NADPH and xanthine oxidases control induction of inflammatory mediator expression by organic dust in the lung.

Exposure to organic dust in animal and agricultural farms and the ensuing lung inflammation are linked to the development of respiratory diseases. We found previously that elevated production of reactive oxygen species (ROS) by aqueous poultry organic dust extract (hereafter referred to as dust extract) mediates induction of proinflammatory mediators in airway epithelial cells. In the present study, we investigated whether ROS generated by NADPH oxidases (NOX) and xanthine oxidase (XO) controls induction of inflammatory mediators by dust extract and the underlying mechanisms in bronchial epithelial cells. Using chemical inhibitors and siRNA targeted knockdown, we found that NOX1, NOX2, NOX4, and XO-derived ROS regulates induction of proinflammatory mediator levels. Like airway epithelial cells in vitro, NOX inhibitor VAS2870 reduced keratinocyte chemoattractant (KC), IL-6, and TNF-α production and 4-hydroxynonenal (4-HNE) staining induced by dust extract in mouse lungs. VAS2870 inhibition of proinflammatory mediators was associated with reduced NFκB and Stat3 activation indicating that NOX generated ROS activates NFκB and Stat3 to induce proinflammatory gene expression. Dust extract increased the membrane association of p47phox in airway epithelial cells indicating NOX2 activation but had no effect on NOX2 protein levels. In summary, our studies have shown that NOX and XO generated ROS control organic dust induction of proinflammatory mediators in airway epithelial cells via NFκB and Stat3 activation.

Silicosis, asbestosis, and pulmonary fibrosis in Ontario, Canada from 1996 to 2019.

BACKGROUND: Silicosis is a fibrotic lung disease caused by exposure to respirable crystalline silica. Historically, silicosis was common among miners and other professions in the 20th century, and in recent decades has re-emerged in coal mining and appeared in new workplaces, including the manufacture of distressed jeans and artificial stone countertops. METHODS: Physician billing data for the province of Ontario between 1992 and 2019 were analyzed across six time-periods (1993-1995, 1996-2000, 2001-2005, 2006-2010, 2011-2015, and 2016-2019). The case definition was two or more billing records within 24 months with a silicosis diagnosis code (ICD-9 502, ICD-10 J62). Cases from 1993 to 1995 were excluded as prevalent cases. Crude incidence rates per 100,000 persons were calculated by time-period, age, sex, and region. Analyses were repeated in parallel for pulmonary fibrosis (PF) (ICD-9 515, ICD-10 J84) and asbestosis (ICD-9 501; ICD-10 J61). RESULTS: From 1996 to 2019, 444 cases of silicosis, 2719 cases of asbestosis and 59,228 cases of PF were identified. Silicosis rates decreased from 0.42 cases per 100,000 in 1996-2000 to 0.06 per 100,000 people in 2016-2019. A similar trend was observed for asbestosis (1.66 to 0.51 per 100,000 persons) but the incidence rate of PF increased from 11.6 to 33.9 per 100,000 persons. Incidence rates for all outcomes were higher among men and older adults. CONCLUSIONS: A decreasing incidence of silicosis was observed in this analysis. However, the incidence of PF increased, consistent with findings from other jurisdictions. While cases of silicosis have been recorded among artificial stone workers in Ontario these cases do not seem to have impacted the population rates thus far. Ongoing, periodic surveillance of occupational diseases is helpful for tracking population-level trends over time.

The Role of the Medical Profession in Occupational Lung Disease and Access to Compensation.

The relationship between exposure to toxins at work and lung diseases continues to be significantly under-recognised in Australia. Medical practitioners are well placed to identify occupational risk factors for disease. They can therefore play a vital role in informing regulatory responses, highlighting dangerous workplaces and supporting access to compensation to assist with better health outcomes for their patients. Increased awareness among medical practitioners of occupational factors can aid early diagnosis and improve patient outcomes by improving access to justice. Medical practitioners should be cognisant of the occupational causes of lung disease in Australia to support appropriate specialist referral and ensure patients can access additional support systems available through legal compensation systems. More broadly, medical professionals and lawyers assisting workers share the common aim of highlighting preventable diseases and advocating for change to help make workplaces safer.

Bacterial extracellular vesicles isolated from organic dust induce neutrophilic inflammation in the lung.

Inhalation of organic dust is an occupational hazard leading to the development of respiratory symptoms and respiratory diseases. Bioaerosols from concentrated animal feeding operations are rich in bacteria and could carry bacterial extracellular vesicles (EVs) that could induce lung inflammation. It is not known if organic dust contains bacterial EVs and whether they modulate lung inflammation. Herein, we show that poultry organic dust contains bacterial EVs (dust EVs) that induce lung inflammation. Treatment of airway epithelial cells, THP-1-monocytes and -macrophages with dust EVs rapidly induced IL-8, IL-6, ICAM-1, proIL-1ß, and TNF-α levels. In airway epithelial cells, induction of inflammatory mediators was due to increased mRNA levels and NF-κB activation. Induction of inflammatory mediators by dust EVs was not inhibited by polymyxin B. Single and repeated treatments of mice with dust EVs increased lung KC, IL-6, and TNF-α levels without significantly altering IL-17A levels. Increases in cytokines were associated with enhanced neutrophil infiltration into the lung. Repeated treatments of mice with dust EVs increased lung mean linear intercept and increased collagen deposition around airways indicating lung remodeling. Peribronchial cell infiltrates and airway epithelial thickening were also observed in treated mice. Because bacterial EVs are nanometer-sized particles, they can reach and accumulate in the bronchiolar and alveolar regions causing lung injury leading to the development of respiratory diseases. Our studies have provided new evidence for the presence of bacterial EVs in organic dust and for their role as one of the causative agents of organic dust-induced lung inflammation and lung injury.

Sentinel approach to detect emerging causes of work-related respiratory diseases.

BACKGROUND: The world of work is continually changing, and this could result in new and emerging risks being introduced, including those that may cause work-related respiratory diseases (WRRD). AIMS: To describe recently emerging and new cases of WRRD and the relevant methodology using data in a national occupational respiratory disease surveillance scheme in the UK. METHODS: Incident cases of respiratory diseases reported by physicians to the Surveillance of Work-related and Occupational Respiratory Disease (SWORD) between January 2015 and December 2017 were included. Potentially emerging respiratory hazards manifesting in SWORD data were identified with the following hierarchical approach: (i) new respiratory disease not previously associated with work, (ii) specific exposure/agent not previously associated with WRRD and (iii) industry and/or occupation not previously associated with WRRD. RESULTS: A total of 1215 cases of WRRD were reported to SWORD between January 2015 and December 2017. No new WRRD were identified. Thirteen potentially emerging causes of occupational asthma were identified, including exposures to agents such as ninhydrin. Four potential new causes were identified for interstitial pneumonia, which included wood and brass dust. Two potentially emerging causes of WRRD were identified for inhalational accidents (green coffee and nitrocellulose), hypersensitivity pneumonitis (diphenylmethane diisocyanate and salami mould), rhinitis (morphine and Amaranthus quitensis) and sarcoidosis (prions and horses). CONCLUSIONS: Continuous monitoring and reporting of any new work-related disease is a critical function of any occupational disease reporting scheme. Potential emerging causes of work-related health risks have been identified by using a simple and systematic way of detecting emerging causes of WRRDs.

Organic dust induces inflammatory gene expression in lung epithelial cells via ROS-dependent STAT-3 activation.

Exposure to dust in agricultural and animal environments, known as organic dust, is associated with the development of respiratory symptoms and respiratory diseases. Inflammation is a key feature of lung pathologies associated with organic dust exposure, and exposure to organic dust induces the expression of several immune and inflammatory mediators. However, information on transcription factors and cellular and molecular mechanisms controlling the production of immune and inflammatory mediators induced by organic dust is limited. In this study, we have identified STAT-3 as an important transcription factor controlling the induction of expression of immune and inflammatory mediators by poultry dust extracts in airway epithelial cells and in mouse lungs and delineated the cellular pathway for STAT-3 activation. Poultry dust extract activated STAT-3 phosphorylation in Beas2B and normal human bronchial epithelial cells and in mouse lungs. Chemical inhibition and siRNA knockdown of STAT-3 suppressed induction of immune and inflammatory mediator expression. Antioxidants suppressed the increase of STAT-3 phosphorylation induced by poultry dust extract indicating that oxidative stress [elevated reactive oxygen species (ROS) levels] is important for the activation. Chemical inhibition and siRNA knockdown experiments demonstrated that STAT-3 activation is dependent on the activation of nonreceptor tyrosine-protein kinase 2 (TYK2) and epidermal growth factor receptor (EGFR) tyrosine kinases. Our studies show that poultry dust extract controls the induction of immune and inflammatory mediator expression via a cellular pathway involving oxidative stress-mediated STAT-3 activation by TYK2 and EGFR tyrosine kinases.

Occupational asthma; the limited role of air-fed respiratory protective equipment.

BACKGROUND: Evidence-based reviews have found that evidence for the efficacy of respiratory protective equipment (RPE) in the management of occupational asthma (OA) is lacking. AIMS: To quantify the effectiveness of air-fed RPE in workers with sensitizer-induced OA exposed to metal-working fluid aerosols in a car engine and transmission manufacturing facility. METHODS: All workers from an outbreak of metal-working fluid-induced OA who had continuing peak expiratory flow (PEF) evidence of sensitizer-induced OA after steam cleaning and replacement of all metal-working fluid were included. Workers kept 2-hourly PEF measurements at home and work, before and after a strictly enforced programme of RPE with air-fed respirators with charcoal filters. The area-between-curve (ABC) score from the Oasys plotter was used to assess the effectiveness of the RPE. RESULTS: Twenty workers met the inclusion criteria. Records were kept for a mean of 24.6 day shifts and rest days before and 24.7 after the institution of RPE. The ABC score improved from 26.6 (SD 16.2) to 17.7 (SD 25.4) l/min/h (P > 0.05) post-RPE; however, work-related decline was <15 l/min/h in only 12 of 20 workers, despite increased asthma treatment in 5 workers. CONCLUSIONS: Serial PEF measurements assessed with the ABC score from the Oasys system allowed quantification of the effect of RPE in sensitized workers. The RPE reduced falls in PEF associated with work exposure, but this was rarely complete. This study suggests that RPE use cannot be relied on to replace source control in workers with OA, and that monitoring post-RPE introduction is needed.

Comparison of airway deposition distributions of particles in healthy and diseased workers in an Egyptian industrial site.

The objective of this study is the prediction and comparison of airway deposition patterns of an industrial aerosol in healthy workers and workers suffering from silicosis. Mass concentrations and related size distributions of particulate matter were measured in the industrial area of Samalut in Minia, Egypt. A novel stochastic lung deposition model, simulating the symptoms of silicosis by chronic bronchial (Br) obstruction and emphysema in the acinar (Ac) region, was applied to compute mass deposition fractions, deposition density, deposition rate and deposition density rate distributions in healthy and diseased workers. In the case of healthy workers, both mass deposition fractions and deposition rates are highest in the first half of the Ac region of the lung, while the corresponding deposition density and deposition density rate distributions exhibit a maximum in the large Br airways. In the case of diseased lungs, bullous emphysema causes a large deposition peak in the region of the bronchioli respiratorii. Regional mass deposition fractions adopt maximum values in the extrathoracic region, except during mouth breathing for bullous emphysema, where Ac deposition can be the most prominent. In general, lung deposition is significantly higher in diseased than in healthy lungs. Indeed, workers suffering from silicosis receive significantly higher Ac doses than healthy workers exposed to the same aerosol. Thus, this illness may progress faster if a diseased worker remains in a strongly polluted area.

Chronic obstructive pulmonary disease in Welsh slate miners.

BACKGROUND: Exposure to respirable crystalline silica (RCS) causes emphysema, airflow limitation and chronic obstructive pulmonary disease (COPD). Slate miners are exposed to slate dust containing RCS but their COPD risk has not previously been studied. AIMS: To study the cumulative effect of mining on lung function and risk of COPD in a cohort of Welsh slate miners and whether these were independent of smoking and pneumoconiosis. METHODS: The study was based on a secondary analysis of Medical Research Council (MRC) survey data. COPD was defined as forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) ratio <0.7. We created multivariable models to assess the association between mining and lung function after adjusting for age and smoking status. We used linear regression models for FEV1 and FVC and logistic regression for COPD. RESULTS: In the original MRC study, 1255 men participated (726 slate miners, 529 unexposed non-miners). COPD was significantly more common in miners (n = 213, 33%) than non-miners (n = 120, 26%), P < 0.05. There was no statistically significant difference in risk of COPD between miners and non-miners when analysis was limited to non-smokers or those without radiographic evidence of pneumoconiosis. After adjustment for smoking, slate mining was associated with a reduction in %predicted FEV1 [ß coefficient = -3.97, 95% confidence interval (CI) -6.65, -1.29] and FVC (ß coefficient = -2.32, 95% CI -4.31, -0.33) and increased risk of COPD (odds ratio: 1.38, 95% CI 1.06, 1.81). CONCLUSIONS: Slate mining may reduce lung function and increase the incidence of COPD independently of smoking and pneumoconiosis.

Unabated occupational risk in a patient with rheumatoid pulmonary fibrosis.

BACKGROUND: This case highlights the importance of considering hypersensitivity pneumonitis (HP) in the differential diagnosis of interstitial lung disease (ILD) and of obtaining an occupational history so that remediable risk factors may be identified and managed. AIMS: To report a case of a chicken sexer with severe rheumatoid arthritis (RA) who developed progressively worsening dyspnoea and restrictive lung disease associated with pulmonary fibrosis. METHODS: Clinical investigation included physical examination, occupational history, pulmonary function tests (PFTs), chest imaging and bronchoalveolar lavage (BAL), as well as serological tests including standard IgE bird feather mixture and local IgG precipitin preparation to chicken excrement. Lung histopathology was examined post-mortem. RESULTS: The patient had worked as a chicken sexer for 29 years with limited control of exposure to chicken bioaerosols. PFTs initially showed mild restriction with a moderate gas transfer defect and computerized tomography of the chest exhibited extensive interstitial infiltrates throughout with severe honeycombing at the bases. Cytology from a BAL revealed multinucleated giant cells (MNGs). Specific serologic tests for bird antigens were negative. Histopathology demonstrated diffuse interstitial fibrosis with honeycombing, poorly formed granulomas and MNGs. CONCLUSIONS: Findings were consistent with a diagnosis of HP with RA-associated ILD. The patient's history of severe RA biased the diagnosis to one of RA-associated ILD and her occupational risk had been less emphatically addressed. Obtaining a thorough occupational history can uncover exposures to workplace respiratory hazards and may create opportunities for intervention to limit morbidity from chronic lung disease.

Gene expression profiling of the effects of organic dust in lung epithelial and THP-1 cells reveals inductive effects on inflammatory and immune response genes.

The intensification and concentration of animal production operations expose workers to high levels of organic dusts in the work environment. Exposure to organic dusts is a risk factor for the development of acute and chronic respiratory symptoms and diseases. Lung epithelium plays important roles in the control of immune and inflammatory responses to environmental agents to maintain lung health. To better understand the effects of organic dust on lung inflammatory responses, we characterized the gene expression profiles of A549 alveolar and Beas2B bronchial epithelial and THP-1 monocytic cells influenced by exposure to poultry dust extract by DNA microarray analysis using Illumina Human HT-12 v4 Expression BeadChip. We found that A549 alveolar and Beas2B bronchial epithelial and THP-1 cells responded with unique changes in the gene expression profiles with regulation of genes encoding inflammatory cytokines, chemokines, and other inflammatory proteins being common to all the three cells. Significantly induced genes included IL-8, IL-6, IL-1ß, ICAM-1, CCL2, CCL5, TLR4, and PTGS2. Validation by real-time qRT-PCR, ELISA, Western immunoblotting, and immunohistochemical staining of lung sections from mice exposed to dust extract validated DNA microarray results. Pathway analysis indicated that dust extract induced changes in gene expression influenced functions related to cellular growth and proliferation, cell death and survival, and cellular development. These data show that a broad range of inflammatory mediators produced in response to poultry dust exposure can modulate lung immune and inflammatory responses. This is the first report on organic dust induced changes in expression profiles in lung epithelial and THP-1 monocytic cells.

Personal respirable dust and respirable crystalline silica exposure in two shafts and a concentrator of a Zambian copper mine.

OBJECTIVES: Since the 1920s, Zambia's mining sector has experienced growth, which has increased the number of mine workers employed in the industry. Consequently, the potential for occupational exposure and prevalence of occupational diseases have also increased. Unfortunately, Zambia does not currently have legislative guidelines for workplace air monitoring and compliance. This study's objectives were to evaluate copper miners' personal exposure to respirable dust and respirable crystalline silica (RCS) and to assess workplace compliance using the European Standard for workplace air monitoring and measurement (EN689:2018). METHODS: This cross-sectional study collected 100 personal respirable dust exposure samples at a Zambian copper mine in 2023. These samples were weighed using NIOSH method 0600 and analyzed for crystalline silica using Fourier transform infrared spectroscopy (KBr pellet) (NIOSH method 7602). Additionally, 253 respirable dust exposure measurements collected at the mine between 2017 and 2022 were included for comparison. RESULTS: The median respirable dust exposure for the 2023 exposure measurements was 0.200 mg/m3 (95th percentile 2.871 mg/m3) compared to 0.400 mg/m3 (95th percentile 3.050 mg/m3) for the historic data. The median RCS exposure was 0.012 mg/m3 (95th percentile 0.163 mg/m3). Using EN689:2018, it was found that from 15 work areas, only six work areas complied with the standard for respirable dust exposure and only seven work areas complied with the standard for RCS exposure. CONCLUSIONS: At the mining site, several work areas had substantial exposure to respirable dust and RCS. Therefore, management needs to prioritize these areas when implementing control measures to reduce dust exposure. For the Zambia mining industry to manage exposure to respirable dust and RCS, it is necessary to implement standardized monitoring strategies. This study has demonstrated that EN689:2018 can be used successfully to determine compliance among Zambian mining work areas.

Occupational Contributions to Respiratory Health Disparities.

Occupation is an important contributor to disparities in respiratory disease, affecting financial status, health-care access, and exposure to hazardous substances. Although occupation and associated exposures are included in the socioecological models, work exposures remain persistently absent from research on health inequities and their contribution to health. This article focuses on the occupational contribution to disparities in asthma, chronic obstructive pulmonary disease, silicosis, coronavirus disease 2019, and lung cancer. Because occupational exposures are largely preventable through proper workplace controls, the recognition of occupational causes of disease can provide an opportunity for interventions to bring about health equity.

Detection and Visualisation of Pneumoconiosis Using an Ensemble of Multi-Dimensional Deep Features Learned from Chest X-rays.

Pneumoconiosis is a group of occupational lung diseases induced by mineral dust inhalation and subsequent lung tissue reactions. It can eventually cause irreparable lung damage, as well as gradual and permanent physical impairments. It has affected millions of workers in hazardous industries throughout the world, and it is a leading cause of occupational death. It is difficult to diagnose early pneumoconiosis because of the low sensitivity of chest radiographs, the wide variation in interpretation between and among readers, and the scarcity of B-readers, which all add to the difficulty in diagnosing these occupational illnesses. In recent years, deep machine learning algorithms have been extremely successful at classifying and localising abnormality of medical images. In this study, we proposed an ensemble learning approach to improve pneumoconiosis detection in chest X-rays (CXRs) using nine machine learning classifiers and multi-dimensional deep features extracted using CheXNet-121 architecture. There were eight evaluation metrics utilised for each high-level feature set of the associated cross-validation datasets in order to compare the ensemble performance and state-of-the-art techniques from the literature that used the same cross-validation datasets. It is observed that integrated ensemble learning exhibits promising results (92.68% accuracy, 85.66% Matthews correlation coefficient (MCC), and 0.9302 area under the precision-recall (PR) curve), compared to individual CheXNet-121 and other state-of-the-art techniques. Finally, Grad-CAM was used to visualise the learned behaviour of individual dense blocks within CheXNet-121 and their ensembles into three-color channels of CXRs. We compared the Grad-CAM-indicated ROI to the ground-truth ROI using the intersection of the union (IOU) and average-precision (AP) values for each classifier and their ensemble. Through the visualisation of the Grad-CAM within the blue channel, the average IOU passed more than 90% of the pneumoconiosis detection in chest radiographs.

Master Clinician and Public Health Practitioner: Selected Occupational and Environmental Pulmonary Cases.

Occupational and environmental exposures contribute to the development and progression of most lung diseases, yet their impact is greatly under-recognized in clinical practice. Clinicians caring for patients with respiratory diseases should maintain a high index of suspicion for occupational and environmental contributing factors. Mastering occupational and environmental medicine clinical decision making requires specialized clinical skills. These skills include obtaining an appropriate work and exposure history; making an assessment of the magnitude and relevance of exposures and their contribution to a patient's respiratory disease; utilizing appropriate resources for evaluation and management of exposure-related disease; and considering socioeconomic and public health factors.

Silicosis in Turkey: Is it an Endless Nightmare or is There Still Hope?

Silicosis is an ancient but still life-threatening occupational lung disease because of its incurable nature. Although its risks are known in many occupational settings and effective control strategies are well established, new cases, even epidemics, continue to occur in different sectors of Turkey. Before taking action, defining the magnitude of the problem is essential. In this concise review, we aimed to present the current situation of silicosis in Turkey. According to the data available to date, silicosis continues to be a major health problem in different sectors. Sandblasting seems to have the highest risk for the development of silicosis. Disease onset at early age and history of short exposure duration may indicate intense silica exposure. After denim sandblasters, dental technicians seem to be the new and recently recognized high-risk occupation group as per the increasing reports. Because of the lack of a definite treatment of silicosis, prevention of the disease should be the main target. Better occupational disease registry systems would be useful to assess the magnitude of the problem. In addition to implementing the necessary regulations, a close inspection of the workplaces for potential risks is essential. Other social and economic factors related with the occurrence of disease, such as unregistered employment rate and unlicensed and uninsured work, should also be considered. Finally, optimal healthcare and better living conditions for patients with silicosis should be ensured.

Radiological appearance of coal mine dust lung diseases in Australian workers.

Coal Mine Dust Lung Disease (CMDLD) encompasses a spectrum of lung diseases caused by prolonged exposure to coal mine dust. This review presents high-resolution computed tomography (HRCT) images from men diagnosed with a CMDLD since the resurgence of these diseases in Queensland in 2015.

Relationship between radiological (X-ray/HRCT), spirometric and clinical findings in dental technicians' pneumoconiosis.

INTRODUCTION: Pneumoconiosis in dental technicians' has rarely been evaluated. OBJECTIVES: To evaluate clinical, functional and radiological impacts of exposure to dust on respiratory functions via chest X-ray (CXR), high-resolution computed tomography (HRCT) and spirometry in dental technicians. METHODS: Demographic data, respiratory symptoms, spirometry results, CXR and HRCT scans of 32 dental technicians were evaluated. The opacities on the radiological images were categorized based on their intensity. We investigated the relation of radiological scores with clinical, radiological and functional findings. RESULTS: The mean age of the study population was 31 ± 9 years and mean employment duration was 14 ± 9 years. Twenty-two (69%) technicians had a history of smoking. The most common symptom was phlegm, while dyspnea prevalence was higher in those with an elevated International Labour Office (ILO) profusion score (P < 0.01). Parenchymal opacities were determined in 10 (31%) technicians by CXR and in 22 (69%) technicians by HRCT (P < 0.01). There was a positive correlation between ILO profusion score and HRCT score (r = 0.765, P < 0.01). ILO profusion score and HRCT score showed positive correlation with employment duration (r = 0.599, P = 0.01; r = 0.514, P = 0.01, respectively), while exhibiting negative correlation with FVC (r = -0.509, P < 0.05; r = -0.627, P = 0.01 respectively), FVC% (r = -0.449, P < 0.05; r = -0.457, P < 0.05, respectively) and forced expiratory volume in 1 s (r = -0.473, P < 0.05; r = -0.598, P = 0.01, respectively). CONCLUSIONS: We believe that a combined approach including spirometry, CXR and HRCT modalities should be employed in demonstrating respiratory disorders associated with exposure to inorganic dusts in dental technicians.

Imaging of Occupational Lung Disease.

Occupational lung diseases span a variety of pulmonary disorders caused by inhalation of dusts or chemical antigens in a vocational setting. Included in these are the classic mineral pneumoconioses of silicosis, coal worker's pneumoconiosis, and asbestos-related diseases as well as many immune-mediated and airway-centric diseases, and new and emerging disorders. Although some of these have characteristic imaging appearances, a multidisciplinary approach with focus on occupational exposure history is essential to proper diagnosis.