A.I.S.T. - Associazione Italiana per lo Studio della Tosse
 

Roma - 30 Giugno 2005
"Inquinamento atmosferico e vie aeree"
nell'ambito del Congresso Mondiale ORL XVIII IFOS

IMPACT OF AIR POLLUTION ON AIRWAYS: EPIDEMIOLOGICAL ASPECTS

G. Viegi*, S. Baldacci, A. Scognamiglio, M. Simoni, S. Maio, F. Pistelli, L. Carrozzi.
Pulmonary Environmental Epidemiology Unit, CNR Institute of Clinical Physiology, Pisa, Italy; * 2004-05 President Elect, European Respiratory Society

Background
     A recent classification of air pollutants has been published by Bernstein et al (Berstein, 2004). It has three subdivisions: a) primary-secondary pollution; b) indoor-outdoor pollutants; c) gaseous-particulate pollutants. Overall, currently the most commonly studied pollutants with regard to human health effects are particles (PM), nitrogen oxides (NOx), and ozone (O3). It is important to remind the terminology of particulate matter, which is a complex mixture of airborne solid and liquid particles, including soot, organic material, sulfates, nitrates, other salts, metals, biological materials. According to the size in micron of the aerodynamic diameter, the following particles partitioning applies: inhalable, PM10; coarse, PM10-PM2.5; fine, PM2.5; ultrafine, PM0.1.
     The so called national ambient air quality standards for criteria air pollutants are periodically updated in view of new evidences provided by epidemiological studies. For instance, in the USA the 1997 standard for PM10 (e.g annual arithmetic mean of 50 µg/m3 ) has been recently halved (Kim, 2004).

Outdoor pollution
     In the year 2000, the American Thoracic Society has issued an official statement on "What constitutes an adverse health effect of air pollution" (ATS, 2000), ranging from increased mortality to odors. Asthma and allergies are included in the list as: a) increased frequency of symptomatic asthmatic attacks; b) increased exacerbations of diseases in persons with chronic cardiopulmonary diseases, such as less able to cope with daily activities (e.g. shortness of breath), increased frequency and/or duration of hospitalizations, increased emergency ward or physician visits, increased pulmonary medication, decreased pulmonary function; c) increased prevalence of wheezing in the chest apart from colds, or of wheezing most days or nights; d) increased incidence or prevalence of chest tightness; e) eye, nose and throat irritation that may interfere with normal activity, if severe.
     Fumes, gases, particles, aerosols act in the airways through cells and mediators: inflammation may lead to bronchial wall thickening and airway narrowing and to asthma; immune mediated responses can lead to asthma and to hypersensitivity responses in parenchyma.
     Bernstein et al (Bernstein, 2004) have enlisted the possible mechanisms of pollutant-associated adverse health effects:
a) PM- or O3- induced pulmonary inflammation;
b) Free radical and oxidative stress generation by transition metals and organic chemical compounds (eg, PAH);
c) Covalent modification of key intracellular proteins;
d) Biologic compounds, such as endotoxins and glucans, which induce inflammation and innate immune effects;
e) Stimulation of nocioreceptor and autonomic nervous system activity, which regulates heart rate variability and airway reactivity;
f) Adjuvant effects in the immune system (e.g. DEPs and transition metal enhancing responses to common environmental allergens);
g) Procoagulant activity by ultrafine particles after access to the systemic circulation;
h) Suppression of normal defense mechanisms (e.g. suppression of alveolar macrophage function).

Riedl and coll (Riedl, 2005) have described the clinical effects of diesel extract particles (DEPs) in nasal provocation studies:
a) Immediate-phase response (minutes): - increases allergen-induced histamine release and symptoms;
b) Short-term response (hours): - increases release-production of C-C chemokines; - increases cellular inflammation; - induces a potent TH2 cytokine milieu in the presence of allergen (e.g. increased IL-4 and decreased IFN-y levels);
c) Intermediate-term response (days): - enhances total and allergen-specific IgE response to allergen; - increases number of IgE-secreting cells in nasal mucosa;
d) Long-term response (days): - enhances primary allergic sensitization.

     Epidemiological studies of chronic respiratory conditions in relation to urban air pollution in adults have been recently reviewed by Viegi and Baldacci (Viegi, 2002; Baldacci, 2002). All the conventional pollutants, such as O3, nitrogen dioxide (NO2), sulphur dioxide (SO2), respirable suspended particulates, have been related to some extent to asthma and allergies. In particular in adults, asthma symptoms or asthma prevalence/incidence have been reported in California and France, whilst allergic sensitization to pollens in Switzerland. Considering short term effects of air pollution on respiratory health of adults, panel studies have shown associations with asthmatic symptoms in the Netherlands, and with lung function reductions in asthmatics in the USA.
     Further, time-series studies have shown associations with asthma hospital admissions in the USA, in Finland and other European countries, and with allergic rhinitis daily consultations in the UK.
     A summary of the combined effect estimates of daily mean particulate pollution had been published in 1994 (Dockery, 1994). Per each 10 µg/m3 increase in PM10, the following % changes in exacerbation of asthma were estimated: 3% asthmatic attacks, 2.9% bronchodilator, 3.4% emergency department visits, 1.9% hospital admissions. Such estimates have been confirmed more recently in Europe through the studies APHEA (Katsouyanni, 1997) and APHEA2 (Aga, 2003). Further, in the APHEA2 study, for the warm season, a 10 µg/m3 increase in the 1-hour O3 concentration has been associated with a 0.33% (95% confidence interval (CI): 0.17-0.52%) increase in daily total mortality, 0.45% (95% CI: 0.22-0.69%) in cardiovascular mortality, and 1.13% (95% CI: 0.62-1.48%) in respiratory mortality (Gryparis, 2004). In another study carried out in Barcelona, O3 was also shown to increase the risk of death in asthmatic patients >14 years (Odds Ratio (OR): 1.90, 95% CI: 1.09-3.30) during spring and summer (Sunyer, 2002). In a French study, a 10 µg/m3 increase in O3 resulted significantly associated with asthma attacks (OR 1.20, 95% CI: 1.03-1.41) on lag two (Desqueyroux, 2002).
     The effect of air pollution seems to act continuously across a wide range of ambient concentrations, far below the national air quality guidelines, without a definite thresholds. For instance, plotting the relative odds of incidence of coughing against three-day mean PM10, it has been demonstrated in the USA a linear relationships with two slopes: the first (smooth) between 5 and 45 µg/m3, the second (steep) between 45 and 80 µg/m3 (Viegi, 2002). Similar findings for respiratory symptoms and lung function have been reported in Switzerland, both for children and adults (Viegi, 2002).
     Ecological studies have shown in adults reduced airflows and increased airway resistance and response to bronchodilator in downtown inhabitants when compared to those living in suburbs in Marseille, France, and larger decline of forced expiratory volume in one second in those exposed to higher concentrations of O3 in the Los Angeles area (Viegi, 2002). In Europe, children living near roads at intense truck traffic have been shown to have lower FEV1, as well as symptoms of asthma (wheezing) and allergic rhinitis (Viegi, 2002). In Italy, the general population sample living in the urban area of Pisa has shown increased frequency of asthma symptoms with respect to the one living in the rural area of Po Delta (Viegi, 2002; Baldacci, 2002), whilst the SIDRIA study has confirmed the deleterious effects of traffic air pollution in children (Ciccone, 1998).
     A peculiar type of air pollution, to be considered as an overlapping form of environmental and occupational exposure, is the one occurred in New York City after the terroristic attack to the World Trade Center (Landrigan, 2004). There was a near 8-fold increase in cough prevalence among firefighters heavily exposed, in respect of those lowly exposed to smoke and dust from September 2001 through March 2002.
     Even the international guidelines on asthma diagnosis and management (GINA, 2002) have recognized the importance of air pollution as risk factor leading to asthma development and exacerbations.
     A series of studies have reported data on the association of air pollution (mainly of oxidizing type) and prevalence or incidence of asthma symptoms / diagnosis in children (Duhme, 1996; Shima, 2002; Mortimer, 2002; Lin 2002; Nicolai, 2003).
     Indeed, McConnell et al (McConnell, 2002) have found for asthma incidence odds ratios of 2.0 (95% CI: 1.1-3.6) and 3.3 (95% CI: 1.9-5.8) in children playing three or more sports outdoors in high PM and in high O3 communities of Los Angeles area, respectively.
     Even lung function growth has been demonstrated to be negatively affected by air pollution. Brunekreef et al (Brunekreef, 1997) have shown a negative correlation between FEV1 in Dutch children living < 300 m from a motorway and number of trucks per week day. Gauderman et al (Gauderman, 2004) in 10-18 yr inhabitants of California have demonstrated a negative correlation between FEV1 growth and NO2 concentration, as well as a positive correlation between the proportion of subjects with FEV1 <80% predicted and PM2.5 concentration.
     The burden of air pollution on European children's health has been recently estimated (Valent, 2004). Among 0-4 yr children, 13796 (2.68 per 10,000) and 9845 (1.91 per 10,000) are estimated to die each year due to outdoor and indoor pollution, respectively.
     A new era of air pollution studies will be devoted in the next future to the ultra-fine particles, i.e. those with an aerodynamic diameter less than 0.1 µg. For instance, von Klot and colleagues (von Klot, 2002) have shown significant independent effects of 5-day means of ultra-fine particles on prevalence of inhaled short-acting beta-2-agonist use, corticosteroid use and wheezing, after taking into account the effect of fine particles.
     A light of hope comes from the observation that the closure of the downtown area of Atlanta to private traffic during the 17 days of the 1996 Summer Olympic Games was associated to a reduction in mean levels of pollutants, especially O3 and PM10, and to a reduction in acute asthma events among children ranging from 11.1 to 44.1% (Friedman, 2001).
     Kunzli et al (Kunzli, 2000) have estimated elevated numbers of asthma attacks yearly attributable to air pollution from PM10: e.g. 24000 in Switzerland, 35000 in Austria, and 243000 in France, for children <15 years; 63000 in Switzerland, 94000 in Austria, and 577000 in France, for adults >15 years.
     With regards to development of asthma and allergies, further research should be devoted in Europe (Viegi, 1998) to study effects of: photochemical mixtures; atmospheric pollution mixtures in cities; atmospheric acidity; long term exposures; short-term peak exposures in special meteorological and topographical circumstances.
     Kim et al (Kim, 2004), in a document titled "Ambient air pollution: health hazards to children" have voiced the concerns of clinical professionals which have to treat an elevated number of children with respiratory disorders. Some relevant recommendations have been issued: among them, the call to promptly review and revise standards for PM10, PM2.5, O3, NO2, and the suggestion to include proximity to roads with heavy traffic and other sources of air pollution when planning the siting of schools and child care facilities.
     At last, it is to mention a recent overview on outdoor air pollution and lung cancer (Vineis, 2004), pointing to an increased risk of lung cancer associated with pollutants such as PM10, PM2.5, SO2, NO2.Indoor pollution
     It is well established that indoor environment contributes significantly to human exposure to pollutants (Viegi, 1999; Rojas-Bracho, 2000; Sarnat, 2000).
     A recent review on human health effects has been published by Viegi et al (Viegi, 2004). Indoor air pollution increases the risk of respiratory symptoms/diseases, atopic sensitization, bronchial hyperresponsiveness, lung cancer, respiratory infections, irritations (Viegi, 1999; Jaakkola, 2000; Simoni, 1998; Simoni, 2002; Simoni 2003; Simoni, 2004).
     Data mostly collected in European dwellings on PM, NO2, volatile organic compounds (VOCs), formaldehyde, dampness/mould and dust mites at home and related health effects have been reviewed for the period 1991-2002 within the European Union funded project denominated "Towards Healthy Air in Dwellings in Europe" (THADE) (Carrer, 2004).
     In Europe, the lowest mean PM level (9.5 µg/m3) in Finland and the highest values in Italy (50 µg/m3) (Viegi, 1999; Carrer, 2004) were measured; in Poland and in Switzerland a significant relation between respiratory symptoms/disease and ETS exposure was found in adults.
     The lowest NO2 values in Scandinavia (range: 10 -15µg/m3) and the highest in Poland (65 µg/m3) were measured (Viegi, 1999; Carrer, 2004): in elderly women, asthma and dyspnea were related to high exposure to gas cooking; in England, gas cooking was a risk for reduced lung function.
     In Po Delta and Pisa Italian indoor studies (Simoni, 2003; Simoni, 2004), acute respiratory conditions were more frequent in presence of high exposure to PM2.5 and NO2 and in presence of environmental tobacco smoke. High exposure to PM2.5 was a risk factor for reduced lung function.
     Measured levels of toluene ranged from 15.1 in England to 37.3 µg/m3 in Germany, similarly to those measured in Italy (Viegi, 1999; Carrer, 2004); in UK the geometric level of formaldehyde was 22.2 µg/m3; a German study showed a significant association of VOCs exposure with irritation symptoms of the upper respiratory tract; in Sweden, asthma was related to newly painted surfaces (OR 1.5; CI 95% 1.0-2.4); formaldehyde resulted an irritant agent for the respiratory tract, and could cause sensitization in exposed children (OR 1.40; CI 95% 0.98-2.0).
     European studies indicate that mites can be present inside more than 50% of the observed dwellings (Viegi, 1999; Carrer, 2004): mite allergens concentrations were generally about 2 µg/m3 of dust and could sensitize exposed subjects; the highest levels were found in Sweden; in Germany exposure to high mite allergen levels was associated with bronchial hyperresponsiveness (OR 2.30; 95% CI 1.03-5.12).
     Visible dampness and mould were present inside 15% of Finnish homes, 25% of Dutch homes, and 35% of Italian dwellings (Viegi, 1999; Carrer, 2004); in a large Finnish survey, exposure to visible mould was associated with an elevated risk of asthma (OR 2.21; 95% CI 1.48-3.28); Swedish subjects exposed to dampness inside their homes had a higher risk of asthma (OR 1.8; 95% CI 1.1-3.0); exposure to dampness was a risk factor for bronchial hyperresponsiveness (OR 5.77; 95% CI 1.17-28.44) in Germany. More recently, Simoni et al (Simoni, 2005 in press), analyzing the data of the largest pediatric epidemiological survey in Italy, have reported a current mould / dampness exposure of 9.5% in children and 10.1% in adolescents and have estimated that about 6% of wheeze and 7% of asthma and cough/phlegm are attributable to such exposure occurred in early life.
     With regard to development of asthma and allergies, further research should be devoted in Europe to establish safe limit values to produce guidelines for indoor exposure, especially in dwellings (Carrer, 2004). There is the urgent need of assessing the effects of both short and long term exposure at home. Studies should be performed in general population samples on the relationship of health and measured indoor levels, taking into account the exposure time and the exposure variability.

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