COVID-19 Marked a Change in the Scope of Occupational Medicine from Occupational to Work-Related Diseases and Total Worker Health®.

The COVID-19 pandemic challenged occupational medicine, while its focus had already shifted from occupational diseases to work-related illnesses. Such a broader scope allowed the inclusion of transmissible diseases among the causes for concern in working settings. COVID-19 has had a profound impact globally, resulting in millions of infections, often lethal. From its appearance, COVID-19 was found to affect specific groups of workers at higher risk of contracting the virus due to their occupation or workplace conditions, which accounts for its consideration as a potential work-related disease. This overview examines various aspects of COVID-19 based on articles published in our journal. Specifically, the epidemiology of COVID-19 is discussed, including mortality rates and groups at higher risk. The diagnosis, measures to prevent contagion, vaccination efforts, long-term effects, and psychosocial factors are also summarized. The emerging picture is that COVID-19 has been a trigger accelerating the change of paradigm of occupational medicine, which is more and more concerned with prevention. Occupational Health contributes to health promotion and Total Worker Health®.

Comparison of extrafine beclomethasone dipropionate/formoterol fumarate dry powder inhaler and pressurized metered-dose inhaler in Chinese patients with asthma: the FORTUNE study.

OBJECTIVE: When selecting inhaled therapies, it is important to consider both the active molecules and the device. Extrafine formulation beclomethasone dipropionate plus formoterol fumarate (BDP/FF) has been available for some years delivered via pressurized metered-dose inhaler (pMDI). More recently, a breath-activated, multi-dose dry-powder inhaler (DPI), the NEXThaler, has been approved. The current study aimed to demonstrate the non-inferiority of BDP/FF delivered via the DPI vs. via the pMDI, in Chinese adults with asthma. METHODS: After a four-week run-in period, when all patients received BDP/FF pMDI 100/6 µg, two inhalations twice daily (BID), patients were randomized equally to BDP/FF pMDI or DPI, both 100/6 µg, two inhalations BID for 12 weeks. The primary objective was to demonstrate non-inferiority of BDP/FF DPI vs. BDP/FF pMDI in terms of average pre-dose morning peak expiratory flow (PEF) over the entire treatment period. RESULTS: Of 252 and 242 patients in the DPI and pMDI groups, respectively, 88.5% and 88.8% completed the study. The primary objective was met, with no statistically significant difference between the treatments in average pre-dose morning PEF, and with the lower limit of the 95% CI above the -15 L/min non-inferiority margin (adjusted mean difference: 5.25 L/min [95% CI: -0.56, 11.06]). Adverse events were reported by 48.4% and 49.6% patients in the DPI and pMDI groups, respectively, most mild or moderate. CONCLUSIONS: The NEXThaler DPI is a similarly effective device to the pMDI for the administration of BDP/FF in adults, so extending the options available for the management of asthma.

Interaction between Occupational and Non-Occupational Arsenic Exposure and Tobacco Smoke on Lung Cancerogenesis: A Systematic Review.

Although a higher lung cancer risk has been already associated with arsenic exposure, the contribution of arsenic and its compounds to the carcinogenic effects of other agents, such as tobacco smoke, is not well characterized. This systematic review examined the relationship between occupational and non-occupational arsenic exposure and tobacco smoking on lung cancer risk using papers published from 2010 to 2022. Two databases, PUBMED and Scifinder, were used for the searches. Among the sixteen human studies included, four were about occupational exposure, and the others were about arsenic in drinking water. Furthermore, only three case-control studies and two cohort studies evaluated an additive or multiplicative interaction. The interaction between arsenic exposure and tobacco smoke seems to be negligible at low arsenic concentrations (<100 µg/L), while there is a synergistic effect at higher concentrations. Finally, it is not yet possible to assess whether a linear no-threshold (LNT) model for lung cancer risk can be applied to the co-exposure to arsenic and tobacco smoke. Although the methodological quality of the included studies is good, these findings suggest that rigorous and accurate prospective studies on this topic are highly needed.

Artificial intelligence based software facilitates spirometry quality control in asthma and COPD clinical trials.

Rationale: Acquiring high-quality spirometry data in clinical trials is important, particularly when using forced expiratory volume in 1 s or forced vital capacity as primary end-points. In addition to quantitative criteria, the American Thoracic Society (ATS)/European Respiratory Society (ERS) standards include subjective evaluation which introduces inter-rater variability and potential mistakes. We explored the value of artificial intelligence (AI)-based software (ArtiQ.QC) to assess spirometry quality and compared it to traditional over-reading control. Methods: A random sample of 2000 sessions (8258 curves) was selected from Chiesi COPD and asthma trials (n=1000 per disease). Acceptability using the 2005 ATS/ERS standards was determined by over-reader review and by ArtiQ.QC. Additionally, three respiratory physicians jointly reviewed a subset of curves (n=150). Results: The majority of curves (n=7267, 88%) were of good quality. The AI agreed with over-readers in 91% of cases, with 97% sensitivity and 93% positive predictive value. Performance was significantly better in the asthma group. In the revised subset, n=50 curves were repeated to assess intra-rater reliability (κ=0.83, 0.86 and 0.80 for each of the three reviewers). All reviewers agreed on 63% of 100 unique tests (κ=0.5). When reviewers set the consensus (gold standard), individual agreement with it was 88%, 94% and 70%. The agreement between AI and "gold-standard" was 73%; over-reader agreement was 46%. Conclusion: AI-based software can be used to measure spirometry data quality with comparable accuracy as experts. The assessment is a subjective exercise, with intra- and inter-rater variability even when the criteria are defined very precisely and objectively. By providing consistent results and immediate feedback to the sites, AI may benefit clinical trial conduct and variability reduction.

Benzene Exposure and MicroRNAs Expression: In Vitro, In Vivo and Human Findings.

MicroRNAs (miRNAs) are important regulators of gene expression and define part of the epigenetic signature. Their influence on human health is established and interest in them is progressively increasing. Environmental and occupational risk factors affecting human health include chemical agents. Benzene represents a pollutant of concern due to its ubiquity and because it may alter gene expression by epigenetic mechanisms, including miRNA expression changes. This review summarizes recent findings on miRNAs associated with benzene exposure considering in vivo, in vitro and human findings in order to better understand the molecular mechanisms through which benzene induces toxic effects and to evaluate whether selected miRNAs may be used as biomarkers associated with benzene exposure. Original research has been included and the study selection, data extraction and assessments agreed with PRISMA criteria. Both in vitro studies and human results showed a variation in miRNAs' expression after exposure to benzene. In vivo surveys also exhibited this trend, but they cannot be regarded as conclusive because of their small number. However, this review confirms the potential role of miRNAs as "early warning" signals in the biological response induced by exposure to benzene. The importance of identifying miRNAs' expression, which, once validated, might work as sentinel molecules to better understand the extent of the exposure to xenobiotics, is clear. The identification of miRNAs as a molecular signature associated with specific exposure would be advantageous for disease prevention and health promotion in the workplace.

CDK4/6 Inhibition Enhances the Efficacy of Standard Chemotherapy Treatment in Malignant Pleural Mesothelioma Cells.

BACKGROUND: The loss of the CDKN2A/ARF (cyclin-dependent kinase inhibitor 2A/alternative reading frame) gene is the most common alteration in malignant pleural mesothelioma (MPM), with an incidence of about 70%, thus representing a novel target for mesothelioma treatment. In the present study, we evaluated the antitumor potential of combining the standard chemotherapy regimen used for unresectable MPM with the CDK4/6 (cyclin-dependent kinase 4 or 6) inhibitor abemaciclib. METHODS: Cell viability, cell death, senescence, and autophagy induction were evaluated in two MPM cell lines and in a primary MPM cell culture. RESULTS: The simultaneous treatment of abemaciclib with cisplatin and pemetrexed showed a greater antiproliferative effect than chemotherapy alone, both in MPM cell lines and in primary cells. This combined treatment induced cellular senescence or autophagic cell death, depending on the cell type. More in detail, the induction of cellular senescence was related to the increased expression of p21, whereas autophagy induction was due to the impairment of the AKT/mTOR signaling. Notably, the effect of the combination was irreversible and no resumption in tumor cell proliferation was observed after drug withdrawal. CONCLUSION: Our results demonstrated the therapeutic potential of CDK4/6 inhibitors in combination with chemotherapy for the treatment of MPM and are consistent with the recent positive results in the MiST2 arm in abemaciclib-treated patients.

Interaction between occupational radon exposure and tobacco smoke: a systematic review.

INTRODUCTION: The risk of lung cancer from radon exposure was small compared to tobacco smoking (BEIR VI), but the relationship between these two carcinogenic agents has yet to be quantitatively estimated. The objective of this systematic review was to evaluate the last evidences on the role of radon occupational exposures and tobacco smoke on lung cancer risk. AREAS COVERED: Thirteen articles were selected using two different databases, PubMed and Scifinder, and were limited to those published from 2010 to 2021. The reference list of selected studies was reviewed to identify other relevant papers. EXPERT OPINION: Seven papers included in this systematic review did not deal with the multiplicative or the additive type of interaction between radon exposure and smoking habit. Six papers discussed the nature of this interaction with a prevalence of the sub-multiplicative model compared to the additive one. Altogether, smoking adjustment did not significantly change lung cancer risk. The included studies might constitute a starting point for updating the models for risk assessment in occupational and residential scenarios, promoting concomitantly the exposure reduction to radon and other cofactors, as recently introduced by Italian Legislative Decree number 101 of 31 July 2020, an application of Euratom Directive 59/2013.

This paper offers an updated overview on lung cancer risk due to occupational exposure to radon together with tobacco smoking habits. It evidences the quantitative role of smoking on radon exposure and discusses their interaction. The results show that smoking adjustments do not significantly modify lung cancer risk at both high and low radon concentrations.

Distribution of the Clinical Manifestations of Alpha 1 Antitrypsin Deficiency in Respiratory Outpatients from an Area of Northern Italy.

BACKGROUND: Alpha 1 antitrypsin deficiency (AATD) is an autosomal codominant genetic condition that affects Caucasians of the European population due to the presence of a deficient allele of the SERPINA1 gene. A frequency of about 1/5,000 individuals has been estimated in Italy. OBJECTIVES: The aim of the study was to evaluate the distribution of the clinical manifestations of severe and intermediate genetic AATD in the geographic area around Parma in Northern Italy. METHOD: 238 subjects were submitted to molecular analysis of the SERPINA1 gene, and data on anthropometric variables, smoking habits, number of packs per year, AAT serum concentration, and clinical manifestations were recorded and presented as mean ± SD or median values (1st quartile; 3rd quartile). RESULTS: The results show a distribution of genetic AATD of 4.1% of the screened population in the area encompassing the city of Parma. PI*MS and PI*MZ were the most common genotypes at 40.9% and 28.2% of the population with genetic AATD, and asthma and emphysema were the most represented clinical manifestations. CONCLUSION: Our study allowed to increase the knowledge of the distribution of genetic AATD in Northern Italy providing information regarding frequencies of genotypes and clinical manifestations of the disorder.

Maternal air pollution exposure during the first trimester of pregnancy and markers of inflammation and endothelial dysfunction.

BACKGROUND: Maternal exposure to air pollutants has been associated with pregnancy complications and adverse birth outcomes. Endothelial dysfunction, an imbalance in vascular function, during pregnancy is considered a key element in the development of pre-eclampsia. Environmental exposure to particulate matter (PM) during the first trimester of pregnancy might increase maternal inflammatory status thus affecting fetal growth, possibly leading to preterm delivery. OBJECTIVES: The purpose of the study was to evaluate possible effects of PM10 and PM2.5 exposure on fetal growth in healthy pregnant women at the end of the first trimester of pregnancy by investigating the relationship between circulating biomarkers of inflammation (IL-6), early systemic prothrombotic effects (CRP, plasma fibrinogen, PAI-1) and endothelial dysfunction (sICAM-1 and sVCAM-1). METHODS: 295 pregnant women were recruited. Individual PM exposure was assigned to each subject by calculating the mean of PM10 and PM2.5 daily values observed during the 30, 60, and 90 days preceding enrolment (long-term) and single lag days back to fourteen days (short-term), and circulating plasma biomarkers were determined. RESULTS: For long-term exposure, we observed an increase in sVCAM-1 and a decrease of PAI-1 levels for each 10 µg/m3 increase in PM10 concentration. Decreases in IL-6 and CRP levels were associated with each 10 µg/m3 PM2.5 increase. For short-term exposure, the levels of sVCAM-1 and PAI-1 were found to be associated with PM10 exposure, whereas fibrinogen levels were associated with PM2.5 exposure. Maternal plasmatic fibrinogen levels were negatively associated with the crown-rump length (p-value = 0.008). DISCUSSION: The present study showed that both long- and short-term exposures to PM are associated with changes in circulating levels of biomarkers in pregnant women reflecting systemic inflammation and endothelial dysfunction/activation. Our findings support the hypothesis that inflammation and endothelial dysfunction might have a central role in modulating the detrimental effects of air pollution exposure during pregnancy.

Sex-Related Differences in Long-COVID-19 Syndrome.

Background: Sex differences have been demonstrated in the acute phase of coronavirus disease 2019 (COVID-19). Women (F) were found to be less prone to develop a severe disease than men (M), but few studies have assessed sex-differences in Long-COVID-19 syndrome. Methods: The aim of this prospective/retrospective study was to characterize the long-term consequences of this infection based on sex. For this purpose, we enrolled 223 patients (89 F and 134 M) who were infected by SARS-CoV-2. In the acute phase of the illness, F reported the following symptoms more frequently than M: weakness, dysgeusia, anosmia, thoracic pain, palpitations, diarrhea, and myalgia-all without significant differences in breathlessness, cough, and sleep disturbance. Results: After a mean follow-up time of 5 months after the acute phase, F were significantly more likely than M to report dyspnea, weakness, thoracic pain, palpitations, and sleep disturbance but not myalgia and cough. At the multivariate logistic regression, women were statistically significantly likely to experience persistent symptoms such as dyspnea, fatigue, chest pain, and palpitations. On the contrary, myalgia, cough, and sleep disturbance were not influenced by sex. Conclusion: We demonstrated that F were more symptomatic than M not only in the acute phase but also at follow-up. Sex was found to be an important determinant of Long-COVID-19 syndrome because it is a significant predictor of persistent symptoms in F, such as dyspnea, fatigue, chest pain, and palpitations. Our results suggest the need for long-term follow-up of these patients from a sex perspective to implement early preventive and personalized therapeutic strategies.

Coronavirus Disease 2019: COSeSco - A Risk Assessment Score to Predict the Risk of Pulmonary Sequelae in COVID-19 Patients.

BACKGROUND: The presence of interstitial pneumonia in coronavirus disease 2019 (COVID-19) patients, as diagnosed through laboratory, functional, and radiological data, provides potential predicting factors of pulmonary sequelae. OBJECTIVES: The objectives were the creation of a risk assessment score for pulmonary sequelae at high-resolution computed tomography (HRCT) through the assessment of laboratory data, lung function, and radiological changes in patients after the onset of COVID-19 interstitial pneumonia and the identification of predictive factors. METHODS: We enrolled 121 subjects hospitalized due to COVID-19 pneumonia in our study. Clinical features, Charlson Comorbidity Index (CCI) score, HRCT score, and blood chemistry data at hospital admission, as well as HRCT score, pulmonary function testing values, exercise capacity by means of a 6-Minute Walk Test (6MWT), and dyspnea perception by the modified Medical Research Council (mMRC) at 4-month follow-up, were all recorded. The variables were elaborated in order to create a predictive model to identify patients at high risk of pulmonary sequelae at HRCT. RESULTS: At the time of follow-up visit, 63% of patients had functional abnormality (diffusion lung capacity and/or total lung capacity <80% of predicted). Age, BMI, CCI, D-dimer, 6MWT, and mMRC were included in the COVID-19 Sequelae Score (COSeSco, ranging 0-15), which was able to individuate COVID-19 patients with radiologic sequelae (HRCT score >10%) at follow-up. The most revelatory COSeSco value that was found to intercept the highest sensitivity (100%) and specificity (77%) was 2. CONCLUSION: The COSeSco - comprising age, BMI, comorbidities, D-dimer, walking distance, and dyspnea perception - makes it possible to identify particularly at-risk COVID-19 patients who are likely to develop pulmonary sequelae assessed by HRCT.

Long-Term Cardiac Sequelae in Patients Referred into a Diagnostic Post-COVID-19 Pathway: The Different Impacts on the Right and Left Ventricles.

Most patients who had COVID-19 are still symptomatic after many months post infection, but the long-term outcomes are not yet well defined. The aim of our prospective/retrospective study was to define the cardiac sequelae of COVID-19 infection. This monocentric cohort study included 160 consecutive patients who had been discharged from the ward or from the outpatient clinic after a diagnosis of COVID-19 and subsequently referred for a follow-up visit. Clinical features' data about the acute phase along with information about the follow-up visit, including ECG and Echocardiographic parameters, were recorded. At an average follow-up of 5 months, echocardiography showed morpho-functional characteristics of both right (RV) and left (LV) ventricles, such as RV dilation, increased pressure in the pulmonary circulation, and bi-ventricular systolic-diastolic dysfunction. When examined using multivariate analysis, independent of age, sex, and co-morbidities, RV and LV changes were significantly associated with chest High-Resolution computed tomography score and hemodynamic Instability (HI), and with C-reactive protein, respectively. Our results suggest that COVID-19 may impact RV and LV differently. Notably, the extent of the pneumonia and HI may affect RV, whereas the inflammatory status may influence LV. A long-term follow-up is warranted to refine and customize the most appropriate therapeutic strategies.

Environmental/Occupational Exposure to Radon and Non-Pulmonary Neoplasm Risk: A Review of Epidemiologic Evidence.

Although Radon (Rn) is a known agent for lung cancer, the link between Rn exposure and other non-pulmonary neoplasms remains unclear. The aim of this review is to investigate the role of Rn in the development of tumors other than lung cancer in both occupational and environmental exposure. Particularly, our attention has been focused on leukemia and tumors related to brain and central nervous system (CNS), skin, stomach, kidney, and breast. The epidemiologic literature has been systematically reviewed focusing on workers, general population, and pediatric population. A weak increase in leukemia risk due to Rn exposure was found, but bias and confounding factors cannot be ruled out. The results of studies conducted on stomach cancer are mixed, although with some prevalence for a positive association with Rn exposure. In the case of brain and CNS cancer and skin cancer, results are inconclusive, while no association was found for breast and kidney cancers. Overall, the available evidence does not support a conclusion that a causal association has been established between Rn exposure and the risk of other non-pulmonary neoplasms mainly due to the limited number and heterogeneity of existing studies. To confirm this result, a statistical analysis should be necessary, even if it is now not applicable for the few studies available.

Overexpression of microRNA­486 affects the proliferation and chemosensitivity of mesothelioma cell lines by targeting PIM1.

Dysregulated levels of microRNAs (miRNAs or miRs), involved in oncogenic pathways, have been proposed to contribute to the aggressiveness of malignant pleural mesothelioma (MPM). Previous studies have highlighted the downregulation of miRNA miR­486­5p in patients with mesothelioma and the introduction of miRNA mimics to restore their reduced or absent functionality in cancer cells is considered an important therapeutic strategy. The aim of the present study was to evaluate the mechanisms through which miRNAs may influence the functions, proliferation and sensitivity to cisplatin of MPM cells. In the present study, a miR­486­5p mimic was transfected into the H2052 and H28 MPM cell lines, and cell viability, proliferation, apoptosis and mitochondrial membrane potential were monitored. miR­486­5p overexpression led to a clear impairment of cell proliferation, targeting CDK4 and attenuating cell cycle progression. In addition, transfection with miR­486­5p mimic negatively regulated the release of inflammatory factors and the expression of Provirus integration site for Moloney murine leukaemia virus 1 (PIM1). The sensitivity of the cells to cisplatin was enhanced by enhancing the apoptotic effects of the drug and impairing mitochondrial function. On the whole, the present study demonstrates that miR­486­5p may play an important role in MPM treatment by targeting multiple pathways involved in tumour development and progression. These activities may be mostly related to the downregulation of PIM1, a crucial regulator of cell survival and proliferation. Furthermore, these results provide support for the combined use of miR­486­5p with chemotherapy as a therapeutic strategy for MPM.

Spirometry: A practical lifespan predictor of global health and chronic respiratory and non-respiratory diseases.

OBJECTIVES: 1. To review and discuss available evidence supporting that spirometry is an overlooked global health marker, that could be used regularly through the lifespan to monitor human health and predict risk of chronic respiratory and other chronic non-communicable diseases (NCDs). 2. To discuss the challenges and opportunities that this proposal faces.Summary of key data. First, spirometry is essential to assess and monitor respiratory health. Second, spirometry adds prognostic value to other well-accepted health markers used in clinical practice, such as blood pressure, body mass index, glucose and blood lipids, by identifying individuals at risk, not only of respiratory diseases, but also of other NCDs, particularly cardiovascular and metabolic disorders. CONCLUSION: Although we acknowledge that research gaps still exist, we propose that spirometry assessed during childhood, adolescence and early and late adulthood can be a reproducible, non-invasive, safe and affordable global health marker to identify individuals in the general population at risk of respiratory and non-respiratory NCDs. In this context, spirometry may act as the caged canaries that miners used to carry into mines to alert them of dangerous accumulations of gases, thus providing an early warning and save lives.

The role of miRNA-221 and miRNA-126 in patients with benign metastasizing leiomyoma of the lung: an overview with new interesting scenarios.

Benign metastasizing leiomyoma (BML) is a rare disease characterized by extrauterine benign leiomyomatosis in patients with a previous or concomitant history of uterine leiomyoma. Currently, there are no specific criteria to predict the metastasizing ability of the uterine leiomyoma and the risk of malignant degeneration of pulmonary BML, and these are the aims of this study. We analyzed 10 uterine (three leiomyomas, four leiomyomas that gave rise to lung BML, three healthy tissues) and 11 pulmonary tissue samples (eight lung BML, three healthy tissues). Interestingly, one of the BML lesions exceptionally evolved into a leiomyosarcoma (case 2). Uterine leiomyoma microvascular density (MVD) was higher in the patients with uterine leiomyomas that gave rise to lung BML, reaching a peak in case 2. Strong positivity for the estrogen (ER) and progesterone (PR) receptors and a low proliferation index (Ki67 < 1%) were discovered both in patients with uterine leiomyoma and in patients with BML. Interestingly, in case 2, the last dedifferentiated leiomyosarcoma showed a weaker ER and PR positivity with a higher proliferation index (Ki67:30%). Regarding the uterine miRNA-126, a trend toward a hypo-expression between uterine leiomyoma and uterine leiomyoma that gave rise to lung BML was discovered, reaching the lowest level in case 2. Considering the pulmonary samples, we observed a higher miRNA-221 and a lower miRNA-126 expression in the leiomyosarcoma. We tried to better elucidate the biological behaviour of this rare disease. The analysis of the miRNA-221 and miRNA-126 could offer new diagnostic, prognostic and therapeutic perspectives.

Conducting spirometry in occupational health at COVID-19 times: international standards.

Spirometry is a commonly performed assessment of lung function for diagnostic purposes as well as for monitoring of chronic lung diseases. The last international standardization of this technique was published in 2005. After 14 years, a group of experts from two leading scientific societies, American Thoracic Society (ATS) and European Respiratory Society (ERS), published a joint position that updated the standardization of spirometry, with an extensive criteria re-organization, including key updates such as: relative contraindications, instrumentation requirement to meet the International Organization for Standardization (ISO) standards, quality assurance, operator training, pre-test requirements, acceptability and usability criteria. New standards underline three key elements to obtain high quality pulmonary function data: an accurate and precise instrumentation, a patient/subject capable of performing acceptable and repeatable measurements, and a motivated technologist to elicit maximum performance from the patient. Never- theless, although COVID-19 pandemic has enormously impacted and limited a widespread application of spirometry, it has prompted much attention on hygienic procedures and on further research on noncontact spirometers.

Clinical and radiological criteria for the differential diagnosis between asbestosis and idiopathic pulmonary fibrosis: Application in two cases.

INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) and asbestosis are pulmonary interstitial diseases that may present overlapping clinical aspects in the full-blown phase of the disease. For both clinical entities the gold standard for diagnosis is histological examination, but its execution poses ethical problems, especially when performed for preventive or forensic purposes. OBJECTIVE: To evaluate the application of internationally accepted clinical, anamnestic and radiological criteria for differential diagnosis between asbestosis and IPF, and to assess the ability to discriminate between the two diseases. Even if clinically similar, the two diseases present extremely different prognostic and therapeutic perspectives. METHODS: Two clinical cases of IPF are reported, in which the differential diagnosis was made by studying occupational exposure to asbestos, the onset and progression of clinical symptoms, and the identification of specific radiological elements by means of chest High Resolution Computed Tomography (HRCT). RESULTS: The diagnosis of IPF could be made on the basis of the absence of significant exposure to asbestos, the early onset and rapid progression of dyspnea and restrictive ventilatory defects, in association with a pulmonary radiological pattern characterized by peculiar elements such as honeycombing. DISCUSSION: The diagnostic procedure adopted to make a differential diagnosis with asbestosis provides practical clinical elements facilitating the differentiation between the two forms of pulmonary fibrosis, a fundamental aspect of the activity of the occupational physician.

Occupational Exposures and Smoking in Eosinophilic Granulomatosis With Polyangiitis: A Case-Control Study.

OBJECTIVE: Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Environmental agents and occupational exposures may confer susceptibility to EGPA, but data are scarce. This study was undertaken to investigate the association between occupational exposures (e.g., silica, farming, asbestos, and organic solvents) and other environmental agents (e.g., smoking) and the risk of EGPA. METHODS: Patients with newly diagnosed EGPA (n = 111) and general population controls (n = 333) who were matched for age, sex, and geographic area of origin were recruited at a national referral center for EGPA. Exposures were assessed using a dedicated questionnaire administered by a specialist in occupational medicine, under blinded conditions. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. RESULTS: Exposures to silica (OR 2.79 [95% CI 1.55-5.01], P = 0.001), organic solvents (OR 3.19 [95% CI 1.91-5.34], P < 0.001), and farming (OR 2.71 [95% CI 1.71-4.29], P < 0.001) were associated with an increased risk of EGPA. Co-exposure to silica and farming yielded an OR of 9.12 (95% CI 3.06-27.19, P < 0.001), suggesting a multiplicative effect between these 2 exposures. Smoking (current and former smokers combined) was significantly less frequent among patients with EGPA compared to controls (OR 0.49 [95% CI 0.29-0.70], P < 0.001). The pack-year index was also lower among patients with EGPA (OR 0.96 [95% CI 0.94-0.98], P < 0.001). The association of silica and farming was primarily aligned with ANCA-positive EGPA, while the association of smoking status and organic solvents was primarily aligned with ANCA-negative EGPA. CONCLUSION: The environment can influence susceptibility to EGPA. Exposure to silica, farming, or organic solvents is associated with an increased risk of EGPA, while smoking is associated with a lower risk. These exposures seem to have distinct effects on different EGPA subsets.