Air pollution

In 2017, the Lancet Commission on Pollution and Health reported an estimated 6.5 million deaths on a global scale attributable to outdoor and indoor air pollution, with predominant effects on COPD (50%) and lung cancer (40%) [1].

The first Global Conference on Air Pollution and Health held in Geneva in October 2018 [2] and the WHO Manifesto for a Healthy Recovery from COVID-19 [3] confirmed the estimate of 7 million premature deaths attributable to air pollution and the percentage of 90% of the world’s population exposed to unacceptable levels of air pollution, concluding that “current knowledge is sufficient to act immediately .... in ten years we will not be able to say that we did not know”.

In September 2021, the WHO published the Global AQG [4], recommending values much more stringent than those accepted by the 2008 European Directive, based on new epidemiological studies that have shown damage to health even from exposure to low levels of air pollutants.

The second WHO Global Conference on Air Pollution and Health, held in Cartagena (Colombia) in March 2025 [5], confirmed these estimates, and participants agreed on a shared goal to reduce the impact on health by 50% by 2040, in order to save millions of lives every year. In addition, new financial commitments and policies for environmental and health protection have been proposed.

The State of Global Air 2025, published by the Health Effects Institute [6], provided a comprehensive analysis of data related to air quality and health impact in countries around the world in 2023: air pollution caused 7.9 million deaths globally, becoming the second risk factor for mortality, even for children under five. Deaths attributable to PM_2.5 were 4.9 million; of these, 171,000 in children under the age of 5 years [6]. In addition, of the total deaths, non-communicable diseases, including heart disease, stroke, diabetes, lung cancer and COPD, account for almost 90% of the disease burden due to air pollution. In the previous edition of the report (2024), it was found that over 700,000 deaths of children under the age of 5 were linked to air pollution; this accounts for 15% of all global deaths in children under five years [7].

In March 2025, the Zero Pollution Monitoring and Outlook 2025 report [8], published by the European Environment Agency (EEA) and the Joint Research Centre (JRC), highlighted that significant progress has been made in Europe in reducing the impact of PM air pollution, with a 45% decrease in premature deaths attributable to PM_2.5 exposure between 2005 and 2022. However, more than 83% of residents in urban areas of the European Union (EU) are exposed, for all air pollutants, to pollution levels above the levels recommended by the WHO, with the exception of sulphur dioxide (SO₂) and benzo(a)pyrene (BaP), indicating persistent air quality problems. Reaching the objective of the Zero Pollution Action Plan (ZPAP) to reduce premature deaths by 55% in 2030 compared to 2005 requires the effective implementation of current and proposed policies, including those related to energy and climate change mitigation.

As far as Italy is concerned, the EEA’s 2022 Air Quality report [9] showed that our country ranks 5th between 30 European countries for years lived with disability (YLD) due to COPD attributable to PM_2.5 in adults over twenty-five years of age (about 70 YLD per 100,000 inhabitants) and 3rd between 23 European countries for hospital admissions for respiratory diseases attributable to O₃ in adults over sixty-five years of age (about 22 hospitalizations per 100,000 inhabitants). In addition, the EEA’s 2025 report on Health Harms from Air Pollution [10] provided estimates of annual premature deaths attributable to exposure to major air pollutants in 2023: in Italy, 43,083 for PM_2.5, 9,064 for NO₂ and 1,123 for O₃.

The Ambient Air Quality Directive 2024/2881/EU [11] entered into force on 10 December 2024, setting new and stricter limits for air pollutants, such as PM_2.5 and NO₂, to be achieved by 2030, with the aim of zero pollution by 2050. The directive brings European standards closer to the recommendations of the WHO (but does not adopt them) and introduces provisions to improve monitoring, coordination and access to information.

On the basis of these premises, air pollution is to be considered the most significant environmental risk factor on a planetary level and in Italy, therefore requiring immediate prevention actions.

Table 1 shows the levels of AQG and intermediate targets recommended by the WHO.

Climate change

The climate crisis is a phenomenon that risks substantially and irreversibly transforming natural ecosystems and the human living environment. 2024 was the hottest year on record (around + 1.55°C compared to the pre-industrial level), with an uninterrupted increase in global temperatures, particularly over the past decade, and an increase in exposure to heat waves globally [12]. Climate change is also intensifying the effects of other environmental exposures, particularly among the most vulnerable populations and regions: sandstorms, forest fires aggravated by drought and land degradation, peaks in local O₃ air pollution, and heavy rainfall.

The Mediterranean is a region particularly vulnerable to climate change “hot spots”: the temperature in the Mediterranean basin is increasing at a rate 20% faster than the global average, leading to a series of changes in the climate system with an increase in the intensity and duration of extreme events, including heat waves and impacts on natural systems and human health [13]. The latest Lancet Countdown report estimated that 84% of heatwave days that occurred in the last 5 years would not have occurred in the absence of climate change [14].

Other extreme weather events such as heavy rainfall can also increase in frequency and intensity in some regions and are sometimes associated with floods and flooding [13]. Such episodes can have a range of acute effects, such as trauma and mortality, but the experience of regions where these episodes are more frequent has also shown health risks due to the proliferation of mould and fungi in flooded homes.

Also in the Mediterranean area, the frequency of drought episodes is increasing, understood as an unusual and prolonged shortage of water availability, caused by reduced rainfall and increased evaporation [15]. Heat and drought in turn increase the frequency of forest fires [13]. Finally, drought leads to the progressive desertification of increasingly large areas: in Italy, the frequency of previously very rare phenomena is increasing, such as dust transport events from desert areas, especially from North Africa. Such dust can be transported thousands of km away, with worsening air quality and possible health effects, particularly respiratory health, in countries affected by the passage of the desert sand cloud [16].

Such exposures associated with climate change can have consequences on respiratory and allergic health, especially in the short term, and, in some cases, even in the long term. However, the respiratory health impact of the climate crisis is very difficult to study and must take into account complex causal mechanisms, which can be directly (e.g., exposure to increasingly higher temperatures) and indirectly (e.g., higher levels of food insecurity, sensitivity to extreme weather events) related to climate change, interacting with population susceptibility, health and socio-demographic conditions, availability of infrastructure and adaptive capacities [13].

In view of the ongoing climatic changes, as also underlined by a recent review by Annesi-Maesano et al. [17], there is increasing evidence that extreme events (including heat waves, forest fires, hurricanes, floods) have a significant impact on respiratory health, posing greater risks for vulnerable populations, such as individuals with pre-existing diseases, children, the elderly and those who work outdoors. Also considering the future scenarios of further intensification of exposures to such events, including in our country, it is urgent to increase awareness and response capacity to protect public health starting from the population groups at greatest risk [18].

Outdoor air pollution

Air pollution is a complex mixture of gases and PM, the latter classified according to aerodynamic diameter. Exposure to these pollutants is a well-established risk factor for both diseases.

• Asthma: exposure to vehicular traffic, in particular NO₂ and PM_2.5, is associated with an increased incidence of asthma in children and an increased risk of exacerbations in all ages. These pollutants act as adjuvants, promoting allergic sensitization and inducing a state of oxidative stress and inflammation in the airways [24, 25].

• COPD: long-term exposure to NO₂ and PM_2.5 is associated with an accelerated decline in lung function and an increased risk of developing COPD, regardless of cigarette smoking. In individuals already suffering from COPD, pollution peaks are correlated with an increase in hospital admissions for acute exacerbations [26, 27].

Indoor pollution and biomass fuels

The home environment is a significant source of exposure to pollutants that can affect respiratory health.

• Passive smoking: It is a known risk factor for both the onset of childhood asthma and the development of respiratory symptoms and COPD in adulthood in non-smokers.

• Indoor allergens: Exposure to dust mites, mold, pet dander, and cockroaches is a primary trigger for the development and exacerbations of allergic asthma [28].

• Biomass fuels: Globally, the burning of biomass (wood, charcoal, animal dung) for cooking and heating in poorly ventilated rooms is one of the main causes of COPD, especially in women in low- and middle-income countries. The smoke generated contains very high levels of PM and toxic substances that cause intense lung inflammation [29].

Occupational exposures

The workplace is another crucial source of exposure to substances that can cause or worsen respiratory diseases. It is estimated that about 15–20% of cases of asthma and COPD in adults are attributable to occupational factors [30].

• Occupational asthma: It is the most common work-related respiratory disease in industrialized countries. It can be triggered by high molecular weight agents (e.g., flours, enzymes, latex) that induce IgE-mediated sensitization, or by low molecular weight substances (e.g., isocyanates, acid anhydrides) that act through complex immunological mechanisms.

• Occupational COPD: Chronic exposure to inorganic dusts (coal, silica in miners), organic dusts (cotton dust in textile workers, grain dusts in farmers), and chemical fumes (e.g., cadmium) is a recognized cause of COPD. These agents induce chronic inflammation and a progressive decline in lung function, acting additively or synergistically with cigarette smoking [31].

VOCs

VOCs represent a heterogeneous category of chemical compounds with high vapor pressure at room temperature. Indoor concentrations are typically 2–5 times higher than outdoor concentrations, reaching 50–500 μg/m³. The main VOCs present in indoor environments are formaldehyde (10–100 μg/m³), benzene, toluene, xylenes, and chlorinated organic compounds. The main sources are building materials and furniture, household cleaning products, cosmetics and personal hygiene products, paints and adhesives. Exposure to VOCs is associated with increased asthma development [relative risk (RR) 1.37] [32]. VOCs can be ubiquitously distributed in home, school, work and recreational environments.

Radon

Radon is a natural gas generated by the radioactive decay of radium, which is found in rocks, soils and derived building materials. It penetrates and spreads in buildings (indoor radon), reaching concentrations that vary from environment to environment. The average concentration in Italy amounts to about 70 Bq/m³, but there are areas at risk with radon gas levels > 300 Bq/m³ [33]. Radon is a certain carcinogen (Group 1) for lung cancer in exposed populations [34]. However, it has also been identified as a potential risk factor for the development and worsening of asthma control, increasing IL-6 and IL-5 levels by 14.9% and 13.4%, respectively, even in patients and healthy subjects with no history of atopy [odds ratio (OR) 1.149] [35, 36].

The main risk factors for asthma and COPD are shown in Table 4.

General population

By the 1990s, it became clear that living in cities was associated with more respiratory symptoms and diseases than living in rural areas [37–39], but also that exposure to air pollution was associated with an increase in mortality and hospitalizations for respiratory causes [40, 41].

Paediatric population

Paediatric evidence from the Italian context confirms a relevant contribution of air pollution, urban green/grey exposures, aeroallergens and indoor pollutants (in particular, VOCs) in rhinitis symptoms and allergic respiratory conditions.

The cross-sectional study conducted by Cilluffo et al. [59] on children aged 8–10 years residing in Palermo showed a significant relationship between characteristics of the urban environment and the prevalence of nasal symptoms attributable to allergic rhinitis. The results showed that a low value of the normalized difference vegetation index (NDVI) (indicator of exposure to urban greenery) is associated with a significant increase (+ 47%) in the probability of reporting symptoms. Similarly, residence within 200 meters of busy traffic roads results in a comparable increase in the risk of rhinitis. The “greyness” indicator, which reflects the density of impermeable surfaces and anthropogenic infrastructures, is coherently associated with both nasal symptoms and other respiratory and ocular symptoms, suggesting the unfavorable effect of urbanized contexts characterized by low biodiversity and greater pollution [59]. The same authors studied the effect of NDVI on asthma control, finding that a reduction in urban greenness was associated with an increased likelihood of having uncontrolled asthma (+ 166%) [60]. Overall, the data support an interpretative model based on a dual pathophysiological mechanism: (1) the scarce presence of urban greenness reduces exposure to environmental microbes and natural components of biodiversity, believed to promote a correct immunological maturation of the respiratory mucosa; (2) proximity to vehicular traffic increases chronic exposure to irritating and oxidizing pollutants (fine PM, NOx, VOC), capable of inducing inflammation of the upper airways, increasing epithelial permeability and promoting allergic sensitization [61].

In a Turin study, a significant role of green availability in modulating paediatric respiratory health was confirmed [62]: children exposed to higher NDVI values were significantly less likely to have asthma (–87%), bronchitis (–86%) and current wheezing (–75%), compared to those exposed to lower levels of vegetation. In addition, the analysis of spirometry values showed a significant reduction in forced expiratory flow between 25 and 75% of forced vital capacity (FEF_25–75) in children residing in less green areas, indicative of possible small airway involvement. Although the study does not directly analyze “greyness”, the reported environmental data show average exposures to NO₂ of 55.6 μg/m³ [62], a value higher than the WHO 2005 guidelines, suggesting an urban context in which scarce vegetation coexists with high levels of traffic pollutants, strengthening the hypothesis of an interaction between urbanization, air quality and respiratory health.

The study by Di Cicco et al. [63] provides particularly useful information on the role of outdoor aeroallergens in causing a worsening of children’s respiratory conditions, with effects that involve both the lower airways and the nasal district in an integrated way. The analysis conducted on children aged 0–17 years residing in Tuscany, hospitalized for asthma or asthmatic symptoms, showed that an increase of 10 granules/m³ of total aeroallergens is associated with an increase (+ 2–4%) in the risk of hospitalization for asthma (OR ≈ 1.02–1.05), with more evident effects in the first 1–2 days after exposure [63]. Particularly relevant is the contribution of the fungal spore Alternaria alternata, known for its high allergenic potential and ability to induce acute inflammatory responses even at low concentration levels. In addition, the increase in aeroallergens produces more marked effects in sensitized children, boys and subjects over 10 years of age, emphasizing the interaction between individual immunological structure and environmental exposure. The temporal dynamics documented in the study (up to 48 hours) are compatible with the immunological processes that follow exposure to aeroallergens and that manifest clinically with symptoms involving both the upper and lower airways [63].

In the main Italian multicenter study dedicated to the evaluation of air quality in schools and its effects on children’s respiratory health, funded by the National Center for Disease Prevention and Control (CCM) of the Ministry of Health, it has been documented that residence near agricultural areas subjected to pesticide treatments is associated with a significant increase in allergic and irritative symptoms in children. In particular, children living near treated crops are more likely to have symptoms of the upper airways (+ 125%), eye disorders (+ 281%) and skin manifestations (+ 160%), compared to their unexposed peers [64].

The “Viadana III” cohort represents one of the main Italian studies on the impact of industrial pollution on respiratory and allergy health in subjects aged 0–21 years, residing in the Viadana (MN) area. The study showed that chronic exposure to PM₁₀, PM_2.5 and NO₂ is associated with a significant increase in health outcomes attributable to paediatric allergy disease. In particular, there is an increase (+ 32%) in allergy visits for every unit increase in PM₁₀ exposure [65].

A cross-border study examined the association between outdoor PM_2.5 concentration, elemental composition of PM (metals and other components) and the prevalence of respiratory diseases (asthma, rhinitis) in primary school children in Sicily and Malta. At higher PM_2.5 levels, a higher probability of asthma was observed (+ 5–6%). These risks were higher when considering individual heavy metals [66].

A recent study investigated the relationship between outdoor air pollution (PM₁₀, NO₂, SO₂) and structural and inflammatory changes of the airways in children aged 3–8 years, with bronchoscopy with broncholavage and bronchial biopsy performed. The study shows that air pollution, particularly PM₁₀, contributes to early structural changes of the airways in children. In particular, in children with wheezing, chronic exposure to PM₁₀ promotes the appearance of bronchial remodelling phenomena and increases eosinophilic inflammation [67]. The same research group evaluated whether acute exposure to air pollutants (PM₁₀, NO₂, SO₂) can influence the antiviral response of the bronchial epithelium in preschool children, showing an association of PM₁₀ and NO₂ levels with impaired epithelial antiviral response [68].

The results described above have been reported in detail in Table 5 and Table 6.

Respiratory mortality and morbidity

The rapidity of climate change is causing a rapid increase in the burden of disease associated with extreme heat and heat waves; the occurrence of these events in some areas of southern and central Europe has doubled in the last twenty years [14].

At the international level, multicenter studies that also included Italian cities (EuroHEAT, PHEWE, EXHAUSTION) and systematic reviews have documented in the last 20 years a consistent effect of heat and heat waves on mortality from respiratory causes, especially in the population aged 75+ years [69, 70]. On heat wave days compared to non-wave days, there are percentage increases of even more than 90% in respiratory mortality in the population aged 65+ years in some Italian cities [69]. The greater vulnerability to heat due to respiratory causes emerges particularly clearly in hospital admissions, which show significant increases only for these diseases, while no increases are observed in hospitalizations for cardiovascular causes [71], probably because these events have a more frequent fatal outcome and therefore manifest themselves as an increase in heat-associated mortality. The recent EXHAUSTION study, thanks to the use of data with high spatial resolution, confirmed significant impacts on respiratory causes, with an increase (+ 27%) in respiratory mortality for temperatures between the 75th and 99th percentile of the area-specific distribution in three European countries [72].

The MultiCityMultiCountry study provided estimates of the impacts of heat on a global scale for the first time, including 532 locations in 33 countries, among which low-income countries and 16 Italian cities. A significant risk of respiratory mortality associated with exposure to extreme temperatures is confirmed in the 40+ age group, increasing with age from 1.14 at 40 years up to 1.25 at 85 years [73].

Systematic reviews of the evidence confirm consistent effects of heat and heat waves on mortality [74–79]. A meta-analysis of 54 articles from 20 countries, including Italy [78], found a strong association between heatwaves and respiratory mortality, with an overall mortality risk of 1.18 [95% confidence interval (CI): 1.09–1.28], although with high heterogeneity between studies, and a stronger association in some countries (e.g., Brazil, China, France, Germany, the Netherlands, Russia and Thailand). In subgroup analyses, the elderly population showed the greatest risks of heat-related mortality, especially during exceptional heat waves, such as the one in summer 2003 [78].

As far as non-fatal outcomes are concerned, effects of heat have been highlighted, in a less consistent way, not only in terms of increased hospital admissions, but also in terms of access to emergency and urgent services and outpatient visits [74–79]. An association between extreme heat or heat waves and respiratory morbidity (RR 1.043; 95% CI 0.995–1.093) was observed, with high heterogeneity between studies, more marked in the elderly and in specific areas [78]. In addition, heat and heat waves are associated with a high risk of asthmatic crises consistently across all age groups (children, adults, elderly) [77].

In the Italian context, thanks to the availability of daily temperature data with high spatial resolution, estimates of the effects of extreme temperatures on cause-specific mortality for the whole national territory are available from the BIGEPI study [80, 81]. The study reported an increased risk of mortality from respiratory diseases (+ 37%) for average temperature increases between the 75th and 99th percentiles of the summer temperature distribution in the years 2006–2015. In terms of attributable cases (%) of the total summer mortality from respiratory causes, about 2% of deaths from these causes are attributable to heat. Thanks to the availability of data with high spatial resolution (1 km × 1 km), the study documents for the first time an impact of heat and cold not only in Italian urban areas, but also in rural areas where there seems to be a high vulnerability.

There is increasing evidence of a possible synergistic effect of heat and some pollutants such as O₃ and fine PM on respiratory mortality [82, 83], in both the national [84] and international context [85–87], but the results vary according to the pollutant and the geographical area under study as they are possibly influenced by local weather and air quality conditions.

Asthma

Allergic rhinitis

COPD

Respiratory infections

General effects of climate change on pollen and mould

Climate change and environmental and occupational exposures are significantly modifying the epidemiology, seasonality and severity of respiratory allergic diseases [129, 134–137]. Rising temperatures, changes in rainfall regimes and increasing air pollutants influence the production, dispersal and allergenicity of pollen and fungal spores, favoring the emergence of new clinically relevant allergens [138]. Among these, Alternaria alternata represents a paradigmatic model of an emerging allergen, associated with even severe forms of asthma [139, 140]. In addition, extreme weather events, such as thunderstorms, are increasingly related to outbreaks of acute asthma “thunderstorm asthma” [141–143].

In particular, global warming and rising CO₂ concentrations affect:

• Duration and intensity of the pollen season, anticipating its beginning and prolonging its end;

• Amount of pollen produced, growing for many allergenic species;

• Geographical distribution of allergenic plant species (migration northwards or to higher altitudes);

• Increase in fungal spores and molds (Alternaria, Cladosporium), especially in warmer and more humid urban and agricultural contexts.

The effects observed on the Italian territory are different between the Alpine and Mediterranean areas.

In alpine and subalpine environments, not only pollen, but also fungal spores remain more prolific [144, 145]. Variable weather conditions create an environment conducive to the production of allergenic spores of Alternaria, Cladosporium, and other genera, aggravating exposure to aeroallergens during allergy season. In addition, allergenic species typical of lowland areas are spreading to higher altitudes, where historically local production was low, as pollen exposure to non-native species (e.g., Ambrosia) is increasing [146].

In Mediterranean areas, an increase in the annual pollen concentration of some species has been found, accentuated by droughts and milder winters [147]. Earlier blooms and longer allergic seasons have been found, particularly for spring-flowering species (e.g., Quercus, Olea) [148] and an increase in atmospheric mold following episodes of heavy rain and flooding [139].

In recent years, several studies and reports have been published that specifically analyze the effects of climate change on pollen, mold and atmospheric allergens in Italy, with significant differences between Alpine and Mediterranean areas [134, 142, 147–150].

Health effects of pollen

The lengthening of pollen seasons and periods of spore presence favors greater allergenic exposure: more exposure time means more likelihood of allergic sensitization even to new allergens or migratory species (e.g., Ambrosia in new areas). Subjects who are already sensitized show more lasting and intense symptoms, with worsening of the quality of life. The consequences of these phenomena are reflected in the increase in allergic rhinoconjunctivitis and allergic asthma in Europe and worldwide. The WHO has estimated that respiratory disorders related to pollen and mold have increased by about 30% in the last two decades, with projections growing towards 2050 [135]. In Italy, a growth in cases of rhinitis and allergic asthma related to pollen and molds has been observed (+ 20–30% in the last 20 years in some regions) [151].

Epidemiological studies consistently report short-term effects of pollen (within 3 days of exposure) on asthma and allergy symptoms, in terms of increases in emergency department admissions, hospital admissions, or patient-reported symptoms (Table 8). Italian studies [63, 152] (Table 9) suggest a significant effect of pollen exposure on the risk of aggravation of asthmatic disease in children.

Allergic asthma

Asthma is often caused or exacerbated by pollen and spores:

• Longer seasons with higher allergen peaks increase asthma exacerbations, especially during periods of peak concentration.

• Extreme weather events such as pollen thunderstorms and heat waves can trigger potentially severe acute asthma attacks.

• Humidity and sudden rainfall in Mediterranean regions can promote the proliferation of molds such as Alternaria, further shifting the allergenic load towards fungal spores, especially in autumn.

The available meta-analyses (Table 8) mainly indicate pollen effects of major grasses in children and the adult population, although individual studies report a risk of exacerbation of asthma and rhinitis also for other taxa, specific to the study areas (e.g., Oleaceae, Ambrosia, Cupressaceae) [154, 155]. Health effects are usually immediate (0–3 days), but may persist for several days up to 7–8 days after exposure. The onset of acute respiratory diseases following violent thunderstorms, such as thunderstorm asthma, has also been known for some time [142, 150]. That is, episodes of severe asthma, even fatal, in which a combination of particularly violent meteorological factors (lightning, wind, rain) and environmental factors (presence of airborne allergenic pollen) causes an increase in respiratory symptoms in sensitive people. The complex mechanism underlying these acute manifestations seems to be mainly determined by the breakdown of pollen grains [142, 150]. Lightning, strong gusts of wind, and rain can cause fractures in the pollen structure, with the consequent escape of microparticles, which, poured into aerosols, can be breathed in and easily penetrate the deep airways. As a result, individuals with asthma or allergies may experience a sudden intensification of symptoms, such as breathing difficulty, coughing, and chest tightness. These events can also lead to fatal episodes [134, 150].

Although this phenomenon has historically been associated with grass pollens, growing evidence suggests a possible role of fungal spores, in particular Alternaria, in contributing to the inhalable allergen load during thunderstorms.

Allergic rhinoconjunctivitis

The lengthening of pollen seasons and periods of spore presence favors greater allergenic exposure:

• More exposure time means more likelihood of allergic sensitization even to new allergens or migratory species (e.g., Ambrosia in new areas).

• Subjects who are already sensitized show more lasting and intense symptoms, with worsening of the quality of life.

General trends in the prevalence of allergic diseases

• The prevalence of allergic rhinoconjunctivitis and allergic asthma is increasing in Europe and worldwide, linked to increased exposure to pollen and aeroallergens, as well as interaction with air pollutants.

• The WHO has estimated that respiratory disorders related to pollen and mold have increased by about 30% in the last two decades, with projections growing towards 2050.

In the Mediterranean areas, there is an increase in cases of allergic rhinitis and allergic asthma linked to pollen and mold (+ 20–30% in the last 20 years in some regions). In specific Alpine contexts, epidemiological studies on Swiss paediatric cohorts indicate that, although traditionally considered “low allergic risk” areas due to the lower presence of allergens and pollutants, an increasing proportion of children show sensitisation to pollen and mould. This suggests that environmental and clinical factors interact complexly even in these mountain environments.

Air pollution

In parallel, air pollution, particularly in urban areas with high traffic density and industrialization, changes the composition of pollen and acts as a co-factor in exacerbating the allergic response. Pollutants such as NO₂, O₃ and PM can alter the surface of pollen grains, with chemical-physical changes that alter pollen functionality and allergen release [158]. Pollen is a class of airborne microbiota which, due to its size (average 30 μm) and structural morphology of the external wall (Hexin sculpturing), easily acts as a carrier for other airborne microparticulates, biotic and otherwise. In this way, the encounter with a pollen-carrier can facilitate inflammatory conditions in the mucous membranes of sensitive subjects, effectively amplifying the reactivity to pollen itself [159].

To confirm this, several epidemiological studies show that, although there are higher pollen concentrations in rural environments, pollinosis is found more frequently and severely in urban areas—a phenomenon attributable precisely to the synergistic effect between pollen and air pollutants, as well as to different exposures and environmental characteristics [131–133].

PM₁₀, PM_2.5 and O₃ play a causal role in facilitating the onset of respiratory symptoms:

• PM can act as a vector for allergens, increasing their penetration into the airways;

• O₃ induces oxidative stress, epithelial damage, and increased permeability of mucous membranes;

• Combined exposure to pollen and pollutants amplifies bronchial inflammation and hyperreactivity.

These synergistic effects can lower the clinical threshold of response to allergens, favoring asthma exacerbations even at moderate pollen concentrations.

In addition, lifestyle and chronic exposure to respiratory stress in urban environments may predispose more to sensitization and the onset of symptoms than those who live permanently in rural or semi-rural contexts, where air quality tends to be better as well as the set of environmental risk factors [158, 159], although epidemiological evidence of pollen-pollutant interaction is still limited [160].

Rhinitis

In patients with rhinitis, exposure to pollen can cause increased symptoms in the short term (nasal and eye symptoms, frequent cough, especially at night), especially in younger age groups and in relation to herbaceous pollens (Graminaceae and Ambrosia) [154, 161].

COPD and respiratory infections

Evidence on the possible effect of pollen on exacerbations of COPD or the risk of respiratory infections is still limited. A multicenter study that also includes Italy suggests a possible association between pollen exposure and risk of SARS-CoV-2 infection, and how this was significantly reduced during the lockdown period [157].

Land use: olive and hazelnut trees examples of intensive agriculture

Intensive agriculture, particularly for traditional crops in the Mediterranean area such as olive trees and, increasingly, hazelnuts, has a significant impact on biodiversity and respiratory health. The expansion of these intensive monocultures, often promoted by the interest of large investors, is leading to the replacement of less profitable traditional crops and even wooded or uncultivated areas, with a consequent alteration of the landscape and a potential loss of soil and aerosporological biodiversity.

Hazelnut and olive trees, characterized by anemophilous pollination, release large quantities of allergenic pollen. In addition, modern production plants, in order to maximize productivity, plan for the insertion in the orchard of a certain number of pollinating varieties, genetically selected to express almost exclusively the male character, in order to increase the extent and duration of the pollen cloud at the time of pollination.

The spread of intensive agriculture, which increases the density of these plants in specific areas, contributes to the significant increase in the concentration of their pollen in the air, aggravating the prevalence and severity of pollinosis in resident populations [162].

Emerging allergens in the course of climate change: the role of Alternaria.

• Effects of climate change on the spread of Alternaria: The increase in average temperatures and the greater frequency of hot and dry periods favor the growth and sporulation of Alternaria. Extreme weather events, such as prolonged droughts followed by heavy rainfall, can lead to peaks in the concentration of fungal spores in the air.

• Health effects: Alternaria alternata is a ubiquitous fungus, whose spores represent one of the most important outdoor fungal allergens. Sensitization to Alternaria is associated with allergic rhinitis, bronchial asthma and, in some cases, severe and potentially fatal asthmatic exacerbations, especially in children and young adults. The major allergen Alt a 1 is now considered a clinically significant exposure marker, with a central role in the IgE-mediated response and pathogenesis of fungal-related asthma.

General population

In the early 1990s, it became clear in Italy that fuel used for cooking or heating was associated with higher prevalence rates of respiratory symptoms or impaired lung function in both males and females, with greater likelihood of coughing, dyspnoea and wheezing if gas cylinders or cookers and stoves fuelled by other non-natural fuels were used [163, 164].

In the 2000s, interest and evidence on passive smoking increased: in over 2,000 non-smoking women, residing in Pisa, Po Delta, Rome and Viterbo, exposure to secondhand smoke by their husband/partner and at work was a risk factor for dyspnea, cough/phlegm, rhinoconjunctivitis, wheezing and attacks of shortness of breath with wheezing, diagnosis/symptoms of asthma, obstructive pulmonary disease (diagnosis of asthma/chronic bronchitis/emphysema) [165].

In the same years, environmental measurements were carried out in the homes of subjects residing in the Po Delta, showing that there were significantly higher indoor NO₂ levels in homes with gas heating and/or gas water heaters. PM_2.5 was significantly higher in smokers’ homes and significantly correlated with the number of cigarettes smoked. In winter, significant associations emerged between bronchitis/asthmatic symptoms and exposure to above-average NO₂ and PM_2.5 values. In summer, this association emerged only for PM_2.5 in non-smokers [166, 167].

There are no recent Italian studies on the general population; most of the studies concerned the paediatric population.

Paediatric population

With regard to the paediatric age, the study by Cibella et al. [168] examined the association between exposure to NO₂ in indoor environments and respiratory symptoms and lung function in a population of adolescents (aged 10–17 years) residing in Palermo and undergoing allergic respiratory health assessment through questionnaires, spirometry and skin prick tests. Indoor NO₂ was significantly higher than outdoor NO₂ in both seasons (p < 0.001). Indoor levels were particularly high in the urban center and in condominium dwellings. Around 25% of adolescents were exposed to indoor NO₂ values above the limit set by the WHO in 2005 (threshold value used: 40 μg/m³). Indoor NO₂ exposure was associated with an increased risk of current asthma. Indoor values > ~32 μg/m³ (spring) and > ~41 μg/m³ (winter) increased the likelihood of current asthma. Exposure to the highest levels of NO₂ was significantly associated with wheezing in the past 12 months, rhinoconjunctivitis, chronic cough, current asthma, and decreased respiratory function. The study also showed that the interaction between allergic sensitization and indoor NO₂ further increases the risk of asthma: among adolescents with allergy and high NO₂, the prevalence of asthma reached 22.4%, compared to 0% in non-allergic people exposed to lower levels [168].

A further study conducted in Palermo between 2015 and 2018 on asthmatic children aged 5 to 16 years longitudinally analyzed the relationship between asthma control and various environmental factors, outdoor (e.g., urban greenness, air pollution, traffic) and indoor (e.g., passive smoking, mold). The results indicate that living in areas with little greenness (NDVI ≤ 0.21) (+ 166%), being exposed to maternal smoke during pregnancy (+ 282%), and living in overcrowded housing conditions (+ 238%) are factors that increase the risk of uncontrolled asthma [60].

The HESE (Health Effects of School Environment) study, one of the main European multicentre projects (Italy, France, Denmark, Norway and Sweden) dedicated to the assessment of air quality in schools and its effects on children’s respiratory health, consistently highlighted that poor classroom ventilation and the accumulation of indoor pollutants, in particular PM₁₀ and CO₂, are associated with a higher prevalence of respiratory symptoms and an objectively measurable reduction in the patency of the upper airways of children, with a dose-response relationship directly involving the nasal district [169]. Within this general framework, the data from the Italian centers, Siena and Udine, take on particular relevance, as they show some of the most critical microenvironmental conditions of the entire European sample, with the highest pollutant values and poorest ventilation.

More recently, the multicenter study [Schools Indoor Pollution and Health Observatory Network in Europe (SINPHONIE) database on chemical and biological pollutants] evaluated children between 6 and 14 years old residing in 23 European countries, including Italy, to define the prevalence of asthma, allergies and respiratory symptoms, considering the differences between different geographical areas. The most common conditions were: allergic rhinitis 17.8%, eczema 16.9%, pollen allergy 12.2%, asthma 7.7%. The most frequently reported symptoms in the last year were: sneezing/stuffy nose (20.8%) and dry cough at night (18.4%), particularly in Southern Europe. The study showed considerable geographical variability in the asthma and allergies of European children, influenced by environmental and socioeconomic factors such as climate, pollution levels, exposure to traffic, presence of mold [170].

In the SINPHONIE study, it was also shown that schoolchildren exposed to concentrations greater than or equal to the average of PM_2.5, benzene, limonene, O₃ and radon were significantly more likely to suffer from upper and lower respiratory disorders [171].

The assessment of endotoxin concentration in the classrooms showed levels that varied according to the geographical area, with the highest averages in Italy and the lowest in Finland. Elevated endotoxin levels were associated with higher odds of upper and lower respiratory symptoms (runny nose, nasal obstruction, cough, dry throat, breathing difficulty, and fever), as well as reduced lung function [172, 173].

The main effects of indoor air pollution on the respiratory health of children and adolescents are shown in Table 10.

Data in Italy

In Italy, in the first population epidemiological studies carried out in the Pisa and Po Delta area, an increased risk of asthma (symptoms and diagnosis) and respiratory functional alterations was observed in subjects occupationally exposed to dust, fumes and gases [177], as well as a higher prevalence of subjects with bronchial hyperreactivity to methacholine in occupationally exposed ex-smokers [178].

The data of the first studies were confirmed by subsequent follow-ups, which showed an increase in the incidence of asthma and rhinitis in subjects occupationally exposed to dust, fumes and gases [49] and an association between exposure in the wood industry and in the textile industry and incidence of bronchial asthma diagnosis [179] 18 years after the first assessment.

In more recent multicenter studies involving the general Italian population, regular exposure to gases, vapors, dusts and fumes in the workplace was associated with a more severe form of bronchial asthma and a higher prevalence of asthma associated with COPD [180].

In asthmatic patients, work is often the cause, contributory cause, or aggravating factor of bronchial asthma. In a study of asthmatic patients performed in Tuscany, 48% reported that the condition was work-related (was caused by work or worsened during work) and that asthma was less controlled and needed continuous treatment with long-acting bronchodilators and inhaled steroids [181] compared to those who did not report work-related asthma.

INAIL data on occupational diseases document an increase in cases of occupational bronchial asthma in the last two years, although their number is still underestimated compared to the epidemiological data previously reported [182].

Prevention and health protection

The prevention of allergic respiratory diseases in the workplace passes through primary, secondary and tertiary prevention, as required by the consensus documents of the main pulmonary and allergological scientific societies [183, 184] and by current Italian legislation (Legislative Decree 81/08).

The primary prevention of allergic respiratory diseases is an activity that involves the elimination or, if not technically possible, the reduction of risk factors present in the workplace. In addition, any new chemicals introduced into these environments should be studied to assess their impact in terms of sensitization or potential irritation of respiratory tract that could worsen an underlying allergic condition.

Improving hygienic conditions in the workplace, through risk assessment and the implementation of mitigation measures, can contribute to primary prevention.

At this level, the role of politics and social partners in supporting these improvement actions, which aim to protect the health of the worker and reduce the socio-economic repercussions of a possible work-related pathology, is fundamental.

Secondary prevention is carried out on workers to intercept those who are developing early and potentially reversible symptoms and signs of a possible work-related respiratory allergic disease. In Italy, health surveillance by the competent doctor is mandatory for workers at risk. Health surveillance is a clinical activity characterized by a medical examination and supplementary tests aimed at assessing the worker’s suitability for the specific task, but it is also an extraordinary opportunity to assess the health of workers exposed to sensitizing substances or bronchoirritants that allow the emergence of work-related respiratory allergic diseases, the effectiveness of which has also been emphasized in the consent documents of the main European scientific societies [183].

Tertiary prevention is an activity carried out on workers already suffering from respiratory allergy in which occupational physicians and allergy/pulmonologist specialists collaborate to adapt the work environment to the new needs of the patient/worker with a view to reducing the socio-economic repercussions related to the respiratory disability that characterizes the patient.

Pollen and moulds: clinical and public health implications

Pharmacological treatment and allergen-specific immunotherapy represent the fundamental pillars of the management of allergic diseases and the control of symptoms. However, non-pharmacological measures to avoid or reduce pollen exposure can be an important complement to therapy and are, in part, already considered in clinical guidelines for asthma and allergic rhinitis. The Italian National Prevention Plan (PNP) also provides for specific measures to reduce exposure to pollen, aimed at protecting the health of allergic people in the workplace (PNP 2020–2025).

For clinicians: it is essential to integrate environmental data (pollen, fungal spores, pollutants) into the risk assessment and personalized management of allergic and asthmatic patients.

For prevention: aerobiological monitoring and early warning systems for thunderstorms and pollution peaks can help raise awareness, to put in place measures to protect people with asthma and allergies, limit direct exposure to pollen (both outdoor and indoor), and reduce the risk of acute events. In urban areas, the management of green spaces in the areas of daily life of allergic or asthmatic subjects is important. To reduce pollen exposure, the replacement of highly allergenic species with plants with low allergenic potential is recommended [187].

For health policies: consider pollen exposure in clinical guidelines for asthma and allergic rhinitis, and inform and educate patients, especially the most vulnerable groups such as children and those more exposed (such as outdoor workers). In the long term, climate change mitigation and air pollution reduction are key interventions to contain the impact of allergic respiratory diseases.

Strategic action on two fronts is therefore essential:

• Aerobiological monitoring with high spatial resolution: a capillary territorial distribution of aerobiological monitoring centers is required. These centers not only record the amount of pollen in circulation and fungal pathogens, often very present in intensive plantations, but also trace the phenology (flowering times) specific to the monoculture areas;

• Timely and localized aerobiological bulletins: the data collected must flow into the drafting of extremely precise and localized bulletins. These information tools, if available with adequate timing, become essential for public health and employment, allowing allergy sufferers to take timely and targeted preventive measures, better managing their drug therapy.

Urban renewal and reforestation

Urban renewal and reforestation are now one of the fundamental pillars of city regeneration in response to the climate crisis. It is not simply a matter of “beautifying” inhabited centers, but of integrating multifunctional green infrastructures, capable of mitigating the “urban heat island” effect, improving air quality by capturing fine dust and promoting the management of rainwater through permeable surfaces.

An effective reforestation project, however, must be guided by rigorous scientific planning, based on:

• Biodiversity and resilience: the use of different native species guarantees greater resistance to pests and climate change, avoiding the fragility typical of monocultures;

• “Allergy-friendly” selection: in line with concerns about respiratory health, it is crucial to select tree essences with low allergenic potential, avoiding the massive concentration of anemophilous species (which entrust fertilization to the wind) near residential areas or schools;

• Ecological connectivity: the creation of green corridors, which connect parks, roof gardens and urban forests, allows the movement of wildlife and the maintenance of ecosystem services in the heart of the urban fabric;

• Psychophysical well-being: the presence of accessible green areas reduces stress levels, promotes physical activity and improves social cohesion, transforming abandoned or degraded industrial areas into new vital lungs for the community. For this reason, they must be managed correctly and made accessible, especially to low-income and more vulnerable population groups (children, the elderly, people with disabilities, pregnant women).

“Green” urban renewal is more necessary than ever, but a careful and qualified (therefore integrated) design of the skills necessary to reconcile plant density and respiratory health is needed. The “Low-Allergy” approach must guide urban reforestation and vertical forests: this means overturning the paradigm of urban green choice, moving from a purely aesthetic or opportunity selection (resistance, rapid growth, poor maintenance) to a selection based on the reproductive biology of plants.

Climate change

The experience of the 2003 heatwave has sparked an increase in awareness of the risks associated with these exposures and the urgency of implementing prevention measures. According to the WHO, a plan for the prevention of the effects of heat must be based on an early warning system of the risks associated with high temperatures, prevention plans targeted at the most vulnerable population and modulated on the basis of alert levels and communication campaigns to the population and training for social and health workers [188].

Italy was one of the first countries in Europe to activate a national program of interventions for the prediction and prevention of the effects of heat waves on health: the “National Operational Plan for the Prevention of the Effects of Heat on Health” of the Ministry of Health [189]. The National Plan is based both on alarm systems for the prevention of the effects of heat on health, called Heat Health Watch Warning Systems (HHWWS), operating in the summer in 27 cities, and on health and social prevention interventions specifically oriented to susceptible population subgroups and modulated on the risk levels of alarm systems. In some cities, the plan provides for the identification of the elderly population susceptible to the effects of heat (registry of susceptible elderly).

In Italy, there are still no specific national plans for the prevention of health and respiratory effects for other types of exposure associated with climate change, such as drought or the transport of desert dust. However, some measures already in place for heat-related risks could be reshaped and extended to these exposures as well: the National Plan for the prevention of the effects of heat on health provides for alert systems, health monitoring and risk communication, useful tools also in the event of other climate-sensitive events that can affect health. Climate adaptation policies and civil protection plans include information and awareness-raising actions that can be extended to all exposures to extreme weather events. Prior communication by weather networks and local health authorities, if active locally, is in fact the only active measure to reduce the exposure of the population to these exposures, in particular of subjects with respiratory diseases [190].

The Ministry of Health has included in its programs the promotion of knowledge on environmental risks and climate change, with attention to asthma, COPD and allergies. The PNP includes the environment, climate and health among the macro-objectives of the plan. Regional climate adaptation policies can strengthen water resource management, improve air quality, and provide information for vulnerable citizens.

Occupational exposure

The electronic health record: possible research applications

The EHR is established by law for all Italian citizens: in accordance with the provisions of article 11 of Legislative Decree 34/2020, it is automatically fed with present and past clinical data and documents. From 2022, the EHR is automatically fed with health data, unless the citizen opposes it (blackout option). The Health Record 2.0 is the updated and enhanced version of the EHR: a personal digital medical record, i.e., an evolution desired by the Ministry of Health for the National Health Service, an engine towards personalized and data-based healthcare.

State bodies or research bodies can access pseudonymized or anonymized data for health planning, evaluation of the quality of care, scientific and statistical research in the medical and epidemiological fields, subject to the authorization process (paragraph 2, article 34—Legislative Decree of 19 May 2020).

The data contained in the EHR could hopefully be the subject of epidemiological studies related to outdoor pollution and/or climate change (emerging infectious diseases, clinical consequences of heat waves, increase in allergic respiratory diseases). By cross-referencing, through geolocation, the data recorded in the EHR with those on air quality, climate, pollen, it would be possible to track new cases, increase in prescriptions for certain drugs and/or their consumption, admissions to the emergency room (or hospitalizations). The ultimate goal would be to collect useful data for the citizen for prevention, surveillance, clinical care. It could be better understood when, where and in whom asthma or COPD exacerbations increase by cross-referencing data by geographical area, average temperatures, peaks and duration of heat waves, pollutant levels, pollen counts. There would be an effective and rapid monitoring of health needs, a “clustering” of clinical risk, for primary and secondary preventive purposes.

Furthermore, subject to the explicit consent of the patient, an individualized alert system could be activated in the event of events (exceeding pollutant thresholds, pollen peaks, fires) capable of exacerbating recorded respiratory diseases, such as asthma or COPD, with a call to intensify therapies or limit environmental exposure.

Finally, in the context of the recording of sensitive patient data, it would be desirable to fill in, but not mandatory, some fields capable of further extending the investigation to the effects of indoor pollution, such as (1) the presence of humidity/mold in the home (yes/no), (2) the type of domestic heating (methane gas/wood/pellets/electricity). Therefore, the EHR integrated with environmental variables could be a useful research tool in the disciplines dealt with by the scientific societies belonging to this Task Force, which is available for their interpretation.

When is an environmental risk factor called a cause of disease?

According to Rothman and Greenland [192], a cause of disease is an event, condition, or characteristic that precedes the disease and that, if it had not occurred, the disease would not have occurred at that time or at all, net of all other factors.

To determine the causality of a relationship between risk factor and disease, Hill’s principles [193] are applied: temporality, i.e., the risk factor must precede disease; the dose-response relationship, i.e., greater exposure to the factor leads to a higher risk; biological plausibility, i.e., that there must be a biological mechanism that supports the association; and other criteria such as strength, consistency, specificity and experimental evidence and consistency of association in different populations and at different times. The latter criterion is particularly relevant because it implies that from a single study it is not possible to conclude a causal association with the disease, but this can only derive from an analysis of the entire set of available evidence, critically evaluated, to take into account any limitations (random and systematic errors) of the studies.

Etiological epidemiological studies use advanced statistical methods to estimate whether differences in disease risk between exposed and unexposed are due to chance or whether they support the hypothesis of a causal relationship.

Study designs in environmental epidemiology

The most widely used approach to study the short-term effects (e.g., for heat) of an environmental exposure is the time-series approach. They are population studies that correlate the daily variation of an environmental factor (e.g., air pollution) to the daily variation in cases of disease.

These studies are based on pooled outcome data, with exposure measured for a certain geographical area (e.g., city) and therefore as the average value of the population, which estimates the effect as an RR of daily mortality (or other outcome) (as a daily number of events) associated with an increase in the daily concentration of the risk factor (estimation not at the individual level, but ecological) and allows the effect of exposure to be assessed days later (time delay or lag).

To assess the long-term effects of an environmental exposure, a commonly adopted study design is the cohort study involving a population sample, stratifying the sample according to the level of exposure to a certain environmental factor (e.g., air pollution) and following the population over time to estimate the incidence of disease in exposed and unexposed (or for different levels of exposure). The main problem with these studies is the possible dropout of participants from the study, which could be influenced by their risk of disease.

The cohort study also allows estimation of an RR by comparing the incidence of disease in exposed and non-exposed patients. Important are the cohort studies of newborns that enroll cohorts of children from birth to evaluate the effect of early exposures on early and/or subclinical outcomes (e.g., biomarkers and epigenetic modifications).

Another common etiological study in environmental epidemiology, especially in the case of rare diseases, is the case-control study that compares risk factors in individuals who develop the outcome and controls (sampled from the population that gave rise to the cases).

Another widely used study, but for descriptive and not causal purposes, is the cross-sectional study: which measures the prevalence of disease and simultaneously detects possible exposures, and for this reason does not allow us to establish whether the exposure occurred before the disease or vice versa, but suggests hypotheses to be tested in etiological studies.

Finally, to evaluate Hill’s principle of consistency of association in different populations and at different times, a study design of extreme importance is the systematic review [194]. A systematic review relies on scientifically rigorous and reproducible methods to synthesize studies on a specific association between exposure (or intervention) and a disease, to understand whether evidence of association (or absence of association) is sufficient or further studies are needed.

The synthesis of the evidence must follow criteria of systematicity, transparency and reproducibility. Through these summaries, it is possible to give an overall assessment of the association between risk factor and disease, as is the case in the monographs of the International Agency for Research on Cancer (IARC), transparent and scientifically based. A rigorous method of synthesis, still little applied in the environmental field, is the GRADE method, which serves to transform epidemiological evidence into clinical recommendations, taking into account the quality of the available evidence and external validity [195].