Issue 2 - "Update on adverse respiratory effects of indoor air pollution". Part 2): Indoor air pollution and respiratory diseases: Perspectives from Italy and some other GARD countries.

OBJECTIVE: to synthesize the Italian epidemiological contribution to knowledge on indoor pollution respiratory impact, and to analyze the perspective of some GARD countries on the health effects of indoor air pollution. RESULTS: Italian epidemiological analytical studies confirmed a strong relationship between indoor air pollution and health in general population. Environmental tobacco smoke, biomass (wood/coal) fuel for cooking/heating and indoor allergens (house dust mites, cat and dog dander, mold/damp) are the most relevant indoor pollution sources and are related to respiratory and allergic symptoms/diseases in Italy and in other GARD countries such as Mexico, Brazil, Vietnam, India, Nepal and Kyrgyzstan. Community-based global health collaborations are working to improve prevention, diagnosis and care of respiratory diseases around the world, specially in low- and middle-income countries, through research and education. CONCLUSIONS: in the last thirty years, the scientific evidence produced on respiratory health effects of indoor air pollution has been extensive, but the necessity to empower the synergies between scientific community and local administrations remains a challenge to address in order to implement effective interventions. Based on abundant evidence of indoor pollution health effect, WHO, scientific societies, patient organizations and other members of the health community should work together to pursue the GARD vision of "a world where all people breathe freely" and encourage policy makers to increase their engagement in advocacy for clean air.

Outdoor air pollution and respiratory health.

The need to address the impact of air pollution on health is reinforced by recent scientific evidence and the 2021 WHO Air Quality Guidelines (AQG). Air pollution is an avoidable risk factor causing a high burden for society with elevated deaths, health disorders, disabilities and huge socio-economic costs, especially in low- and middle-income countries. We have evaluated recent evidence from international reports, systematic reviews and official websites of international agencies. Growing evidence shows a causal relationship between air pollution exposure and acute lower respiratory infections, chronic obstructive pulmonary disease, asthma and lung cancer. Exposure to air pollution in both the short- and long-term has a serious impact on respiratory health. Harmful effects occur even at very low pollutant concentration levels, and there are no detectable thresholds below which exposure may be considered safe. The adverse respiratory health effects of air pollutants, even at low levels, are confirmed by recent epidemiological studies. Scientific respiratory societies and patient associations, along with other stakeholders in the health sector, should increase their engagement and advocacy to raise awareness of clean air policies and the latest WHO AQG.

Single breath nitrogen test as predictor of lung function decline and COPD over an 8-year follow-up.

BACKGROUND: The single breath nitrogen (SBN2) test was proposed for early detection of "small airways disease" in the seventies. Few longitudinal studies have subsequently evaluated the relationships between SBN2 test measurements and lung function decline or COPD incidence. AIM: This study evaluates whether SBN2 test abnormalities may be significant predictors of lung function decline and COPD incidence over an 8-year follow-up. STUDY DESIGN AND METHODS: In this longitudinal study, 907 adults (20+ years old; 56% males) from the prospective Po River Delta epidemiological study underwent SBN2 test at baseline and spirometry testing at both baseline and follow-up 8-year apart. Multinomial and multiple regression models were used to assess associations of SBN2 indexes and rates of FEV1 decline or risk of COPD incidence over time, after adjusting for sex, height and baseline age, FEV1 and smoking status. COPD was defined according to either GOLD or ATS-ERS criteria. RESULTS: Among SBN2 indexes, only the slope of alveolar plateau (N2-slope) was significantly associated with rates of FEV1 decline (7.93 mL/year for a one-unit change in N2-slope, p<0.0001), and with an increased risk of developing COPD as defined by GOLD (RR 1.81, 95%CI 1.29-2.52, mild; RR 2.78, 95%CI 1.70-4.53, moderate or severe obstruction) and ATS-ERS criteria (RR 1.62, 95%CI 1.14-2.29, mild; RR 3.40, 95%CI 1.72-6.73, moderate or severe obstruction). CONCLUSION: In this population-based study, N2-slope from SBN2 test is a significant predictor of lung function decline and COPD incidence over an 8-year follow-up, confirming the role of the "small airways disease" in the natural history of COPD.

Densità di popolazione e SARS-CoV-2: uno studio epidemiologico di urban health.

Despite SARS-CoV-2 transmission being a complex phenomenon, greater population density seems to be a risk factor. The aim of this study was to analyze through an epidemiologic urban health approach the relationship between population density and SARS-CoV-2 incidence using data which are comparable with regard to testing strategies. All 10,300 SARS-CoV-2 confirmed cases between October and December 2020 were included. We conducted separate analysis by gender standardizing and stratifying by age and month. In the Province Capital (p.d.=765 inhabitants/km2), standardized SARS-CoV-2 incidence rate was higher than the expected, both in men (SIR=1.17, 95%CI=1.12;1.22, p<0.0001) and women (SIR=1.20, 95%CI=1.15;1.25, p<0.0001). In municipalities with p.d. >200 inhabitants/km2, standardized SARS-CoV-2 incidence rate was similar to the expected (p>0.05). In municipalities with p.d. <200 inhabitants/km2, standardized SARS-CoV-2 incidence rate was lower than the expected, both in men (SIR=0.85, 95%CI=0.81;0.90, p<0.0001) and women (SIR=0.84, 95%CI=0.80;0.88, p<0.0001). Stratified analysis by months with likelihood ratio test showed heterogeneity of the p.d. effect in men and women (p<0.05). SARS-CoV-2 incidence rate seemed to be higher in most densely populated areas, both in men and women. Our results confirmed the great importance of restrictive measures as well as the importance of limiting the epidemic wave in the initial stages and could help guide pandemic management strategies according to urban context and population density.

Lorlatinib for advanced ROS1+ non-small-cell lung cancer: results of the IFCT-1803 LORLATU study.

INTRODUCTION: ROS1-rearranged (ROS1+) non-small-cell lung cancer (NSCLC) is a rare lung cancer with limited treatment options. Phase I-II studies with ROS1-tyrosine kinase inhibitors (TKIs) included small numbers of patients and real-world data are lacking. We investigate the efficacy and safety of lorlatinib, a third-generation TKI targeting ALK and ROS1, in patients with ROS1+ NSCLC treated through an expanded access program. METHODS: Consecutive patients with advanced ROS1+ NSCLC treated with lorlatinib between October 2015 and June 2019 were included. Data were collected from medical records. The primary endpoint was progression-free survival. RESULTS: Out of the 80 patients included, 47(59%) were female, 49(62%) never smokers (less than 100 cigarettes over the lifetime), and 68(85%) had stage IV NSCLC at diagnosis. Most frequent histology was adenocarcinoma (95%) and median age was 58.2 years. At the time of lorlatinib initiation, 51(64%) patients had brain metastases and 55(81%) were PS 0-1. Lorlatinib was administered as second/third/fourth/fifth+ line in 29%/28%/18%/26% of patients. All patients previously received at least one ROS1 TKI, and 55(69%) previously received chemotherapy. Median follow-up from lorlatinib initiation was 22.2 months. Median progression-free survival and overall survival from lorlatinib initiation were 7.1 months [95% confidence interval (CI) 5.0-9.9 months] and 19.6 months (95% CI 12.3-27.5 months). Median duration of treatment with lorlatinib was 7.4 months (95% CI 6.5-13.1 months). Overall response and disease control rates were 45% and 82%, respectively. The central nervous system response rate was 72%. Treatment was stopped due to toxicity in 10 patients (13%). The safety profile was consistent with previously published data. CONCLUSIONS: Lorlatinib is a major treatment option for advanced refractory ROS1+ NSCLC in treatment strategy.

Issue 1 - "Update on adverse respiratory effects of outdoor air pollution". Part 1): Outdoor air pollution and respiratory diseases: A general update and an Italian perspective.

OBJECTIVE: to summarize the main updated evidence about the health effects of air pollution and to focus on Italian epidemiological experiences on the respiratory effects. RESULTS: the recent literature indicates that there is strong evidence for causal relationships between PM2.5 air pollution exposure and all-cause mortality as well as mortality from acute lower respiratory infections, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lung cancer. A growing body of evidence also suggests causal relationships with type II diabetes and impacts on neonatal mortality from low birth weight and short gestation as well as neurologic effects in both children and adults. Italy, a Southern European country, faces a more threatening air pollution challenge because of the effects of both anthropogenic pollutants and natural dust (particulate matter, PM). The 2020 Report of the European Environment Agency highlighted the number of premature deaths in Italy attributable to main pollutants: 52,300 for PM2.5, 10,400 for NO2 and 3,000 for O3 in 2018. In Italy, original time series and analytical epidemiological studies showed increased cardio-respiratory hospital admissions and mortality and increased risk of respiratory diseases in people living in urban areas. CONCLUSIONS: adverse health effects of air pollutants, even at low levels, have been confirmed by recent epidemiological studies. Further studies should focus on the potential link between air pollution exposure and respiratory infections. This topic has become particularly important in the current SARS-COV-2 pandemic. Based on strong scientific evidence, the Italian government, which hosts the Global Alliance against Chronic Respiratory Diseases (GARD)-Italy at the Ministry of Health, the scientific respiratory societies and the patients' associations, as well as others in the health sector and civil society, must increase their engagement in advocacy for clean air policies, especially in light of the new Air Quality Guidelines of the World Health Organization.

Urban grey spaces are associated with increased allergy in the general population.

BACKGROUND: the built environment in urban areas may have side effects on children's respiratory health, whilst less is known for adulthood. AIM: to assess the association between increasing exposure to grey spaces and allergic status in an adult general population sample. METHODS: 2070 subjects (age range 15-84 yrs), living in Pisa/Cascina, Italy, were investigated in 1991-93 through a questionnaire on health status and risk factors, skin prick test (SPT), serum Immunoglobulins E (IgE), and serum antibodies to benzo(a)pyrene diol epoxide (BPDE)-DNA adducts. Land-cover exposure within a 1000 m buffer from each subject's home address was assessed through the CORINE Land Cover program (CLC 1990) within the FP7/HEALS project (2013-2018). Participants' residential addresses were geocoded and the proportion of surrounding grey spaces was calculated. Through logistic regression models, adjusting for potential confounding factors, the effect of a 10% increase in grey spaces exposure on allergic biomarkers/conditions was assessed; the relationship with serum antibodies to BPDE-DNA adducts positivity was also analyzed. RESULTS: A 10% increase in grey spaces coverage was associated with a higher probability of having SPT positivity (OR 1.07, 95% CI 1.02-1.13), seasonal SPT positivity (OR 1.12, 1.05-1.19), polysensitization (OR 1.11, 1.04-1.19), allergic rhinitis (OR 1.10, 1.04-1.17), co-presence of SPT positivity and asthma/allergic rhinitis (OR 1.16, 1.08-1.25), asthma/allergic rhinitis (OR 1.06, 1.00-1.12), presence of serum antibodies to BPDE-DNA adducts positivity (OR 1.07, 1.01-1.14). CONCLUSIONS: grey spaces have adverse effects on allergic status and are related to a biomarker of polycyclic aromatic hydrocarbons exposure in adulthood. Thus, they may be used as a proxy of urban environmental exposure.

[MET exon 14 splicing sites mutations: A new therapeutic opportunity in lung cancer]. / Les mutations des sites d'épissage de l'exon 14 de MET. Une nouvelle opportunité thérapeutique dans le cancer du poumon.

The mutations leading to MET exon 14 skipping represent a new class of molecular alterations described in various cancers. These alterations are observed in 2 to 3 % of cases of non-small cell lung cancer (NSCLC). Several cases of NSCLC carrying such alterations and achieving objective response to MET tyrosine kinase inhibitorshave recently been published. This review summarizes the molecular mechanisms responsible for MET exon 14 skipping as well as the consequences of the loss of this exon on receptor activity. We also describe the clinical characteristics of patients with METΔ14 mutations. Finally, we address the issues related to the detection of these mutations in lung cancer, and the need to anticipate resistance to MET inhibitors.

RItA: The Italian severe/uncontrolled asthma registry.

BACKGROUND: The Italian severe/uncontrolled asthma (SUA) web-based registry encompasses demographic, clinical, functional, and inflammatory data; it aims to raise SUA awareness, identifying specific phenotypes and promoting optimal care. METHODS: Four hundred and ninety three adult patients from 27 Italian centers (recruited in 2011-2014) were analyzed. RESULTS: Mean age was 53.8 years. SUA patients were more frequently female (60.6%), with allergic asthma (83.1%). About 30% showed late onset of asthma diagnosis/symptoms (>40 years); the mean age for asthma symptoms onset was 30.2 years and for asthma diagnosis 34.4 years. 97.1% used ICS (dose 2000 BDP), 93.6% LABA in association with ICS, 53.3% LTRAs, 64.1% anti-IgE, 10.7% theophylline, and 16.0% oral corticosteroids. Mean FEV1 % pred of 75.1%, median values of 300/mm3 of blood eosinophil count, 323 kU/L of serum total IgE, and 24 ppb of FENO were shown. Most common comorbidities were allergic rhinitis (62.4%), gastroesophageal reflux (42.1%), sinusitis (37.9%), nasal polyposis (30.2%), and allergic conjunctivitis (30.2%). 55.7% of SUA patients had exacerbations in the last 12 months, 9.7% emergency department visits, and 7.3% hospitalizations. Factors associated with exacerbation risk were obesity (OR, 95% CI 2.46, 1.11-5.41), psychic disorders (2.87, 0.89-9.30-borderline), nasal polyps (1.86, 0.88-3.89-borderline), partial/poor asthma treatment adherence (2.54, 0.97-6.67-borderline), and anti-IgE use in a protective way (0.26, 0.12-0.53). Comparisons to severe asthma multicenter studies and available registries showed data consistency across European and American populations. CONCLUSIONS: An international effort in the implementation of SUA patients' registries could help to better understand the clinical features and to manage severe asthma, representing a non-negligible socioeconomic burden for health services.

Characteristics and predictors of allergic rhinitis undertreatment in primary care.

Although allergic rhinitis is considered a raising medical problem in many countries it is often undertreated. The reasons for this phenomenon are not completely clear.The aim of this study is to evaluate factors associated with allergic rhinitis under-/no treatment.A sample of 518 allergic rhinitis patients recruited by their primary care physicians, as a part of the ARGA study, were invited to fill in a specific questionnaire regarding rhinitis symptoms, treatment, and rhinitis-related work/social disability. Chi-square test and logistic regression were performed to assess risk factors for allergic rhinitis under-/no treatment.Over one out of four patients had no treatment despite the symptoms and 13.5% were inadequately treated. Participants with asthma (OR 0.47, 95% CI 0.30-0.75) and conjunctivitis (0.44, 95% CI 0.27-0.71) were at lower risk of allergic rhinitis under-/no treatment: in asthmatics this reduction was related mainly to the concomitant asthma treatment (OR 0.19, 95% CI 0.10-0.37).Asthmatics with under-/not treated rhinitis had the highest prevalence of rhinitis-related quality of life impairment.Under-/no treatment for allergic rhinitis is still rather frequent despite the relevance of this disease. The simultaneous presence of asthma and an anti-asthmatic therapy are able to influence positively the treatment. Targeted interventions toward a better characterization and a tight follow-up of rhinitis patient without asthma are needed.

Air quality of nursing homes and its effect on the lung health of elderly residents.

In industrialized countries the elderly spend most of their time indoors. The elderly may be at a higher risk of suffering from indoor air pollution-related diseases compared to the rest of the population, because of their increased exposure to potential indoor risk factors. This editorial aims to critically analyze the recent literature regarding this important topic. Results of studies performed on the elderly living in nursing homes clearly highlight that they are at risk of respiratory health impairment, even at moderate air pollutant concentrations, particularly if they are over 80 years of age and living in poorly ventilated nursing homes. The future epidemiological research on ageing and respiratory diseases should investigate the underlying biological and physiological mechanisms, in addition to the adverse health effects of potential indoor risk factors, in order to help defining effective strategies for healthy ageing.

Allergy and asthma: Effects of the exposure to particulate matter and biological allergens.

The prevalence of asthma and allergies including atopy has increased during the past decades, particularly in westernized countries. The rapid rise in the prevalence of such diseases cannot be explained by genetic factors alone. Rapid urbanization and industrialization throughout the world have increased air pollution and population exposures, so that most epidemiologic studies are focusing on possible links between air pollution and respiratory diseases. Furthermore, a growing body of evidence shows that chemical air pollution may interact with airborne allergens enhancing the risk of atopic sensitization and exacerbation of symptoms in sensitized subjects. These phenomena are supported by current in vitro and animal studies showing that the combined exposure to air pollutants and allergens may have a synergistic or additive effect on asthma and allergies, although there is an insufficient evidence about this link at the population level. Further research is needed in order to elucidate the mechanisms by which pollutants and biological allergens induce damage in exposed subjects. The abatement of the main risk factors for asthma and allergic diseases may achieve huge health benefits. Thus, it is important to raise awareness of respiratory allergies as serious chronic diseases which place a heavy burden on patients and on society as a whole.

COPD management according to old and new GOLD guidelines: an observational study with Italian general practitioners.

BACKGROUND: Guideline recommendations for COPD management are only partially applied within primary care clinical practice. OBJECTIVE: To compare the COPD management by Italian general practitioners (GPs) according to either the old GOLD (oGOLD) or the new GOLD (nGOLD) guidelines. RESEARCH DESIGN AND METHODS: Observational study in different Italian areas. A total of 176 GPs enrolled their patients with a COPD diagnosis. Questionnaires were used to collect data on: COPD symptoms, disease severity, exacerbations, prescribed pharmacological and non-pharmacological treatments. COPD severity was estimated according to oGOLD and nGOLD guidelines. RESULTS: A total of 526 subjects had complete information to assess COPD severity level according to guidelines (symptoms level, spirometry, history of exacerbations). The investigated subjects were more frequently males (71.2%) with a mean age of 72.5 years, and ex-smokers (44.4%). GPs reported sufficient control of the disease in 47.2% of the subjects with over two exacerbations in the last 12 months. Most patients have moderate COPD (51.5%), according to oGOLD, and belong to D groups (high risk, more symptoms) (45.6%), according to nGOLD. Overall, a low use of post-bronchodilator spirometry (65.1%) and of pulmonary rehabilitation (13.4%) was shown. The results highlighted a low prescriptive appropriateness but with higher value according to nGOLD than oGOLD: 61.4% vs 35.6%. STUDY LIMITATIONS: Prescription data only provide limited information to judge prescribing quality, thus the results have to be evaluated with caution; moreover, this study was not designed to assess the difference between oGOLD and nGOLD. CONCLUSIONS: Guideline recommendations are applied only partially within clinical practice. A higher prescriptive appropriateness is shown by GPs using nGOLD classification. This might be due to the fact that nGOLD, with respect to oGOLD, takes into account anamnestic usual features considered by GPs in their clinical practice.

The ARGA study with Italian general practitioners: prescriptions for allergic rhinitis and adherence to ARIA guidelines.

BACKGROUND: General practitioners (GPs) are the healthcare professionals to whom patients with rhinitis firstly refer for their symptoms. OBJECTIVE: In the present study, we assessed drug prescriptions for allergic rhinitis (AR) and evaluated prescriptive adherence to ARIA treatment guidelines. METHODS: Data on 1379 AR patients were collected by 107 Italian GPs. Adherence to ARIA guidelines was evaluated according to AR severity classification. RESULTS: AR was diagnosed by GPs as mild intermittent for 46.2% of patients, mild persistent for 26.6%, moderate-severe intermittent for 20.2%, and moderate-severe persistent for 7%; 43.7% of AR patients had concomitant asthma. The most frequently prescribed therapeutic groups were antihistamines (anti-H, 76%) and nasal corticosteroids (NCS, 46%). Anti-H were significantly used more often to treat AR alone than AR + asthma (85 vs. 68%, p < 0.001), whereas NCS were used more often to treat AR + asthma than AR alone (50 vs. 42%, p = 0.01). Among patients with only mild intermittent AR, 39% were prescribed combined therapy. Among patients with moderate-severe persistent AR, 30% of those with AR alone and 18% of those with AR + asthma were prescribed monotherapy based on anti-H. GPs were more compliant with ARIA guidelines while treating AR alone (57%) than AR + asthma (46%) patients. The adherence increased according to the severity grade and was satisfactory for moderate-severe persistent AR (89% for AR alone and 95% for AR + asthma). CONCLUSIONS: Adherence to ARIA guidelines is satisfactory only for treatment of more severe patients, thus GPs often tend to treat patients independently from ARIA guidelines. Since prescription data only provide limited information to judge prescribing quality, some deviation from the gold standard are to be expected.

Adverse respiratory effects of outdoor air pollution in the elderly.

Compared to the rest of the population, the elderly are potentially highly susceptible to the effects of outdoor air pollution due to normal and pathological ageing. The purpose of the present review was to gather data on the effects on respiratory health of outdoor air pollution in the elderly, on whom data are scarce. These show statistically significant short-term and chronic adverse effects of various outdoor air pollutants on cardiopulmonary morbidity and mortality in the elderly. When exposed to air pollution, the elderly experience more hospital admissions for asthma and chronic obstructive pulmonary disease (COPD) and higher COPD mortality than others. Previous studies also indicate that research on the health effects of air pollution in the elderly has been affected by methodological problems in terms of exposure and health effect assessments. Few pollutants have been considered, and exposure assessment has been based mostly on background air pollution and more rarely on objective measurements and modelling. Significant progress needs to be made through the development of 'hybrid' models utilising the strengths of information on exposure in various environments to several air pollutants, coupled with daily activity exposure patterns. Investigations of chronic effects of air pollution and of multi-pollutant mixtures are needed to better understand the role of air pollution in the elderly. Lastly, smoking, occupation, comorbidities, treatment and the neighbourhood context should be considered as confounders or modifiers of such a role. In this context, the underlying biological, physiological and toxicological mechanisms need to be explored to better understand the phenomenon through a multidisciplinary approach.

Congruence between international guidelines and mite specific immunotherapy prescribing practices.

Both rhinitis (ARIA) and asthma (GINA) guidelines recommend allergen-specific immunotherapy (SIT) tailored to the specific levels of severity of each disease. Real world studies evaluating congruence between these recommendations and prescribing practice in the single patient with comorbidity are lacking. An observational polycentric study was carried out in 518 patients recruited from 34 allergy centers throughout Italy. A questionnaire was administered to each consecutive patient over a span of four months. Taking into account guideline recommendations for both diseases, concomitant in the same patient, three subsets resulted: patients not eligible for SIT (11%); patients eligible for SIT for one disease only (60%); patients eligible for SIT for both diseases (29%). SIT was prescribed in 257 (49.6%) subjects. The level of SIT prescription was about 50% in all three groups. Consistent with the ARIA guidelines, a correlation between the prescription of SIT and the severity of rhinitis was documented (r=0.87; p=0.001). An association with asthma severity was found (p=0.02), but the trend was inconsistent with the GINA recommendations. Young age was the most important factor for SIT prescription both in the eligible for one disease and in the eligible for both diseases subset. The tendency towards worsening of symptoms was a factor for SIT in the eligible for one disease subset. In mite allergic patients with rhinitis and asthma comorbidity, the severity of rhinitis and the young age are the most important factors driving the SIT prescription. The congruence of SIT prescription was better for the ARIA than GINA guidelines.

Definition, epidemiology and natural history of COPD.

Chronic obstructive pulmonary disease (COPD) is the fifth cause of morbidity and mortality in the developed world and represents a substantial economic and social burden. Patients experience a progressive deterioration up to end-stage COPD, characterised by very severe airflow limitation, severely limited and declining performance status with chronic respiratory failure, advanced age, multiple comorbidities and severe systemic manifestations/complications. COPD is frequently underdiagnosed and under-treated. Today, COPD develops earlier in life and is less gender specific. Tobacco smoking is the major risk factor for COPD, followed by occupation and air pollution. Severe deficiency for alpha(1)-antitrypsin is rare; several phenotypes are being associated with elevated risk for COPD in the presence of risk factor exposure. Any patient presenting with cough, sputum production or dyspnoea should be assessed by standardised spirometry. Continued exposure to noxious agents promotes a more rapid decline in lung function and increases the risk for repeated exacerbations, eventually leading to end-stage disease. Without major efforts in prevention, there will be an increasing proportion of end-stage patients who can live longer through long-term oxygen therapy and assisted ventilation, but with elevated suffering and huge costs. Smoking prevention and smoking cessation are the most important epidemiological measurements to counteract chronic obstructive pulmonary disease epidemics.

[Epidemiology of the chronic obstructive pulmonary disease: environmental and occupational risk]. / Epidemiologia della broncopneumopatia cronico-ostruttiva: fattori di rischio ambientali ed occupazionali.

FACTORS. Chronic Obstructive Pulmonary Disease (COPD) is a very important cause of morbidity and mortality in industrialized and developing countries. According to the World Health Organization (WHO), in 2020 COPD will become the third leading cause of death all over the world. To date, several risk factors for developing COPD have been studied. They can act either singly or interacting among themselves in a synergistic way. Smoking habits and aging are the most important factor for development and exacerbation of COPD, but environmental conditions, such as air pollution and work exposure, can be relevant factors. Recommendations for the prevention of COPD, beside the promotion of smoking cessation, may be air pollution abatement and control of professional exposure. In view of historical trend of risk factors exposure, further epidemiological studies are necessary for a better knowledge of COPD natural history.