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Environmental tobacco smoke remains a major risk factor, for both smokers and non-smokers, able to trigger the initiation and/or the progression of several human diseases. Although in recent times governments have acted with the aim of banning or strongly reducing its impact within public places and common spaces, environmental tobacco smoke remains a major pollutant in private places, such as the home environment or cars. Several inflammatory and long-term biomarkers have been analysed and well-described, but the list of mediators modulated during the early phases of inhalation of environmental tobacco smoke needs to be expanded. The aim of this study was to measure the short-term effects after exposure to side-stream smoke on Nerve Growth Factor and its receptors Tropomyosin-related kinase A and neurotrophin p75, molecules already described in health conditions and respiratory diseases. Twenty-one non-smokers were exposed to a home-standardized level of SS as well as to control smoke-free air. Nerve Growth Factor and inflammatory cytokines levels, as well the expression of Tropomyosin-related kinase A and neurotrophin receptor p75, were analysed in white blood cells. The present study demonstrates that during early phases, side-stream smoke exposure induced increases in the percentage of neurotrophin receptor p75-positive white blood cells, in their mean fluorescent intensity, and in gene expression. In addition, we found a positive correlation between the urine cotinine level and the percentage of neurotrophin receptor-positive white blood cells. For the first time, the evidence that short-term exposure to side-stream smoke is able to increase neurotrophin receptor p75 expression confirms the very early involvement of this receptor, not only among active smokers but also among non-smokers exposed to SS. Furthermore, the correlation between cotinine levels in urine and the increase in neurotrophin receptor p75-positive white blood cells could represent a potential novel molecule to be investigated for the detection of SS exposure at early time points.

OBJECTIVE Assessment of the feasibility and effectiveness of a brief intervention for smoking cessation in people living with HIV (PLWH). SETTING Multicenter cohort prospective study involving PLWH from 10 Italian infectious disease centers. METHODS During routine HIV care, clinicians delivered the 5As brief intervention (Ask, Advise, Assess, Assist, Arrange) to each patient who enrolled in the study, following the European AIDS Clinical Society guidelines. At study end, participating clinicians evaluated their own adherence to intervention: "standard" if counseling was delivered in at least half of the follow-up visits, "soft" if less. The main outcome measure was smoking abstinence ≥6 months. Abstinence predictors were evaluated using a Cox-proportional hazard regression model. RESULTS One thousand eighty-seven PLWH-patients (age 47.9 ± 10.8, male 73.5%) were followed for a median of 23 months (interquartile range 21-25). At baseline, current smokers were 561 (51.6%). Standard intervention was performed in 4 of 10 centers and included 343 smokers; soft intervention was performed in 6 centers (218 smokers). At last visit, 35 patients in standard (10.8%) and 6 in soft intervention (2.8%) achieved self-reported tobacco abstinence ≥6 months (P = 0.0009). Overall, the 5As intervention led to 7.3% 6-month interruptions. In the multivariable analysis, significant predictors for 6-month smoking cessation were: lower Fagerstrom score, stage of change (preparation/contemplation vs. precontemplation), and standard intervention. CONCLUSION Adherence to the 5As brief intervention emerged as a critical factor for success. In fact, compared with soft intervention, the standard intervention significantly increased abstinence, highlighting that clinicians need more time and supporting tools to encourage PLWH to quit smoking.

Tobacco worker’s lung (TWL) is a type of hypersensitivity pneumonitis (HP) affecting workers exposed to tobacco leaves and molds in the humidified environment of the tobacco production industry. Limited epidemiological data point to a prevalence of TWL that is not negligible and probably underestimated. As in other types of HP, an acute vs. chronic presentation depends on the pattern of the exposure. Therefore, the clinical presentation can vary from an acute influenza-like syndrome, mostly self-limiting with the removal of the exposure, to an insidious onset of cough, exertional dyspnea, fatigue and weight loss in chronic presentations, where fibrotic changes may be observed. The main treatment strategy is the removal of the exposure to tobacco dust and molds, while the main aim of corticosteroid therapy is to reduce morbidity and prevent complications, namely the development of pulmonary fibrosis and permanent lung dysfunction. Despite the fact that TWL is quite well described, preventive measures are not usually adopted in the tobacco production industry. We present here a state of the art review of this neglected, preventable, but still prevalent and occupational-related subtype of HP.

Gold nanoparticles (AuNPs) are considered nontoxic upon acute exposure, at least when they are equal or above 5 nm size. However, the safeguard mechanisms contributing to maintain cell viability are scarcely explored so far. Here, we investigated the cyto-protective role of Glyoxalase 1 (Glo1), a key enzyme involved in the control of deleterious dicarbonyl stress, in two human cell types of the respiratory tract, after an acute exposure to AuNPs with a main size of 5 nm. We found that the redox sensitive Nrf-2-mediated up-regulation of Glo1 was crucial to protect cells from AuNPs-induced toxicity. However, cells challenged with a pro-inflammatory/pro-oxidative insult become susceptible to the pro-apoptotic effect of AuNPs. Notably, the surviving cells undergo epigenetic changes associated with the onset of a partial epithelial to mesenchymal transition (EMT) process (metastable phenotype), driven by the increase in dicarbonyl stress, consequent to Glo1 inactivation. As a physiological respiratory epithelium is required for the normal respiratory function, the knowledge of the protective mechanisms avoiding or (when challenged) promoting its modification/damage might provide insight into the genesis, and, most importantly, prevention of potential health effects that might occur in subjects exposed to AuNPs, through targeted surveillance programs, at least under specific influencing factors., publishedVersion

In a nationwide Italian sample of people living with HIV (PLWH), the prevalence of smoking, nicotine dependence, propensity to stop smoking, and cardiovascular profile were investigated. The nicotine dependence by Fagerström test and the propensity to stop according to the stages of change were evaluated. Associations between smoking habits and patients' characteristics were analyzed using an unconditional logistic regression model. Among 1,087 PLWH (age 47.9 ± 10.8 years, men 73.5%), the prevalence of current smokers was 51.6%. The median of Fagerström test was 4 (interquartile range 2-6); 60.1% of the smokers were in precontemplation, 17.6% in contemplation, 18.7% in preparation, and 3.6% in action. In a logistic multivariate model, current smoking was associated with male sex, being divorced/widowed, Caucasian ethnicity, dyslipidemia, atherosclerotic cardiovascular disease risk, psychiatric comorbidity, hepatitis C virus infection, and alcohol abuse. Low high-density lipoprotein cholesterol level was associated with high nicotine dependence. More than 50% of PLWH were current smokers, one-third of them showed a high or very high degree of dependence. Our findings draw attention to the need of smoking cessation strategies for PLWH.

Background Occupational eosinophilic bronchitis (OEB) has been described only as anecdotal case reports. Objective We investigated the clinical and inflammatory characteristics of subjects with OEB identified in a cohort of subjects who completed a specific inhalation challenge (SIC) with occupational agents. Methods In this retrospective multicenter study, OEB was defined by (1) a fall in FEV1 less than 15% during the SIC and the absence of nonspecific bronchial hyperresponsiveness both before and after the SIC and (2) a postchallenge increase of 3% or more in sputum eosinophils. The subjects who fulfilled these criteria were compared with 226 subjects with a negative SIC and 30 subjects with a positive SIC who failed to show baseline nonspecific bronchial hyperresponsiveness. Results An isolated increase in postchallenge sputum eosinophils was documented in 33 of 259 subjects (13%) with a negative SIC. These subjects reported significantly more often an isolated cough at work compared with the negative and positive SIC controls. When compared with positive SIC controls, the subjects with OEB experienced less frequently work-related wheezing and reported a shorter duration of symptoms at work. The sensitivity of the post-SIC increase in fractional exhaled nitric oxide in identifying OEB among subjects with a negative SIC was low, ranging from 43% to 24% using cutoff values of 8 ppb to 17.5 ppb, whereas the specificity was high (90%-97%). Conclusions This study highlights the relevance of induced sputum analysis in the investigation of work-related asthma symptoms to identify isolated increases in sputum eosinophils that are consistent with a diagnosis of OEB.

BACKGROUND: While acrylates are well-known skin sensitizers, they are not classified as respiratory sensitizers although several cases of acrylate-induced occupational asthma (OA) have been reported.OBJECTIVE: To evaluate the characteristics of acrylate-induced OA in a large series of cases and compare those with OA induced by other low-molecular-weight (LMW) agents.METHODS: Jobs and exposures, clinical and functional characteristics, and markers of airway inflammation were analyzed in an international, multicenter, retrospective cohort of subjects with OA ascertained by a positive inhalation challenge to acrylates (n = 55) or other LMW agents (n = 418) including isocyanates (n = 125).RESULTS: Acrylate-containing glues were the most prevalent products, and industrial manufacturing, dental work, and beauty care were typical occupations causing OA. Work-related rhinitis was more common in acrylate-than in isocyanate-induced asthma (P < .001). The increase in postchallenge fractional exhaled nitric oxide was significantly greater in acrylate-induced OA (26.0; 8.2 to 38.0 parts per billion [ppb]) than in OA induced by other LMW agents (3.0; -1.0 to 10.0 ppb; P < .001) or isocyanates (5.0; 2.0 to 16.0 ppb; P = .010). Multivariable models confirmed that OA induced by acrylates was significantly and independently associated with a postchallenge increase in fractional exhaled nitric oxide (≥17.5 ppb).CONCLUSIONS: Acrylate-induced OA shows specific characteristics, concomitant work-related rhinitis, and exposure-related increases in fractional exhaled nitric oxide, suggesting that acrylates may induce asthma through different immunologic mechanisms compared with mechanisms through which other LMW agents may induce asthma. Our findings reinforce the need for a reevaluation of the hazard classification of acrylates, and further investigation of the pathophysiological mechanisms underlying their respiratory sensitizing potential.

BACKGROUND: Although sensitizer-induced occupational asthma (OA) accounts for an appreciable fraction of adult asthma, the severity of OA has received little attention. OBJECTIVE: The aim of this study was to characterize the burden and determinants of severe OA in a large multicenter cohort of subjects with OA. METHODS: This retrospective study included 997 subjects with OA ascertained by a positive specific inhalation challenge completed in 20 tertiary centers in 11 European countries during the period 2006 to 2015. Severe asthma was defined by a high level of treatment and any 1 of the following criteria: (1) daily need for a reliever medication, (2) 2 or more severe exacerbations in the previous year, or (3) airflow obstruction. RESULTS: Overall, 162 (16.2%; 95% CI, 14.0%-18.7%) subjects were classified as having severe OA. Multivariable logistic regression analysis revealed that severe OA was associated with persistent (vs reduced) exposure to the causal agent at work (odds ratio [OR], 2.78; 95% CI, 1.50-5.60); a longer duration of the disease (OR, 1.04; 95% CI, 1.00-1.07); a low level of education (OR, 2.69; 95% CI, 1.73-4.18); childhood asthma (OR, 2.92; 95% CI, 1.13-7.36); and sputum production (OR, 2.86; 95% CI, 1.87-4.38). In subjects removed from exposure, severe OA was associated only with sputum production (OR, 3.68; 95% CI, 1.87-7.40); a low education level (OR, 3.41; 95% CI, 1.72-6.80); and obesity (OR, 1.98; 95% CI, 0.97-3.97). CONCLUSIONS: This study indicates that a substantial proportion of subjects with OA experience severe asthma and identifies potentially modifiable risk factors for severe OA that should be targeted to reduce the adverse impacts of the disease. (C) 2019 Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma & Immunology

Lo stress e le violenze morali nei luoghi di lavoro, come indicato dai dati epidemiologici, sono in costante aumento e rappresentano una causa di alterazione dello stato di salute dei lavoratori, con importanti ricadute negative sui soggetti, sulle aziende e sulla società. Nel caso descritto qui di seguito, le violenze morali e la disfunzionalità organizzativa, una delle principali fonti di stress correlato al lavoro, sono state intenzionalmente impiegate quale mezzo mobbizzante nei confronti di un lavoratore da parte dei suoi superiori (mobbing verticale). Attraverso il procedimento giudiziario, intrapreso dal lavoratore per vedersi riconosciuto vittima di mobbing, è stato possibile ripercorrere e identificare le ragioni e le modalità dell'azione mobbizzante, l'eziopatogenesi della conseguente psicopatologia, la sua strutturazione e la manifestazione sintomatologica. L'esame del caso permette di formulare delle considerazioni riguardo la necessità che i casi di mobbing siano trattati all'interno di un team multidisciplinare (medico di famiglia, medico del lavoro, psichiatra e medico legale) al fine di garantire un efficace trattamento terapeutico e la tutela del lavoratore nei diversi ambiti previsti dalla legge.

Introduction To study new disease-exposure associations, we created a pilot network (namely MAREL – MAlattie e Rischi Emergenti sul Lavoro ) of occupational disease consultation centres of the Italian national health service to which patients are referred for potentially work-related diseases. Methods The MAREL network included in 2016 five occupational disease consultation centres of university hospitals located in central-northern Italy. Patients were referred to the MAREL consultation centres by their general practitioners, occupational physicians or other specialists for the investigation of the putative occupational origin of a disease. Each centre collected cases of putative occupational origin through a structured and standardised data collection form. We collected data on: diagnosis; personal habits; occupational history; exposure to risk factors; physician’s opinion on the possible causal relationship between disease and occupation. Data were coded according to national and international classifications. Results The data collection started in 2016, enrolling 1516 cases of putative occupational diseases. Musculoskeletal disorders were the most represented conditions: intervertebral lumbar disc degeneration (11.2%), spondylitis (6.3%), tendinopathies (4.9%), arthritis (4.8%), upper limb mononeuropathies (4.4%), and shoulder disorders (3.7%). The most frequently reported exposures were related to biomechanical overload: manual material handling (29.5%, out of 1811), hand-arm vibrations (13.9%), repetitive movements of the upper limb (10.9%), whole-body vibrations (7.6%), awkward posture of the upper limb (7.1%), and awkward body posture (4.5%). Discussion The exposure to biomechanical overload seems to play a role in generating potentially work-related conditions. Expanding the MAREL network to other occupational disease consultation centres in 2017 and 2018, we will contribute to already existing surveillance systems (i.e. MALPROF) by the detection of new and emerging occupational diseases and risks.

Background Currently available studies show that removal of subjects affected by occupational asthma from exposure does not always lead to an improvement in respiratory function. The cause of this is still unclear. The aim of our study was to evaluate in 2017 lung function and severity of asthma in subjects who underwent specific inhalation challenge (SIC) between 2006 and 2015 for work-related asthma. Methods Clinical charts of 35 workers who underwent SIC have been evaluated. They were interviewed by telephone using a questionnaire to asses demographic data, respiratory symptoms and work disability. The severity of asthma was evaluated according to the GINA guidelines and asthma control was assessed by Asthma Control Questionnaire (ACQ). 18 workers agreed also to perform also spirometry. Results 10 subjects had a positive SIC and 25 a negative SIC. Subjects with positive SIC had more frequently moderate persistent asthma treated with a combination of inhaler steroids and a bronchodilator (67%) and those with negative SIC had more frequently intermittent asthma (65%) treated with salbutamol as needed (p Conclusions Subjects who have had a positive SIC showed more severe asthmatic symptoms with lower asthma control despite current pharmacological therapy. They also had a higher RV than subjects with negative SIC. This could be a relevant parameter to evaluate in subjects with occupational asthma to improve asthma control.

Objectives: We evaluated the effects of the Italian 2005 smoking ban in public places on the prevalence of smoking, quitting and cigarette consumption of young workers. Data and Methods: The dataset was obtained from non-computerized registers of medical examinations for a population of workers with apprenticeship contracts residing in the province of Viterbo, Italy, in the period 1996–2007. To estimate the effects of the ban, a segmented regression approach was used, exploiting the discontinuity introduced by the application of the law on apprentices’ smoking behavior. Results: It is estimated that the Italian smoking ban generally had no effect on smoking prevalence, quitting ratio, or cigarette consumption of apprentices. However, when the estimates were applied to subpopulations, significant effects were found: −1% in smoking prevalence, +2% in quitting, and −3% in smoking intensity of apprentices with at least a diploma.

Environmental pollution is one of the main factors responsible for reducing fertility in males. Lead is one of the major heavy metal contaminants that impairs several organs; it preferentially accumulates in male reproductive organs and alters sperm quality both in vivo and in vitro. However, the underlying mechanisms remain unclear. Sertoli cells (SCs) provide structural and physiological support to spermatogenic cells within seminiferous tubules. Therefore, changes in SCs affect the developing germ cells and alter spermatogenesis. This study aimed to assess whether exposure to subtoxic doses of adversely affects SC functioning in higher mammals. Purified and functional porcine neonatal SCs were exposed to lead acetate at three different concentrations. Lead exposure decreased the mRNA expression and protein levels of inhibin B and anti-Mullerian hormone (AMH) compared to control, indicating loss of FSH-r integrity in terms of 17-β-oestradiol production under FSH stimulation. In addition, we observed an increase in the mRNA levels of Akt and mTOR, and the phosphorylation of p38 and Akt in SCs exposed to lead at all concentrations compared to unexposed control SCs. In conclusion, lead is toxic to SCs, even at low concentrations, and is expected to alter spermatogenesis.

Background Detecting new disease-exposure associations is an important public health issue. We created a pilot network (MAREL - MAlattie e Rischi Emergenti sul Lavoro) of occupational disease consultation centres of Italian university hospitals to which patients are referred for potentially work-related diseases. Methods The MAREL network currently includes five occupational disease consultation centres of university hospitals located in central-northern Italy. Patients are referred to these consultation centres by their general practitioners, occupational physicians or other specialists for the investigation of the putative occupational origin of the disease. Each centre collects cases of putative occupational origin through a structured and standardised data collection form. We collect data on: diagnosis; personal habits; occupational history; exposure assessment for potentially associated risk factors; physician’s opinion on the possible causal relationship between disease and occupation. Data are coded according to national and international classifications. Results The data collection started in 2016. We collected 1516 cases of putative occupational diseases. Intervertebral lumbar disc degeneration was the most represented condition (n=170, 11.2%). Apart from musculoskeletal disorders, cases of asthma were the most frequently reported (n=59, 3.9%). About 11% of patients were construction workers. The most frequently reported exposures were: manual material handling (29.5%, out of 1811), hand-arm vibrations (13.9%), and repetitive movements of the upper limb (10.9%). Discussion The MAREL network will be expanded to other occupational disease consultation centres in 2017 with the aim to contribute to already existing surveillance systems (i.e. MALPROF) by the detection of new and emerging occupational diseases and risks.

Work-related asthma is one of the most relevant work-related diseases worldwide, causing a high socio-economical burden. In the last decades, many countries experienced huge modifications in work organisations. These changes made people to move from traditional sectors to the tertiary sectors and non-industrial indoor working environments. Non-industrial indoor workplaces are characterised by a new concept of building, with a new structure, new materials, forced ventilation, tight construction and a potential exposure to new risk factors for work-related asthma, such as new chemicals and biological agents able to cause or exacerbate asthma. The actual scientific evidence suggests an increased risk of asthma among workers exposed to cleaning agents in indoor working environment and moulds in damp buildings. Also volatile organic compounds (VOCs) and environmental tobacco smoke could be considered triggers of asthma, even if their role is still under debate. Because of the increasing numbers of subjects working in non-industrial indoor environments and the scientific evidence of an increased risk of asthma in indoor environment, there is a need of public health intervention towards the prevention of work-related asthma, also in this specific setting.

Background Occupational health surveillance is an important issue in many countries since working conditions and occupational exposures are rapidly changing. We aim to create a network of occupational disease consultation centres of Italian university hospitals to which patients are referred for potentially work-related diseases. Methods The pilot network, namely MAREL (MAlattie e Rischi Emergenti sul Lavoro), will include five occupational disease consultation centres of university hospitals located in central-northern Italy. Patients are referred to these consultation centres by their general practitioners, occupational physicians or other specialists for the investigation of the putative occupational origin of the disease. Each centre will collect cases of putative occupational origin through a structured and standardised data collection form. An online database platform will be developed collecting data on: diagnosis; personal habits; occupational history; exposure assessment for potentially associated risk factors; physician’s opinion on the possible causal relationship between disease and occupation. The data will be coded according to national and international classifications. To detect emerging disease-exposure associations we intend to apply the proportional reporting ratio used in pharmacosurveillance and adopted by the French occupational disease surveillance system (RNV3P). Results The data collection is going to start in 2016. Preliminary data will be available in due course. The detection of new disease-exposure associations is an important public health issue, especially as large numbers of new technologies, products and duty cycles are regularly introduced. Discussion The Italian network MAREL will contribute to already existing surveillance systems (i.e. MALPROF) by the detection of new and emerging occupational diseases and risks and will foster the development of preventive measures stimulating research related to this field.

Introduction: Polyciclic aromatic hydrocarbons (PAH) are environmental pollutants produced by incomplete combustion of organic materials; some of which are carcinogens and associated to cardiovascu...

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.

Background Silicosis is mediated by macrophages, their soluble mediators, and extracellular matrix molecules. In this study, we investigated the effects of silica and/or hyaluronate (HA) on several alveolar macrophage responses. Methods We evaluated glycosaminoglycan (GAG) production by radiolabeled precursors, nitric oxide (NO) release by its oxidation product, phagocytic activity by Candida albicans internalization, and the secretion of two fibrogenic cytokines, tumor necrosis factor (TNF)-α and transforming growth factor (TGF)-β, by specific assays. Results Silica significantly reduced GAG secretion, particularly HA secretion. Alone, it decreased Candida uptake; associated with HA, it enhanced the reduction. Silica and Candida reduced NO release, which was not significantly affected when silica- or Candida-exposed cells were also treated with HA. TNF-α and TGF-β activities were stimulated by silica but reduced by HA. Conclusions The results suggest that silica and HA modify alveolar macrophage functional differentiation. Silica- and HA-induced modifications of the microenvironment could determine whether the response proceeds toward healing and repair or toward lung chronic pathology.

Occupational and environmental exposure to the heavy metal cadmium (Cd) and its inhalation from cigarette smoke are associated with emphysema. Many growth factors and extracellular matrix (ECM) cell signaling molecules are directly involved in the epithelial bronchial cell pathway. This study investigated the direct effects of Cd on the production of several ECM components in human bronchial epithelial cells (BEAS-2B) that were exposed in vitro for 48 h to sub-toxic and toxic concentrations of Cd. Gene expression of collagens, metalloproteases (MMPs), integrins, tenascin and vitronectin were quantified by RT-PCR. To study apoptosis cascade, annexin assay and cellular cytotoxicity by MTT assay were performed. We also investigated whether an imbalance in the TGFβ/TGFβ receptor (TGFβR) expression mediated Cd effects. The results showed the sub-toxic Cd dose significantly increased tenascin, vitronectin, β1 and β5 integrin gene expression. The toxic Cd dose decreased type IV and V collagen, α1, α2 and β3 integrins. Both Cd doses down-regulated type I collagen and up-regulated metalloproteases. Each Cd dose caused a different imbalance in the complex pattern of TGFβ and its receptors. No alteration in classic apoptotic marker protein expression was observed in presence of the sub-toxic dose of Cd, suggesting this metal alters ECM production without apoptotic activation. In conclusion, all these data show even sub-toxic Cd dose exposure alters the specific gene expression of several ECM components that are crucially implicated in the mechanical properties of lung parenchyma supporting the hypothesis that the mechanism underlying Cd-induced lung disease may involve downstream changes in TGFβ/TGFβR signaling.

We investigated whether the presence of (+)-anti-benzo(a)pyrene diolepoxide adducts to serum albumin (BPDE-SA) among workers exposed to benzo(a)pyrene (BaP) and unexposed reference controls was influenced by genetic polymorphisms of cytochrome P4501A1 (CYP1A1), microsomal epoxide hydrolase (EHPX), glutathione S-transferases M1 (GSTM1) and P1 (GSTP1), all involved in BaP metabolism. Exposed workers had significantly higher levels of adducts (0.124 ± 0.02 fmol BPTmg(-1) SA, mean ± SE) and a higher proportion of detectable adducts (40.3%) than controls (0.051 ± 0.01 fmol BPT mg(-1) SA; 16.1%) (p = 0:014 and p = 0:012). Smoking increased adduct levels only in occupationally exposed workers with the GSTM1 deletion (GSTM1 null) (p = 0:034). Smokers from the exposed group had higher adduct levels when they were CYP1A1 *1/*1 wild-type rather than heterozygous and homozygous for the variant alleles (CYP1A1 *1/*2 plus *2/*2) (p = 0:01). The dependence of BPDE-SA adduct levels and frequency on the CYP1A1 *1/*1 genotype was most pronounced in GSTM1-deficient smokers. Exposed workers with GSTM1 null/GSTP1 variant alleles had fewer detectable adducts than those with the GSTM1 null/GSTP1*A wild-type allele, supporting for the first time the recent in vitro finding that GSTP1 variants may be more effective in the detoxification of BPDE than the wild-type allele. Logistic regression analysis indicated that occupational exposure, wild-type CYP1A1*1/*1 allele and the combination of GSTM1 null genotype+EHPX genotypes associated with predicted low enzyme activity were significant predictors of BPDE-SA adducts. Though our findings should be viewed with caution because of the relatively limited size of the population analysed, the interaction between these polymorphic enzymes and BPDE-SA adducts seems to be specific for high exposure and might have an impact on the quantitative risk estimates for exposure to polycyclic aromatic hydrocarbons.

The CC16 microprotein is the main secretory product of Clara cells, which are epithelial cells lining lung airways. In crossing through the bronchoalveolar/blood barrier, CC16 diffuses passively into plasma. Serum CC16 (sCC16) has recently been proposed as a biomarker for detecting Clara cell impairments. The aim of this study was to assess if sCC16 concentrations are reduced in a group of healthy young smokers. A group of 118 healthy young males volunteered to take part in the study. Each subject answered a questionnaire, and provided blood and urine samples. Serum CC16, urinary cotinine and creatinine were measured. Median serum CC16 concentrations were lower in smokers than in non-smokers (11.3 mug l(-1) vs 14.6 mug l(-1); p = 0.005; N = 89 and 29, respectively) but did not correlate with either the daily or the life-time cigarette consumption, or with urinary cotinine concentrations. sCC16 did not correlate with age or body mass index in the whole study population or in the groups of smokers and non-smokers. These results suggest the reduction in sCC16 concentrations in a group of healthy young smokers may be an early effect of cigarette smoking.

The present molecular epidemiology study was carried out to evaluate the genotoxic effects of occupational exposure to antineoplastic drugs (ANP). The study was conducted in 52 hospital workers involved in the preparation, handling or administration of ANP in a hospital in Perugia (central Italy) and in 52 non-exposed control subjects matched for age, gender and smoking habits to the exposed subjects. Both comet assay and the micronucleus test were used to evaluate genome damage in peripheral blood lymphocytes in study subjects. The extent of primary DNA damage, as evaluated by the comet assay, was significantly increased in exposed personnel with respect to matched controls. On the other hand, no significant differences in micronuclei frequency was observed between the two groups. Multivariate linear regression analysis showed an association between years of occupational exposure over 10 years and higher extent of primary DNA damage in the exposed group. The results of this study confirm that handling ANP without appropriate precautions carries a genotoxic risk for exposed healthcare workers. These results address the need for regular biological effect monitoring of staff occupationally-exposed to ANP.

OBJECTIVE--The aim was to assess the determinants of benzo(a)pyrenediol epoxide adducts to haemoglobin (BaPDE-Hb) in workers exposed to polycyclic aromatic hydrocarbons (PAHs). METHODS--This was a study of the correlations between the concentrations of PAHs in air, 1-hydroxyprene in urine, and BaPDE-Hb adduct concentration in the blood in 206 men working in steel foundries and one graphite electrode producing plant, taking into consideration confounding factors such as smoking and dietary habits. RESULTS--BaPDE-Hb adduct concentration was correlated (r = 0.26; p = 0.0002) with the airborne PAH concentration and was influenced by tobacco consumption but not by dietary habits. Benzo(a)-pyrene concentration in air, 1-hydroxypyrene concentration in urine, and duration of exposure to PAHs were not associated with the adduct concentration. CONCLUSION--Although environmental exposure to PAHs was statistically associated with BaPDE-Hb adduct concentration, differences between individual subjects in the metabolism of benzo(a)pyrene probably play an important part in determining the amount of BaPDE-Hb adducts formed.

Carbon monoxide (CO) poisoning is still common, especially in houses where the sources of CO are numerous and particularly insidious. In 1991, we observed 11 people who were affected by acute CO poisoning; 8 cases of which occurred in the home and 3 in the working environment. Home poisoning often affected more than one person; the cause of the intoxication was always the result of a faulty heating system associated with poor ventilation of rooms. Our experience confirms that CO is an insidious threat more common than is generally believed which can cause incidences of extremely dangerous poison ing, sometimes representing a difficult challenge to medical practitioners. A deeper knowledge and correct prevention of this problem are the primary means of reducing the proportions of this risk.

Since occupational and environmental exposure to the heavy metal Cadmium (Cd) affects human health this study investigated the effects of exposure to a single, or multiple, sub-toxic Cd concentrations on sub-confluent and confluent human osteoblast growth and expression of specific bone differentiation markers. RT-PCR quantified gene expression of type I collagen, metalloprotease (MMP13), runt-related transcription factor-2 (RUNX2), osterix, osteocalcin, osteonectin, alkaline phosphatase, integrins and bone sialoprotein (BSP). Expression of fibroblast growth factors 1 and 2 (FGF1, FGF2), transforming growth factor-β3 (TGFβ3) and bone morphogenetic protein-2 (BMP2) were also evaluated to determine whether Cd-related effects were mediated by an imbalance in expression. Depending on osteoblast concentration and maturation stages, Cd inhibited or stimulated cell growth, decreased type I collagen, increased MMP13, FGF1 and BMP2 gene expression and stimulated the mineralization process only in continuously exposed cultures. These results suggest that in vivo, acute or chronic exposure to sub-toxic Cd concentrations may affect bone formation differently and support the hypothesis that Cd-induced bone disorders may involve downstream changes in growth factor expression. The results are of interest in forensic and occupational medicine in establishing preventive measures to reduce professional exposure risks.

Fire-eater's lung, an acute exogenous lipoid pneumonia, is caused when street performers accidentally inhale pyrofluids. We report the case of a young fire-eater who, 12 hours after inhaling an iso-alkane-based pyrofluid, developed fever, dyspnoea, dry cough and intense right chest pain. Radiographic signs of pneumonia emerged two days later. Computed tomography (CT) scans visualized an irregular area of parenchymal consolidation with an air bronchiologram and peripheral ground-glass opacities in the right middle lobe. The diagnostic work-up included microbiological and lung function tests, optic fibre bronchoscopy and an in-depth cyto-immunological analysis of bronchoalveolar lavage fluid. Symptoms gradually improved over a few days. A CT scan one month later showed the thickened parenchymal area in the right middle lobe had almost completely disappeared.

Background Carpal tunnel syndrome (CTS) is a socially and economically relevant disease caused by compression or entrapment of the median nerve within the carpal tunnel. This population-based case-control study aims to investigate occupational/non-occupational risk factors for surgically treated CTS. Methods Cases (n = 220) aged 18-65 years were randomly drawn from 13 administrative databases of citizens who were surgically treated with carpal tunnel release during 2001. Controls (n = 356) were randomly sampled from National Health Service registry records and were frequency matched by age-gender-specific CTS hospitalization rates. Results At multivariate analysis, risk factors were blue-collar/housewife status, BMI ≥ 30 kg/m2, sibling history of CTS and coexistence of trigger finger. Being relatively tall (cut-offs based on tertiles: women ≥165 cm; men ≥175 cm) was associated with lower risk. Blue-collar work was a moderate/strong risk factor in both sexes. Raised risks were apparent for combinations of biomechanical risk factors that included frequent repetitivity and sustained force. Conclusion This study strongly underlines the relevance of biomechanical exposures in both non-industrial and industrial work as risk factors for surgically treated CTS.

Background Carpal tunnel syndrome (CTS) is a socially relevant condition associated with biomechanical risk factors. We evaluated age-sex-specific incidence rates of in-hospital cases of CTS in central/northern Italy and explored relations with marital status. Methods Seven regions were considered (overall population, 14.9 million) over 3–6-year periods between 1997 and 2002 (when out-of-hospital CTS surgery was extremely rare). Incidence rates of in-hospital cases of CTS were estimated based on 1) codified demographic, diagnostic and intervention data in obligatory discharge records from all Italian public/private hospitals, archived (according to residence) on regional databases; 2) demographic general population data for each region. We compared (using the χscore test) age-sex-specific rates between married, unmarried, divorced and widowed subsets of the general population. We calculated standardized incidence ratios (SIRs) for married/unmarried men and women. Results Age-standardized incidence rates (per 100,000 person-years) of in-hospital cases of CTS were 166 in women and 44 in men (106 overall). Married subjects of both sexes showed higher age-specific rates with respect to unmarried men/women. SIRs were calculated comparing married vs unmarried rates of both sexes: 1.59 (95% confidence interval [95% CI], 1.57–1.60) in women, and 1.42 (95% CI, 1.40–1.45) in men. As compared with married women/men, widows/widowers both showed 2–3-fold higher incidence peaks during the fourth decade of life (beyond 50 years of age, widowed subjects showed similar trends to unmarried counterparts). Conclusion This large population-based study illustrates distinct age-related trends in men and women, and also raises the question whether marital status could be associated with CTS in the general population.

Background Silicosis is caused by inhaling free crystalline silica. Few case reports have addressed the risk of silicosis in the jewelry trade where chalk molds containing a high percentage of silica are used in casting. We conducted a cross-sectional study involving 100 goldsmiths exposed to silica. Methods All workers replied to a questionnaire and underwent a clinical examination, pulmonary function tests, a chest X-ray and a high-resolution CT scan. Results High-resolution CT visualized signs of silicosis in 23 cases, confirmed by standard chest X-rays in 10. In the 23 workers with CT evidence of silicosis Total Lung Capacity, FEV1 and the Lung Diffusing Capacity did not differ from the workers without the disease. Pulmonary function tests did not correlate with silica exposure. Conclusion In this study we demonstrate that use of chalk molds in casting in jewelry causes silicosis. The composition of the dust could be responsible of the high prevalence observed. Am. J. Ind. Med. 50:577–583, 2007. © 2007 Wiley-Liss, Inc.

Background The results of a cross-sectional study aimed to evaluate whether genetic polymorphisms (biomarkers of susceptibility) for CYP1A1, EPHX and GSTM1 genes that affect polycyclic aromatic hydrocarbons (PAH) activation and detoxification might influence the extent of primary DNA damage (biomarker of biologically effective dose) in PAH exposed workers are presented. PAH-exposure of the study populations was assessed by determining the concentration of 1-hydroxypyrene (1OHP) in urine samples (biomarker of exposure dose). Methods The exposed group consisted of workers (n = 109) at a graphite electrode manufacturing plant, occupationally exposed to PAH. Urinary 1OHP was measured by HPLC. Primary DNA damage was evaluated by the alkaline comet assay in peripheral blood leukocytes. Genetic polymorphisms for CYP1A1, EPHX and GSTM1 were determined by PCR or PCR/RFLP analysis. Results 1OHP and primary DNA damage were significantly higher in electrode workers compared to reference subjects. Moreover, categorization of subjects as normal or outlier highlighted an increased genotoxic risk OR = 2.59 (CI95% 1.32–5.05) associated to exposure to PAH. Polymorphisms in EPHX exons 3 and 4 was associated to higher urinary concentrations of 1OHP, whereas none of the genotypes analyzed (CYP1A1, EPHX, and GSTM1) had any significant influence on primary DNA damage as evaluated by the comet assay. Conclusion The outcomes of the present study show that molecular epidemiology approaches (i.e. cross-sectional studies of genotoxicity biomarkers) can play a role in identifying common genetic risk factors, also attempting to associate the effects with measured exposure data. Moreover, categorization of subjects as normal or outlier allowed the evaluation of the association between occupational exposure to PAH and DNA damage highlighting an increased genotoxic risk.

The present study investigated the sources of discomfort and the symptoms reported by earthquake victims residing in temporary emergency prefabricated accommodation (prefab). The investigation was carried out by means of a questionnaire. 203 prefab occupants and 132 inhabitants of houses, who were chosen as reference population, replied in winter and 233 prefab occupants and 154 inhabitants of houses replied in summer. In both seasons more people living in prefabs identified dry air, stuffy air, stale air, dust, dampness, uncomfortable temperature and bad odours as sources of discomfort. They also complained of general symptoms (headache, irritability, insomnia, difficulty in concentration) and irritative symptoms of the eyes, upper and lower airways and skin. Multiple regression analysis identified the type of accommodation as the variable that most influenced the onset of general, ocular, upper and lower airway symptoms. Intrinsic characteristics of the prefabs (being constructed with synthetic materials, combustion sources, poor ventilation and insulation) and psychosocial factors e. losing their home, could have contributed to the onset of symptoms.

The aims of this study were (a) to assess blood cadmium (B-Cd) concentrations and to establish a tentative reference interval; (b) to identify significant determinants of B-Cd, in a population from Umbria, Central Italy, which was not occupationally exposed to cadmium (Cd). Four hundred and thirty-four healthy blood-donors volunteered to answer a questionnaire and provide a blood sample for B-Cd analysis, which was performed by graphite furnace atomic absorption spectrophotometry. Blood Cd concentrations ranged from non-detectable values, i.e. below 0.1 microgram/l up to 3.4 micrograms/l and were not normally distributed. The median values and the 95th percentiles were 0.7 and 2.0 micrograms/l, respectively. Concentrations of B-Cd were more than double in smokers than in non-smokers, median values being 1.1 micrograms/l and 0.5 microgram/l, respectively. In current smokers, B-Cd values correlated with the number of cigarettes smoked daily (rs = 0.40, P = 0.0001) and with the cumulative exposure to cigarette smoke (rs = 0.35, P = 0.0001). Concentrations of B-Cd correlated with age in the non-smokers, but not in the smokers and were significantly higher in women than in men only in the non-smokers. Both in smokers and non-smokers, B-Cd concentrations were similar in subjects living in urban or in rural areas. In the whole study population the lower and the upper tentative reference limit were0.1 and 2.2 micrograms/l, respectively, as computed by a non-parametric rank-based method. The upper limit was approximately double in smokers than in non-smokers (3.1 micrograms/l and 1.6 micrograms/l, respectively). Our results show that B-Cd concentrations in a general population from Umbria are in the range reported for general populations in Northern Italy and other European Countries. Smoking was the strongest determinant of B-Cd concentrations and age had a lesser effect.

Objectives: To assess the prevalence of work-related complaints and symptoms in employees in an air-conditioned office building (Building AC) in a mild climatic area (Italy). No discomfort had previously been reported. Methods: A total of 198 employees in Building AC and 281 controls working in three naturally ventilated buildings (Building NV) answered a questionnaire investigating work-related complaints and symptoms. Results: A significantly higher percentage of workers in Building AC reported a lack of comfort in the working environment as compared with the controls (30.6% versus 18.9%). The most common complaints were strong lighting, high temperature, and dry, dusty, and/or stuffy air. The prevalence of ocular, upper airway, and cutaneous symptoms was significantly higher (29.8% versus 14.9%, 25.3% versus 9.6%, and 14.1% versus 3.6%, respectively). No significant difference was observed in respiratory or general symptoms. Logistic regression analysis showed that working with video display units and photocopiers influenced ocular symptoms; upper airway and cutaneous symptoms were influenced by female gender and working in the air-conditioned building. Conclusions: In an apparently healthy air-conditioned office building, complaints and symptoms are reported more often than in a naturally ventilated edifice, but the prevalence is lower than that usually observed in sick buildings. Symptoms are influenced by individual and work-related characteristics.

OBJECTIVE: This study assessed the efficacy of preventive measures in a graphite electrode plant aimed at reducing occupational exposure to polycyclic aromatic hydrocarbons (PAHs). METHODS: Electrode workers (n = 146) answered a questionnaire and provided an end of shift urine sample. Urinary 1-hydroxypyrene (1-hpur), a biological marker of exposure to PAHs, was measured by high performance liquid chromatography coupled with: (a) fluorescence detection. 1- Hydroxypyrene concentrations were compared with the concentrations measured before implementing the preventive measures; and (b) those of a control group of 54 men not occupationally exposed to PAHs. RESULTS: After implementation of preventive measures, median concentrations 1- hpur were significantly reduced in some groups of workers: by -24%, - 37% and -30% in workers at the green electrode unit, one baking impregnation unit, and the laboratory, respectively. In workers at a second baking impregnation unit, in end product finishing and in the power station 1-hpur concentrations were unchanged. Urinary 1-hp concentrations were still significantly higher in each group of workers than in the control group (p < 0.001 for any comparison). Concentrations in the workers varied with the type of job, the highest values being found in workers engaged in the power station, in the two baking impregnation units and in the green electrode unit. CONCLUSIONS: Implementing preventive measures significantly reduced exposure to PAHs at a graphite electrode plant. The reduction in median and peak concentrations of 1-hpur, which reflects total exposure to, and internal dose of PAHs, was most evident in workers employed in the units where preventive measures had been taken. Despite an overall reduction, further preventive measures are needed to minimise exposure to PAHs and consequently the risk of adverse health effects.