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The allergic asthma phenotype is characterized by a T helper type 2 (Th2) immune response, based on Immunoglobulin E (IgE)-mediated type 1 hypersensitivity reactions. Total IgE is the sum of all IgE types produced by the human body and is used as a biomarker of inflammation in asthma. We analysed data collected in 143 asthma cases (median age 42.1 years) from the general Italian population (GEIRD survey; 2008–2010) to identify single nucleotide polymorphisms (SNPs) in candidate genes that are associated with total IgE in adult subjects with asthma. These patients reported respiratory symptoms in response to perennial allergens and provided data on 166 SNPs tagging 50 candidate genes or gene regions. Replication of the statistically significant results was performed in 842 asthma cases from other European countries (ECRHS II survey; 1998–2002). SNP rs549908 in interleukin 18 (IL18) gene was significantly associated with total IgE in GEIRD, and this result was replicated in ECRHS II. SNP rs1063320 in the human leukocyte antigen G (HLA-G) gene was identified in GEIRD, but this association was not replicated in ECRHS II. Further investigating IL18 and its biological pathways could be important for developing new therapeutic targets, due to its involvement in inflammatory response processes.

Obesity is a growing medical and social problem worldwide. The control of energy homeostasis in the brain is achieved by various regions including the arcuate hypothalamic nucleus (ARH). The latter comprises a number of neuronal populations including the first order metabolic neurons, appetite-stimulating agouti-related peptide (AgRP) neurons and appetite-suppressing proopiomelanocortin (POMC) neurons. Using an in vivo reductionist approach and POMCCre-dependent CRISPR-Cas9, we demonstrate that miR-15a-5p protects from obesity. Moreover, we have identified Bace1, a gene previously linked to energy metabolism imbalance, as a direct target of miR-15a-5p. This work warrants further investigations of non-coding RNA-mediated regulation of energy homeostasis and might contribute to the development of novel therapeutic approaches to treat metabolic diseases.

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.

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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

Chronic obstructive pulmonary disease (COPD) is caused by exposure to noxious particles and gases. Smoking is the main risk factor, but other factors are also associated with COPD. Occupational exposure to vapours, gases, dusts and fumes contributes to the development and progression of COPD, accounting for a population attributable fraction of 14%. Workplace pollutants, in particular inorganic dust, can initiate airway damage and inflammation, which are the hallmarks of COPD pathogenesis. Occupational COPD is still underdiagnosed, mainly due to the challenges of assessing the occupational component of the disease in clinical settings, especially if other risk factors are present. There is a need for specific education and training for clinicians, and research with a focus on evaluating the role of occupational exposure in causing COPD. Early diagnosis and identification of occupational causes is very important to prevent further decline in lung function and to reduce the health and socio-economic burden of COPD. Establishing details of the occupational history by general practitioners or respiratory physicians could help to define the occupational burden of COPD for individual patients, providing the first useful interventions (smoking cessation, best therapeutic management, etc.). Once patients are diagnosed with occupational COPD, there is a wide international variation in access to specialist occupational medicine and public health services, along with limitations in workplace and income support. Therefore, a strong collaboration between primary care physicians, respiratory physicians and occupational medicine specialists is desirable to help manage COPD patients' health and social issues.

Obesity, a growing threat to the modern society, represents an imbalance of metabolic queues that normally signal to the arcuate hypothalamic nucleus, a critical brain region sensing and regulating energy homeostasis. This is achieved by various neurons many of which developmentally originate from the proopiomelanocortin (POMC)-expressing lineage. Within the mature neurons originating from this lineage, we aimed to identify non-coding genes in control of metabolic function in the adulthood.In this work, we used microRNA mimic delivery and POMCHere we found that mature neurons originating from the POMC lineage employ miR-29a to protect against insulin resistance obesity, hyperphagia, decreased energy expenditure and obesity. Moreover, we validated the miR-29 family as a prominent regulator of the PI3K-Akt-mTOR pathway. Within the latter, we identified a direct target of miR-29a-3p, Nras, which was up-regulated in those and only those mature POMCThus, the first to our knowledge case of in situ Cre-dependent CRISPR-Cas9-mediated knock-out of microRNAs in a specific hypothalamic neuronal population helped us to decipher a critical metabolic circuit in adult mice. This work significantly extends our understanding about the involvement of neuronal microRNAs in homeostatic regulation.

Respiratory oscillometry is gaining global attention over traditional pulmonary function tests for its sensitivity in detecting small airway obstructions. However, its use in clinical settings as a diagnostic tool is limited because oscillometry lacks globally accepted reference values. In this scoping review, we systematically assessed the differences between selected oscillometric reference equations with the hypothesis that significant heterogeneity existed between them. We searched bibliographic databases, registries and references for studies that developed equations for healthy adult populations according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A widely used Caucasian model was used as the standard reference and compared against other models using Bland–Altman and Lin's concordance correlational analyses. We screened 1202 titles and abstracts, and after a full-text review of 67 studies, we included 10 in our analyses. Of these, three models had a low-to-moderate agreement with the reference model, particularly those developed from non-Caucasian populations. Although the other six models had a moderate-to-high agreement with the standard model, there were still significant sex-specific variations. This is the first systematic analysis of the heterogeneity between oscillometric reference models and warrants the validation of appropriate equations in clinical applications of oscillometry to avoid diagnostic errors.

European Commission, H2020 [101016167]; Regional Health Authority (Azienda Zero), Veneto Region, Italy; Health Research Institute of Asturias (ISPA), Spain, Porru S, Monaco MGL, Spiteri G, Carta A, Pezzani MD, Lippi G, Gibellini D, Tacconelli E, Dalla Vecchia I, Sala E, Sansone E, De Palma G, Bonfanti C, Lombardo M, Terlenghi L, Pira E, Mansour I, Coggiola M, Ciocan C, Godono A, Tardon A, Rodriguez-Suarez MM, Fernandez-Tardon G, Jimeno-Demuth FJ, Castro-Delgado RV, Iglesias Cabo T, Scapellato ML, Liviero F, Moretto A, Mason P, Pavanello S, Volpin A, Vimercati L, Tafuri S, De Maria L, Sponselli S, Stefanizzi P, Caputi A, Gobba F, Modenese A, Casolari L, Garavini D, D'Elia C, Mariani S, Filon FL, Cegolon L, Negro C, Ronchese F, Rui F, De Michieli P, Murgia N, Dell'Omo M, Muzi G, Fiordi T, Gambelunghe A, Folletti I, Mates D, Calota VC, Neamtu A, Perseca O, Staicu CA, Voinoiu A, Fabiánová E, Bérešová J, Adamčáková ZK, Nedela R, Lesňáková A, Holčíková J, Boffetta P, Abedini M, Ditano G, Asafo SS, Visci G, Violante FS, Zunarelli C, Verlato G

Co-exposures and polysensitization to several pollen species are very common in real life practice. However, little information exists on allergic symptoms and airway inflammation related to natural pollen exposure in large general population samples.To assess the combined effect of sensitization and/or exposure to one or more pollen species on Fraction of exhaled Nitric Oxide (FeNO) levels.Within Gene Environment Interactions in Respiratory Diseases (GEIRD) multicase-control study, 1070 adults from the general population of Verona, Italy, underwent a clinical evaluation including standardized interview, spirometry, skin prick test to inhalants and FeNO measurement. Pollen exposure was assumed, when the mean pollen concentration in the previous week was above the cutoff established by the Italian Aerobiological Monitoring Network.Subjects sensitized to one or more pollen species were respectively 15.5% and 29.6%. FeNO levels were directly related to the number of both pollen species around and pollen-related sensitizations. Median FeNO levels were directly related to number of pollen species around and pollen sensitization. FeNO levels increased from 15.4 ppb (p. 25-p. 75 = 9.9-21.0) outside the pollen season to 17.5 ppb (11.2-30.5) when there were ≥3 pollen species around. Likewise FeNO levels rose from 14.8 ppb (10.0-22.3) in not sensitized subjects, to 16.7 (10.1-25.0) in monosensitized and further to 20.4 (12.3-40.6) in poly-sensitized. According to multivariable quantile regression, median FeNO was 17.9 ppb higher (p. 25-p. 75 = 12.5-23.3) for subjects sensitized and exposed to more than one pollen species, compared to subjects who were neither sensitized nor exposed. Differences in FEV1/FVC between groups were less pronounced (Airways inflammation, evaluated by FeNO, increases in dose-dependent manner from subjects monosensitized to pollen species to those poly-sensitized, especially when asthma-like symptoms on pollen exposure are also reported. This should be considered by allergists during natural pollen seasons when evaluating both pulmonary function and airways inflammation.

Purpose Occupational exposure to inorganic dust and fumes in the year preceding disease has been associated with increased pneumococcal pneumonia risk, but the impact of prior cumulative exposure has not been characterized. Methods We studied 3184 cases of invasive pneumococcal disease with pneumonia. The case index date was the day the infection was diagnosed. We selected six controls for each case from the Swedish population registry; each control was assigned the index date of their corresponding case. We linked job histories to a job-exposure matrix to calculate a cumulative exposure index, intensity-years, by multiplying the duration (maximum 5 years) of each exposure with the level of exposure (0 for unexposed, 1 for low and 4 for high). We used conditional logistic analyses to estimate the odds ratio (OR) of invasive pneumococcal disease with pneumonia adjusted for comorbidities, educational level, income and other occupational exposures. Results Taking other occupational exposures into account, greater than 5 intensity-years of exposure to silica dust or to fumes was each associated with increased odds for invasive pneumococcal disease with pneumonia (OR 2.53, 95% CI 1.49–4.32) and (OR 2.24, 95% CI 1.41–3.55), respectively. Five intensity-years or less of exposure to silica dust or fumes manifested lower odds (OR 1.45, 95% CI 1.20–1.76) and (OR 1.05, 95% CI 0.94–1.16), respectively. Conclusion This study adds evidence that the risk of pneumococcal pneumonia increases with increasing cumulative exposure to dust and fumes, indicating the importance of cumulative exposure.

Studies investigating the association between urinary Polycyclic Aromatic Hydrocarbons (PAHs) and asthma in children provided inhomogeneous results. We aimed to use Mediation Analysis to discover whether a link between urinary PAHs and lung function exists and if it might be ascribed to a direct or a symptom-mediated (indirect) effect in children with asthma. This single-center prospective study was conducted in Palermo, Italy, between March and July 2017 and involved 50 children with persistent mild-moderate asthma, aged 6–11 years. At each time visit (day 0, 30, 60, and 90), physical examination, spirometry, and urine collection for detection of urinary cotinine and PAHs were performed. A symptom score was computed. The sum of individually calculated molar mass of nine PAH metabolites (ΣPAH), naphthalene metabolites (ΣPAHn) and phenanthrene metabolites (ΣPAHp) were calculated. Three children withdrew from the study due to technical problems (n = 1) and adverse events (n = 2). PAHs indirect effects on FEV1 (ΣPAH: −0.011, p = 0.04; ΣPAHn: −0.011, p = 0.04; ΣPAHp: −0.012, p < 0.001) and FVC (ΣPAH: −0.012, p = 0.02; ΣPAHn: −0.0126, p = 0.02; ΣPAHp: −0.013, p < 0.001) were statistically significant. In conclusion, PAHs exposures have significant indirect (symptom-mediated) effects on lung function, emphasizing the role of PAHs-induced respiratory morbidity in decreasing lung function in children with asthma.

follow-up studies on registries of severe/uncontrolled asthma (SUA) patients are scanty.to analyze baseline and follow-up characteristics of SUA patients and their longitudinal patterns.180 adult patients (age ≥15 yrs) were investigated at baseline and 12-month follow-up through the Italian SUA registry (RItA). Latent transition analysis (LTA) was performed to detect cross-sectional SUA phenotypes and longitudinal patterns. Risk factors for longitudinal patterns were assessed through logistic regression.a significant/borderline improvement of asthma control outcomes in the last 2-4 weeks emerged at follow-up with respect to baseline for: daily activities limitations (Δ -16%), frequent diurnal symptoms (Δ -25%), uncontrolled asthma symptoms according to ACT (Δ -26%). Last 12-month use of oral corticosteroids was less frequent at follow-up than at baseline (Δ -25%). Health status improvement was confirmed by lung function test results. Through LTA, two longitudinal patterns were detected considering last 12-month control outcomes: "persistence/worsening" (53.9%), "under control/improvement" (46.1%). A lower likelihood of having "persistence/worsening" SUA was exhibited by patients under anti-IgE (OR 0.38, 95% CI 0.17-0.84) and inhaled corticosteroids-bronchodilator association treatment (OR 0.13, 95% CI 0.01-1.26, borderline value), while a higher likelihood was shown by older age at first asthma diagnosis (OR 1.04, 95% CI 1.01-1.07).the implementation of a SUA registry, the availability of patient-level data and the application of an innovative longitudinal analysis allowed to observe a general improvement in asthma control, one year after baseline, and a lower risk of SUA "persistence/worsening" in patients under anti-IgE and regular ICS-bronchodilator association use.

Early life conditions are associated with lung function and the development of respiratory and non-respiratory illnesses. The relationship with birthweight (BW), however, is conflicting. We examined associations of self-reported BW with lung function and the development of respiratory and also non-respiratory diseases within the GEIRD (Gene–Environment Interaction in Respiratory Diseases) project, an Italian multi-centre, multi-case control study involving cases of COPD, asthma, allergic rhinitis and controls. Multinomial logistic regression was performed with case/control status as response variable; BW as main determinant; and adjusting for sex, age and smoking status. Of the 2287 participants reporting BW, 6.4% (n = 147) had low BW (

Background: Very few studies have examined whether marital/relationship status affects respiratory diseases. Objective: Assess the association of relationship status (Rstatus: domestic partnership/civil union/marriage, cohabitation with non-partners, being single) with current (CA) and past asthma (PA), allergic (AR) and non-allergic rhinitis (NAR), and chronic bronchitis (CB). Methods: Data were collected in the frame of GEIRD, a population-based, multicase-control survey. Among 2531 subjects (age 21–86, female 50%) who underwent standardized interviews, skin prick and lung function tests, 575 cases of CA, 268 cases of PA, 968 cases of AR, 462 cases of NAR, 265 cases of CB without airflow obstruction and 832 controls were identified. The association of Rstatus with respiratory diseases was evaluated by logistic regression for CB and multinomial regression for CA and PA and for AR and NAR, adjusting for sex, age, smoking, education, employment status, the centre and the interaction between sex and relationship status. Results: The Rstatus was not associated with CA and PA, nor with AR and NAR. An interaction between sex and Rstatus (p=0.004) was identified when considering CB. After adjustment for potential confounders, in women living with non-partners and in single women the likelihood of CB was significantly higher than in women in a domestic partnership/civil union/marriage (OR=2.81, 95%C.I.:1.62-4.87 and OR=2.71, 95%C.I.:1.43-5.14, respectively). There was no association between the Rstatus and CB in men. Conclusions: These findings suggest a higher risk of chronic bronchitis in women without a partner, while relationship status has not been found to be associated with asthma or rhinitis in both sexes.

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.

International audience; Background: Gene-environment interactions are relevant for several respiratory diseases. This communication raises the hypothesis that the severity of COVID-19, a complex disease where the individual response to the infection may play a significant role, could partly result from a gene-environment interaction between air-pollution and Alpha-1 Antitrypsin (AAT) genes.Methods: To evaluate the impact of the AAT and air pollution interaction on COVID-19, we introduced an AAT*air pollution global risk score summing together, in each country, an air pollution score (ozone, nitrogen dioxide and fine particulate matter) and an AAT score (which sums the ranked frequency of MZ, SZ, MS). We compared this global score with the ranking of European countries in terms of death number per million persons.Results: The ranking of the AAT*air pollution global risk score matched the ranking of the countries in terms of the observed COVID-19 deaths per 1M inhabitants namely in the case of the first European countries: Belgium, UK, Spain, Italy, Sweden, France. We observed parallelism between the number of COVID deaths and the AAT*air pollution global risk in Europe. AAT anti-protease, immune-modulating and coagulation-modulating activities may explain this finding, although very speculatively.Conclusions: Even if further studies taking into account genetic background, population density, temporal dynamics of individual epidemics, access to healthcare, social disparities and immunological response to SARS-CoV2 are needed, our preliminary observation, urges to open a discussion on gene-environment interactions in COVID-19.

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.

RationaleThe increasing incidence of extreme wildfire is becoming a concern for public health. Although long-term exposure to wildfire smoke is associated with respiratory illnesses, reports on the association between short-term occupational exposure to wildfire smoke and lung function remain scarce.MethodsIn this cross-sectional study, we analyzed data of 218 Royal Canadian Mounted Police officers (mean age: 38±9 years) deployed at the Fort McMurray wildfire in 2016. Individual exposure to air pollutants was calculated by integrating the duration of exposure with the air quality parameters obtained from the nearest air quality monitoring station during the phase of deployment. Lung function was measured using spirometry and body plethysmography. Association between exposure and lung function was examined using principal component linear regression analysis, adjusting for potential confounders.ResultsThe participants were predominantly male (71%). Mean forced expiratory volume in 1 second (FEV1), and residual volume (RV) were 76.5±5.9 and 80.1±19.5 (% predicted). A marginal association was observed between air pollution and higher RV [β: 1.55; 95%CI: -0.28 to 3.37 per interquartile change of air pollution index], but not with other lung function indices. The association between air pollution index and RV was significantly higher in participants who were screened within the first three months of deployment [2.80; 0.91 to 4.70] than those screened later [-0.28; -2.58 to 2.03], indicating a more acute effect of air pollution on peripheral airways.ConclusionAcute short-term exposure to wildfire-associated air pollutants may impose subtle but clinically important deleterious respiratory effects, particularly in the peripheral airways.

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.

The area of Civitavecchia (Lazio region, Central Italy) has been a reason of concern in the past because of environmental air contamination. The aim of this study was to evaluate the association between air pollution from different sources and respiratory symptoms and lung function in the population. A sample of 1177 residents underwent medical examination and lung function tests. Information on individual characteristics, histories of exposure and medical history were collected through a validated questionnaire. Long-term exposure to industrial, harbour, biomass combustion emissions (PM10) and urban traffic (NOx) at residential address was assessed using a Lagrangian dispersion model. The associations between exposure and wheezing and dyspnea were assessed using logistic regression models, while modified Poisson regression models were used to evaluate cough with phlegm. Relationships between exposure and lung function were analysed using linear mixed-effects models and cross-correlation. PM10 emissions from the harbour were associated with lower lung function parameters (FEV1: &beta, = &ndash, 0.12, 95% CI &ndash, 0.21 &ndash, 0.03, p = 0.02, FEV1/FVC: &beta, 1.67, (&ndash, 3.10 &ndash, 0.23), p = 0.02. This association was observed also in healthy subjects, but not in females. We found, even if at low exposure level, an effect of environmental PM10 exposure from harbour on lung function.

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.

The increasing incidence of extreme wildfire is becoming a concern for public health. Although long-term exposure to wildfire smoke is associated with respiratory illnesses, reports on the association between short-term occupational exposure to wildfire smoke and lung function remain scarce. In this cross-sectional study, we analyzed data from 218 Royal Canadian Mounted Police officers (mean age: 38 ± 9 years) deployed at the Fort McMurray wildfires in 2016. Individual exposure to air pollutants was calculated by integrating the duration of exposure with the air quality parameters obtained from the nearest air quality monitoring station during the phase of deployment. Lung function was measured using spirometry and body plethysmography. Association between exposure and lung function was examined using principal component linear regression analysis, adjusting for potential confounders. In our findings, the participants were predominantly male (71%). Mean forced expiratory volume in 1 s (FEV1), and residual volume (RV) were 76.5 ± 5.9 and 80.1 ± 19.5 (% predicted). A marginal association was observed between air pollution and higher RV [β: 1.55; 95% CI: −0.28 to 3.37 per interquartile change of air pollution index], but not with other lung function indices. The association between air pollution index and RV was significantly higher in participants who were screened within the first three months of deployment (2.80; 0.91 to 4.70) than those screened later (−0.28; −2.58 to 2.03), indicating a stronger effect of air pollution on peripheral airways. Acute short-term exposure to wildfire-associated air pollutants may impose subtle but clinically important deleterious respiratory effects, particularly in the peripheral airways.

Introduction: Although several socio-environmental factors have been established to influence asthma quality of life (AQL), the influence of neighbourhood environment on AQL has not been explored systematically. Objective: To estimate the association between neighbourhood environment and AQL. Methods: Among 131 clinically diagnosed asthma patients (mean age 37±19 years), information about neighbourhood environment was obtained from a structured questionnaire containing items about domicile, locality, closeness to noisy places (such as bus or railway station, airport, market, nearby road, etc.), and residential proximity to green/blue space. AQL was assessed using the previously validated Bengali version of the asthma quality of life questionnaire (AQLQ-S). Results: 42% of the study population was male. Mean AQLQ-total, AQLQ-activity and AQLQ-emotional function scores were 171±34, 54±14 and 29±6, respectively. In multivariable linear regression model adjusted for age, sex, educational qualification, socioeconomic status, and FEV1 (%predicted), residential proximity to green/blue space was significantly associated with better AQLQ-activity [regression coefficient (β): 5.3; 95% confidence interval (CI): 0.2 to 10.4]. On the other hand, residential proximity to noisy places was negatively associated with AQLQ-emotional function [β: -3.3; 95%CI: -6.5 to -0.04]. Conclusion: Neighbourhood environment such as lack of proximity to green/blue space and closeness to noisy places can negatively influence the quality of life in asthma.

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.

Currently, there is no cure to stop or reverse the progression of neuronal loss in neurodegenerative diseases while they are becoming an epidemic in gradually aging societies. Stress- and age-related dysregulation of posttranscriptional regulatory network may contribute to functional decline and loss of affected neurons. This chapter reviews the involvement of microRNAs in neurodegenerative diseases with the focus on Parkinson’s disease. We also highlight the phenomenon of age-related decline of neuronal microRNAs. Deciphering the changes in expression levels of microRNAs and their targets may help uncover mechanisms of disease progression. We compare approaches to study such microRNAs in the context of neurodegenerative disorders and, in particular, Parkinson’s disease. This review also categorize Parkinson’s disease postmortem brain microRNA profiling studies. Thus, we attempt to provide an insight into future research endeavors and clinical applications related to the roles of microRNAs in neurodegeneration.

Background: Occupational exposures to metal fumes and inorganic dust have been associated with increased pneumonia risk, but the risk of invasive pneumococcal disease (IPD) has not been characterized previously. Methods: We studied 4 438 cases 20 to 65 years of age from a Swedish national registry of invasive infection caused by Streptococcus pneumoniae. The case index date was the day the infection was diagnosed. Six controls for each case, matched for gender and age, 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, hospital discharge and mortality. We applied a job-exposure matrix (JEM) to characterize occupational exposures. We used conditional logistic analyses, adjusted for co-morbidities and SES, to estimate the odds ratio (OR) of IPD and the subgroup with pneumonia, associated with selected occupations and exposures the year before index date. Results: Welders manifested increased risk of IPD (OR 2.99, 95% confidence interval (CI) 2.09 - 4.30). Occupations likely to have exposure to fumes based on a JEM-assignment were also associated with elevated odds of IPD (OR 2.40, 95% CI 1.72-3.36). Risk associated with IPD with pneumonia followed a similar pattern with the highest occupational odds observed among welders (OR 3.28, 95% CI 2.22-4.84). Conclusions: Work as welder and occupational exposure to fumes increase the odds for IPD. Welders and potentially others with relevant exposures should be offered pneumococcal vaccination. Funding Statement: Swedish Heart and Lung Foundation, Swedish Council for Working Life, Health, and Welfare (FORTE) and by grants from the Swedish state under the agreement between the Swedish government and the county councils, the ALF-agreement, 74570. Declaration of Interests: All authors have completed the Unified Competing Interest form at www.icmje/coi_disclosure.pdf (available in request from the corresponding author): KT, IQ, OA, NM, RN, ADH, PDB and LS do not have any conflict of interest to report. Ethical Approval Statement: The Gothenburg Committee of Ethics approved the study (Dnr 729-16).

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 10 mm were offered confirmatory testing with QuantiFERON (R)-TB Gold In-Tube (QFT-GIT).RESULTS: Of the 2666 TST-positive migrants aged 250/100 000 person-years.CONCLUSION: Our data showed a high proportion of LTBI among individuals coming from intermediate TB burden countries.

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