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Background Airway obstruction is a key feature of asthma and chronic obstructive pulmonary diseases (COPD). Smoking habits and workplace exposures to vapors, gas, dusts, and fumes (VGDF) could cause or exacerbate airway obstruction. The aim of this study is to evaluate the risk of airway obstruction due to smoking and workplace exposure, and their interaction, in a large population-based study. Methods In this cross-sectional study, a sample (n = 6153) of the Swedish population aged between 24 and 76 years underwent a questionnaire, clinical examination, blood test, and spirometry to gather information on airway obstruction classified by Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria or American Thoracic Society (ATS)/European Respiratory Society (ERS) criteria, risk factors, and confounders. Occupational exposures to VGDF were rated according to a specific job-exposure matrix. Adjusted logistic regression models were used to evaluate risk factors for airway obstruction in smokers and nonsmokers. Results In total, 9.8% had airway obstruction by GOLD criteria and 10.3% by ATS/ERS. Smokers with a high likelihood of exposure to VGDF had a higher risk of airway obstruction than those not exposed (odds ratio [OR]: 1.74, 95% confidence interval [CI]: 1.15-2.65 by GOLD; OR: 1.58, 95% CI: 1.06-2.37 by ATS/ERS) especially those >50 years of age. In smokers highly exposed to VGDF, risk estimates were higher than in the whole population, and the interaction between high exposure to VGDF and smoking further increased the risk of airway obstruction. Conclusions This study suggests a possible role for interaction between cigarette smoking and VGDF exposure on the risk of airway obstruction.

Francesco Menzella,1 Marco Bonavia,2 Matteo Bonini,3 Maria D’Amato,4 Salvatore Lombardo,5 Nicola Murgia,6 Vincenzo Patella,7,8 Massimo Triggiani,9 Girolamo Pelaia10 1Pneumology Unit, Arcispedale Santa Maria Nuova, Azienda USL di Reggio Emilia-IRCCS, Reggio Emilia, Italy; 2Pneumologia Riabilitativa - Ospedale Ge-Arenzano, ASL3-, Genoa, Italy; 3Department of Cardiovascular and Thoracic Sciences, Università Cattolica del Sacro Cuore, Rome, Italy; 4Respiratory Department- Monaldi Hospital AO Dei Colli, Naples, Italy; 5Pneumology Unit, Ospedale Giovanni Paolo II, Lamezia Terme, Italy; 6Section of Occupational Medicine, Respiratory Diseases and Toxicology, University of Perugia, Perugia, Italy; 7Division of Allergy and Clinical Immunology, Department of Medicine ASL Salerno, Santa Maria Della Speranza Hospital, Salerno, Italy; 8Postgraduate Program in Allergy and Clinical Immunology, University of Naples Federico II, Naples, Italy; 9Division of Allergy and Clinical Immunology, University of Salerno, Fisciano, Italy; 10Department of Health Sciences, Respiratory Unit, University “Magna Graecia” of Catanzaro, Catanzaro, ItalyCorrespondence: Francesco MenzellaPneumology Unit, Arcispedale Santa Maria Nuova, Azienda USL di Reggio Emilia-IRCCS, Reggio Emilia, ItalyTel +390522296073Email Francesco.Menzella@ausl.re.itPurpose: Severe eosinophilic asthma (SEA) is characterized by high eosinophilia, severe symptoms, important comorbidities, frequent exacerbations, and poor asthma control. Benralizumab, targeting the interleukin-5 receptor alpha, proved effective in inducing rapid eosinophil depletion and amelioration of symptoms and lung function; it also allowed to reduce exacerbations and the use of oral corticosteroids (OCS). The present case series, spanning different subtypes of SEA, aimed at expanding the real-world experience with benralizumab in Italy.Patients and Methods: We collected data from SEA patients treated with benralizumab, at baseline and during treatment. We focused on the effects of benralizumab in the following conditions and endpoints: i) overlap between high-IgE and high-eosinophilic asthma; ii) presence of nasal polyposis as comorbidity; iii) corticosteroid-sparing effect; iv) patient perception.Results: Ten SEA patients (females: N=7; age range: 19– 70 years) referred to 8 Italian Centers and treated with benralizumab were included, presenting with several comorbidities such as non-allergic disease (8/10), atopy (3/10), high IgE (5/10) and nasal polyposis (6/10). Overall, benralizumab yielded optimal disease control in all patients, particularly in terms of rapid clinical and functional improvement, decreased systemic steroid need (OCS therapy was completely discontinued in 7 cases) and amelioration of patient quality of life, except for 1 case, in whom other conditions not related to benralizumab therapy interfered with the patient perception.Conclusion: Our findings further support the efficacy and safety of benralizumab observed in randomized clinical trials, providing even better results for lung function improvement.Keywords: benralizumab, IL-5 receptor, oral corticosteroids, overlap IgE/eosinophilic asthma, polyposis, real world, severe eosinophilic asthma

The prevalence of asthma in Italy is estimated to be around 4%; it affects approximately 2,000,000 citizens, and up to 80-90% of patients have mild-to-moderate asthma. Despite the clinical relevance of mild-to-moderate asthma, longitudinal observational data are very limited, including data on disease progression (worsening vs. improvement), the response to treatment, and prognosis. Studies are needed to develop long-term, observational, real-life research in large cohorts. The primary outcomes of this study will be based on prospective observation and the epidemiological evolution of mild and moderate asthma. Secondary outcomes will include patient-reported outcomes, treatments over time, disease-related functional and inflammatory patterns, and environmental and life-style influences.This study, called the Mild/Moderate Asthma Network of Italy (MANI), is a research initiative launched by the Italian Respiratory Society and the Italian Society of Allergology, Asthma and Clinical Immunology. MANI is a cluster-based, real world, cross-sectional, prospective, observational cohort study that includes 20,000 patients with mild-to-moderate asthma. (ClinicalTrials.gov Identifier: NCT04796844).Despite advances in asthma care, several research gaps remain to be addressed through clinical research. This study will add important new knowledge about long-term disease history, the transferability of clinical research results to daily practice, the efficacy of currently recommended strategies, and their impact on the burden and evolution of the disease.MANI:Mild/Moderate Asthma Network of ItalySANI:Severe Asthma Network ItalyGINA:Global Initiative for AsthmaSABA:short acting β2-agonistsICS:inhaled corticosteroidsCRF:Case Report Form.

BackgroundGastroesophageal reflux disease (GERD) has been reported to be significantly associated with chronic rhinosinusitis, but the strength of the association is still debated.AimsTo evaluate the strength of the association between gastritis/GERD and non-allergic rhinitis (NAR)/allergic rhinitis (AR)/sinusitis.MethodsWe investigated 2887 subjects aged 20–84 years, who underwent a clinical visit in seven Italian centres (Ancona, Palermo, Pavia, Terni, Sassari, Torino, Verona) within the study on Gene Environment Interactions in Respiratory Diseases, a population-based multicase-control study between 2008 and 2014. Subjects were asked if they had doctor-diagnosed “gastritis or stomach ulcer (confirmed by gastroscopy)” or “gastroesophageal reflux disease, hiatal hernia or esophagitis”. The association between NAR/AR/sinusitis and either gastritis or GERD was evaluated through relative risk ratios (RRR) by multinomial logistic regression.ResultsThe prevalence of gastritis/GERD increased from subjects without nasal disturbances (22.8% = 323/1414) to subjects with AR (25.8% = 152/590) and further to subjects with NAR (36.7% = 69/188) or sinusitis (39.9% = 276/691). When adjusting for centre, sex, age, education level, BMI, smoking habits and alcohol intake, the combination of gastritis and GERD was associated with a four-fold increase in the risk of NAR (RRR = 3.80, 95% CI 2.56–5.62) and sinusitis (RRR = 3.70, 2.62–5.23) with respect to controls, and with a much smaller increase in the risk of AR (RRR = 1.79, 1.37–2.35)..ConclusionThe study confirmed the association between gastritis/GERD and nasal disturbances, which is stronger for NAR and sinusitis than for AR.

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.

Background: It is not clear whether mepolizumab is differently effective in allergic and nonallergic severe eosinophilic asthmatics (SEA) in real life. Objective: We tested mepolizumab effectiveness in allergic/nonallergic SEA in real life. A strict criterion to identify the 2 phenotypes was used. Method: We retrospectively considered 134 consecutive patients divided into allergic, with a positivity to at least 1 allergen to prick tests and/or IgE values ≥100 UI/mL (severe allergic eosinophilic asthma [SAEA]; n: 97–72.4%), and nonallergic, with no prick test results and normal IgE levels n: 37–27.6%). They had taken mepolizumab for at least 6 months. Results: After 10.9 ± 3.7 months, improvements in FEV1%, FEF25–75%, exacerbation numbers, blood eosinophil (BE) counts, fractional exhaled nitric oxide (FENO) (ppb), percentages of patients that stopped/reduced short-acting β2-agonists (SABAs) or oral corticosteroid (OC), observed after treatment, were similar in both groups. Only Asthma Control Test (ACT) increases were higher in SNAEA (8 [5–9]) than in SAEA (5 [2.5–8.5]; p = 0.016). However, no differences were found after treatment in percentages of subjects with ACT ≥20, as well as with FEV1 >80%, FEF25–75 >65%, exacerbations ≤2, BE 1% (β = −0.110; p = 0.266), FEF25–75% (β = −0.228; p = 0.06), BE counts (β = −0.012; p = 0.918), FENO (β = 0.234; p = 0.085), ACT (β = 0.046; p = 0.660), and exacerbations (β = −0.070; p = 0.437). No different associations between lung function and SNAEA occurrence when compared to SAEA condition (FEV1 >80%: OR = 1.04 [95% CI: 0.43–2.55], p = 0.923; FEF25–75 >65%: OR = 0.41 [95% CI: 0.08–2.03], p = 0.272) were detected. Neither all other parameters, such as ACT >20 (OR = 0.73 [95% CI: 0.32–1.63], p = 0.440), presence of exacerbations (OR = 1.35 [95% CI: 0.55–3.27], p = 0.512), SABA discontinuation (OR = 1.16 [95% CI: 0.40–3.39], p = 0.790), and OC cessation/reduction (OR = 3.44 [95% CI: 0.40–29.27], p = 0.258), were differently associated with 1 or the other phenotype. Conclusion: Mepolizumab can be considered as a valid therapeutic choice for either allergic or nonallergic SEA in real life.

ObjectivesOccupational exposures to metal fumes have been associated with increased pneumonia risk, but the risk of invasive pneumococcal disease (IPD) has not been characterised previously.MethodsWe studied 4438 cases aged 20–65 from a Swedish registry of invasive infection caused by Streptococcus pneumoniae. The case index date was the date the infection was diagnosed. Six controls for each case, matched for gender, age and region of residency, were selected from the Swedish population registry. Each control was assigned the index date of their corresponding case to define the study observation period. We linked cases and controls to the Swedish registries for socioeconomic status (SES), occupational history and hospital discharge. We applied a job–exposure matrix to characterise occupational exposures. We used conditional logistic analyses, adjusted for comorbidities and SES, to estimate the OR of IPD and the subgroup pneumonia–IPD, associated with selected occupations and exposures in the year preceding the index date.ResultsWelders manifested increased risk of IPD (OR 2.99, 95% CI 2.09 to 4.30). Occupational exposures to fumes and silica dust were associated with elevated odds of IPD (OR 1.11, 95% CI 1.01 to 1.21 and OR 1.33, 95% CI 1.11 to 1.58, respectively). Risk associated with IPD with pneumonia followed a similar pattern with the highest occupational odds observed among welders and among silica dust exposed.ConclusionWork specifically as a welder, but also occupational exposures more broadly, increase the odds for IPD. Welders, and potentially others with relevant exposures, should be offered pneumococcal vaccination.

Purpose Chronic obstructive pulmonary disease (COPD) is associated with several co-morbidities and non-infectious rhinitis (NIR) has emerged as a new possible co-morbidity. The primary aim of this study is to confirm a previously reported association between NIR and COPD in a multicentre population over time. The secondary aim is to investigate the course over time of such an association through a comparison between early- and late-onset COPD. Methods This study is part of the European Community Respiratory Health Survey (ECRHS). A random adult population from 25 centres in Europe and one in Australia was examined with spirometry and answered a respiratory questionnaire in 1998–2002 (ECRHS II) and in 2008–2013 (ECRHS III). Symptoms of non-infectious rhinitis, hay fever and asthma, and smoking habits were reported. Subjects reporting asthma were excluded. COPD was defined as a spirometry ratio of FEV1/FVC Results Non-infectious rhinitis was significantly more prevalent in subjects with COPD compared with no COPD (48.9% vs 37.1%, p Conclusion Non-infectious rhinitis was significantly more common in subjects with COPD at a mean age of 43. Ten years later, the association was weaker. The findings indicate that NIR could be associated with the early onset of COPD.

ObjectivesWheat flour exposure in bakers can elicit respiratory and skin symptoms. Scarce data are available on the prevalence of such conditions in bakers. We investigated the prevalence of work-related rhinitis, asthma-like symptoms and dermatitis in bakers according to job task and type of allergens involved.MethodsOf the 229 traditional bakeries in Verona area who were invited to participate in a cross-sectional survey, 211 (92%) accepted; 727 employees in these bakeries answered a modified version of a questionnaire on job tasks; allergen exposure within the bakery; and work-related nasal, asthma-like and skin symptoms during 2010–2014. Determinants of work-related nasal, asthma-like or skin disorders were separately evaluated using different logistic models.ResultsThe prevalence of work-related nasal and asthma-like symptoms was, respectively, 15.1% and 4.2% in bakery shop assistants, increasing to 25.7% and 9.5% in bakers using only wheat flour, and further to 31.8% and 13.6% in bakers using flour and additives, and then to 34.1% and 18.2% in bakers using flour with additives and multigrain (pConclusionsBakers using additives alone or with multigrain are at a high risk of experiencing nasal and asthma-like symptoms.

Rationale: Workplace inhalational hazards remain common worldwide, even though they are ameliorable. Previous American Thoracic Society documents have assessed the contribution of workplace exposures to asthma and chronic obstructive pulmonary disease on a population level, but not to other chronic respiratory diseases. The goal of this document is to report an in-depth literature review and data synthesis of the occupational contribution to the burden of the major nonmalignant respiratory diseases, including airway diseases; interstitial fibrosis; hypersensitivity pneumonitis; other noninfectious granulomatous lung diseases, including sarcoidosis; and selected respiratory infections. Methods: Relevant literature was identified for each respiratory condition. The occupational population attributable fraction (PAF) was estimated for those conditions for which there were sufficient population-based studies to allow pooled estimates. For the other conditions, the occupational burden of disease was estimated on the basis of attribution in case series, incidence rate ratios, or attributable fraction within an exposed group. Results: Workplace exposures contribute substantially to the burden of multiple chronic respiratory diseases, including asthma (PAF, 16%); chronic obstructive pulmonary disease (PAF, 14%); chronic bronchitis (PAF, 13%); idiopathic pulmonary fibrosis (PAF, 26%); hypersensitivity pneumonitis (occupational burden, 19%); other granulomatous diseases, including sarcoidosis (occupational burden, 30%); pulmonary alveolar proteinosis (occupational burden, 29%); tuberculosis (occupational burden, 2.3% in silica-exposed workers and 1% in healthcare workers); and community-acquired pneumonia in working-age adults (PAF, 10%). Conclusions: Workplace exposures contribute to the burden of disease across a range of nonmalignant lung conditions in adults (in addition to the 100% burden for the classic occupational pneumoconioses). This burden has important clinical, research, and policy implications. There is a pressing need to improve clinical recognition and public health awareness of the contribution of occupational factors across a range of nonmalignant respiratory diseases.

Background Although general practitioners (GPs) are frequently the first healthcare professionals whom asthma patients refer to for their symptoms, few studies have explored the extent of adherence to guidelines for asthma management based on data provided directly by GPs. Aims of the present study were to assess drug prescriptions for asthma by GPs and to evaluate prescriptive adherence to GINA guidelines (GL) and its relationship with disease control in real life. Methods 995 asthmatic patients (45% males, mean age 43.3 ± 17.7 yrs) were enrolled by 107 Italian GPs distributed throughout the country. Data on diagnosis, disease severity, prescribed anti-asthmatic drugs and control were collected through questionnaires filled out by GPs taking into consideration the 2009 GINA Guidelines. Data on drug use and chronic sinusitis, nasal polyposis, chronic bronchitis, emphysema were reported by patients through a self-administered questionnaire. Results The large majority of patients were classified by GPs as having intermittent (48.4%) or mild persistent asthma (25.3%); 61% had co-morbid allergic rhinitis (AR). The prevalent therapeutic regimen used by patients was a combination of inhaled corticosteroids (ICS) plus long-acting β2-agonists (LABA) (54.1%), even in the intermittent/mild persistent group. ICS as mono-therapy or in combination with other drugs but LABA, was the second most frequently adopted treatment (14.4%). In general, the GPs adherence to GL treatment indications was 28.8%, with a significant association with a good asthma control (OR 1.85, 95% CI 1.18–2.92). On the other hand, comorbidity (OR 0.52, 95% CI 0.32–0.84), moderate (0.44, 0.28–0.69) and severe (0.06, 0.02–0.20) persistent asthma showed significant negative effects on asthma control. Conclusions Our results show that over-treatment of intermittent/mild persistent asthma is frequent in the GPs setting while therapeutic regimens are more appropriately applied for moderate/severe asthma. In general, we found low adherence to GINA GL treatment recommendations even if its relevance in asthma control was confirmed.

Background: Asthma is the most common chronic disease in childhood. Maintaining Asthma Control (AC) is the goal of GINA guidelines. Therapeutic educational pathway (TEP) can help to reduce the use of health care and to achieve AC. The effect of TEP with the telemedicine did not yet investigate. Aim: to assess the impact of the TEP together with a mobile app (DragONE, freely available in apple and play store) and a portable spirometer (SmartOne MIR, Italy) in a cohort of 50 asthmatic children, 6-11 yrs. Methods: Children were randomized into TEP and no TEP group (1:1). Children attended visits every month for a 3 months follow-up period. DragONE and SmartOne were provided to all parents. Children performed PEF two times per day and recorded symptoms. Children completed CACT and a detailed medical history. Urinary cotinine, nicotine and polycyclic aromatic hydrocarbons metabolites were measured throughout the study as possible modifier in AC. The least square mean difference, adjusted for different risk factors was applied in order to assess the inter visit change in C-ACT scores between TEP and No TEP. A p-value≤0.05 was considered significant. Results: a significant improvement in AC was observed from T1 to T4 only in TEP, the different variation in C-ACT was significantly higher in TEP than No TEP (Tab.1). Conclusions: this study confirms the importance of TEP in pediatric asthma, suggesting that it may help in asthma management.

Background: Idiopathic pulmonary fibrosis (IPF) is characterized by progressive loss of lung function with high mortality within the first 5 years from diagnosis. In 2011–2014, two drugs, pirfenidone and nintedanib, have been approved worldwide for prevention of IPF progression. National IPF-registries have been established in both Finland and Sweden. Our study explored potential differences in the care of IPF in these two countries. Methods: Patients included consecutively in the Finnish and Swedish IPF-registries from January 1, 2014 through December 31, 2016 were included in the study. Data on demographics and lung function at the time of inclusion were collected. Access to antifibrotic drugs and data on disease outcomes, mortality and the proportion of patients who underwent lung transplantation, was collected during a 3-year follow up. Results: One-hundred and fifty-two patients from the Finnish and 160 patients from the Swedish IPF-cohorts were included in the study. At inclusion, Finnish patients were significantly older than the Swedish patients (74.6 years vs 72.5 years, p = 0.017). The proportion of non-smokers was significantly higher in the Finnish cohort (41.7% vs 26.9%, p = 0.007). Forced vital capacity (FVC), % of predicted (78.2 vs 71.7 for Finnish and Swedish patients, respectively, p = 0.01) and diffusion capacity for carbon monoxide (DLCO), % of predicted (53.3 vs 48.2 for Finnish and Swedish patients, respectively, p = 0.002) were significantly higher in the Finnish cohort compared to the Swedish cohort at the time of inclusion. During the 3-year follow up period, 45 (29.6%) Finnish and 111 (69.4%) Swedish patients, respectively, were initiated on treatment with an antifibrotic drug (pirfenidone or nintedanib) (p < 0.001). When comparing possible determinants of treatment, patients with higher FVC % were less likely to start antifibrotic drugs (OR 0.96, 95%CI 0.93–1.00, p < 0.024). To be resident in Sweden was the main determinant for receiving antifibrotic drugs (OR 5.48, 95%CI 2.65–11.33, p < 0.0001). No significant difference in number of deaths and lung transplantation during the follow up period was found. Conclusions: This study highlights differences concerning how IPF patients are treated in Finland and Sweden. How these differences will influence the long-term outcome of these patients is unknown.

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.

In Parkinson’s disease (PD), respiratory disturbances have been reported and the effect of levodopa on respiratory function remains controversial. The objective of this study was to evaluate pulmonary function utilizing spirometric and subjective evaluations in mild to moderated PD. Thirty-four consecutive sporadic PD patients (Hoehn and Yahr scale: 1–3) were prospectively evaluated using clinimetric scales, spirometry and modified Borg scale, all in off- and on-conditions. To check the respiratory function, a follow-up was performed at 4 years in a subgroup of these patients. Spirometric results were normal for all patients in both the on- and off-conditions at baseline. After levodopa administration, in addition to a significant improvement in subjective state of breathing discomfort, the mean forced expiratory volume in 1 s (FEV1), vital capacity (VC), forced vital capacity (FVC) values and their mean percentages predicted values (FEV1%, VC%, FVC%) were significantly increased (p

Introduction: Pulmonary alveolar proteinosis (PAP) is a rare, diffuse lung disease characterized by alveolar filling with lipoproteinaceous material. While most PAP is considered idiopathic, occupational etiologies, such as silica exposure causing “silicoproteinosis,” are recognized. Aim: To systematically review the occupational contributions to PAP. Methods: We identified and reviewed relevant publications through January 2017 using PubMed and manual review of identified papers’ references. We included publications that described at least 10 cases of PAP and that also noted the number with occupations involving likely exposure to various vapors, gases, dusts, and/or fumes (VGDF) or with presumably occupational VGDF exposures. We calculated the prevalence of occupational exposures generally and silica exposure specifically. Results: We included 24 publications with a total of 1413 cases (range: 11-241 cases/publication). The mean prevalence of occupational exposure was 29% (median: 30%, range: 0-59%). Thirteen publications specifically addressed silica exposure; mean prevalence in those studies was 6% (median: 6%, range: 0-22%). Studies that collected information about exposure through questionnaire generally reported a higher prevalence of exposure. Three publications included comparison to controls: one found a higher prevalence of self-reported occupational inhalational exposure in cases (34%) than controls (20%) (p=0.07); two were histopathological investigations of the same cases that found more birefringent particles (p Conclusions: Nearly one third of PAP in cases series is associated with work-related exposures.

Introduction: Cancer is a well-known risk factor of thromboembolism (VTE) and lung adenocarcinoma is associated with an increased risk. Mutation analyses of epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) identify subgroups of lung adenocarcinoma with different epidemiological and clinical features. How the mutational status affects the risk of VTE is still unknown. Aims: To evaluate the occurrence of VTE in patients with EGFR and ALK mutations compared with non-mutated lung adenocarcinoma. Material and Methods: A retrospective longitudinal design was used. Patients with lung adenocarcinoma diagnosed and/or treated at Karolinska University Hospital, Stockholm, Sweden between the years 2009-20015 were included. All patients underwent a predictive test, divided in 3 subgroups based on the predictive tests result (EGFR- or ALK-mutated, no detected mutation). Event-free time of patients by their mutation status and treatment was assessed using cox regression analysis. Results: 310 patients were included. A VTE occurred in 24.2% of the patients. Mutation of EGFR was associated with a decreased risk (HR 0.35, 95%CI 0.17-0.69, p=0.003) in similarity with ALK-mutated lung adenocarcinomas (HR 0.44, 95%CI 0.21-0.91, p=0.03). Treatment with thyrosin-kinase inhibitors (TKI) seems to further reduce the risk of VTE compared to other treatments (HR 0.18, 95%CI 0.06-0.49, p=0.001). Conclusions: The results of this study indicate that patients with adenocarcinoma bearing a EGFR or ALK mutation have a decreased risk of VTE compared with other patients with lung adenocarcinoma. Targeted therapy with TKI seems to be safer and to reduce risk of VTE compared to standard chemotherapy.

Background The aim of this population-based study was to investigate the risk of developing noninfectious rhinitis (NIR) in subjects with chronic obstructive pulmonary disease (COPD). Materials and methods This is a longitudinal population-based study comprising 3,612 randomly selected subjects from Gothenburg, Sweden, aged 25–75 years. Lung function was measured at baseline with spirometry and the included subjects answered a questionnaire on respiratory symptoms. At follow-up, the subjects answered a questionnaire with a response rate of 87%. NIR was defined as symptoms of nasal obstruction, nasal secretion, and/or sneezing attacks without having a cold, during the last 5 years. COPD was defined as a spirometry ratio of forced expiratory volume in 1 second divided by forced vital capacity (FEV1/FVC) 40 years. Smoking, atopy, and occupational exposure to gas, fumes, or dust were also associated with new-onset NIR. COPD, smoking, and atopy remained individual risk factors for new-onset NIR in the logistic regression analysis. Conclusions This longitudinal population-based study of a large cohort showed that COPD is a risk factor for developing NIR. Smoking and atopy are also risk factors for NIR. The results indicate that there is a link present between upper and lower respiratory inflammation in NIR and COPD., Video abstract

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.

In 2014, the Italian severe/uncontrolled asthma (SUA) registry was released to improve asthma care, awareness, knowledge on natural history, phenotypes. Aim: to characterize Italian SUA patients. Methods: The web-based registry, containing demographic, clinical, functional, inflammatory data, included 492 SUA patients (by GINA guidelines) from 3 Italian centres (Pisa, Perugia, Ancona). Results: SUA patients were more frequently females (60.9%), obese/overweight (64.7%), with a mean age of 53.8 yrs. 36.9% had asthma familiarity, 83.1% allergic asthma, 77.2% perennial symptoms. A late-onset of asthma symptoms (30yr) and a late first diagnosis (34yr) were observed. Other than the combination bronchodilator/corticosteroid, 51.6% of patients received antileukotrienes, 19.5% anticholinergics, 15.8% oral corticosteroids, 69.4% anti-IgE. In the last 12 months, SUA patients had 1.5±2.4 mean number of exacerbations, 9.7% had an emergency department visit and 7.3% hospitalization, 57.5% took oral steroids for exacerbations. The median blood eosinophil count was 300/mm 3 . The median FENO was 22 ppb. 65 patients performed induced sputum: 64.6% had an eosinophilic asthma phenotype (sputum Eos ≥ 3%), 13.8% neutrophilic (sputum Neu ≥ 76%), 16.9% paucigranulocytic. Comorbidities included allergic rhinitis (62.4%), gastro-oesophageal reflux (42.1%), nasal polyposis (30.2%), allergic conjunctivitis (30.2%), aspirin hyper-sensitivity (22%). Conclusion: Italian SUA patients are characterized by late symptoms onset and diagnosis, indices of eosinophilic inflammation, high burden in terms of health care costs and comorbidity. Supported by: the Italian Medicines Agency; an unrestricted grant of Roche.

Although asthma is usually considered to originate in childhood, adult-onset is being increasingly reported. Aim: to assess factors associated to early- (

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.

Acute-onset irritant-induced asthma is a phenotype with onset promptly after a single, high-level exposure to irritants in subjects without pre-existing asthma. Our aim was to study new-onset adult asthma in relation to acute inhalations in a population-based study. We used longitudinal data of 3,141 ECRHS III participants from 24 study centres (52% women, aged 39-67 years) with no reported history of asthma or related symptoms in previous contacts. Details of acute inhalations ("incident at home, work or elsewhere involving exposure to high levels of vapours, gases, dusts or fumes") during the last follow-up (mean 11.3 years) were reported. Associations between inhalations and new-onset asthma during follow-up were analysed using multivariable logistic mixed regression analyses adjusted for sex, age, follow-up time, smoking status and centre. 82 participants (2.6%) had developed asthma during follow-up (2.3 new cases per 1000 person-years). An acute inhalation during follow-up was reported by 188 participants (6.0%), and was associated with new-onset asthma (odds ratio (OR) 2.8; 95% confidence interval 1.4-5.5). This association was predominated by inhalations in the workplace (52% of all; OR 5.1 (2.3-11)) while inhalations elsewhere were not associated with asthma (OR 0.9; 0.2-3.8). The increased asthma risk of inhalations at work was much stronger (p for interaction 0.02) in women (OR 10; 4.0-26) than in men (OR 1.2; 0.2-9.4). Analyses using current asthma based on symptoms or medication showed consistent findings for inhalations at work; OR 8.8 (3.8-20) in women and 0.4 (0.1-3.0) in men (p for interaction 0.0002). We conclude that acute inhalations at work may induce asthma, particularly in women.

Objectives: To estimate the effects of smoking, gender and occupational exposure on the risk of developing severe pulmonary fibrosis (PF), including dose-response and interaction effects. Methods: National case-control study of 171 patients (cases) who had started a long-term oxygen therapy for PF in Sweden between February 1997 and April 2000, and 719 random control participants from the general population. Of these cases, 137 had probable idiopathic PF (IPF). The ORs for smoking, gender and occupational exposure were estimated using Mantel-Haenszel analysis and conditional logistic regression, controlling for age and year of diagnosis. Results: The adverse effect of smoking was amplified by male gender and occupational exposure, OR 4.6 (95% CI 2.1 to 10.3) for PF, and OR 3.0 (1.3 to 6.5) for IPF, compared with in non-exposed women. Higher cumulative smoking exposure was linearly associated with increased risks. Compared with smoking less than 10 pack-years, smoking >= 20 pack-years was associated with increased risk of PF and IPF, OR 2.6 (1.4 to 4.9) and OR 2.5 (1.3 to 5.0), respectively. Conclusions: Smoking has a dose-related association with increased risk of severe PF. Men with a history of smoking and occupational exposure is a particular risk group for developing severe PF.

Background The diagnosis of chronic obstructive pulmonary disease (COPD) is based on airflow obstruction. In epidemiological studies, spirometric data have often been lacking and researchers have had to rely almost solely on questionnaire answers. The aim of this study is to assess the diagnostic accuracy of questionnaire answers to detect COPD. Methods A sample of the Swedish general population without physician-diagnosed asthma was randomly selected and interviewed using a respiratory questionnaire. All eligible subjects aged 25–75 years (n = 3892) performed spirometry for detection of airflow obstruction using Global Initiative for Chronic Obstructive Lung Disease (GOLD) or American Thoracic Society (ATS)/European Respiratory Society (ERS) criteria. Sensitivity, specificity, positive likelihood ratio (LR+), positive predictive values (PPVs), and negative predictive values (NPVs) were calculated to define diagnostic accuracy of questionnaire answers. Results The sensitivity of the question “Have you been diagnosed by a physician as having COPD or emphysema?” in detecting airflow obstruction was 5.7% using GOLD, and 9.8% using ATS/ERS, criteria; specificity was 99.7% for GOLD and 99.5% for ATS/ERS. Sensitivity, specificity, and PPV were higher for the question compared to self-reported symptoms of chronic bronchitis in identifying subjects with airflow obstruction. Conclusions The high specificity and good PPV suggest that the question “Have you been diagnosed by a physician as having COPD or emphysema?” is more likely to identify those who do not have airflow obstruction, whereas the low sensitivity of this question could underestimate the real burden of COPD in the general population.

Background 2,5-hexanedione (2,5-HD) is the main neurotoxic metabolite of methyl-n-butyl ketone (MBK) and n-hexane, and known to cause polyneuropathy. The aim of our study was to compare the urinary levels of 2,5-HD between cases with cryptogenic polyneuropathy and the general Swedish population, and to elucidate the role of certain external factors. Methods Morning urine samples were collected from 114 cases with cryptogenic polyneuropathy (77 men and 37 women) and 227 referents (110 men and 117 women) randomly selected from the population registry. None had any current occupational exposure to n-hexane or MBK. The urine samples were analysed by a gas chromatographic method based on acidic hydrolysis. Results Cases had statistically higher urinary levels of 2,5-HD (0.48 mg/L) than the general population (0.41 mg/L) and men higher excretion than women (0.48 mg/L and 0.38 mg/L, respectively). There was no difference in 2,5-HD levels between current smokers and non-smokers. Occupational exposure to xylene, alcohol consumption and ever exposed to general anaesthesia were associated with lower excretion in men while for occupational exposure to nitrous oxide in women higher excretion was seen. Higher excretion of 2,5 HD was inversely related to increasing age. Conclusions Significantly higher levels of urinary 2,5-HD were seen in men and cryptogenic polyneuropathy cases seemingly unexposed to n-hexane. Hypothetically, this might be due to either differences in metabolic patterns or some concealed exposure. The difference in means between cases and the general population is small and can therefore not allow any firm conclusions of the causality, however.

BACKGROUND: Occupational exposure to irritants is associated with chronic bronchitis. The aim of this study was to elucidate whether repeated peak exposures with respiratory symptoms, gassings, to sulphur dioxide (SO2) and other irritant gases could increase the risk of chronic bronchitis. METHODS: The study population comprised 3,060 Swedish pulp mill workers (84% males) from a cohort study, who completed a comprehensive questionnaire with items on chronic bronchitis symptoms, smoking habit, occupational history, and specific exposures, including gassings. 2,037 have worked in sulphite mills. Incidence rates and hazard ratios (HRs) for the observation period, 1970-2000, in relation to exposure and the frequency of repeated gassings to SO2 and other irritant gases were calculated. RESULTS: The incidence rate for chronic bronchitis among workers with repeated gassings was 3.5/1,000 person-years compared with 1.5/1,000 person-years among unexposed workers (HR 2.1, 95% confidence interval (CI) 1.4-3.1). The risk was even higher in the subgroup with frequent gassings (HR 3.2, 95% CI 2.0-5.2), particularly among never-smokers (HR 8.7, 95% CI 3.5-22). CONCLUSIONS: Repeated gassings to irritant gases increased the incidence of chronic bronchitis in our study population during and after work in pulp mills, supporting the hypothesis that occupational exposures to irritants negatively affect the airways. These results underscore the importance of preventive actions in this work environment.

Despite only sporadic observations, the use of medical oxygen-ozone therapy is a largely diffused treatment for lumbar disk herniation that has failed to respond to conservative management. Combined intradiscal and periganglionic injection of medical ozone and periganglionic injection of steroids are presumed to have a cumulative effect enhancing the overall outcome of treatment for pain caused by disk herniation. To our knowledge, this is the first reported case of stroke during such medical application. The patient had Anton's syndrome as a result of top of the basilar hypoperfusion.

Background The association between chronic respiratory diseases and work disability has been demonstrated a number of times over the past 20 years, but still little is known about work disability in occupational cohorts of workers exposed to respiratory irritants. This study investigated job or task changes due to respiratory problems as an indicator of work disability in pulp mill workers occupationally exposed to irritants. Methods Data about respiratory symptoms and disease diagnoses, socio-demographic variables, occupational exposures, gassing episodes, and reported work changes due to respiratory problems were collected using a questionnaire answered by 3226 pulp mill workers. Information about work history and departments was obtained from personnel files. Incidence and hazard ratios for respiratory work disability were calculated with 95% confidence intervals (CI). Results The incidence of respiratory work disability among these pulp mill workers was 1.6/1000 person-years. The hazard ratios for respiratory work disability were increased for workers reporting gassings (HR 5.3, 95% CI 2.7-10.5) and for those reporting physician-diagnosed asthma, chronic bronchitis, and chronic rhinitis, when analyzed in the same model. Conclusions This cohort study of pulp mill workers found that irritant peak exposure during gassing episodes was a strong predictor of changing work due to respiratory problems, even after adjustment for asthma, chronic bronchitis, and chronic rhinitis.

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.

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.

This paper presents data on the prevalence of co-occurring substance use and psychiatric disorders among newly imprisoned males in Italy. Interviewers conducted semi-structured clinical interviews with n=302 male detainees seven days after their admission to the prison of Perugia from August 2005 through July 2006. Over half of male detainees (54.3%) had either a substance use disorder or another psychiatric disorder. One of every five detainees (20.9%) had comorbid substance use and psychiatric disorders. Compared to detainees with psychiatric disorder only, substance use disorder only, or no disorder, detainees with comorbid substance use and psychiatric disorders were significantly more likely to have severe impairment in the areas of employment, substance abuse, family and social functioning, and psychiatric symptoms. Findings underscore the need for careful diagnostic screening at intake, access to treatment during detention, and an effective transition to services at the time of release.

The clinical efficacy of immunotherapy, either by high dose sublingual-swallow therapy (SLIT) or subcutaneous immunotherapy (SCIT), has been demonstrated in patients with pollinosis but few studies have been carried out analysing differences in these treatments in terms of an improvement of clinical and allergic phlogosis parameters. The aim of this double-blind placebo-controlled study is to investigate the efficacy of high dose SLIT and SCIT using a purified standardized Juniperus ashei extract in a population of allergic patients monosensitized to cypress. Forty patients with cypress-allergic rhino conjunctivitis were administered therapeutic or placebo SLIT or SCIT for 12 months. Laboratory parameters were studied, namely the eosinophil cationic protein (ECP) level in nasal lavage and in serum, as well as the number of eosinophils (EOS) in peripheral blood and in nasal lavage and the level of eosinophil chemotactic activity (ECA). These parameters were correlated with clinical symptoms, evaluated by means of the clinical symptoms score (CSS). After SCIT and SLIT the levels of ECP and ECA were reduced in nasal lavage. We also observed a significant reduction in the values of ECP in serum in the patients treated with SLIT. EOS were unchanged in peripheral blood, but significantly reduced in nasal lavage. These data were in accordance with the improvement of clinical symptoms, supported by the close correlation between CSS and laboratory parameters. Our data confirm a clinical improvement correlated with a decline in inflammation parameters after one year of immunotherapy, supporting the hypothesis that treatment with a major allergen of cypress is able to change the course of allergic rhinitis.

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.

In Europe, continuing medical education is one of the main instruments for improving physicians' performance and ensuring adequate health care for citizens. Recent regulations have made such continuing education compulsory in Italy. Considering the particular features of occupational medicine, the Italian Society of Industrial Medicine and Industrial Hygiene (S.I.M.L.I.I.) recently set up a specific education and accreditation programme for occupational physicians, called the "Excellence Accreditation Scheme". The programme is based on the findings of a survey among occupational physicians, carried out in collaboration with the National Institute of Occupational Safety and Prevention (I.S.P.E.S.L.), which enquired into their training and continuing education needs. The programme started in 2003, and its first edition-presented here-involved more than 400 physicians specialising in occupational health.

Objectives Little is known about the Hymenoptera venom allergy impact on work ability and the effect of venom immunotherapy (VIT) on work. The objective of this study was to evaluate the prevalence and predictors of work disability in patients treated with VIT and the effects of VIT on occupational functioning. Methods 181 patients, aged 18–71 years, treated with VIT while working, were investigated by questionnaire. Participants were classified into employed and self-employed and, based on work exposure to Hymenoptera, into three risk categories: high risk, occasionally high risk and low risk. Work disability was defined as having to have changed jobs/tasks and/or suffered economic loss because of Hymenoptera venom allergy. Predictors of work disability were assessed in logistic regression models. Results 31 (17%) patients reported work disability. Being self-employed and having the severe reaction at work were associated with work disability (p

Particulate air pollution is known to be associated with cardiovascular disease. The relation of particulate air pollution with cerebrovascular disease (CVD) has not been extensively studied, particularly in relation to different subtypes of stroke. A time-series study was conducted to evaluate the association between daily air pollution and acute stroke unit hospitalizations in Mantua, Italy. We analyzed 781 CVD consecutive patients living in Mantua county admitted between 2006-08. Data on stroke types, demographic variables, risk factors were available from the Lombardia Stroke Registry. Daily mean value of particulate matter with a diameter