.3% higher risk of car- relevance of these interactions, and to further explore the diorespiratory mortality compared with those who were risk factors for asthma associated with long-term air pol- under the age of 65. People who were not married had a lution exposure in patients of diferent ages. Moreover, 4.1% higher risk of all-cause mortality and a 4.7% higher when diferentiating between the efects of various risk risk of cardiorespiratory mortality than those married factors, it is important to remember that asthma is not [56]. a single disease [71]. In addition, the risk of both allergic Importantly, it has been observed that antioxidant met- and non-allergic asthma seems to increase with increas- abolic pathways become increasingly compromised with ing BMI as previously reported in children [72]. Finally, ageing. Older people are also particularly sensitive to the associations between early-life environmental exposures short-term efects of ozone exposure [50]. It is becoming and asthma have been found in non atopic subjects [73, increasingly clear that ageing is strongly associated with 74]. Recently, air pollution has also been associated with increased plasma viscosity and cardiac functions abnor- Table 1 Efect modifcation of socioeconomic vulnerability malities, mainly due to cardiac arrhythmias [75–77]. for 10 mg/m3 increase of PM10-2.5, with 95% confdence Terefore, elderly patients are more susceptible than interval. Modifed from Ho et al. [56] younger patients to the adverse efects of climate change Socioeconomic OR at lag 0 (all OR at lag 0 due to their higher incidence of cardiovascular disease. vulnerability (individual cause mortality) (cardiorespiratory Another important issue is the relationship between cli- level) mortality) mate change and microbial infections. It has been sug- Age gested that the rapid and intense climate changes related > 65 1.044 [1.029, 1.059] 1.053 [1.029, 1.078] to global warming can create conditions that promote < 65 1.047 [0.994, 1.103] 1.045 [0.920, 1.186] the spread of epidemic diseases. For instance, heavy - Gender falls increase the availability of breeding places for pests Female 1.057 [1.014, 1.102] 1.062 [0.998, 1.131] such as bugs and rats, which contaminate drinking water Male 1.033 [1.018, 1.049] 1.030 [1.009, 1.052] supplies. Moreover, parasitic and viral diseases transmit- Socioeconomic status ted by mosquitoes are very sensitive to climate changes Economically inactive 1.055 [1.039, 1.070] 1.056 [1.030, 1.081] [78–80]. Economically active 1.024 [0.992, 1.057] 1.019 [0.974, 1.066] Other mechanisms involved in climate change include Marital status air temperature increases in urban areas, a phenomenon Non-married 1.041 [1.018, 1.065] 1.047 [1.004, 1.093] called “heat island.” Tis efect is particularly relevant Married 1.034 [1.013, 1.056] 1.030 [1.003, 1.056] for people living in these areas, especially those who are afected by cardiovascular and/or respiratory dis- Italic text indicates results with signifcant diference between vulnerable and non-vulnerable groups eases. It also has a signifcant impact on the most fragile Patella et al. Clin Mol Allergy (2018) 16:20 Page 7 of 11

population groups (e.g., elderly and poor people). In fact, the recording of seasonal peaks of airborne pollen con- these people have less access to air conditioning and centrations. Te SIAAIC TF believes that compliance tend to stay more outdoors (e.g., streets, squares) where with the provisions of the Decalogue can help meet the they are more exposed to urban overheating. In addi- campaign goal, that is, reducing the concentrations tion, exposure to outdoor air pollution combined with of airborne allergenic pollen in the cities. Among the exposure to allergenic pollen can trigger severe asthma forthcoming activities, the TF is preparing aerobiology attacks. A reduction in emergency hospital admissions courses, as well as the creation of a national SIAAIC aer- after the implementation of prevention programs sup- obiology network for the monitoring of allergies across ports the view of a causal link between air pollution and the country. exacerbations of chronic respiratory diseases [80]. Behind the initiatives of the SIAAIC TF on “Air Pollu- tion and Climate Change,” there is the authors’ opinion, The SIAAIC task force on air pollution and climate change: which is supported by recent studies, that the prevention the decalogue “Allergy Safe Tree” of allergies can be implemented by public administra- In April 2014, the Italian Society of Allergology, Asthma tions through a careful choice of non allergenic trees and and Clinical Immunology (Società Italiana di Allergolo- plants. Likewise, a careful selection of ornamental plants gia, Asma ed Immnunologia Clinica, SIAAIC) estab- can contribute to reduce pollen levels in the private sec- lished the Task Force (TF) on “Air Pollution and Climate tor (condos, sports, malls and industrial green areas) Change.” [77]. Tese aspects are of high relevance as parks and Te SIAAIC TF launched a project divided into 3 suc- gardens are primarily visited by both children and elderly cessive steps. Te frst step involved the establishment of people, who are susceptible to allergic sensitisation and a multidisciplinary expert group, including high-profle respiratory diseases. Finally, allergen exposure within academic, institutional and associative fgures working the parks is particularly dangerous when combined with in the feld of “Air Pollution and Climate Change” at the climate conditions characterized by rising temperatures legal, environmental and institutional levels. SIAAIC that can promote pollen production, taking into account Allergists and Clinical Immunologists were clearly the fact that urbanization and high levels of vehicle emis- involved in this group. Te second step of the project sions correlate with a higher frequency of pollen-induced (“exploratory step”) included the collection of national respiratory allergy [4]. and European data on climate and environmental changes. Te third step of the TF’s work, still underway, Conclusion focused on the preparation of a fnal document (Report Te efects of global warming on human health are sup- or Guidelines) to raise awareness about “Air Pollution ported by many ofcial documents which emphasize and Climate Change” and their impact on Immunological the importance of air pollution on the rising incidence and Allergic Diseases. Te TF also planned the produc- of many respiratory diseases. Climate change, by modi- tion of a “synthetic” version of the document intended for fying major climatic variables, infuences directly and the public, as well as the preparation of a Decalogue to indirectly the formation of air pollutants. Both global be sent to local administrators with a set of rules aimed warming and solar radiation contribute to the formation at protecting public health. Starting from this initial of secondary pollutants in the atmosphere, especially proposal, and as a result of its regular activities during tropospheric ozone. All these factors can explain, at least these years, the Task Force on Air Pollution and Climate partly, the increasing incidence of respiratory and aller- Change of the Italian Society of Allergology, Asthma and gic diseases in diferent parts of the world. Recent fore- Clinical Immunology (SIAAIC) has proposed a National casts suggest that climate change will persist for several Healthcare Program to help the cities’ public adminis- decades (IPCC 2013). It is likely that we will face the trations in choosing non allergenic trees in public parks. impact of climate change for at least the next 50 years. Te “DECALOGUE: ALLERGY SAFE TREE” document Te efects of climate change are already here and their suggests how to use non allergenic trees in gardens and negative consequences cannot be easily avoided or pre- public parks [81, 82] (Fig. 1). vented. In many patients with respiratory diseases like As the subtitle indicates, the Decalogue plans to carry asthma, symptomatic treatment with bronchodilators or out a prevention campaign to reduce the amount of pol- inhaled corticosteroids is sufcient to control disease. len in the air without sacrifcing public green areas. To However, there are patients who do not achieve control this end, the document adopted by the SIAAIC TF pro- despite treatment with the best current therapy. Tis poses “simple actions” concerning the management and heterogeneity of asthma and allergic diseases is increas- care of plants, targeting several factors afecting allergen ingly appreciated based primarily on recent cluster analy- concentrations, including the “pollen calendar,” namely ses, molecular phenotyping, biomarkers and diferential Patella et al. Clin Mol Allergy (2018) 16:20 Page 8 of 11

Fig. 1 Prevention campaign to reduce the amount of pollen in the air without renouncing to public parks and green spaces Patella et al. Clin Mol Allergy (2018) 16:20 Page 9 of 11

responses to targeted and non-targeted therapies [83]. 4. D’Amato G, Holgate ST, Pawankar R, Ledford DK, Cecchi L, Al-Ahmad M, Al-Enezi F, Al-Muhsen S, Ansotegui I, Baena-Cagnani CE, Baker DJ, Tis can be explained, at least in part, by diferent patient Bayram H, Bergmann KC, Boulet LP, Buters JT, D’Amato M, Dorsano S, exposure to climate change and air pollution. A joint Douwes J, Finlay SE, Garrasi D, Gómez M, Haahtela T, Halwani R, Hassani efort among scientists of diferent disciplines together Y, Mahboub B, Marks G, Michelozzi P, Montagni M, Nunes C, Oh JJ, Popov TA, Portnoy J, Ridolo E, Rosário N, Rottem M, Sánchez-Borges M, with public administrations is highly desirable to limit Sibanda E, Sienra-Monge JJ, Vitale C, Annesi-Maesano. Meteorological present and future harm to human health as a result of conditions, climate change, new emerging factors, and asthma and interaction between climate change and air pollution. related allergic disorders. A statement of the World Allergy Organiza- tion. World Allergy Organ J. 2015;8(1):1–52. https​://doi.org/10.1186/ Authors’ contributions s4041​3-015-0073-0. VP, GF, DM, AG, MAC, DDB, AG, MP, AP, ER, CS, MTV, AZ have been partecipated 5. de Hartog JJ, Hoek G, Mirme A, Tuch T, Kos GP, ten Brink HM, Brunekreef equally participate in the review, drafting, and fnal approval of the manu- B, Cyrys J, Heinrich J, Pitz M, Lanki T, Vallius M, Pekkanen J, Kreyling WG. script. All authors read and approved the fnal manuscript. Relationship between diferent size classes of particulate matter and meteorology in three European cities. J Environ Monit. 2005;7:302–10. Author details 6. Donaldson K, Stone V, Clouter A, Renwick L, MacNee W. Ultrafne parti- 1 Division Allergy and Clinical Immunology, Department of Medicine ASL cles. Occup Environ Med. 2001;58(211–216):199. Salerno, “Santa Maria della Speranza” Hospital, Battipaglia, Salerno, Italy. 2 Post- 7. Pekkanen J, Kulmala M. Exposure assessment of ultrafne particles graduate Program in Allergy and Clinical Immunology–University of Naples in epidemiologic time-series studies. Scand J Work Environ Health. Federico II, Naples, Italy. 3 Air Pollution and Climate Change Task Force 2004;30(Suppl 2):9–18. of the Italian Society of Allergology, Asthma and Clinical Immunology (SIAAIC), 8. D’Amato G, Baena-Cagnani CE, Cecchi L, Annesi-Maesano I, Nunes C, Milan, Italy. 4 Laboratory of Environmental Analysis, Department of Public Ansotegui I, D’Amato M, Liccardi G, Sofa M, Canonica WG. Climate Health, ASL Salerno, Salerno, Italy. 5 Department of Cardiac, Thoracic and Vas- change, air pollution and extreme events leading to increasing cular Sciences, University of Padua, Padua, Italy. 6 Association of International prevalence of allergic respiratory diseases. Multidiscip Respir Med. Culture, Athena of Paestum, Capaccio‑Paestum, Salerno, Italy. 7 Former Primary 2013;8(1):12. https​://doi.org/10.1186/2049-6958-8-12. of Unit of Pediatry, Hospital of Eboli, Salerno, Italy. 8 International Court 9. Bai Y, Sun Q. Fine particulate matter air pollution and atherosclerosis: of the Environment Foundation (ICEF), Rome, Italy. 9 Department of Medicine mechanistic insights. Biochim Biophys Acta. 2016;4165(16):30150–7. and Surgery, University of Parma, Parma, Italy. 10 Unit of Internal Medicine, https​://doi.org/10.1016/j.bbage​n.2016.04.030. Department of Experimental and Clinical Medicine, University of Florence, 10. Yitshak Sade M, Novack V, Ifergane G, Horev A, Kloog I. Air pollution Florence, Italy. 11 Department of Interdisciplinary Medicine, University of Bari, and ischemic stroke among young adults. Stroke. 2015;46(12):3348–53. Bari, Italy. 12 Department of Studies and Researches, Movimento Ecologista https​://doi.org/10.1161/STROK​EAHA.115.01099​2. 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