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.
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.
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%).
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.
This study aimed to investigate whether workplace factors and occupations are associated with SARS-CoV-2 infection or severe COVID-19 in the later waves of the pandemic.
We studied 552 562 cases with ...a positive test for SARS-CoV-2 in the Swedish registry of communicable diseases, and 5985 cases with severe COVID-19 based on hospital admissions from October 2020 to December 2021. Four population controls were assigned the index dates of their corresponding cases. We linked job histories to job-exposure matrices to assess the odds for different transmission dimensions and different occupations. We used adjusted conditional logistic analyses to estimate odds ratios (OR) for severe COVID-19 and SARS-CoV-2 with 95% confidence intervals (CI).
The highest OR for severe COVID-19 were for: regular contact with infected patients, (OR 1.37, 95% CI 1.23-1.54), close physical proximity (OR 1.47, 95% CI 1.34-1.61), and high exposure to diseases or infections (OR 1.72, 95% CI 1.52-1.96). Mostly working outside had lower OR (OR 0.77, 95% CI 0.57-1.06). The odds for SARS-CoV-2 when mostly working outside were similar (OR 0.83, 95% CI 0.80-0.86). The occupation with the highest OR for severe COVID-19 (compared with low-exposure occupations) was certified specialist physician (OR 2.05, 95% CI 1.31-3.21) among women and bus and tram drivers (OR 2.04, 95% CI 1.49-2.79) among men.
Contact with infected patients, close proximity and crowded workplaces increase the risks for severe COVID-19 and SARS-CoV-2 infection. Outdoor work is associated with decreased odds for SARS-CoV-2 infection and severe COVID-19.
Mepolizumab (MEP) has been recently introduced to treat severe eosinophilic asthma. Trials have demonstrated a significant effectiveness in this asthma phenotype. We evaluated MEP efficacy on lung ...function, symptoms, asthma exacerbations, biologic markers, steroid dependence and controller treatment level in real-life.
We retrospectively analyzed 134 severe asthmatics (61 males; mean age 58.3 ± 11; mean FEV1%:72 ± 21), treated with MEP for at least 6 months (mean duration:10.9 ± 3.7 months).
FEV1% improved significantly after MEP. Mean FEF25-75 also increased from 37.4 ± 25.4% to 47.2 ± 27.2% (p < 0.0001). Mean baseline blood eosinophil level was 712 ± 731/μL (8.4 ± 5.2%) decreasing to 151 ± 384/μL (1.6 ± 1.6%) (p < 0.0001), FENO levels decreased likewise. MEP treatment also led to a significant ACT improvement (mean pre:14.2 ± 4.4; mean post:20.5 ± 28) and exacerbations significantly fell from 3.8 ± 1.9 to 0.8 ± 1.1 (p < 0.0001). 74% of patients were steroid-dependent before MEP. 45.4% and 46.4% of them showed a suspension and dose reduction respectively (p < 0.0001). A significant number reduced also ICS doses. Only 67% of subjects used SABA as needed before MEP, falling to 20% after MEP. About 40% of patients highlighted a maintenance therapy step-down. Subjects showing an omalizumab treatment failure before MEP had a similar positive response when compared with omalizumab untreated patients.
In real-life, MEP improved significantly all outcomes even small airway obstruction, suggesting its possible role also in distal lung region treatment. Furthermore, it demonstrated its high effectiveness in OC/ICS-sparing, in reducing SABA as needed and in stepping-down maintenance therapy. MEP is a valid alternative for patients with previous omalizumab treatment failure.
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrosing interstitial pneumonia of unknown cause associated with the histopathologic and/or radiologic pattern of usual interstitial ...pneumonia (UIP). Occupational risk factors have been proposed to be associated with UIP. The aim of this case-control study is to evaluate the relationship between UIP pattern and occupational exposure in Southern Europe.
Sixty nine cases with a UIP radiological pattern at CT-scan were selected from a clinical database of the University Hospital of Perugia, Umbria, between January 2010 and December 2013. Controls (n = 277) not reporting doctor diagnosed pulmonary fibrosis, were ascertained casually among general population from the same catching area of cases. Data were collected by a questionnaire used previously in a similar study. Logistic regression models, adjusted for gender, age and smoking, were performed to evaluate the association between UIP and occupational exposure.
Farmers, veterinarians and gardeners (OR = 2.73, 95%CI = 1.47-5.10), metallurgical and steel industry workers (OR = 4.80, 95%CI = 1.50-15.33) were occupations associated with UIP. Metal dust and fumes and organic dust were risk factors for UIP. Increasing the length of occupational exposure in jobs at risk of pulmonary fibrosis, increased the risk of having UIP.
This case control study confirm partially the results from previous similar studies. Some discrepancies could be explained by the different geographical origins of the population under study, reflecting also different occupational exposures.
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.
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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.
The efficiency of clustered regularly interspaced short palindromic repeats (CRISPR) guide RNA (gRNA) targeting is critical for CRISPR associated protein 9 (Cas9)-dependent genomic modifications. ...Here, we developed Noodles, an all-in-one system to test the on-target activity of gRNAs easily and efficiently. Single-strand annealing repair mechanism of the split luciferase gene allows a positive selection of gRNAs efficiently driving nuclease activity of Cas9 from Streptococcus pyogenes (SpCas9). Our system can reliably validate in silico-predicted gRNAs before implementing them for in vitro and in vivo applications. Altogether, Noodles might be an asset for researchers and bioengineers, saving their time and efforts, while keeping the screening efficient and sensitive.
•All-in-one dual-luciferase system to easily probe on-target activity of gRNAs based on homology-directed repair mechanism.•Easy-to-subclone spCas9-based 2-plasmid system comprising Renilla luciferase for transfection efficiency control.
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Fractional exhaled nitric oxide (FE
) is used to assess of airway inflammation; diagnose asthma and monitor adherence to advised therapy. Reliable and accurate reference values for FE
are needed for ...both non-smoking and current smoking adults in the clinical setting. The present study was performed to establish reference adult FE
values among never-smokers, former smokers and current smokers.
FE
was measured in 5265 subjects aged 25-75 years in a general-population study, using a chemiluminescence (Niox ™) analyser according to the guidelines of the American Thoracic Society and the European Respiratory Society. Atopy was based on the presence of immunoglobulin E (IgE) antibodies to common inhalant allergens (measured using Phadiatop® test). Spirometry without bronchodilation was performed and forced vital capacity (FVC), forced expired volume in 1 s (FEV
) and the ratio of FEV
to FVC values were obtained. After excluding subjects with asthma, chronic bronchitis, spirometric airway obstruction and current cold, 3378 subjects remained. Equations for predictions of FE
values were modelled using nonparametric regression models.
FE
levels were similar in never-smokers and former smokers, and these two groups were therefore merged into a group termed "non-smokers". Reference equations, including the 5th and 95th percentiles, were generated for female and male non-smokers, based on age, height and atopy. Regression models for current smokers were unstable. Hence, the proposed reference values for current smokers are based on the univariate distribution of FE
and fixed cut-off limits.
Reference values for FE
among respiratory healthy non-smokers should be outlined stratified for gender using individual reference values. For current smokers separate cut-off limits are proposed.
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