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.

Asthma incidence can be influenced by climate change in Italy: findings from the GEIRD study-a climatological and epidemiological assessment.

An association between climatic conditions and asthma incidence has been widely assumed. However, it is unclear whether climatic variations have a fingerprint on asthma dynamics over long time intervals. The aim of this study is to detect a possible correlation of the Summer North Atlantic Oscillation (S-NAO) index and the self-calibrated palmer drought severity index (scPDSI) with asthma incidence over the period from 1957 to 2006 in Italy. To this aim, an analysis of non-stationary and non-linear signals was performed on the time series of the Italian databases on respiratory health (ISAYA and GEIRD) including 36,255 individuals overall, S-NAO, and scPDSI indices to search for characteristic periodicities. The ISAYA (Italian Study on Asthma in Young Adults) and GEIRD (Gene Environment Interactions in Respiratory Diseases) studies collected information on respiratory health in general population samples, born between 1925 and 1989 and aged 20-84 years at the time of the interview, from 13 Italian centres. We found that annual asthma total incidence shared the same periodicity throughout the 1957-2006 time interval. Asthma incidence turned out to be correlated with the dynamics of the scPDSI, modulated by the S-NAO, sharing the same averaged 6 year-periodicity. Since climate patterns appear to influence asthma incidence, future studies aimed at elucidating the complex relationships between climate and asthma incidence are warranted.

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.

8-isoprostane in exhaled breath condensate after experimental exposure to wood smoke in humans.

Wood smoke, a well-known indoor and outdoor air pollutant, may cause adverse health effects through oxidative stress. In this study 8-isoprostane, a biomarker of oxidative stress, was measured in exhaled breath condensate (EBC) and urine before and after experimental exposure to wood smoke. The results were compared with measurements of other biomarkers of oxidative stress and inflammation. Thirteen subjects were exposed first to clean air and then, after 1 week, to wood smoke in an exposure chamber during 4-hour sessions. Exhaled breath condensate, exhaled nitric oxide, blood and urine were sampled before and at various intervals after exposure to wood smoke and clean air. Exhaled breath condensate was examined for 8-isoprostane and malondialdehyde (MDA), while exhaled air was examined for nitric oxide, serum for Clara cell protein (CC16) and urine for 8-isoprostane. 8-isoprostane in EBC did not increase after wood smoke exposure and its net change immediately after exposure was inversely correlated with net changes in MDA (r(s)= -0.57, p= 0.041) and serum CC16 (S-CC16) (r(p)= -0.64, p= 0.020) immediately after the exposure. No correlation was found between 8-isoprostane in urine and 8-isoprostane in EBC. In this study controlled wood smoke exposure in healthy subjects did not increase 8-isoprostane in EBC.

Characteristics and predictors of allergic rhinitis undertreatment in primary care.

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

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

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

Isoniazid preventive treatment: predictors of adverse events and treatment completion.

SETTING: Villa Marelli Institute (VMI), Niguarda Ca'Granda Hospital, Milan, Italy. BACKGROUND: A recent report on the fatal side effects of isoniazid preventive therapy (IPT) from the United States has re-ignited discussion on the safety of this intervention. OBJECTIVE: To evaluate IPT feasibility, treatment completion and adverse events (AE) and their determinants under field conditions. METHODS: Data from consecutive subjects undergoing IPT at the VMI were recorded in an electronic database from 1992 to 2009. Logistic regression analysis was performed to detect completion and AE determinants. RESULTS: A total of 11,963 patients were included in the study. AE (odds ratio [OR] 2.70, 95%CI 2.22-3.28) and human immunodeficiency virus positive status (OR 5.20, 95%CI 2.10-12.93) were the main determinants of treatment interruption among Italians, while social weakness (no housing/job; OR 2.88, 95%CI 2.43-3.42), AEs (OR 1.33, 95%CI 1.15-1.53, 2.22-3.28) and screening in undocumented subjects (OR 1.20, 95%CI 1.01-1.44) prevailed among foreigners. Age was the main determinant of transaminase increase (OR 1.03, 95%CI 1.03-1.04), as were AEs of the gastrointestinal (OR 1.02, 95%CI 1.02-1.03), central nervous (OR 1.02, 95%CI 1.02-1.05) and peripheral nervous systems (OR 1.04, 95%CI 1.02-1.05). CONCLUSION: This analysis demonstrates the feasibility and safety of IPT, with determinants of interruption and AEs being predictable and addressable.

Exhaled breath condensate, nasal eosinophil cationic protein level and nasal cytology during immunotherapy for cypress allergy.

Interest in cypress allergy is widely rising: an increasing number of studies have pointed out the efficacy of immunotherapy to reduce cypress-related symptoms and drug use. Cypress immunotherapy is well tolerated, but there are few studies dealing with its sub-clinical effects on the airways. The aim of this investigation is to assess the effects of immunotherapy on airways by the analysis of exhaled breath condensate (EBC), nasal lavage fluid (NAL) and nasal cytology. Fifteen mono-sensitized to cypress pollen patients have been observed, among them 9 have been treated with sub-cutaneous immunotherapy (SCIT), 3 with sub-lingual immunotherapy (SLIT) and 3 which were not treated underwent EBC, NAL and nasal cytology out of the pollen season. 8-isoprostane in EBC, Eosinophil cationic protein (ECP) and inflammatory cells in nasal cytology were also evaluated. The median value of 8-isoprostane in EBC was 18.58 pg/ml in patients who did not undergo immunotherapy, 49.38 pg/ml in SCIT patients and 13.41 pg/ml in SLIT subjects. The median value of ECP in nasal lavage was higher in non- treated subjects (27.3 mg/l) than in those treated with SCIT (1 mg/l)(p less than 0,05) or SLIT (2.6 mg/l). All nasal cytology specimens did not show any sign of inflammation. In conclusion SLIT seems to be well tolerated and to reduce significantly the levels of ECP in nasal lavage. In addition the levels of 8-isoprostane in EBC among SCIT patients were unexpectedly high and need to be further evaluated.

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.

[Permanent education, updating and accreditation in occupational medicine: the contribution of the Italian Society of Occupational Medicine and Industrial Hygiene (SIMLII) in the first decade of the 21st century]. / Formazione, aggiornamento ed accreditamento in Medicina del Lavoro: il contributo della Società Italiana di Medicina del Lavoro e Igiene Industriale (SIMLII) nel primo decennio del 2000.

BACKGROUND: Permanent education of health workers is obligatory under Italian legislation and is managed by the Ministry of Health through its Permanent Education Programme. METHODS: In 2000 the Italian Society of Occupational Medicine and Industrial Hygiene (SIMLII), set up and implemented a programme of Permanent Education and Accreditation for specialists in occupational medicine, based on participation in "non-mandatory" and "mandatory" educational activities. "Non-mandatory" activities were chosen by the individual physician for education in topics related to occupational medicine. "Mandatory" educational activities, which were organised by the Society, included in-depth analysis of the Society's guidelines related to specific topics in occupational medicine. RESULTS AND DISCUSSION: The Guidelines study course played a pre-eminent role in the Society's permanent education programme and was greatly appreciated by all participants. The Board of the Society has recently approved a new Plan of Permanent Education, identifying the means (Guidelines, Consensus Documents) whereby occupational physicians can improve their professional standards. The Plan's aims are to facilitate accreditation and also to identify and promote high-quality updating programmes which will lead to recognition of 'professional excellence". Crucial to its success will be a 3-year on-line learning programme (MeLA) that SIMLII has just implemented, which will enable occupational physicians to acquire credits in "Occupational Medicine and Workplace Safety", as required by current Italian legislation. This article summarizes SIMLII activities over the past ten years in the field of permanent medical education for occupational physicians.

[Are targeted interventions needed in foreigner workers with latent tubercular infection? A study on anti-tubercular treatment compliance among health care workers]. / C'è esigenza di interventi mirati nei lavoratori stranieri affetti da infezione tubercolare latente? Uno studio sulla compliance alla terapia antitubercolare in operatori sanitari.

INTRODUCTION: Health care workers (HCWs) are at high risk of latent tubercular infection (LTBI). In this study predictors of anti-tubercular treatment interruption in HCWs with LTBI are evaluated. METHODS: 1056 HCWs with LTBI were followed up to register adverse events and predictors of treatment interruption. RESULTS: 289 workers did not complete the treatment. Predictors of treatment interruption were adverse events (OR 1.47; 95CI% 1.07-2.03) and to be born in South-America (OR 1.55; 95CI% 1.06-2.26). CONCLUSION: The higher risk in South-Americans supports the need of targeted formative interventions on these workers.

[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.

Acute pneumonia in a fire-eater.

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-alkanebased 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.