Physiology and Biomarkers for Surveillance of Occupational Lung Disease.

Respiratory surveillance is the process whereby a group of exposed workers are regularly tested (or screened) for those lung diseases which occur as a result of a specific work exposure. Surveillance is performed by assessing various measures of biological or pathological processes (or biomarkers) for change over time. These traditionally include questionnaires, lung physiological assessments (especially spirometry), and imaging. Early detection of pathological processes or disease can enable removal of a worker from a potentially harmful exposure at an early stage. In this article, we summarize the physiological biomarkers currently used for respiratory surveillance, while commenting on differences in interpretative strategies between different professional groups. We also briefly review the many new techniques which are currently being assessed for respiratory surveillance in prospective research studies and which are likely to significantly broaden and enhance this field in the near future.

Medical diagnosis at the point-of-care by portable high-field asymmetric waveform ion mobility spectrometry: a systematic review and meta-analysis.

Non-invasive medical diagnosis by analysing volatile organic compounds (VOCs) at the point-of-care is becoming feasible owing to recent advances in portable instrumentation. A number of studies have assessed the performance of a state-of-the-art VOC analyser (micro-chip high-field asymmetric waveform ion mobility spectrometry, FAIMS) for medical diagnosis. However, a comprehensive meta-analysis is needed to investigate the overall diagnostic performance of these novel methods across different medical conditions. An electronic search was performed using the CAplus and MEDLINE database through the SciFinder platform. The review identified a total of 23 studies and 2312 individuals. Eighteen studies were used for meta-analysis. A pooled analysis found an overall sensitivity of 80% (95% CI, 74%-85%,I2= 62%), and specificity of 78% (95% CI, 70%-84%,I2= 80%), which corresponds to the overall diagnostic performance of micro-chip FAIMS across many different medical conditions. The diagnostic accuracy was particularly high for coeliac and inflammatory bowel disease (sensitivity and specificity from 74% to 97%). The overall diagnostic performance was similar across breath, urine, and faecal matrices with sparse logistic regression and random forests algorithms resulting in higher diagnostic accuracy. Sources of variability likely arise from differences in sample storage, sampling protocol, method of data analysis, type of disease, sample matrix, and potentially to clinical and disease factors. The results of this meta-analysis indicate that micro-chip FAIMS is a promising candidate for disease screening at the point-of-care, particularly for gastroenterology diseases. This review provides recommendations that should improve the techniques relevant to diagnostic accuracy of future VOC and point-of-care studies.

Follow-up of Soluble Mesothelin-Related Protein Levels in Participants With Asbestos-Related Disorders.

BACKGROUND: Asbestos exposure is associated with the development of the cancer malignant mesothelioma (MM). Measurement of soluble mesothelin-related protein (SMRP) has been suggested as a method for detection of MM in its early stages. We prospectively examined SMRP levels in participants with asbestos exposure who are a group at a high risk of development of MM. METHODS: This study was a follow-up of our cohort of 322 asbestos-exposed participants. No further participants developed MM or malignancy over the study period. Mean follow-up time was 22.9 months. RESULTS: Mean (standard deviation) SMRP levels at baseline and follow-up were 0.94 (0.79) and 0.91 (0.86) nmol/L (p = 0.1033), respectively. Mean SMRP levels of the healthy individuals exposed to asbestos at baseline was significantly lower than those of participants with asbestosis and pleural plaques alone; similar patterns were found on follow-up measurements. There was a statistically significant effect of age on serial SMRP measurements. Our study confirms higher levels in participants with nonmalignant asbestos-related disorders. Levels decreased in asbestos-related disorders other than asbestosis, where a small increase was observed. We did not detect any further cases of malignancy. CONCLUSION: Monitoring programs for early detection of MM need to take into account increased SMRP levels found in benign asbestos-related diseases.

Investigating cystic lung disease: a respiratory detective approach.

The cystic lung diseases are rare orphan lung disorders that most physicians will see infrequently in their everyday practice. Diagnostic and treatment options have improved over recent decades, with opportunities for slowing rate of progression and improving outcome for patients. This review provides a summary of the clinical approach to these lung disorders, including how to differentiate between different imaging patterns, clinical features, differential diagnosis and characteristics of the commonest presenting disorders. EDUCATIONAL AIMS: To understand the clinical, pathological and radiological features of cystic lung disordersTo explore the differential diagnosis of cystic lung diseaseTo be familiar with the key features (clinical, radiological, physiological and pathological) of the commoner cystic lung diseases, which assist in differentiating between these.

Characteristics of asbestos fibers in lung tissue from occupational and environmental asbestos exposure of lung cancer patients in Busan, Korea.

The Asbestos Injury Relief Act in Korea requires that asbestos exposure be assessed through clinical examination and chest computed tomography (CT). However, a more specific measurement of asbestos characteristics in the lung tissue may be appropriate. We aimed to investigate the asbestos burden and characterize asbestos fibers in patients with lung cancer and ultimately assess the relationship between occupational and environmental asbestos exposure and lung cancer in Korea. We evaluated 37 lung cancer patients (LCPs) from Busan. The factors affecting asbestos burden in LCPs were analyzed using a multiple regression analysis. History of asbestos exposure (environmental/occupational), male sex, and old age were the main factors affecting asbestos burden in lung tissues of LCPs. These factors had an approximate 37% adjusted coefficient of determination. There was a significant difference in the length of asbestos fibers (4.06-37.6 µm vs. 4.26-91.7 µm) and aspect ratio (4.5-151.9 vs. 5.6-735.6) between those who were occupationally exposed to asbestos and those who were environmentally exposed (P < 0.01). Therefore, both environmental/occupational exposure to asbestos should be strongly managed to reduce the risk of lung cancer, and exposure should be assessed according to the characteristics of asbestos fibers in the lung tissue.

Respiratory surveillance for coal mine dust and artificial stone exposed workers in Australia and New Zealand: A position statement from the Thoracic Society of Australia and New Zealand.

Coal mine lung dust disease (CMDLD) and artificial stone (AS) silicosis are preventable diseases which have occurred in serious outbreaks in Australia recently. This has prompted a TSANZ review of Australia's approach to respiratory periodic health surveillance. While regulating respirable dust exposure remains the foundation of primary and secondary prevention, identification of workers with early disease assists with control of further exposure, and with the aims of preserving lung function and decreasing respiratory morbidity in those affected. Prompt detection of an abnormality also allows for ongoing respiratory specialist clinical management. This review outlines a medical framework for improvements in respiratory surveillance to detect CMDLD and AS silicosis in Australia. This includes appropriate referral, improved data collection and interpretation, enhanced surveillance, the establishment of a nationwide Occupational Lung Disease Registry and an independent advisory group. These measures are designed to improve health outcomes for workers in the coal mining, AS and other dust-exposed and mining industries.

Artificial stone-associated silicosis: a rapidly emerging occupational lung disease.

INTRODUCTION: Artificial stone is an increasingly popular material used to fabricate kitchen and bathroom benchtops. Cutting and grinding artificial stone is associated with generation of very high levels of respirable crystalline silica, and the frequency of cases of severe silicosis associated with this exposure is rapidly increasing. AIM: To report the characteristics of a clinical series of Australian workers with artificial stone-associated silicosis. METHODS: Respiratory physicians voluntarily reported cases of artificial stone-associated silicosis identified in their clinical practices. Physicians provided information including occupational histories, respiratory function tests, chest radiology and histopathology reports, when available. RESULTS: Seven male patients were identified with a median age of 44 years (range 26-61). All were employed in small kitchen and bathroom benchtop fabrication businesses with an average of eight employees (range 2-20). All workplaces primarily used artificial stone, and dust control measures were poor. All patients were involved in dry cutting artificial stone. The median duration of exposure prior to symptoms was 7 years (range 4-10). Six patients demonstrated radiological features of progressive massive fibrosis. These individuals followed up over a median follow-up period of 16 months (IQR 21 months) demonstrated rapid decline in prebronchodilator forced expiratory volume in 1 s of 386 mL/year (SD 204 mL) and forced vital capacity of 448 mL/year (SD 312 mL). CONCLUSIONS: This series of silicosis in Australian workers further demonstrates the risk-associated high-silica content artificial stone. Effective dust control and health surveillance measures need to be stringently implemented and enforced in this industry.

Coal workers' pneumoconiosis: an Australian perspective.

Coal workers' pneumoconiosis (CWP) is an untreatable but preventable lung disease arising from chronic inhalation of coal dust. Recent reports of CWP in Queensland, along with international data, suggest that there is a resurgence in pneumoconiosis. The prevalence of CWP varies considerably between countries. In Australia, there is no mandatory reporting system and no national data on the prevalence of CWP. The symptoms and manifestations of CWP vary depending on the composition of the inhaled dust, duration of exposure, stage of disease and host-related factors. CWP may develop into progressive massive fibrosis (PMF), which can be fatal. Radiological assessment should be performed according to evidence-based standards using the ILO (International Labour Office) International Classification of Radiographs of Pneumoconioses. As preventing exposure to coal dust prevents CWP, it is important to implement and enforce appropriate standards limiting exposure. In Australia, these standards currently vary between states and are not in keeping with international understanding of the levels of coal dust that cause disease. Longitudinal screening programs are crucial for monitoring the health of coal workers to identify individuals with early-stage disease and prevent progression from mild disease to PMF. We recommend: standardisation of coal dust exposure limits, with harmonisation to international regulations; implementation of a national screening program for at-risk workers, with use of standardised questionnaires, imaging and lung function testing; development of appropriate training materials to assist general practitioners in identifying pneumoconiosis; and a system of mandatory reporting of CWP to a centralised occupational lung disease register.

mTOR treatment in lymphangioleiomyomatosis: the role of everolimus.

The orphan lung disease lymphangioleiomyomatosis (LAM) has until recently been untreatable other than by lung transplantation. However, improved understanding of underlying disease mechanisms has revealed the central role of constitutive up-regulation of the mammalian target of rapamycin (mTOR) pathway in this disease. Although other pathways exist and are under investigation for treatment, several mTOR inhibitors are currently available and emerging information suggests that these may have some efficacy in preventing loss of lung function in LAM. This paper summarizes current understanding of treatment with mTOR inhibitors in LAM, and everolimus in particular. It outlines pharmacokinetics and pharmacodynamics relevant to the clinician, recent clinical studies, and issues with potential side effects. mTOR treatment is not yet available in most countries for LAM, but current data for treatment efficacy are impressive, and it is hoped that mTOR inhibition will soon be recognised as an important treatment of this disease.