Issue 3-The occupational burden of respiratory diseases, an update.

INTRODUCTION AND AIMS: Workplace exposures are widely known to cause specific occupational diseases such as silicosis and asbestosis, but they also can contribute substantially to causation of common respiratory diseases. In 2019, the American Thoracic Society (ATS) and the European Respiratory Society (ERS) published a joint statement on the occupational burden of respiratory diseases. Our aim on this narrative review is to summarise the most recent evidence published after the ATS/ERS statement as well as to provide information on traditional occupational lung diseases that can be useful for clinicians and researchers. RESULTS: Newer publications confirm the findings of the ATS/ERS statement on the role of workplace exposure in contributing to the aetiology of the respiratory diseases considered in this review (asthma, COPD, chronic bronchitis, idiopathic pulmonary fibrosis, hypersensitivity pneumonitis, infectious pneumonia). Except for COPD, chronic bronchitis and infectious pneumonia, the number of publications in the last 5 years for the other diseases is limited. For traditional occupational lung diseases such as silicosis and asbestosis, there are old as well as novel sources of exposure and their burden continues to be relevant, especially in developing countries. CONCLUSIONS: Occupational exposure remains an important risk factor for airways and interstitial lung diseases, causing occupational lung diseases and contributing substantially in the aetiology of common respiratory diseases. This information is critical for public health professionals formulating effective preventive strategies but also for clinicians in patient care. Effective action requires shared knowledge among clinicians, researchers, public health professionals, and policy makers.

Work-related interstitial lung disease: what is the true burden?

Interstitial lung diseases (ILDs) include a large variety of fibrotic lung conditions caused by genetic and environmental factors. Occupational exposures might also play a significant role, but the real health burden is currently unknown. Here, we aim to evaluate the role of work-related exposures in ILDs, focussing on idiopathic pulmonary fibrosis (IPF) and hypersensitivity pneumonitis (HP). We performed a focused review of the literature on work-related HP and IPF over the past 5 years. Using a meta-analytic approach, we quantified the occupational burden of IPF and HP, and estimated that occupational exposures to metal, silica and environmental tobacco smoke increased IPF risk with a pooled odds ratio of 1.7 (95% CI 1.42-2.03). The proportion of HP cases related to workplace exposure was 17% (95% CI 7-28). Our review supports the hypothesis that occupational exposures are a significant risk factor in the aetiopathogenesis of IPF and HP. We recommend that further research be performed to identify the underlying occupational factors and the maximum permitted exposure to reduce the associated IPF and HP burden.

Latent tuberculous infection among foreign-born individuals applying to shelters in the metropolitan area of Milan.

SETTING: Screening for latent tuberculous infection (LTBI) of groups at high risk of active tuberculosis (TB) is a key component of the End TB Strategy. OBJECTIVE: To conduct a retrospective descriptive analysis of LTBI rates among foreign-born individuals applying to shelters in the metropolitan area of Milan, Italy. DESIGN: All foreign-born individuals registering for accommodation centres in the city of Milan from November 2009 to April 2017 were screened for active TB and LTBI. Individuals aged <36 years with a tuberculin skin test (TST) induration of >10 mm were offered confirmatory testing with QuantiFERON®-TB Gold In-Tube (QFT-GIT). RESULTS: Of the 2666 TST-positive migrants aged <36 years who underwent LTBI confirmation testing, 1322 (49.6%) tested negative, 1339 (50.2%) were positive and five (0.2%) had indeterminate results. In the multivariate analysis, TB incidence in the country of origin and age were significantly associated with QFT-GIT positivity. Although estimated TB incidence in Eritrea, Morocco and Romania was 100/100 000 person-years (py), the probability of being QFT-GIT-positive in individuals from these countries were not statistically significantly different from individuals from countries with TB incidence > 250/100 000 person-years. CONCLUSION: Our data showed a high proportion of LTBI among individuals coming from intermediate TB burden countries.

RItA: The Italian severe/uncontrolled asthma registry.

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

Silica particle size and shape: in vitro effects on extracellular matrix metabolism and viability of human bronchial epithelial cells.

Crystal micro-morphology and dimension of silica particles could be responsible for the high prevalence of silicosis as recently found among goldsmiths. In the present study we investigated two samples of silica particles with different surface sizes and shapes for their capacity to induce changes in ECM component production. In addition we investigated if their different effects could be related to cytotoxicity and apoptotic effects. Human bronchial epithelial cells were cultured with or without a sample of Silica used for casting gold jewellery, named in our experiments Silica P or a commercial sample of Silica with different physical and chemical properties, named in our experiments Silica F. After 48 h of exposure PCR analysis determined levels of several matrix components. As induction of the apoptosis cascade, annexin assay, caspase 3 activity and cellular cytoxicity by MTT assay were assayed. Silica F promoted fibronectin, MMP12, tenascin C and Integrins b5 gene expressions more than Silica P. Silica P stimulated more TGFß1 and its TGFßR1 receptor than Silica F. Cytotoxic effects were induced by the two samples of Silica. On the contrary, no alteration in classic apoptotic marker protein expression was observed in presence of either Silica F or Silica P, suggesting silica particles affect ECM production and metalloproteases through a mechanism that does not involve apoptotic activation. Different Silica micromorphology and TGFß signal pathway are linked to lung fibrotic effects but the potential role Silica in apoptotic and toxic reaction remains to be ascertained.

[Epidemiological evidence of possible musculoskeletal, cardiovascular and neoplastic effects in professional drivers]. / Le evidenze epidemiologiche sui possibili danni muscoloscheletrici, cardiovascolari e neoplastici nei lavoratori del settore dei trasporti terrestri.

The road and rail transport sector, since the several work tipology and risk factors for workers safety and health, is an area where assessing exposure effects is very difficult. Muscoskeletal cardiovascular and neoplastic diseases are the disorders more frequently associated to professional drivers. The role of professional driving is rather well-defined in low back pain occurence, correlated to whole body vibration exposure. Professional drivers are at higher risk of ischemic cardiovascular diseases, but it is not clear whether the risk is attributable just to the occupational exposures or also to their life-style risk factors. Evidence of an excess of risk for lung, genito-urinary and hemolymphopoietic cancer is clear in the scientific literature for professional drivers. Anyway the lack in the control of confounding factors, in exposure assessment force to be very cautious in results interpretation.

[Reduction of tobacco smoking among physicians of a hospital in central Italy]. / Riduzione dell'abitudine al fumo di tabacco tra i medici di un'Azienda Ospedaliera dell'Italia centrale.

This study assessed the variations in smoking habit in physicians in a General Hospital in Central Italy in 12 years. Data were collected from medical records of workers who underwent health surveillance in 1998-99 and in 2010-11. The prevalence of smokers was 26.3% (male 25.6%, female 27.6%) in 1998-99 and 19.2% (male 19.8%, female 18.5%) in 2010-11. As compared to 1998-99, the prevalence of smokers in 2010-11 was reduced in both sex and in all age classes. Despite the relevant reduction, the prevalence of smokers among physicians remains still high. Occupational physicians could play an important role against tobacco smoking, as they can provide a brief counseling to all smoking physicians during medical health surveillance at workplace and take part in worksite health promotion programmes.

[Prolonged exposure to crystalline silica Min-U-Sil-5 influences apoptosis or extracellular matrix genes expression in human bronchial epithelial cells]. / L'esposizione prolungata alla silice cristallina Min-U-Sil-5 influenza l'espressione di geni della matrice extracellulare o coinvolti nell'apoptosi in cellule epiteliali bronchiali umane BEAS-2B.

Crystalline silica (Min-U-Sil-5) induces oxidative stress in human bronchial epithelial cells (BEAS-2B), through the intracellular accumulation of ROS that cause oxidative damage leading to the degradation of extracellular matrix (ECM) proteins and to the loss of cell adhesion molecules inducing apoptosis and genotoxic damage. This paper briefly summarizes some of the recent findings from our laboratories with emphasis on the molecular events by which the cronic and cumulative exposure to crystalline silica can induce cellular damage that promotes changes in extracellular matrix and in apoptosis gene expression.

[Smoking in the workplace: role of occupational physicians]. / Abitudine al fume di tabacco nei luoghi di lavoro: ruolo del Medico del Lavoro Competente.

In many industrialized countries smokers have been observed in high prevalence among workers with poor educational status, who are usually exposed to major occupational risks. The smoking habit and passive smoking may by themselves, or through interactions with other occupational risk factors, cause the onset of serious diseases. Therefore health reasons and the legal obligation to observe the smoking ban in the workplace make it essential to prevent and combat smoking in the workplace and to promote smoking cessation in workers who smoke. This initiative should benefit not only workers' health and well-being but also company finances. The Occupational Physician should engage in diverse activities ranging from encouraging young people not to start smoking to providing programmes to encourage workers who smoke to abandon the habit. For example, he or she should i) inform managers, supervisors and workers about the high risks linked to smoking, passive smoking and obligations established by law ii) collect information about the smoking habit among workers and supply workers with the so-called minimal clinical intervention during routine health surveillance appointments and iii) collaborate with specific health promotion programmes in the workplace.

[Smoking ban observance in a general hospital]. / Il rispetto del divieto di fumare in un'Azienda Ospedaliera.

Passive smoking is one of the main risk factors for severe chronic diseases. Hospitals are appropriate settings for promoting tobacco smoking cessation and preventing passive smoking. Moreover, since 2003 Italian Law (no 3/2003) forbids smoking in enclosed workplaces. The smoking ban should be strictly observed in hospitals. This study assessed smoking ban observance and exposure to ETS in a group of paramedical personnel working in a General Hospital (n=1037). Each subject answered a self-administered questionnaire. The prevalence of smokers was 31.2% in females and 31.5% in males. 83% of non-smokers and 66.6% of smokers approved the smoking ban in the hospital but 39.6% of non-smokers and 17.4% of smokers stated it was not observed. Percentages of, respectively, 57.0% and 31.1% in 2004 had dropped in 2005 and in 2006, after Law no 3/2003 was implemented. More than 90% of paramedical personnel declared that workers usually smoked in the workplace. 11.1% of non-smokers reported they were often exposed to ETS and 50% sometimes. These result show the smoking ban was not fully observed in the Hospital, where many workers reported they were exposed to ETS. Occupational Physicians should encourage health workers to stop smoking by offering appropriate counselling.

[Crystalline silica can induce oxidative stress by inhibiting glyoxalase system in bronchial epithelial cells]. / La silice cristallina (Min-U-Sil 5) induce stress ossidativo inibendo l'espressione del sistema delle gliossalasi in cellule bronchiali umane (BEAS-2B).

UNLABELLED: Chronic inflammation and reactive oxygen species (ROS) production induced by crystalline silica are involved in the development of silicosis and lung cancer pathogenesis. ROS can generate lipid peroxydation of cell membranes that can produce methylglyoxal (MG), a strong cell proliferation inhibitor and apoptosis inducer. MG is naturally removed by glyoxalase I (GI) and glyoxalase II (GII) through a glutathione (GSH) dependent mechanism. Therefore mRNA expression of glyoxalases is correlated to MG concentration and oxidative stress. OBJECTIVES: evaluate oxidative stress induced by crystalline silica by glyoxalases mRNA expression and methylglyoxal concentration MATERIAL AND METHODS: In bronchial epithelial cell culture (BEAS-2B), exposed to 50 microg/cm2 crystalline silica (Min-U-Sil 5), for 2, 6, 12, and 24 hours, GI and GII mRNA levels and MG intracellular concentration were measured respectively by Real-Time PCR and HPLC. RESULTS: Crystalline silica exposure induced a significant reduction in mRNA expression of glyoxalases and an increase of MG intracellular concentration. CONCLUSIONS: The results suggest a possible use of MG and mRNA expression of GI and GII as crystalline silica induced oxidative stress indicators.

[Smoke habit in a population of apprentices in middle of Italy]. / Abitudine al fumo in una popolazione di apprendisti dell'Italia centrale.

This study assessed the smoking habit in 7,159 apprentices (females: 53.3%) in central Italy. In the period 1996-2006, each apprentice underwent a compulsory health examination to assess fitness for work carried out by specialists in Occupational Medicine. Demographic data and information on schooling, smoking habit, alcohol and coffee intake were collected by a questionnaire. Overall, 51.9% of apprentices were smokers. Smokers were fewer among female apprentices than among the males (48.3% vs 55.9%; chi-square test, p < 0.001). No decrease in the prevalence of smokers was evident during the study period. Low educational level, and daily intake of alcohol and coffee significantly increased the risk of being a smoker. Finding a high percentage of smokers among Italian apprentices with a low educational level who are employed in jobs for which few qualifications are required indicates the need for work-place activities against tobacco smoking habit. Specialists in Occupational Medicine who perform regular health surveillance of workers could play a role in the anti-smoking campaign by integrating their routine work with brief counselling sessions aimed at preventing smoking in young workers and helping smokers to stop and by collaborating in work-place health promotion programmes.

Comparative in vitro studies on the fibrogenic effects of two samples of silica on epithelial bronchial cells.

The small dimension and particle shape of silica in gypsum used to prepare moulds for lost wax casting might be responsible for the high prevalence of silicosis in gold jewellery. To test this hypothesis, human pulmonary epithelial cell (BEAS-2B) cultures were exposed to two samples of silica with different crystal micro-morphologies: Silica Powder (Silica P) which is used in casting gold jewellery, and no powder Silica (Silica F). Extracellular matrix (ECM) production was evaluated using radio-labelled precursors and quantified by RT-PCR analysis. Expression of basic fibroblast growth factor (FGF2) and its receptor (FGFR2) was also evaluated. The results demonstrated Silica P particles had a very fine lamellar crystalline structure while Silica F was characterized by larger rounded crystals. Silica P stimulated collagen production significantly more than Silica F and downregulated laminin and metalloprotease expression. Both silica samples down-regulated FGF2 but only Silica F enhanced FGF2 receptor expression. In conclusion each Silica sample promoted a profibrotic lung microenvironment in a different manner and also elicited different FGF2 signalling pathways. The data confirm that different micromorphology of Silica particles affects the fibrogenic potential and the molecular mechanisms of dust pathogenicity.

Induced sputum, exhaled breath condensate and nasal lavage fluid in electroplating workers exposed to chromium.

Occupational exposure to chromium may cause airway inflammation and bronchial asthma. In this study we investigated the effect of chromium on the respiratory tract of exposed and non-exposed electroplating workers using spirometry and analysis of induced sputum (IS), exhaled breath condensate (EBC) and nasal lavage fluid (NLF). In both groups spirometry was normal; chromium in induced sputum was higher in exposed workers (7.90 +/- 0.855 microg/L, vs 1.78 +/- 0.075 microg/L; p<0.001); no significant difference was found in induced sputum cellularity. Median nitrite concentration in EBC was significantly higher in exposed subjects (4.35 micromol/L, 5 degrees -95 degrees percentile: 1.88-10.13 vs 0.11 micromol/L, 5-95 percentile: 0-0.72) (p<0.001). IL-6 and TNF-alpha were not detectable in EBC. Median IL-6 concentration in nasal lavage fluid was higher in exposed workers (5.72 pg/ml, 5-95 percentile: 0-65.25 pg/ml vs 0.28 pg/ml, 5-95 percentile: 0-1.7 pg/ml) (p<0.01). No differences in Eosinophil Cationic Protein concentration were found. TNF-alpha was not detectable in NLF. Chromium in induced sputum correlated with nitrites in EBC. For the first time three non-invasive methods were used to assess changes in respiratory tract in workers exposed to chromium. The results suggest chromium exerts an inflammatory/irritative action on airways.

Lead poisoning caused by Indian ethnic remedies in Italy.

BACKGROUND: Complementary or alternative medicine has become widespread in Western Countries and since the remedies are "natural" they are believed to be free of toxic effects and health risks. Ethnic remedies may contain lead, other metals and toxic substances. OBJECTIVES: To show how lead poisoning as a result of using ethnic remedies may be severe enough to cause serious damage to health, and to increase awareness among family doctors and occupational physicians of the risks associated with ethnic remedies. METHODS AND RESULTS: Description of ethnic remedy-related lead poisoning in 2 native Italian adults, with clinical, laboratory and toxicological data. CONCLUSIONS: When metal poisoning is diagnosed, ethnic remedies should be included among the putative sources so as to avoid erroneous attribution to workplace exposure and application of unneeded preventive measures.

[Report on the activities carried out in the research project of the Ministry of Instruction, University, and Research entitled "Environmental and occupational exposure to inorganic lead: assessment of toxic effects of current doses and related preventive measures"]. / Presentazione delle attività svolte nell'ambito del progetto di ricerca MIUR "Esposizione ambientale ed occupazionale a piombo inorganico: studio degli effetti tossici conseguenti alle dosi correnti e delle relative misure preventive".

It is here presented the project sustained by the Ministry of Public Instruction, University and Research "Environmental and Occupational Exposure to Inorganic Lead: assessment of human health effects due to current doses and preventive measures" ruled out between 2001 and 2003. The aim of the study was to investigate about the toxic effects related to current occupational exposures to inorganic lead (particularly those effects concerning blood pressure, carcinogenic risk, nervous and immunological systems), to identify hypersusceptibility conditions, particularly the ALAD genetic polymorphism and to evaluate the role of traditional biomarker and the possibility of introducing new ones. In the present article the procedures followed during the project lasting and the contribution of each Unit are described. The results of the research, presented in detail in the current issue, do confirm the inadequacy of the biological exposure index nowadays ruled by Lex 25/2002.

[Effects of inorganic lead exposure on the autonomic nervous system and on the variability of heart rate among workers at a battery plant]. / Effetti dell'esposizione a piombo inorganico sul sistema nervoso autonomo e sulla variabilità della frequenza cardiaca in lavoratori di una fabbrica di accumulatori.

Inorganic Lead can cause a toxic effect on Central Nervous System, Peripheral Nervous System and Autonomic Nervous System (ANS). A damage of the ANS can determine an heart rate variability (HRV) reduction. In this study 43 battery workers exposed to inorganic lead with mean PbB = 31.63 microg/dl (DS 14.77 microg/dl) and 35 not exposed subjects underwent to an evaluation of heart rate variability by specific tests. Heart rate variability in the exposed group was, for some tests (lying to standing, lying to standing-standing to lying) reduced compared with not exposed subjects and for other tests (Valsalva manouvre, lying to standing-standing to lying) correlated with PbB and Zinc Protoporphyrin (ZPP), but not with BMI, age and smoking habits. This study, like others conducted on similar populations, suggest an effect of occupational inorganic lead exposure on Autonomic Nervous System and heart rate variability

[ALAD polymorphism and indicators of dose and effects of occupational exposure to inorganic lead]. / Polimorfismo ALAD ed indicatori di dose e di effetto dell'esposizione professionale a piombo inorganico.

The delta-aminolevulinate dehydrase (ALAD) genetic polymorphism was investigated along with biomarkers of lead exposure and effect on 333 male workers, occupationally exposed to lead, with blood lead levels (PbB) higher than 100 microg/l. ALAD genotype frequencies were distributed as expected among Caucasians. Workers bearing at least one ALAD-2 allele showed PbB values slightly higher than those from ALAD-1-1 subjects, who also exhibited higher urinary delta-aminolevulinic acid (ALAU) and blood zinc protoporphyrin (ZPP) levels. The plasmatic lead (PbP)/PbB ratio was similar in both groups. Exposure and effect biomarkers were significantly each other correlated among ALAD-1-1 subjects only, who showed also a significant inverse relationship between ALAD activity and ZPP values. Results confirm previous studies, supporting the hypothesis that ALAD polymorphism may interfere with toxico-kinetic and toxico-dynamic parameters of occupational exposure to Pb.

[Chemical pollution of indoor air and its effects on health]. / Inquinanti chimici dell'aria interna ed effetti sulla salute.

Many studies have demonstrated how exposure to chemical pollutants in indoor air has adverse effects on health and comfort. Volatile organic compounds (VOCs), formaldehyde, ozone, particulates, fibres and environmental tobacco smoke have all been implicated. VOCs include a wide range of chemical substances which irritate mucosa. Many are neurotoxic and some are suspected or known to be carcinogenic e.g. benzene. Formaldehyde, the simplest and most common aldehyde in indoor air, is a powerful irritant to the skin, eyes, nose and upper airways. Given its close association with nasal-pharyngeal tumours, it has recently been classified as a certain carcinogen for humans. Exposure to ozone may cause airway irritation and inflammation, reduce the ventilation function and increase reversible bronchial reactivity. In the general population it increases the mortality rate and the number of hospital admissions for respiratory diseases. Airborne particles, a mixture of organic and inorganic substances, are powerful irritants for the eyes and mucosa and can cause adverse cardiovascular effects. Apart from indoor environments, exposure to asbestos fibres has been associated with an increased risk of respiratory diseases such as pneumoconiosis lung cancer and mesothelioma. Synthetic mineral fibres cause transient irritation and inflammation of the skin, eyes and upper airways. Recent observations have confirmed that exposure to environmental tobacco smoke, which is widespread in workplaces, increases the risk of lung cancer, irritative respiratory and ocular symptoms and cardiovascular diseases.