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Objectives. The purpose of this study was to investigate bisphenol A (BPA) and its role in the induction of oxidative stress and confirm the same for tobacco smoke. Methods. A total of 223 young, healthy students (7&ndash, 19 years old) were recruited in Chivasso, Italy. A spot of urine of each subject was analyzed to quantify BPA, cotinine, and 15F2t-isoprostane. Results. BPA showed a slight increase of concentration proportional with increasing age, even though the 11&ndash, 14 years age group had slightly lower results, inducing a V-shape. The same trend was observed for 15F2t-isoprostane and cotinine. The result of piecewise linear robust regression shows a break point of the effect of BPA on 15F2t-isoprostane at 6 ng/mg CREA (p &lt, 0.001). At higher levels, 15F2t-isoprostane shows an exponential increase by more than threefold for each one-log unit of BPA. An increase of oxidative stress due to BPA was observed, but only from 6 ng/mg of CREA up. Passive tobacco smoke is also able to induce an increase in oxidative stress. Conclusion. Prevention against BPA and passive tobacco smoke represents an important tool for promoting the highest health standard.

Purpose: nurses are exposed to formaldehyde when managing surgical samples that are to be later transferred to histopathology. We evaluated the conditions favouring the risk of exposure to this toxic reagent and the effect of measures to prevent it. Methods: we conducted a cross-sectional study where 94 female workers were enrolled as being potentially exposed to formaldehyde. From each nurse were collected: (1) personal air-formaldehyde by a personal dosimeter (8 hours), (2) a standardized questionnaire, (3) a urine sample to test 15-F2t-isoprostane, malondialdehyde, cotinine. Results: the results indicate a marked difference related to the adoption of the under vacuum sealing procedure, as an alternative to formaldehyde for preserving tissues. Nurses using the under vacuum sealing system in the operating rooms are exposed to levels of formaldehyde 75% lower than those who do not use that system. Oxidative stress biomarkers (15-F2t-isoprostane, malondialdehyde) are significantly higher in nurses using formaldehyde (p < 0.001) and in the absence of the under vacuum sealing system (p = 0.027), in particular in those workers who use liquid formaldehyde in the operating theatre (p = 0.012). Conclusions: analysis of the biological biomarkers confirms a direct responsibility of air formaldehyde on the onset of oxidative stress while the use of the under vacuum sealing technique is associated with a significant reduction of the exposure to air-formaldehyde and redox status. Our findings can be useful to characterize the environmental health risk in operating theatres and to plan preventive measures such as the under vacuum sealing procedure.

Background: forced oscillation technique (FOT) is a non–invasive method used to assess respiratory mechanics. The main parameters, resistance (R) and reactance (X); inspiratory (Rinsp), expiratory (Rexp) and total (Rtot); can be obtained at different frequencies and with a minimal cooperation. This makes FOT fit for epidemiological studies. Aim: to investigate reproducibility and acceptability of FOT in assessing the respiratory function in school-aged children and adolescents. Methods: 159 subjects have been studied by FOT, 100 from primary and 59 from high school. The measurements were considered of high quality (HQ) if the standard deviations (SD) of Rinsp, Rexp and Rtot were less than 0,7 and the ratio between SD and each R parameter was less than 0,3. If just one condition was met, the measurement was considered acceptable (AQ). Results: HQ and AQ measurements were obtained respectively from 81% and 98% of subjects. Learning and age effect on the variance was considered. The best reproducibility was achieved at 5 Hz in 151 children. The distribution of the results is reported in the table. Conclusions: measurements obtained by FOT have proved to have high acceptability and good reproducibility. This confirms that FOT can be efficiently used in epidemiological studies, particularly in school age.

Background: environmental pollution, mostly in urban area, represents an increasing burden in human health (WHO, Global update 2005). However, the effects of pollutants on the respiratory impedance are not well known, especially in childhood and adolescence. Aim: to investigate the impact of environmental exposure on the respiratory function in school-aged children. Methods: 175 children (from 7 to 19 years) underwent to spirometry and impedance measurement by using forced oscillation technique (FOT, Resmon PRO FULL, Restech, Italy). Total respiratory resistance at 5 Hz (R tot5 ), total respiratory reactance at 5 Hz (X tot5 ) and FEV 1 /FVC% were compared to the level of exposure to pollutants, reported by patients through questionnaire and measured through a urinary biomarker of tobacco smoke exposure (cotinine). The relative risk (OR) of abnormal R tot5 , X tot5 and FEV 1 /FVC% have been computed by means of logistic regression analysis for the level of exposure to pollutants (table). Results: both spirometry and FOT parameters revealed a risk of impairment of the respiratory function in active smokers. Furthermore, FOT parameters demonstrated a reduction of the respiratory function also in children exposed to passive smoking and high traffic. Conclusions: high traffic exposure and active and passive exposure to tobacco smoke can reduce the respiratory function in childhood.

Background: Asthma and allergy often go hand-in-hand. In the frame of GEIRD Network (www.geird.org), the aim of our study was to assess the clinical relevance of positive skin prick test reactions to inhalant allergens considering self-reported asthma symptoms. Methods: 2178 subjects were enrolled (ranges 20-69). Rhinasthma QoL questionnaire score was recorded while atopy was defined as at least one SPT positive (diameter of reaction ≥3 mm). Asthma was defined by self-reported asthmatic symptoms confirmed by a medical doctor during the lifetime. The correlation between sensitization and asthma was assessed using ordinal logistic regression analysis classifying the Rhinasthma in tertiles. RESULTS: 391 subjects declared to have had asthma in their lives (132 with attacks in the last year). The risk (OR) of ever asthma (controlling for allergic rhinitis) was 2.98 folds (CI 95% 2.23-3.97) in atopic versus non atopic subjects and 35.7 (CI 95% 23.6-54.1) in subjects with both asthma and rhinitis. 77% of the atopic asthmatics had more than 1 SPT positive (median 5 SPT positive). Cat allergy was the best predictor of having asthma (OR 3.33, CI 95% 1.98-5.61) followed by pollens (OR 2.6 CI 95% 1.5-4.2) and dust mites (OR 1.71, CI 95% 1.08-2.71). The OR of being in the higher tertile of Rhinasthma score increased for each mm of increase of the diameter of the largest SPT reaction. The increase of risk (OR 3.2) was high in subjects with associated rhinitis. Conclusion: This study emphasizes the importance of evaluating the clinical relevance of positive skin prick tests considering the atopy and the intensity of SPT reaction as predictor of more severe asthma, particularly if associated to allergic rhinitis.

Risk monitoring in childhood is useful to estimate harmful health effects at later stages of life. Thus, here we have assessed the effects of tobacco smoke exposure and environmental pollution on the respiratory health of Italian children and adolescents using spirometry and the forced oscillation technique (FOT). For this purpose, we recruited 188 students aged 6&ndash, 19 years living in Chivasso, Italy, and collected from them the following data: (1) one filled out questionnaire, (2) two respiratory measurements (i.e., spirometry and FOT), and (3) two urine tests for Cotinine (Cot) and 15-F2t-Isoprostane (15-F2t-IsoP) levels. We found a V-shape distribution for both Cotinine and 15-F2t-IsoP values, according to age groups, as well as a direct correlation (p = 0.000) between Cotinine and tobacco smoke exposure. These models demonstrate that tobacco smoke exposure, traffic, and the living environment play a fundamental role in the modulation of asthma-like symptoms (p = 0.020) and respiratory function (p = 0.007). Furthermore, the results from the 11&ndash, 15-year group indicate that the growth process is a protective factor against the risk of respiratory disease later in life. Lastly, the FOT findings highlight the detrimental effects of tobacco smoke exposure and urbanization and traffic on respiratory health and asthma-like symptoms, respectively. Overall, monitoring environmental and behavioral factors in childhood can provide valuable information for preventing respiratory diseases in adulthood.

Background Formaldehyde (FA) is a suspected human carcinogen capable of inducing oxidative stress through different metabolic ways. FA may originate from tobacco smoke, several environmental sources, as well as occupational sources, like furnishing industries specialized in the production of pressed-wood and laminate products. Object Our aim was to investigate the role of tobacco smoke and occupational exposure to air-FA in the induction of oxidative stress status by comparing FA-exposed with non-exposed subjects who smoked or did not. Methods Enrollment of 105 subjects was made in an industry of plastic laminates, including both workers directly exposed to FA and non-exposed office personnel, as control group. 15-F 2t isoprostane (15-F 2t IsoP), detected by ELISA technique and urinary cotinine, detected by GC-MS, were used for evaluating oxidative stress and tobacco smoke exposure, respectively. Air-FA levels were detected by GC-MS. Results FA concentrations were significantly higher in subjects occupationally exposed than the controls. Smoking habits and air-FA exposures independently induce the formation of 15-F 2t IsoP and increase the oxidative stress level. Conclusions Our findings show, for the first time, that 15-F 2t IsoP presents a dependency from both the smoking habit and air-FA exposures, and consequently, that these breathable pollutants could be considered as two important independent risk factors in increasing the oxidative stress in human beings.

It is well known that asthma prevalence has been increasing all over the world in the last decades. However, few data are available on temporal trends of incidence and remission of asthma.To evaluate the rates of asthma incidence and remission in Italy from 1940 to 2010.The subjects were randomly sampled from the general Italian population between 1991 and 2010 in the three population-based multicentre studies: ECRHS, ISAYA, and GEIRD. Individual information on the history of asthma (age at onset, age at the last attack, use of drugs for asthma control, co-presence of hay-fever) was collected on 35,495 subjects aged 20-84 and born between 1925-1989. Temporal changes in rates of asthma incidence and remission in relation to age, birth cohort and calendar period (APC) were modelled using Poisson regression and APC models.The average yearly rate of asthma incidence was 2.6/1000 (3,297 new cases among 1,263,885 person-years). The incidence rates have been linearly increasing, with a percentage increase of +3.9% (95%CI: 3.1-4.5), from 1940 up to the year 1995, when the rates begun to level off. The stabilization of asthma incidence was mainly due to a decrease in the rates of atopic asthma after 1995, while non-atopic asthma has continued to increase. The overall rate of remission was 43.2/1000person-years, and it did not vary significantly across generations, but was associated with atopy, age at asthma onset and duration of the disease.After 50 years of a continuous upward trend, the rates of asthma incidence underwent a substantial stabilization in the late 90s. Despite remarkable improvements in the treatment of asthma, the rate of remission did not change significantly in the last seventy years. Some caveats are required in interpreting our results, given that our estimates are based on self-reported events that could be affected by the recall bias.

Background: Epidemiological studies have documented large international variations in the prevalence of asthma, and ‘westernization’ seems to play an important role in the development of the disease. The aims of this study were to compare the prevalence of respiratory symptoms in migrant and nonmigrant children resident in Italy, and to examine the effect of length of time living in Italy. Methods: Data were collected in a large cross-sectional study (SIDRIA-2) performed in 12 Italian centres, using standardized parental questionnaires. For the 29 305 subjects included in the analysis (6–7 and 13–14 years old), information about place of birth and parental nationality was available. Results: There were 1012 children (3%) born outside of Italy, mainly in East Europe. Lifetime asthma and current wheeze were generally significantly less common among children born abroad than among children born in Italy (lifetime asthma: 5.4% and 9.7% respectively, P

Background/Aims: Up to now, few cost-of-illness (COI) studies have estimated the cost of adult asthma at an individual level on general population samples. We sought to evaluate the cost of current asthma from the societal perspective in young Italian adults and the determinants of cost variation. Methods: In 2000, a COI study was carried out in the frame of the Italian Study on Asthma in Young Adults on 527 current asthmatics (20–44 years) screened out of 15,591 subjects from the general population in seven centres. Detailed information about direct medical expenditures (DMEs) and indirect costs due to asthma was collected at an individual level over the past 12 months. Results: The mean annual cost per patient was EUR 741 (95% CI: 599–884). DMEs represented 42.8% of the total cost, whereas the remaining 57.2% was indirect costs. The largest component of DMEs was medication costs (47.3%; 23.0% was due to hospitalization). The mean annual cost per patient ranged from EUR 379 (95% CI: 216–541)for well-controlled asthmatics to EUR 1,341 (95% CI: 978–1,706) for poorly controlled cases that accounted for 46.2% of the total cost. Poor control, coexisting chronic cough and phlegm, and low socio-economic status were significantly associated with high DMEs and indirect costs. Conclusions: In Italy, asthma-related costs were substantial even in unselected patients and were largely driven by indirect costs. Since about half of the total cost was due to a limited proportion of poorly controlled asthmatics, interventions aimed at these high-cost patients could reduce the economic burden of the disease.

BACKGROUND Environmental factors are likely to be involved in explaining the wide geographical variation in asthma and atopic diseases that has been documented in many recent epidemiological studies. AIM To evaluate to what extent climate and outdoor NO2 pollution can explain the geographical variation in the prevalence of asthma and allergic rhinitis, and to estimate the relative risk for exposure to different levels of these two factors. METHODS The impact of climate and long-term exposure to nitrogen dioxide (NO2) pollution on asthma and allergic rhinitis was assessed in a cross-sectional study, carried out during 1998 to 2000 on young adults aged 20 to 44 years (n = 18 873), living in 13 areas from two different Italian climatic regions (subcontinental and Mediterranean). RESULTS Mediterranean areas had a significantly higher prevalence of asthma-like symptoms (P < 0.001), higher annual mean temperature (16.2 degrees C vs. 12.9 degrees C), lower temperature range (16.0 C degrees vs. 22.1 degrees C) and lower NO2 levels (31.46 microg/m3 vs. 57.99 microg/m3) than subcontinental ones. Mediterranean climate was associated with an increased risk of wheeze (OR = 1.23; 95% CI 1.13 to 1.35), tightness in the chest (OR = 1.21; 95% CI 1.11 to 1.33), shortness of breath (OR = 1.21; 95% CI 1.08 to 1.36) and asthma attacks (OR = 1.19; 95% CI 1.07 to 1.31). After adjusting for climate, an increase of 18.3 microg/m3 in NO2 levels moderately increased the risk of asthma attacks (OR = 1.13; 95% CI 0.98 to 1.32), tightness in the chest (OR = 1.11; 95% CI 0.98 to 1.26) and wheeze (OR = 1.11; 95% CI 0.96 to 1.28). When the levels of outdoor NO2 exposure rose, the prevalence of allergic rhinitis increased significantly in the Mediterranean region (OR = 1.38; 95% CI 1.12 to 1.69), but not in the subcontinental one (OR = 1.03; 95% CI 0.83 to 1.28). CONCLUSION Our results show that the prevalence of asthma increases when annual mean temperature increases and temperature range decreases. Furthermore, climate interacts with NO2 outdoor exposure, increasing the risk for allergic rhinitis in people exposed to high stable temperatures. A long-term role for the effect of traffic pollution on asthma is also suggested.

Background Air pollution and tobacco smoke can induce negative effects on the human health and often leads to the formation of oxidative stress. Objective The purpose of this study was to clarify the role of the urbanization degree and of passive exposure to tobacco smoke in the formation of oxidative stress. Thus, a group of non-smoking adolescents was recruited among those who live and attend school in areas with three different population densities. To each subject a spot of urine was collected to quantify 15-F 2t isoprostane as a marker of oxidative stress and cotinine as a marker of passive exposure to tobacco smoke. Furthermore, respiratory functionality was also measured. Results Multiple linear regression analysis results showed a direct correlation ( p 2t isoprostane with both the urbanization and passive smoke. Lung function parameters proved significantly lower for the subjects living in the most populous city of Torino. Conclusion This remarks the negative effect that urbanization has on the respiratory conditions. Lastly, lung functionality presented a low inverse correlation with 15-F 2t isoprostane, suggesting an independent mechanism than that of the urban factor.

Acute urticaria is a common disorder that often prompts patients to seek treatment in the emergency room (ER). There are few data on acute urticaria presenting in ER.This study aimed to provide demographic and clinical data of patients presenting with acute urticaria at an ER of an Italian general hospital covering an area of about 90,000 inhabitants. The predictive factors of the length of stay in the ER had also been investigated.The database of ER patients was searched for urticaria by ICD-9 code and by keywords in the diagnosis description. All the medical records of the identified patients were reviewed and the length of stay in ER was noted.A total of 459 patients were admitted to ER with acute urticaria in a 1-year period corresponding to 1.01% of total ER visits and to 1.2 admission per day. Angioedema was present in 139 cases (30.3%), fever in 55 (12%). Twenty-nine patients fulfilled the criteria of anaphylaxis. Triggers could be identified in 193 cases (42%): drugs in 20.7%, insects bites (10.2%), foods (7.4%) and contact urticaria in 3.7%. Anaphylaxis (p0.001), food (p0.05) and drugs (p0.05) as triggers were significant and independent predictive factors of the length of stay in ER.Patients with acute urticaria are frequently referred to the emergency room, but only in a few cases urticaria is associated with severe allergic manifestations. Drug and food hypersensitivity, together with anaphylaxis, are the best predictors of the length of stay in ER.

Purpose of this study was to study the oxidative stress status through the urinary 15-F(2t)-isoprostane (15-F(2t)-isoP) among a group of 168 adolescents, differently exposed to passive tobacco smoke. Subjects were enrolled, with written informed consent, between two populations of students living and attending school in two areas with different levels of urbanization in Piedmont Region, North-Western Italy. A general linear model (GLM) analysis was performed to evaluate the role of air pollution, dependent from selected degree of urbanization and of passive exposure to tobacco smoke, quantified through cotinine, in the synthesis of 15-F(2t)-isoP, measured with ELISA technique. Formaldehyde (FA) concentration in air was also evaluated as a primary confounding factor in oxidative stress but no significant differences between the two sites were found. Conversely, direct relationship between oxidative stress status and residence of adolescents was found: oxidative stress level was 31% higher for adolescents living in Chivasso (urban site) than for those living in Casalborgone (countryside area). Furthermore, also passive tobacco smoke exposure proved to play another important direct role in the distribution of 15-F(2t)-isoP levels (p0.0001). Lastly, an inversely proportional relationship was found between the age of adolescents and 15-F(2t)-isoP (p0.0001). Finally, the detection of such a sensitive biological response as a consequence of limited differences of environmental pollution and exposure to tobacco smoke passively breathed could provide new and useful knowledge for the appraisal of preventive strategies, particularly for young subjects.

BACKGROUND: Only few longitudinal studies on the course of asthma among adults have been carried out. OBJECTIVE: The aim of the present prospective study, carried out between 2000 and 2009 in Italy, is to assess asthma remission and control in adults with asthma, as well as their determinants. METHODS: All the subjects with current asthma (21-47 years) identified in 2000 in the Italian Study on Asthma in Young Adults in 6 Italian centres were followed up. Asthma remission was assessed at follow-up in 2008-2009 (n = 214), asthma control at baseline and follow-up. Asthma remission and control were related to potential determinants by a binomial logistic and a multinomial logistic model. Separate models for remission were used for men and women. RESULTS: The estimate of the proportion of subjects who were in remission was 29.7% (95%CI: 14.4%;44.9%). Men who were not under control at baseline had a very low probability of being in remission at follow-up (OR = 0.06; 95%CI:0.01;0.33) when compared to women (OR = 0.40; 95%CI:0.17;0.94). The estimates of the proportion of subjects who were under control, partial control or who were not under control in our sample were 26.3% (95%CI: 21.2;31.3%), 51.6% (95%CI: 44.6;58.7%) and 22.1% (95%CI: 16.6;27.6%), respectively. Female gender, increasing age, the presence of chronic cough and phlegm and partial or absent asthma control at baseline increased the risk of uncontrolled asthma at follow-up. CONCLUSION: Asthma remission was achieved in nearly 1/3 of the subjects with active asthma in the Italian adult population, whereas the proportion of the subjects with controlled asthma among the remaining subjects was still low.

Summary Background Tuberculosis (TB) contact tracing is a valid public health measure to control the spread of TB infection in low-burden settings. The aim of this study was to assess the yield of the Piedmont TB contact investigation program and to evaluate the role of its main determinants. Methods The Piedmont TB notification systems were used to identify index TB cases. All cases were classified by contagiousness (sputum-smear-positive, AFB+; culture-positive, CULT+; other-than-defined). TB contacts were screened for active and latent TB infection by clinical manifestations and Tuberculin Skin Test (TST). Results 833 index TB cases with at least one contact were identified; 4441 contacts were screened, and 3942 (82.8%) were evaluated. TB contacts aged ≤35 years, regular and household contacts had a higher probability of being evaluated; foreign-born TB contacts were the least traceable. Higher rates of TB infection were observed in contacts at 35 years of age or younger who also lived in the same household with index cases or exposed to AFB+ or CULT+ index cases. Conclusion More efforts should be focused on young TB contacts, since they are likely to be new infections. An early identification and treatment of TB Infection in this group contributes to the prevention and control of TB transmission. The program should also be extended to the contacts of CULT+ cases.

Besides environmental triggers, a family history of asthma is a strong risk factor for the development of asthma in offspring. The pooled data from 13,963 interviews of randomly selected, 20 to 48 yr-old participants from the 30 centers of the European Community Respiratory Health Survey (ECRHS) were analyzed with conventional logistic regression and a Class A regressive model adapted for the segregation of various transmission modes in families. The asthma prevalence in the interviewed index generation was 6.9% (95% confidence interval [CI]: 6.5 to 7.3), and in the parent generation was 6.1% (5.8 to 6.4). As with asthma prevalence, the risk of a subject having asthma if a parent had asthma also had a large geographic variation across the survey centers. The mean risk if a father had asthma was 2.9 (2.4 to 3.5), and If the mother had asthma was 3.2 (2.6 to 3.9). The risk increased to 7.0 (3.9 to 12.7) if both parents were affected. For developing extrinsic asthma, extrinsic asthma in any parent was a greater risk factor (4.9 [3.9 to 6.0]) than intrinsic asthma of the parent (1.5 [0.8 to 2.6]), and the risk for women was slightly higher than that for men (4.3 [3.3 to 5.5] versus 3.6 [2.6 to 5.0]). Applying different segregation models, only a model for a two-allele gene with a codominant inheritance could not be rejected, assuming a major gene with a population frequency of 24.2%. Further results make a multilocus/threshold model likely. In conclusion, a history of asthma in parents is a strong risk factor for asthma in the offspring. Under the assumptions of the applied segregation analysis, at least one major gene exists which could be a gene involved also in allergy. However, asthma is not fully described by a single-gene model. The risk for asthma varies within the European countries, and should be seen in the context of a complex genetic and environmental pathophysiology.

Migration from low- and middle-income countries to high-income countries increasingly determines the severity of tuberculosis (TB) cases in the adopted country. Socially marginalized groups, about whom little is known, may account for a reservoir of TB among the immigrant populations. We investigated the rates of and risk factors for Mycobacterium tuberculosis transmission, infection, and disease in a cohort of 27,358 socially marginalized immigrants who were systematically screened (1991–2010) in an area of Italy with low TB incidence. Overall TB and latent TB infection prevalence and annual tuberculin skin testing conversion rates (i.e., incidence of new infection) were 2.7%, 34.6%, and 1.7%, respectively. Prevalence of both TB and latent TB infection and incidence of infection increased as a function of the estimated TB incidence in the immigrants’ countries of origin. Annual infection incidence decreased with time elapsed since immigration. These findings have implications for control policy and immigrant screening in countries with a low prevalence of TB.

Background: This study is aimed at providing a real-world evaluation of the economic cost of persistent asthma among European adults according to the degree of disease control [as defined by the 2006 Global Initiative for Asthma (GINA) guidelines]. Methods: A prevalence-based cost-of-illness study was carried out on 462 patients aged 30–54 years with persistent asthma (according to the 2002 GINA definition), who were identified in general population samples from 11 European countries and examined in clinical settings in the European Community Respiratory Health Survey II between 1999 and 2002. The cost estimates were computed from the societal perspective following the bottom-up approach on the basis of rates, wages and prices in 2004 (obtained at the national level from official sources), and were then converted to the 2010 values. Results: The mean total cost per patient was EUR 1,583 and was largely driven by indirect costs (i.e. lost working days and days with limited, not work-related activities 62.5%). The expected total cost in the population aged 30–54 years of the 11 European countries was EUR 4.3 billion (EUR 19.3 billion when extended to the whole European population aged from 15 to 64 years). The mean total cost per patient ranged from EUR 509 (controlled asthma) to EUR 2,281 (uncontrolled disease). Chronic cough or phlegm and having a high BMI significantly increased the individual total cost. Conclusions: Among European adults, the cost of persistent asthma drastically increases as disease control decreases. Therefore, substantial cost savings could be obtained through the proper management of adult patients in Europe.

To the Editors: Mycobacterium tuberculosis transmission is affected by several key factors, such as contagiousness of the index tuberculosis (TB) case, immune status and susceptibility of the exposed TB contact, duration and patterns of contact between the index TB case and the exposed TB contact, and characteristics of the environment within which such contact occurs [1–3]. Tracing strategies that allow the early identification and appropriate treatment of TB contacts with latent TB infection (LTBI) or active TB should be a priority of TB control programmes with adequate resources [3, 4]. In agreement with the guidelines laid out by the Italian Ministry of Health, the Piedmont Region has activated and regularly updated TB contact investigation procedures [5]. We used data from the Piedmont Region TB contact investigation programme to assess the role of selected risk factors for TB infection (TBI) among TB contacts in the city of Turin, Italy. For each suspected or confirmed pulmonary TB case, active contact investigation was conducted among household members, close contacts and regular contacts, defined according to the stone-in-the-pond method [6]. Passive investigation was used for occasional contacts [5]. The Piedmont TB notification systems were used to identify pulmonary TB cases between January 2002 and December 2008. TB cases were classified into three categories of contagiousness: 1) sputum smear-positive and culture-positive (acid-fast bacillus positive (AFB+)); 2) sputum smear-negative but culture-positive (CULT+); and 3) sputum smear-negative and culture-negative or not examined, i.e. other than defined (OtD). Interviews were conducted with each TB case to identify TB contacts, defined as anyone having shared air …

Background: Chronic cough is characterized by sensory neuropathy. Vitamin B-12 (cobalamin) deficiency (Cbl-D) causes central and peripheral nervous system damage and has been implicated in sensory neuropathy and autonomic nervous system dysfunction. Objective: We evaluated whether Cbl-D has a role in chronic, unexplained cough. Design: Laryngeal threshold (histamine concentration that provokes a 25% decrease in the midinspiratory flow), bronchial threshold (histamine concentration that provokes a 20% decrease in the forced expiratory volume in 1 s), and cough threshold (histamine concentration that causes 5 coughs) in response to an inhaled histamine were assessed in 42 patients with chronic, unexplained cough [27 Cbl-D patients and 15 patients without Cbl-D (Cbl-N)] before and after intramuscular injections of cobalamin for 2 mo. Laryngeal, bronchial, and cough hyperresponsiveness was diagnosed when histamine concentration thresholds were 8 mg/mL. Seven Clb-D and 3 Cbl-N patients underwent an oropharyngeal biopsy before treatment. Results: Cbl-D patients had a higher prevalence of laryngeal hyperresponsiveness than did Cbl-N patients (92.6% compared with 66.7%; P = 0.03), a thinner oropharyngeal epithelium [133.7 lm (95% CI: 95, 172 lm) compared with 230.8 lm (95% CI: 224, 237 lm); P = 0.002], a lower number of myelinated nerve fibers [2.25/mm 2 (95% CI: 1.8, 2.7/mm 2 ) compared with 3.44/mm 2 (95% CI: 3, 3.8/mm 2 ); P = 0.05], and a higher immunoreactive score for nerve growth factor (NGF) [6.7 (95% CI: 6, 7.3) compared with 2.8 (95% CI: 2.5, 3.1); P = 0.02]. After cobalamin supplementation, symptoms and laryngeal, bronchial, and cough thresholds were significantly improved in Cbl-D but not in Cbl-N patients. Conclusions: This study suggests that Cbl-D may contribute to chronic cough by favoring sensory neuropathy as indicated by laryngeal hyperresponsiveness and increased NGF expression in pharyngeal biopsies of Cbl-D patients. Cbl-D should be considered among factors that sustain chronic cough, particularly when cough triggers cannot be identified. Am J Clin Nutr 2011;93:542‐8.

Background: Restrictive definitions of current asthma are used in epidemiological studies to achieve a highly specific classification of subjects. However, undiagnosed asthmatics should be taken into account to correctly evaluate the impact of the disease in the general population. Methods: In an Italian multi-centre cross-sectional survey carried out in 1998–2000, 18,647 responders (20–44 years old) to a screening questionnaire were classified as having physician-diagnosed current asthma or current respiratory symptoms. Similarities in the risk factor profile and in the socioeconomic burden were considered suggestive of undiagnosed current asthma. Results: In Italy, the prevalence of physician-diagnosed current asthma was 4.9% (95% CI 4.4–5.4), while that of ‘asthma attacks and/or use of anti-asthmatic drugs in the past 12 months without a diagnosis of asthma’ (ADWD) was 1.5% (95% CI 1.3–1.7). Allergic rhinitis was highly associated with diagnosed current asthma [relative risk ratio (RRR) 12.48; 95% CI 9.12–17.07; reference category: neither asthma during lifetime nor current respiratory symptoms] and with ADWD (RRR 8.42; 95% CI 6.33–11.19). Chronic cough/phlegm was homogeneously associated with all the respiratory conditions, and the strongest relationship was with ADWD (RRR 7.79; 95% CI 4.95–12.25). Subjects with ADWD and diagnosed current asthmatics were characterised by high and homogeneous percentages of individuals who reported productivity losses (19.0 and 15.1%) and hospitalisations (9.2 and 6.2%) because of respiratory problems in the past year. Conclusions: The impact of current asthma seems to be largely underestimated among Italian adults, since the individuals with ADWD may be undiagnosed current asthmatics.

Background Perennial rhinitis (PR), chronic rhinosinusitis (CRS), or both, asthma, and gastroesophageal reflux disease (GERD) are the most frequent triggers of chronic cough (CC). Extrathoracic airway receptors might be involved in all 3 conditions because asthma is often associated with PR/CRS and gastroesophageal refluxate might reach the upper airway. We previously found that most patients with rhinosinusitis, postnasal drip, and pharyngolaryngitis show laryngeal hyperresponsiveness (LHR; ie, vocal cord adduction on histamine challenge) that is consistent with an irritable larynx. Objective We sought to evaluate the role of LHR in patients with CC. Methods LHR and bronchial hyperresponsiveness (BHR) to histamine were assessed in 372 patients with CC and in 52 asthmatic control subjects without cough (asthma/CC−). In 172 patients the challenge was repeated after treatment for the underlying cause of cough. Results The primary trigger of CC was PR/CRS in 208 (56%) patients, asthma in 41 (11%) patients (asthma/CC+), GERD in 62 (17%) patients, and unexplained chronic cough (UNEX) in 61 (16%) patients. LHR prevalence was 76% in patients with PR/CRS, 77% in patients with GERD, 66% in patients with UNEX, 93% in asthma/CC+ patients, and 11% in asthma/CC− patients. Upper airway disease was found in most (95%) asthma/CC+ patients and in 6% of asthma/CC− patients. BHR discriminated asthmatic patients and atopy discriminated patients with PR/CRS from patients with GERD and UNEX. Absence of LHR discriminated asthmatic patients without cough. After treatment, LHR resolved in 63% of the patients and improved in 11%, and BHR resolved in 57% and improved in 18%. Conclusions An irritable larynx is common in patients with CC and indicates upper airway involvement, whether from rhinitis/sinusitis, gastric reflux, or idiopathic sensory neuropathy.

Background The association between smoking habits and asthma is complex because subjects with asthma could avoid smoking, whereas smoking could increase asthma severity or incidence. Purpose The relation between asthma in childhood (0–10 years) and smoking initiation in the second decade (11–20 years) was investigated using the database of the Italian Study on Asthma in Young Adults, performed in 1998–2000 on people aged 20–45 years. Methods The cumulative incidence of smoking initiation was compared among (1) subjects not reporting asthma attacks in the first 20 years of life (n = 17,384), (2) subjects reporting asthma onset in the first decade and no disease remission by the age of 20 years (n = 305), (3) subjects reporting asthma onset in the first decade and remission in the first and second decades (n = 573). Results Among men, the cumulative incidence of smoking onset was higher among nonasthmatics (49%) than among asthmatics (35.6%), and intermediate among asthmatics with disease remission (44.2%) ( p = .001). These differences were larger in males born between 1953 and 1965, and tended to decrease in males born between 1966 and 1979: cumulative incidence of smoking onset decreased from 54.3% to 43.8% in nonasthmatics, whereas it remained stable in asthmatics (from 36.8% to 35%). Women, instead, had similar cumulative incidence of smoking initiation, irrespective of asthma onset or remission ( p = .849). Conclusion Asthma in childhood reduces smoking initiation during the subsequent teenage in men, but not in women. This protective effect tends to fade when asthma remission occurs. In the last decades, smoking initiation has decreased among nonasthmatic males, but not among asthmatic males.

Chronic rhinosinusitis (CRS) has been reported to be associated with increased values of exhaled nitric oxide (ENO), which could not be entirely explained by the association between CRS and asthma. The aim of this study was to investigate the variables associated with increased ENO in patients with CRS.This was a prospective cross-sectional descriptive study of 93 consecutive patients with CRS. The effect on ENO of age, gender, atopy, asthma, respiratory symptoms without bronchial hyperresponsiveness (BHR), and nasal polyps was evaluated by multiple regression analysis.Nasal polyps (P = .01), asthma (P.001), and respiratory symptoms without BHR (P = .01) were the only independent variables associated with increased ENO. The prevalence of asthma was significantly higher in subjects with nasal polyps (61% vs 29.4%), P = .005, whereas the prevalence of respiratory symptoms without BHR was higher in those without nasal polyps (44.1% vs 15.3%, P = .003). Respiratory symptoms without BHR were associated with significantly higher ENO and prevalence of sputum eosinophilia (eosinophils3%) in patients with nasal polyps compared with those without nasal polyps (68.2 vs 24.0 ppb, P = .001; 60% vs 8.3%, P = .03, respectively).The presence of nasal polyps in patients with CRS was associated with increased asthma prevalence as well as increased ENO levels. Respiratory symptoms without BHR were associated with eosinophilic airway inflammation and increased ENO only in patients with nasal polyps. These findings suggest important clinical and biologic differences between the two types of CRS, with and without nasal polyps.

In a multicenter, prospective, randomized, open-label study of isoniazid-preventive therapy (IPT) for latent tuberculosis infection, illegal immigrants from countries where tuberculosis is highly endemic were enrolled at two clinical sites in Northern Italy. Of 208 eligible subjects, 82 received supervised IPT at a dose of 900 mg twice weekly for 6 mo (Regimen A), 73 received unsupervised IPT 900 mg twice weekly for 6 mo (Regimen B), and 53 received unsupervised IPT 300 mg daily for 6 mo (Regimen C). Supervised IPT was delivered at either one tuberculosis clinic or one migrant clinic. The probability of completing a 26-wk regimen was 7, 26, and 41% in Regimens A, B, and C, respectively (p < 0.005, Log- rank test calculated using Kaplan-Meier plots). The mean time to dropout was 3. 8, 6, and 6.2 wk in Regimens A, B, and C, respectively (p = 0.003 for regimen A versus either Regimens B or C). Treatment was stopped in five subjects (2.4%) because of adverse events. The rate of completion of preventive therapy for latent tuberculosis infection among illegal immigrants was low. Supervised, clinic-based administration of IPT significantly reduced adherence. Alternative strategies to implement preventive therapy in illegal immigrants are clearly required.

Objective: Surgical resection is the treatment of choice to cure patients with non-small-cell lung cancer (NSCLC); nevertheless, the assessment of the lower limit of surgical tolerance remains difficult. Ventilatory inefficiency (measured as the ventilation to CO 2 production ratio (V' E /V' CO2 slope) is a survival predictor in pulmonary hypertension (PH) and chronic heart failure (CHF) and is considered a marker of PH in chronic obstructive pulmonary disease (COPD). The aim of this study was to investigate the role of V' E /V' CO2 slope as preoperative mortality and morbidity predictor in COPD patients submitted to lung resection for NSCLC and considered operable according to current standards. Methods: A retrospective analysis was performed in 145 consecutive COPD patients with lung cancer (128 males and 17 females), with a mean age of 64 years (range: 41—82 years) who were referred for preoperatory evaluation. Because of bronchial obstruction or reduced pulmonary diffusion capacity for carbon monoxide (D L,CO ), all these patients were considered operable only after a cardiopulmonary exercise test showed a preserved cardiopulmonary function. Results: A total of 98 lobectomies, eight bilobectomies and 39 pneumonectomies (13 left and 26 right) were performed. Twenty-one patients (14.5%) suffered severe cardio-respiratory complications; 15/106 patients (14.2%) after lobectomy/bilobectomy and 6/39 (15.4%) after pneumonectomy. Five patients (3.4%) died within 30 days after surgery (3/106 after lobectomy/bilobectomy (2.8%) and 2/ 39 after pneumonectomy (5.1%)). Considering all functional parameters before surgery and the postoperative predicted values, a logistic regression analysis individuated the V' E /V' CO2 slope as the only independent mortality predictor (odds ratio (OR): 1.24 z = 2.77; p < 0.007). The V' O2 peak was instead the best predictor for the occurrence of severe cardiopulmonary postoperative complications (OR: 0.05, z = -2.39, p < 0.02). Conclusions: In COPD patients, a high V' E /V' CO2 slope before lung resection is an independent mortality predictor even in the presence of an acceptable cardiopulmonary performance. COPD patients with high V' E /V' CO2 slope before surgery must be carefully screened to exclude pulmonary hypertension, especially before surgical procedures with large parenchymal exeresis.

Background Epidemiological studies have provided evidence that exposure to vehicular traffic increases the prevalence of respiratory symptoms and may exacerbate pre-existing asthma in children. Self-reported exposure to road traffic has been questioned as a reliable measurement of exposure to air pollutants. The aim of this study was to investigate whether there were specific effects of cars and trucks traffic on current asthma symptoms (i.e. wheezing) and cough or phlegm, and to examine the validity of self-reported traffic exposure. Methods The survey was conducted in 2002 in 12 centers in Northern, Center and Southern Italy, different in size, climate, latitude and level of urbanization. Standardized questionnaires filled in by parents were used to collect information on health outcomes and exposure to traffic among 33,632 6–7 and 13–14 years old children and adolescents. Three questions on traffic exposure were asked: the traffic in the zone of residence, the frequency of truck and of car traffic in the street of residence. The presence of a possible response bias for the self-reported traffic was evaluated using external validation (comparison with measurements of traffic flow in the city of Turin) and internal validations (matching by census block, in the cities of Turin, Milan and Rome). Results Overall traffic density was weakly associated with asthma symptoms but there was a stronger association with cough or phlegm (high traffic density OR = 1.24; 95% CI: 1.04, 1.49). Car and truck traffic were independently associated with cough or phlegm. The results of the external validation did not support the existence of a reporting bias for the observed associations, for all the self-reported traffic indicators examined. The internal validations showed that the observed association between traffic density in the zone of residence and respiratory symptoms did not appear to be explained by an over reporting of traffic by parents of symptomatic subjects. Conclusion Children living in zones with intense traffic are at higher risk for respiratory effects. Since population characteristics are specific, the results of validation of studies on self-reported traffic exposure can not be generalized.

Background Reliable clinical or laboratory markers of chronic idiopathic urticaria (CIU) duration are not available. Angioedema, autologous serum skin test (ASST) results, and antithyroid antibodies have been inconsistently associated with longer urticaria duration. Objective To investigate the association of clinical and laboratory parameters with CIU duration, including systemic hypertension, because activation of the coagulation cascade pathway may contribute to the pathogenesis of CIU. Methods We performed a prospective study of a cohort of 228 consecutive adult patients with CIU of moderate to severe intensity referred to 2 outpatient allergy clinics and followed up for a 3- to 5-year period. The association of clinical and laboratory parameters (sex, atopy, markers of autoimmunity, antithyroid antibodies, positive ASST result, Helicobacter pylori infection, and hypertension) with urticaria duration was analyzed using semiparametric multivariable proportional hazards models (Cox regression) using remission as main outcome measure. Results Apart from systemic hypertension (hazard ratio, 0.71; 95% confidence interval, 0.53-0.95; P =.02), none of the considered parameters influenced CIU remission of our patients; 74% and 54% of our patients with and without hypertension, respectively, still had CIU after 5 years. Conclusions Our results show, for the first time to our knowledge, that hypertension is associated with extended duration of CIU. This observation, together with the previous findings that point to vascular and coagulation involvement in CIU, may suggest a new approach to antihistamine-refractory CIU treatment, including adequate treatment of hypertension.

development of an algorithm to estimate the prevalence of obstructive lung diseases (OLD) through record linkage of administrative health data sources in three Italian areas.AULSS 12 Veneziana, city of Torino, ASL10 Firenze.all residents in the three areas in the period 2002-2004 (N = 1,944,471 on 30th June 2003).crude prevalence, standardized prevalence with 95% confidence intervals.the following data sources were used to identify OLD cases: hospital discharges (HD), health-tax exemptions (HTE), death causes (DC) and drug prescriptions (DP). All patients diagnosed with (from HD) or dead because of chronic bronchitis, emphysema and asthma have been included in the analysis. We defined as a prevalent case a subject found in each year in at least one of the four data sources. We reported the absolute and relative contribution of each information system by area, age, gender and year of interest. We performed a sensitivity analysis using more restrictive criteria to identify prevalent cases (two or more DPs per year).DP was the most relevantsource in identifying cases (from 86 to 88%). The relative contribution ofHD ranged from 3 to 5%. In 2003, standardized prevalence of OLD ranged from 5.35% in Firenze to 6.02% in Venezia. Venezia showed a higher prevalence in children aged 0-14years and a lower prevalence in older age groups (64 years) compared to other centers. Overall, the prevalence was higher among males. The use of more restrictive criteria in case identification substantially reduces the estimated prevalence, particularly in younger age-groups and to a lesser extent, in older age-groups.the algorithm provides estimates with differences between centres. The validity of this algorithm (in terms of sensitivity and positive predictive value) needs to be evaluated through further ad hoc studies.

tuberculosis is a global heath priority and the surveillance systems are essential tools to control the spread of the disease. The objectives are to estimate: the incidence tuberculosis in Piedmont for the period 2001-03, using multiple sources of information; the sensitivity of the regional system for the surveillance of tuberculosis; the impact ofimmigration from areas with high prevalence of tuberculosis.deterministic linkage between electronic databases and estimate of non-observed cases of microbiologically confirmed tuberculosis, using the 'capture-recapture method'.the Piedmonti population was the study base. Tuberculosis cases were identified from the integrated Regional Tuberculosis Surveillance System (SSR- TB), the Tuberculosis Laboratory Registry (RL-TB), and the Regional Registry of Inpatient Records (SDO).1790 cases of tuberculosis were recorded, in 28.6% (512) of the cases the disease was observed among individuals from countries with high prevalence of tuberculosis. Microbiologically confirmed cases of tuberculosis were 1254 (70%), while pulmonary cases were 1233 (69%). The annual crude incidence of tuberculosis (per 100,000 inhabitants) was 14.1 cases, 31.5% of whom were attributable to immigration from countries with high prevalence of tuberculosis. The incidence among immigrants was 122.4 cases, while that of microbiologically confirmed cases was 9.8 cases. The overall estimated sensitivity, for the microbiologically confirmed cases, was 97%, while the sensitivity of SSR-TB was 90%.Our estimate of tuberculosis incidence in Piedmont is about two times as great as that given by the WHO for Italy (8 cases per 100,000 inhabitants). The fraction of incident cases attributable to immigration from countries with high prevalence of tuberculosis is also consistent with that estimated in other industrialized countries undergoing high immigration flows. The integration of surveillance systems is essential to obtain accurate and timely estimates of the tuberculosis epidemiology.

Obesity, physical activity, and dietary habits are distinct but strongly interrelated lifestyle factors that may be relevant to the prevalence of wheeze and asthma in children. Our goal was to analyze the relationship of body mass index (BMI), regular sports participation, TV viewing, and diet with current wheezing and asthma.We investigated 20,016 children, aged 6-7 years, who were enrolled in a population-based study. Parents completed standardized questionnaires. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs), while adjusting for several confounders and simultaneously considering BMI, regular sports activity, TV viewing and selected dietary items.A total of 1575 children (7.9%) reported current wheezing and 1343 (6.7%) reported current asthma. In a multivariate model, an elevated BMI was associated with wheeze and current asthma: children from the highest quintile (compared with the lowest quintile) had an increased risk of wheeze (OR = 1.47; CI = 1.20-1.82) or current asthma (1.61; 1.28-2.01). Wheeze or asthma was not associated with regular sports activity. Subjects who spent 5 or more hours per day watching television were more likely to experience wheeze (1.53; 1.08-2.17) or current asthma (1.51; 1.04-2.2) compared with those who viewed TV less than 1 hour a day. Adding salt to food was strongly and independently associated with current wheeze (2.58; 1.41-4.71) and current asthma (2.68; 1.41-5.09).Our data support the hypothesis that high body weight, spending a lot of time watching television, and a salty diet each independently increase the risk of asthma symptoms in children.

Summary Introduction Exhaled nitric oxide (FE NO ) is a reliable non-invasive marker of airway inflammation. In 2003 FE NO chemiluminescence analyzer (NIOX ® ; Aerocrine AB, Solna, Sweden) was approved by U.S. Food and Drug Administration for monitoring asthma therapy. Recently, the same company developed a portable device using electrochemical sensors (NIOX-MINO ® ; Aerocrine AB). The aim of our study was to compare NIOX-MINO ® FE NO values to those obtained by NIOX ® and to calculate a correction equation. Methods Two adequate measurements obtained by NIOX ® and NIOX-MINO ® were recorded in 32 subjects (16 females, mean age 41 years). Results FE NO values measured by NIOX-MINO ® were systematically higher than those obtained by NIOX ® (47.1ppb, IC 95% 35.2–59.1 and 36.9ppb, IC 95% 25.0–49.0, respectively). There was a significant correlation ( r =0.998, p NO measured by the two analyzers and the following conversion equation was calculated as: FE NO(NIOX ® ) =−1.656(SE=0.61)+0.808(SE=0.009)× FE NO(NIOX-MINO ® ) Discussion FE NO values measured by the portable nitric oxide analyzer are reliable and strongly correlated with values obtained by the standard stationary device, with a systematic difference observed between the two instruments' values that can be described by the conversion equation we provided. This equation will help clinicians and researchers to compare data obtainable by the two analyzers.

It has been suggested that cough from captopril may originate from an increased sensitivity of receptors in the extrathoracic airway (EA). To explore this hypothesis, we assessed the responsiveness of EA and bronchi and the cough sensitivity to inhaled histamine in nine hypertensive patients with captopril-induced cough (group 1) during treatment and one month after withdrawal of the drug treatment. Nine patients who were asymptomatic while receiving captopril (group 2) and nine patients receiving no current treatment (group 3) served as controls. The EA responsiveness was assessed by using the maximal midinspiratory flow (MIF50) as an arbitrary index of EA constriction and was expressed as the histamine concentration causing a 25 percent decrease in MIF50 (PC25MIF50). PC15FEV1 was the index of bronchial responsiveness and PCcough (dose causing five or more coughs) was that of cough sensitivity. Airway hyperresponsiveness (EA-HR or BHR) was diagnosed when PC25MIF50 or PC15FEV1 were 8 mg/ml or lower. Patients with captopril-cough, as compared with controls, had significantly lower values of PC25MIF50, PC15FEV1, and PCcough; EA-HR and BHR were found, respectively, in seven and three of these patients and in none of the control subjects. In all the patients of group 1, cough and EA-HR resolved after withdrawal of captopril treatment, while BHR persisted in one. PC25MIF50, PC15FEV1, and PCcough were all significantly improved. Our findings suggest that cough during captopril therapy may originate from receptors in the EA.

This work reports the results of an environmental survey carried out in an industrial area in the Province of Turin: its main aim is to assess the levels of iron and aluminium in the outside air during the period from July to September to assess the influence of industrial activity (a cast-iron and aluminium foundry) which is interrupted during the month of August, on the level of metals present in the air. Conducting the analysis during this period of time made it possible to avoid the confounding effect of pollution due to domestic central heating. The measurements were taken from nine areas at different distances from the foundry in the area and according to the direction of the prevailing winds, as deduced from the historical data. The results of this survey show a statistically significant difference in iron and aluminium levels in the outside air in the geographic areas between the two main periods examined: during August (no foundry activity) v/s July-September (foundry activity). The values recorded are: Aluminium 0.4+/-0.45 microg/m(3) v/s 1.12+/-1.29 microg/m(3) (p