Trends in the prevalence of asthma and allergic rhinitis in Italy between 1991 and 2010.

The prevalence of asthma increased worldwide until the 1990s, but since then there has been no clear temporal pattern. The present study aimed to assess time trends in the prevalence of current asthma, asthma-like symptoms and allergic rhinitis in Italian adults from 1990 to 2010. The same screening questionnaire was administered by mail or phone to random samples of the general population (age 20-44 yrs) in Italy, in the frame of three multicentre studies: the European Community Respiratory Health Survey (ECRHS) (1991-1993; n = 6,031); the Italian Study on Asthma in Young Adults (ISAYA) (1998-2000; n = 18,873); and the Gene Environment Interactions in Respiratory Diseases (GEIRD) study (2007-2010; n = 10,494). Time trends in prevalence were estimated using Poisson regression models in the centres that repeated the survey at different points in time. From 1991 to 2010, the median prevalence of current asthma, wheezing and allergic rhinitis increased from 4.1% to 6.6%, from 10.1% to 13.9% and from 16.8% to 25.8%, respectively. The prevalence of current asthma was stable during the 1990s and increased (relative risk 1.38, 95% CI 1.19-1.59) from 1998-2000 to 2007-2010, mainly in subjects who did not report allergic rhinitis. The prevalence of allergic rhinitis has increased continuously since 1991. The asthma epidemic is not over in Italy. During the past 20 yrs, asthma prevalence has increased by 38%, in parallel with a similar increase in asthma-like symptoms and allergic rhinitis.

Risk factors of new-onset asthma in adults: a population-based international cohort study.

BACKGROUND: The occurrence of new-onset asthma during adulthood is common, but there is insufficient understanding of its determinants including the role of atopy. OBJECTIVE: To assess the risk factors for the development of new-onset asthma in middle-aged adults and to compare them according to atopy. METHODS: A longitudinal analysis of 9175 young adults who participated in two surveys of the European Community Respiratory Health Survey (ECRHS) conducted 9 years apart. FINDINGS: We observed 179 cases of new-onset asthma among 4588 participants who were free of asthma and reported at the beginning of the follow-up that they had never had asthma (4.5 per 1000 person-years). In a logistic regression, the following risk factors were found to increase the risk of new-onset asthma: female gender (OR: 1.97; 95% confidence interval (CI): 1.38, 2.81), bronchial hyperresponsiveness (3.25; 2.19, 4.83), atopy (1.55; 1.08, 2.21), FEV(1) < 100 % predicted (1.87; 1.34, 2.62), nasal allergy (1.98;1.39,2.84) and maternal asthma (1.91; 1.13; 3.21). Obesity, respiratory infections in early life and high-risk occupations increased the risk of new-onset asthma although we had limited power to confirm their role. Among the atopics, total IgE and sensitization to cat were independently related to the risk of new-onset asthma. The proportion of new-onset asthma attributable to atopy varied from 12% to 21%. CONCLUSION: Adults reporting that they had never had asthma were at a substantial risk of new-onset asthma as a result of multiple independent risk factors including lung function. Atopy explains a small proportion of new-onset adult asthma.

The Gene-Environment Interactions in Respiratory Diseases (GEIRD) Project.

The role of genetic and environmental factors, as well as their interaction, in the natural history of asthma, allergic rhinitis and chronic obstructive pulmonary disease (COPD) is largely unknown. This is mainly due to the lack of large-scale analytical epidemiological/genetic studies aimed at investigating these 3 respiratory conditions simultaneously. The GEIRD project is a collaborative initiative designed to collect information on biomarkers of inflammation and oxidative stress, individual and ecological exposures, diet, early-life factors, smoking habits, genetic traits and medication use in large and accurately defined series of asthma, allergic rhinitis and COPD phenotypes. It is a population-based multicase-control design, where cases and controls are identified through a 2-stage screening process (postal questionnaire and clinical examination) in pre-existing cohorts or new samples of subjects. It is aimed at elucidating the role that modifiable and genetic factors play in the occurrence, persistence, severity and control of inflammatory airway diseases, by way of the establishment of a historical multicentre standardized databank of phenotypes, contributed by and openly available to international epidemiologists. Researchers conducting population-based surveys with standardized methods may contribute to the public-domain case-control database, and use the resulting increased power to answer their own scientific questions.

What defines airflow obstruction in asthma?

Asthma guidelines from the Global Initiative for Asthma (GINA) and from the National Heart, Lung, and Blood Institute provide conflicting definitions of airflow obstruction, suggesting a fixed forced expiratory volume in 1 s (FEV(1))/forced vital capacity (FVC) cut-off point and the lower limit of normality (LLN), respectively. The LLN was recommended by the recent American Thoracic Society/European Respiratory Society guidelines on lung function testing. The problem in using fixed cut-off points is that they are set regardless of age and sex in an attempt to simplify diagnosis at the expense of misclassification. The sensitivity and specificity of fixed FEV(1)/FVC ratios of 0.70, 0.75 and 0.80 versus the LLN were evaluated in 815 subjects (aged 20-44 yrs) with a diagnosis of asthma within the framework of the European Community Respiratory Health Survey. In males, the 0.70 ratio showed 76.5% sensitivity and 100.0% specificity, the 0.75 ratio 100.0% sensitivity and 92.4% specificity, and the 0.80 ratio 100.0% sensitivity but 58.1% specificity. In females, the 0.70 ratio showed 57.3% sensitivity and 100.0% specificity, the 0.75 ratio 91.5% sensitivity and 95.9% specificity, and the 0.80 ratio 100.0% sensitivity but 72.9% specificity. The fixed cut-off points cause a lot of misidentification of airflow obstruction in young adults, with overestimation with the 0.80 ratio and underestimation with the 0.70 ratio. In conclusion, the GINA guidelines should change their criteria for defining airflow obstruction.

Underestimation of airflow obstruction among young adults using FEV1/FVC <70% as a fixed cut-off: a longitudinal evaluation of clinical and functional outcomes.

BACKGROUND: Early detection of airflow obstruction is particularly important among young adults because they are more likely to benefit from intervention. Using the forced expiratory volume in 1 s (FEV(1)) to forced vital capacity (FVC) (FEV(1)/FVC) <70% fixed ratio, airflow obstruction may be underdiagnosed. The lower limit of normal (LLN), which is statistically defined by the lower fifth percentile of a reference population, is physiologically appropriate but it still needs a clinical validation. METHODS: To evaluate the characteristics and longitudinal outcomes of subjects misidentified as normal by the fixed ratio with respect to the LLN, 6249 participants (aged 20-44 years) in the European Community Respiratory Health Survey were examined and divided into three groups (absence of airflow obstruction by the LLN and the fixed ratio; presence of airflow obstruction only by the LLN; presence of airflow obstruction by the two criteria) for 1991-1993. LLN equations were obtained from normal non-smoking participants. A set of clinical and functional outcomes was evaluated in 1999-2002. RESULTS: The misidentified subjects were 318 (5.1%); only 45.6% of the subjects with airflow obstruction by the LLN were also identified by the fixed cut-off. At baseline, FEV(1) (107%, 97%, 85%) progressively decreased and bronchial hyperresponsiveness (slope 7.84, 6.32, 5.57) progressively increased across the three groups. During follow-up, misidentified subjects had a significantly higher risk of developing chronic obstructive pulmonary disease and a significantly higher use of health resources (medicines, emergency department visits/hospital admissions) because of breathing problems than subjects without airflow obstruction (p<0.001). CONCLUSIONS: Our findings show the importance of using statistically derived spirometric criteria to identify airflow obstruction.

Quality-of-life and asthma-severity in general population asthmatics: results of the ECRHS II study.

BACKGROUND: Health-related quality-of-life (HRQL) has been poorly studied in large samples of asthmatics from the general population. HRQL and its relationship to asthma-severity were assessed among 900 asthmatics enrolled in the European Community Respiratory Health Survey. METHODS: Among asthmatics, 864 completed the short form-36 (SF-36) questionnaire and 477 also completed the Asthma Quality-of-life Questionnaire (AQLQ). A 4-class asthma-severity scale, combining clinical items, forced expiratory volume in 1 s and the level of treatment and the different asthma-severity components (each of the clinical items and hospitalization) were studied in relation to HRQL. RESULTS: Mean SF-36 Physical Component Summary (PCS) and Mental Component Summary (MCS) scores (45.5 and 48.8 respectively) were lower than expected in a general population. The mean total AQLQ score was 5.8. The AQLQ score and to a lesser extent the PCS score were significantly related to the 4-class asthma-severity scale, although the risk of having a lower HRQL score did not vary proportionally across the levels of severity. Asthma-severity had no impact on the MCS score. Asthma attack frequency and hospitalization were associated with both total AQLQ and PCS scores, whereas nocturnal symptoms and lung function were more strongly related to the AQLQ and PCS score respectively. CONCLUSION: In population-based asthmatics, the specific AQLQ questionnaire, and also to a lesser extent the generic SF-36 questionnaire, were sensitive to asthma-severity. Frequencies of asthma attacks, of nocturnal symptoms and hospitalization for asthma have independent impact on HRQL.

The socio-economic burden of asthma is substantial in Europe.

BACKGROUND: Few data are available on the asthma burden in the general population. We evaluated the level and the factors associated with the asthma burden in Europe. METHODS: In 1999-2002, 1152 adult asthmatics were identified in the European Community Respiratory Health Survey (ECRHS)-II and the socio-economic burden (reduced activity days and hospital services utilization in the past 12 months) was assessed. RESULTS: The asthmatics with a light burden (only a few reduced activity days) were 13.2% (95% CI: 11.4-15.3%), whereas those with a heavy burden (many reduced activity days and/or hospital services utilization) were 14.0% (95% CI: 12.1-16.1%). The burden was strongly associated with disease severity and a lower quality of life. Obese asthmatics had a significantly increased risk of a light [relative risk ratio (RRR) = 2.17; 95% CI: 1.18-4.00] or a heavy burden (RRR = 2.77; 95% CI: 1.52-5.05) compared with normal/underweight subjects. The asthmatics with frequent respiratory symptoms showed a threefold (RRR = 2.74; 95% CI: 1.63-4.61) and sixfold (RRR = 5.76; 95% CI: 3.25-10.20) increased risk of a light or a heavy burden compared with asymptomatic asthmatics, respectively. Moreover, the lower the forced expiratory volume in 1 s % predicted, the higher the risk of a heavy burden. The coexistence with chronic cough/phlegm only increased the risk of a heavy burden (RRR = 1.88; 95% CI: 1.16-3.06). An interaction was found between gender and IgE sensitization, with nonatopic asthmatic females showing the highest risk of a heavy burden (21.6%; 95% CI: 16.9-27.1%). CONCLUSIONS: The asthma burden is substantial in Europe. A heavy burden is more common in asthmatics with obesity, frequent respiratory symptoms, low lung function, chronic cough/phlegm and in nonatopic females.

The course of asthma during pregnancy in a recent, multicase-control study on respiratory health.

BACKGROUND: Over the years it has been widely stated that approximately one-third of asthmatic women experience worsening of the disease during pregnancy. However, the literature has not been reviewed systematically and the meta-analytic reviews include old studies. This study aimed to examine whether the prevalence of worsening asthma during pregnancy is still consistent with prior estimate or it has been reduced. METHODS: A detailed Clinical Questionnaire on respiratory symptoms, medical history, medication, use of services, occupation, social status, home environment and lifestyle was administered to random samples of the Italian population in the frame of the Gene Environment Interactions in Respiratory Diseases (GEIRD) study. Only clinical data belong to 2.606 subjects that completed the clinical stage of the GEIRD study, were used for the present study. RESULTS: Out of 1.351 women, 284 self-reported asthma and 92 of them had at least one pregnancy. When we considered the asthma course during pregnancy, we found that 16 women worsened, 31 remained unchanged, 25 improved. Seven women had not the same course in the different pregnancies and 13 did not know. The starting age of ICS use almost overlaps with that of asthma onset in women with worsening asthma during pregnancy (19 years ± 1.4), unlike the other women who started to use ICS much later (30.3 years ± 12). In addition, the worsening of asthma was more frequent in women with an older age of onset of asthma (18 years ± 9 vs 13 years ± 10). Among women who completed the ACT during the clinical interview, the 50% of women who experienced worsening asthma during pregnancy (6/12) had an ACT score below 20. CONCLUSION: Asthma was observed to worsen during pregnancy in a percentage much lower to that generally reported in all the previous studies. There is still room in clinical practice to further reduce worsening of asthma during pregnancy by improving asthma control, with a more structured approach to asthma education and management prepregnancy.

Chronic productive cough in young adults is very often due to chronic rhino-sinusitis.

BACKGROUND: Chronic productive cough is a common clinical problem; often potential causes outside the lower respiratory tract are forgotten or ignored. The aim of this study was to make a precise etiopathogenetic diagnosis of chronic productive cough in young adults. METHODS: In a clinical setting, 212 subjects (mean age 41+/-5 years) who had reported chronic productive cough in a previous postal survey of a young adult population underwent within two years clinical and functional investigations following a rational diagnostic approach. Two pulmonologists independently established the diagnosis using a clinically structured interview on nasal and respiratory symptoms, spirometry and other tests when appropriate (bronchodilator test or methacholine bronchial challenge, chest radiography); if rhino-sinusitis was suspected, subjects underwent an ENT examination with nasal endoscopy and/or sinus computed tomography. RESULTS: At the end of the diagnostic procedure, 87 subjects (41%) no longer had chronic productive cough and had normal function. Fifty-eight subjects (27%) had chronic rhino-sinusitis; seventeen subjects (8%) had asthma, and of these fourteen also had chronic rhino-sinusitis; 50 subjects (24%) had COPD stage 0+, of these seven also had chronic rhino-sinusitis. Chronic rhino-sinusitis was more frequent in females than in males (p<0.05). CONCLUSIONS: Both in clinical practice and in epidemiological studies, it is important to consider that the origin of chronic productive cough could be frequently outside the lower respiratory tract; a consistent percentage of young adults with persistent productive cough has indeed chronic rhino-sinusitis.

Effects of celiprolol on the bronchial reactivity in asthma.

In 10 patients with bronchial asthma but normal ventilatory function, celiprolol, a cardioselective beta-adrenoreceptor antagonist, did not significantly affect forced expiratory volume in 1 second (FEV1) or airways resistance (Raw). In contrast, metoprolol substantially reduced FEV1 and increased Raw. In addition, compared with metoprolol, celiprolol induced a greater recovery of FEV1 and Raw after methacholine-induced bronchoconstriction.

The role of functional respiratory tests in predicting pneumothorax during lung needle biopsy.

In 243 of 945 patients having lung percutaneous needle biopsy, we retrospectively evaluated 10 independent variables that potentially influence the incidence of pneumothorax (PNX): age, sex, lesion size, number of needle passes, needle intrapulmonary route, distance of the lesion from the chest wall, FEV1, FVC, residual volume, and total lung capacity percent predicted. The subjects considered (mean age, 61 years; 192 men and 51 women) performed respiratory function tests within 1 year of the procedure. The sample was also subdivided into four functional groups: restricted patients, obstructed ones, obstructed with alveolar hyperinflation patients, and normal subjects. The variables significantly correlated to PNX were the length of the needle intraparenchymal route (p<0.05) and the distance of the lesion from chest wall greater than 0 cm (p<0.01). None of the functional parameters was determinant in predicting PNX occurrence. Bronchial obstruction was not significantly associated with a higher risk of PNX. Nevertheless, when alveolar hyperinflation was associated with bronchial obstruction, the risk increased significantly (odds ratio, 2.38).

Distribution of bronchial nonspecific reactivity in the general population.

We investigated 654 subjects of a small Lombardy (Italy) town between 15 and 64 years of age who were representative of the general population. By clinical examination, the sample included 535 normal subjects (164 normal smokers, 341 normal nonsmokers, 30 normal subjects with acute upper respiratory illness within 30 days before the challenge), 50 with chronic bronchitis, 26 with asthma, and 43 with allergic rhinitis. Subjects whose FEV1 was 75 percent or more than the predicted value (654) underwent methacholine bronchial challenge by means of 1 percent metered-dose solution. The test result was considered positive at a drop of more than 15 percent in FEV1 (compared with buffer). Normal smokers and all of the groups with disease had a significantly different distribution of reactivity compared with normal nonsmokers. The difference between asthmatic and these "normal" subjects was highly significant; nevertheless, a clear cut-off between the two groups does not appear to exist.

Lung function abnormalities after bone marrow transplantation in children: has the trend recently changed?

STUDY OBJECTIVES: To evaluate early and late lung function abnormalities and their predictors in a large sample of children who underwent bone marrow transplantation (BMT) for leukemias in the 1990s, highlighting changes with respect to the 1980s. DESIGNS: Prospective cohort. SETTING: A university department of pediatrics. PARTICIPANTS: Seventy-five consecutive children who underwent BMT were enrolled in the study (median age, 11 years; range, 6 to 19 years; 45 male and 30 female children). Twenty-three children received autologous BMT, and 52 children received allogeneic BMT; 50 children completed the study. MEASUREMENTS: Clinical examinations and lung function tests were performed before BMT, and 3 to 6 months, 12 months, and 24 months after BMT. RESULTS: Before BMT, at 3 to 6 months after BMT, and at 24 months after BMT, 44%, 85%, and 62% of children, respectively, had altered lung function in the absence of persistent respiratory symptoms. Between 3 months and 6 months after BMT, a restrictive pattern was the most frequent abnormality. The only predictive factors for late abnormalities were transplantation performed in the advanced disease phase (odds ratio [OR], 6.75; p = 0.005) and bronchopulmonary infections (OR, 3.9; p < 0.05). CONCLUSIONS: These data suggest that a significant proportion of children who undergo BMT, especially if for leukemia in advanced phase, have early and late pulmonary abnormalities. These abnormalities, especially the late ones, seem to be more severe than patients reported in studies analyzing children undergoing BMT in the 1980s. This could be due to the more intensive front-line treatment protocols employed for treatment of children with acute leukemia in the 1990s.

Lung cancer resection: the prediction of postsurgical outcomes should include long-term functional results.

STUDY OBJECTIVES: To assess (1) the possibility of predicting long-term postoperative lung function, and (2) the usefulness of maximal oxygen consumption (O(2)max) as a criterion for operability and as a predictor of long-term disability. DESIGN: Prospective study. SETTING: Outpatients and inpatients of a university hospital. PARTICIPANTS: Sixty-two consecutive patients (mean +/- SD age, 62 +/- 8 years; 51 male and 11 female patients) were preoperatively evaluated for lung cancer resection (pneumonectomy or bilobectomy [n = 14] and lobectomy [n = 48]). MEASUREMENTS: Clinical examination and recorded respiratory symptoms and spirometry results before surgery and 6 months after surgery. If predicted postoperative FEV(1) (ppoFEV(1)) was < 40%, patients underwent exercise testing; if O(2)max was between 10 mL/kg/min and 20 mL/kg/min, patients underwent a split-function study. RESULTS: All the patients with ppoFEV(1) > or = 40%-even those patients (26%) with FEV(1) < 80%-underwent thoracotomy without further tests. Seven patients with ppoFEV(1) < 40% underwent exercise testing, and three of them underwent a split-function study. Nine patients (15%; including six patients with COPD and one patient with asthma) had immediate postoperative complications (pneumonia [n = 5] and respiratory failure [n = 4]); seven of these patients had ppoFEV(1) > or = 40%. ppoFEV(1) significantly underestimated the actual postoperative FEV(1) (poFEV(1); p < 0.001) 6 months after pneumonectomy or bilobectomy but was reliable for actual poFEV(1) after lobectomy. Two patients with predicted postoperative O(2)max > 10 mL/kg/min became oxygen dependent and had marked limitation of daily living. CONCLUSIONS: ppoFEV(1) > or = 40% reliably identifies patients not requiring further tests and not at long-term risk of respiratory disability. O(2)max, effective for defining the immediate surgical risk, is not useful in predicting long-term disability.

Lung function in survivors of childhood acute lymphoblastic leukemia.

STUDY OBJECTIVES: To evaluate lung function in patients cured from childhood acute lymphoblastic leukemia (ALL) with chemotherapy alone or plus bone marrow transplantation (BMT). Pulmonary toxicity is a well-recognized side effect of many ALL treatments. DESIGN: Cross-sectional study conducted at least 3 years after cessation of therapy. SETTING: Outpatient pneumology department of the University Hospital. PATIENTS: Forty-four subjects (age range at observation, 6 to 23 years): 21 treated only with intensive Berlin-Frankfurt-Munster (BFM)-type chemotherapy for newly diagnosed ALL (group A), and 23 treated with chemotherapy plus BMT (group B). MEASUREMENTS: A detailed history of smoking habit, respiratory symptoms, and diseases was recorded directly from the patients with the aid of their parents. A complete physical examination and lung function testing (lung volumes and diffusion capacity for carbon monoxide [DLCO]) were performed in all subjects. RESULTS: No patient reported acute or chronic respiratory symptoms or diseases. In group A patients, lung function was in the normal range, except for three subjects in whom there was an isolated impairment of DLCO. In group B patients, lung function was markedly impaired, with more than half the patients having an abnormal DLCO. A statistically significant difference was found between the two groups for FVC (p = 0.022) and DLCO (p = 0.004). CONCLUSIONS: Intensive, BFM-type frontline chemotherapy is not associated with late pulmonary dysfunction; however, retreatment including BMT can frequently injure the lung. Thus, in patients who undergo BMT and whose life expectancy is long, careful monitoring of lung function and counseling about avoiding additional lung risk factors is recommended.

Mechanisms for isolated volume response to a bronchodilator in patients with COPD.

We hypothesized that an altered effect of lung inflation on airway caliber may in part explain the isolated volume response to bronchodilators, i.e., an increase of forced vital capacity (FVC) without change in 1-s forced expiratory volume (FEV(1)). Small-airway caliber was measured by high-resolution computed tomography at functional residual capacity and total lung capacity in five chronic obstructive pulmonary disease patients with an isolated increase of FVC (FVC responders) and five with an increase of both FVC and FEV(1) (FVC-FEV(1) responders) after inhalation of salbutamol. In FVC-FEV(1) responders, the airway diameter increased with the cube root of increase in lung volume but was unchanged or even decreased in four of five FVC responders. FVC responders had more severe emphysema, as inferred from lung function and imaging studies, than FVC-FEV(1) responders. We speculate that longitudinal traction or space competition (Verbeken EK, Cauberghs M, and Van de Woestijne KP, J Appl Physiol 81: 2468-2480, 1996) are possible underlying mechanisms. We conclude that the isolated volume response to bronchodilators is associated with severe emphysema and likely results from an altered effect of lung inflation on airway caliber.

Breathing patterns and HbSaO2 changes during nocturnal sleep in patients with Duchenne muscular dystrophy.

A night-time polygraphic sleep recording with continuous HbSaO2 monitoring was performed in 11 chair-bound Duchenne muscular dystrophy patients with severe restrictive lung disease but with blood gas values within normal limits when awake. No abnormalities of sleep pattern were detected. Nocturnal sleep did not have significant adverse effects on respiration. However, in 6 patients, infrequent central apnoeas or hypopnoeas occurred which were associated with falls in HbSaO2 greater than those that have been reported to be in normal subjects. The magnitude of HbSaO2 falls appeared to be significantly correlated with functional residual capacity values. Overall, the findings revealed a relatively preserved, although unstable, blood O2 balance during nocturnal NREM and REM sleep in patients with Duchenne muscular dystrophy, even in an advanced stage of their illness.

A clinical, EEG and CT study in 21 cases of chronic respiratory failure.

A clinical, EEG and CT study was carried out on 21 patients with chronic stable respiratory failure. The neurological disturbances and mental deterioration observed were of a mild degree, and no severe alterations were detected at EEG. CT showed cerebral atrophy, but the type and prevalence did not differ substantially between patients studied and normal sex- and age-matched control subjects. The data gave evidence that in chronic stable respiratory failure cerebral function is only slightly affected.

The burden of COPD in Italy: results from the Confronting COPD survey.

Chronic obstructive pulmonary disease (COPD) is a disease state characterized by airflow limitation that is not fully reversible, and progressive lung function decline. In Italy, an estimated 2.6 million men and women have COPD, and the disease causes around 18 000 deaths each year. In addition to mortality, morbidity from COPD results in substantial use of secondary healthcare resources. The burden of COPD in Italy may be due to the underdiagnosis of the disease by healthcare professionals, particularly in the early stages of the disease, and a lack of awareness among physicians of recommended treatment practices. In an attempt to address the need for information on the burden of COPD, a large-scale international survey, Confronting COPD in North America and Europe, assessed clinical outcomes, use of healthcare resources and loss of productivity in the workplace, and the economic cost of this disease in Italy and six other countries. In Italy, the economic analysis of the survey data showed that the mean annual cost of COPD to the healthcare system was Euro 1261.25 per patient Indirect costs were estimated at Euro 47.29 per patient, bringing the societal cost of the disease to Euro 1308.54 per patient. Three-quarters of the direct per patient cost of COPD in Italy were accounted for by inpatient hospitalizations (Euro 963.10), suggesting that interventions aimed at preventing exacerbations could alleviate the burden of COPD in Italy. The high impact of COPD on the Italian healthcare system is also likely to be a consequence of the underdiagnosis and undertreatment of the disease, suggesting that costs may be reduced by increasing the utilization of spirometry as a diagnostic tool, and improving physician adherence to treatment guidelines. Patients with severe COPD and other comorbidities showed higher costs (Euro 6366 and Euro 1861, respectively) than patients with mild disease (Euro 441) or no comorbidities (Euro 1021), underlying the importance of smoking cessation interventions to prevent disease progression.