Defense and protection mechanisms in lung exposed to asbestiform fiber: the role of macrophage migration inhibitory factor and heme oxygenase-1.

Fluoro-edenite (FE), an asbestiform fiber, is responsible for many respiratory pathologies: chronic obstructive diseases, pleural plaques, fibrosis, and malignant mesothelioma. Macrophage migration inhibitory factor (MIF) is one of the first cytokines produced in response to lung tissue damage. Heme oxygenase-1 (HO-1) is a protein with protective effects against oxidative stress. It is up regulated by several stimuli including pro-inflammatory cytokines and factors that promote oxidative stress. In this research, the in vivo model of sheep lungs naturally exposed to FE was studied in order to shed light on the pathophysiological events sustaining exposure to fibers, by determining immunohistochemical lung expression of MIF and HO-1. Protein levels expression of HO-1 and MIF were also evaluated in human primary lung fibroblasts after exposure to FE fibers in vitro. In exposed sheep lungs, MIF and HO-1 immunoexpression were spread involving the intraparenchymal stroma around bronchioles, interstitium between alveoli, alveolar epithelium and macrophages. High MIF immunoexpression prevails in macrophages. Similar results were obtained in vitro, but significantly higher values were only detected for HO-1 at concentrations of 50 and 100 µg/mL of FE fibers. MIF and HO-1 expressions seem to play a role in lung self-protection against uncontrolled chronic inflammation, thus counteracting the strong link with cancer development, induced by exposure to FE. Further studies will be conducted in order to add more information about the role of MIF and HO-1 in the toxicity FE-induced.

Pleural Plaques and the Risk of Lung Cancer in Asbestos-exposed Subjects.

Rationale: Asbestos exposure is associated with a dose-dependent risk of lung cancer. The association between lung cancer and the presence of pleural plaques remains controversial.Objectives: To define the relationship between pleural plaques and lung cancer risk.Methods: Subjects were from two cohorts: 1) crocidolite mine and mill workers and Wittenoom Township residents and 2) a mixed-asbestos-fiber, mixed-occupation group. All subjects underwent annual review since 1990, chest X-ray or low-dose computed tomography scan, and outcome linkage to national cancer and mortality registry data. Cox regression, with adjustment for age (as the underlying matching time variable), was used to estimate hazard ratios (HRs) for lung cancer incidence by sex, tobacco smoking, asbestos exposure, presence of asbestosis, and pleural plaques.Measurements and Main Results: For all 4,240 subjects, mean age at follow up was 65.4 years, 3,486 (82.0%) were male, 1,315 (31.0%) had pleural plaques, and 1,353 (32.0%) had radiographic asbestosis. Overall, 3,042 (71.7%) were ever-smokers with mean tobacco exposure of 33 pack-years. In total, 200 lung cancers were recorded. Risk of lung cancer increased with cumulative exposure to cigarettes, asbestos, and presence of asbestosis. Pleural plaques did not confer any additional lung cancer risk in either cohort (cohort 1: HR, 1.03; 95% confidence interval, 0.64-1.67; P = 0.89; cohort 2: HR, 0.75; 95% confidence interval, 0.45-1.25; P = 0.28).Conclusions: The presence of pleural plaques on radiologic imaging does not confer additional increase in the risk of lung cancer. This result is consistent across two cohorts with differing asbestos fiber exposures and intensity.

Pulmonary Function and CT Scan Imaging at Low-Level Occupational Exposureto Asbestos.

Background: In spite of the reduced exposure level, and its ban in numerous countries, compensation claims for asbestos-related diseases are far from decreasing. Methods: We used retrospective exposure assessment techniques to explore respiratory function and a computerized tomography (CT) scan in relation to past asbestos exposure in 115 male workers retired from an acrylic and polyester fiber plant. Based, on detailed information on exposure circumstances, we reconstructed a cumulative exposure estimate for each patient. Results: Time-weighted average exposure in our study population was 0.24 fibers/ml (95% confidence inteval (CI) 0.19-0.29), and the average cumulative exposure was 4.51 fibers/mL-years (95% CI 3.95-5.07). Exposure was elevated among maintenance workers, compared to other jobs (p = 0.00001). Respiratory function parameters did not vary in relation to the exposure estimates, nor to CT scan results. Risk of interstitial fibrosis showed a significant upward trend (Wald test for trend = 2.62, p = 0.009) with cumulative exposure to asbestos; risk associated with 5.26 fibers/mL-years or more, was 8-fold (95% CI 1.18-54.5). Conclusions: Our results suggest that a CT scan can detect pleuro-parenchymal lung alterations at asbestos exposure levels lower than previously thought, in absence of respiratory impairment. Further studies are required to validate our techniques of retrospective assessment of asbestos exposure.

The natural course of lung function decline in asbestos exposed subjects with pleural plaques and asbestosis.

While there is a good knowledge of the natural course of lung function in interstitial lung diseases (ILD) like idiopathic lung fibrosis (IPF), many ambiguities remain in patients with asbestosis. Therefore, we evaluated the change in lung function in asbestos exposed subjects with pleural plaques and asbestosis and analysed corresponding morphology of computer tomography of the thorax. METHODS: 93 asbestos exposed subjects with pleural plaques and asbestosis were analysed retrospectively at the Klinikum Bergmannsheil of the Ruhr-University of Bochum. Parameters of lung function were obtained at least twice and annual changes of FVC, TLC and DLCOsb were calculated. In addition, we assessed the predominant pattern in high-resolution computer tomography of the thorax (HRCT) and differentiated three phenotypes: p (pleural) -type, f (fibrosis) -type and m (mixed) -type. RESULTS: FU data are available in 56/93 (60.2%) patients. The annual deterioration (Mean ±â€¯SEM) of FVC is -31.46 ±â€¯17.34 ml, of TLC -55.55 ±â€¯25.67 ml, of DLCOsb -0.38 ±â€¯0.07 mmol/min/kPa and of DLCOva -0.05 ±â€¯0.01 mmol/min/kPa/L. A categorical change of FVC > -100 ml was found in 12/56 (21.4%) and 18/56 (32.1%) patients showed an annual loss of TLC > -100 ml. The greatest annual decline of FVC was observed in patients with the fibrotic phenotype on HRCT (-76.76 ±â€¯66.43 ml) and the mixed phenotype (-81.52 ±â€¯24.79 ml), while the pleural phenotype was less affected (-10.52 ±â€¯25.07 ml). CONCLUSION: More than 20% of our cohort have a progressive disease with an annual loss of FVC > -100 ml. Patients with the fibrotic-phenotype or mixed-phenotype on HRCT are particularly at risk.

Prediction of pneumoconiosis by serum and urinary biomarkers in workers exposed to asbestos-contaminated minerals.

Workers processing nephrite, antigorite, or talc may be exposed to paragenetic asbestos minerals. An effective screening method for pneumoconiosis in workers exposed to asbestos-contaminated minerals is still lacking. The objective of this study was to assess the diagnostic accuracy of serum and urinary biomarkers for pneumoconiosis in workers exposed to asbestos-contaminated minerals. We conducted a case-control study in a cohort of stone craft workers in Hualien, where asbestos, nephrite, antigorite, and talc are produced. A total of 140 subjects were screened between March 2013 and July 2014. All subjects received a questionnaire survey and a health examination that included a physical examination; chest X-ray; and tests for standard pulmonary function, fractional exhaled nitric oxide, serum soluble mesothelin-related peptide (SMRP), fibulin-3, carcinoembryonic antigen (CEA), and urinary 8-Oxo-2'-deoxyguanosine (8-OHdG)/creatinine. After excluding subjects with uraemia and chronic obstructive pulmonary disease (COPD), we included 48 subjects with pneumoconiosis and 90 control subjects without pneumoconiosis for analysis. In terms of occupational history, 43/48 (90%) case subjects and 68% (61/90) of the control subjects had processed asbestos-contaminated minerals, including nephrite, antigorite, and talc. The case group had decreased pulmonary function in forced vital capacity (FVC), forced expiratory volume in one second, and forced expiratory flow between 25% and 75% of the FVC. The levels of SMRP, fibulin-3, urinary 8-OHdG/creatinine, and CEA were higher in the case group than in the control group. Subjects exposed to nephrite had significantly higher SMRP levels (0.84 ± 0.52 nM) than subjects exposed to other types of minerals (0.60 ± 0.30 nM). A dose-response relationship was observed between the SMRP level and the severity of pneumoconiosis. Machine learning algorithms, including variables of sex, age, SMRP, fibulin-3, CEA, and 8-OHdG/creatinine, can predict pneumoconiosis with high accuracy. The areas under the receiver operating characteristic curves ranged from 0.7 to 1.0. We suggest that SMRP and fibulin-3 could be used as biomarkers of pneumoconiosis in workers exposed to asbestos-contaminated minerals.

Association between increased small airway obstruction and asbestos exposure in patients with asbestosis.

BACKGROUND: Asbestos exposure may cause asbestos-related lung diseases including asbestosis, pleural abnormalities and malignancies. The role of asbestos exposure in the development of small airway obstruction remains controversial. Anatomic and physiologic small airway abnormalities may develop as part of the pathophysiologic process of asbestosis. We hypothesized that inhalation of asbestos may induce small airway defects in addition to asbestosis and pleural abnormalities. METHODS: In total, 281 patients with newly diagnosed asbestosis were evaluated. Clinical data were collected from the patients' medical charts. The patients were classified into various stages according to their chest X-ray findings using the International Labour Organization classification. Pulmonary function was evaluated by plethysmography and the forced oscillation technique. RESULTS: Expiratory flow, including the predicted values of the maximum expiratory flow between 25% and 50% of the forced vital capacity (MEF25-50 ), was significantly lower in the different stages of asbestosis. Accordingly, the predicted percentage of R5 -R20 was significantly higher with increasing stages of asbestosis. Furthermore, the duration of exposure to asbestos was significantly associated with the forced expiratory volume in the first second (FEV1 )/forced vital capacity (FVC) ratio and the predicted percentage of MEF25 or MEF50 according to the regression analysis in non-smoking patients with asbestosis. The predicted percentage of FEV1 or the FEV1 /FVC ratio was significantly lower and the predicted percentage of R5 -R20 was significantly higher in smokers than non-smokers. CONCLUSIONS: The patients with asbestosis have small airway obstructive defects that are significantly associated with asbestos exposure.

[Analysis of changes in radiographic lung image and lung ventilation disorders in workers occupationally exposed to chrysotile in the past]. / Analiza zmian w obrazie radiologicznym pluc i zaburzen czynnosci wentylacyjnej pluc u pracowników zawodowo narazonych na azbest chryzotylowy w przeszlosci.

BACKGROUND: The adverse health effects of occupational exposure to asbestos dust may occur several years after first exposure. The objective of the study was to assess the relationship between lesions in the respiratory system and the factors contributing to occupational exposure to asbestos described in the first medical examination as well as to analyze the factors responsible for the progression of these changes in further medical tests. MATERIAL AND METHODS: The study group comprised 591 former workers of asbestos processing plant "Gambit" in Lubawka. The results of medical examinations carried out in 2001-2012 were assessed. Statistical inference was performed based on bilateral significance tests at the 0.05 level of significance. RESULTS: A higher risk of interstitial lung changes along with an increase in the cumulative concentration of asbestos was indicated; for the employees with the highest exposure, the adjusted odds ratio (OR) was 1.63 (95% confidence interval (CI): 0.99-2.71), while for changes with the severity degree qualifying for asbestosis diagnosis, the risk was significantly increased, over fivefold higher, compared to subjects employed in the lowest exposure. The analysis of the relationship between the progression of interstitial changes and the exposure to asbestos dust showed a fourfold higher risk of the progression in workers employed in the highest exposure. Mean values of FEV1 (forced expiratory volume in 1 s), FVC (forced vital capacity), FEV1/FVC (forced expiratory volume in 1 s to forced vital capacity) were significantly lower in the subjects working in a higher asbestos exposure. The effect of tobacco smoking on the occurrence of interstitial lung changes and their progression was also confirmed. CONCLUSIONS: The results of prophylactic medical examinations of the health status of workers formerly employed in the plants using chrysotile indicate the importance andthe need for a long-term clinical follow-up and the promotion of anti-smoking prevention in this group of former employees. Med Pr 2017;68(2):247-258.

The evidence of benefits of exercise training in interstitial lung disease: a randomised controlled trial.

BACKGROUND: Uncertainty exists regarding the clinical relevance of exercise training across the range of interstitial lung diseases (ILDs). OBJECTIVE: To establish the impact of exercise training in patients with ILDs of differing aetiology and severity. METHODS: 142 participants with ILD (61 idiopathic pulmonary fibrosis (IPF), 22 asbestosis, 23 connective tissue disease-related ILD (CTD-ILD) and 36 with other aetiologies) were randomised to either 8 weeks of supervised exercise training or usual care. Six-minute walk distance (6MWD), Chronic Respiratory Disease Questionnaire (CRDQ), St George Respiratory Questionnaire IPF-specific version (SGRQ-I) and modified Medical Research Council dyspnoea score were measured at baseline, 9 weeks and 6 months. MEASUREMENTS AND MAIN RESULTS: Exercise training significantly increased 6MWD (25 m, 95% CI 2 to 47 m) and health-related quality of life (CRDQ and SGRQ-I) in people with ILD. Larger improvements in 6MWD, CRDQ, SGRQ-I and dyspnoea occurred in asbestosis and IPF compared with CTD-ILD, but with few significant differences between subgroups. Benefits declined at 6 months except in CTD-ILD. Lower baseline 6MWD and worse baseline symptoms were associated with greater benefit in 6MWD and symptoms following training. Greater gains were seen in those whose exercise prescription was successfully progressed according to the protocol. At 6 months, sustained improvements in 6MWD and symptoms were associated with better baseline lung function and less pulmonary hypertension. CONCLUSIONS: Exercise training is effective in patients across the range of ILDs, with clinically meaningful benefits in asbestosis and IPF. Successful exercise progression maximises improvements and sustained treatment effects favour those with milder disease. TRIAL REGISTRATION NUMBER: Results, ACTRN12611000416998.

Global DNA hypomethylation has no impact on lung function or serum inflammatory and fibrosis cytokines in asbestos-exposed population.

PURPOSE: To examine the effect of asbestos exposure on global DNA methylation and determine whether lung function and inflammatory and fibrosis biomarkers are correlated with the methylation state. METHODS: A total of 26 healthy subjects without asbestos exposure (Group 1), 47 healthy subjects with exposure (Group 2), and 52 subjects with benign asbestos-related disorders (ARDs) (Group 3) participated in this cross-sectional study. Blood global 5-methylcytosine (5mC) and serum TNF-α, collagen IV, CCL5 and CC16 concentrations were analyzed using enzyme-linked immunosorbent assay-like assays. Spirometric maneuvers were performed to assess lung function. RESULTS: Decreased 5mC levels were observed in Groups 2 and 3 compared to Group 1, irrespective of lung function (p < 0.01). There was no significant change in 5mC between Groups 2 and 3. Overall, 5mC was negatively correlated with CCL5 and collagen IV (p < 0.05), but no significant inverse relationship was found between 5mC and CCL5 or collagen IV in each group. Additionally, both 5mC and CC16 were inversely associated with FEV1/FVC% (p = 0.001, adjusted R 2 = 0.145) for non-smokers, and consistently significant inverse relationships were found between CC16 and FEV1/FVC%, independent of asbestos exposure. CONCLUSIONS: Asbestos exposure causes global DNA hypomethylation. DNA hypomethylation has no influence on serum biomarkers and lung function in asbestos-exposed population with or without pleural and pulmonary parenchymal abnormalities.

UK asbestos imports and mortality due to idiopathic pulmonary fibrosis.

BACKGROUND: Previous studies have demonstrated that the rising mortality due to mesothelioma and asbestosis can be predicted from historic asbestos usage. Mortality due to idiopathic pulmonary fibrosis (IPF) is also rising, without any apparent explanation. AIMS: To compare mortality due to these conditions and examine the relationship between mortality and national asbestos imports. METHODS: Mortality data for IPF and asbestosis in England and Wales were available from the Office for National Statistics. Data for mesothelioma deaths in England and Wales and historic UK asbestos import data were available from the Health & Safety Executive. The numbers of annual deaths due to each condition were plotted separately by gender, against UK asbestos imports 48 years earlier. Linear regression models were constructed. RESULTS: For mesothelioma and IPF, there was a significant linear relationship between the number of male and female deaths each year and historic UK asbestos imports. For asbestosis mortality, a similar relationship was found for male but not female deaths. The annual numbers of deaths due to asbestosis in both sexes were lower than for IPF and mesothelioma. CONCLUSIONS: The strength of the association between IPF mortality and historic asbestos imports was similar to that seen in an established asbestos-related disease, i.e. mesothelioma. This finding could in part be explained by diagnostic difficulties in separating asbestosis from IPF and highlights the need for a more accurate method of assessing lifetime occupational asbestos exposure.

Physical activity in people with asbestos related pleural disease and dust-related interstitial lung disease: An observational study.

This study aimed to measure the levels of physical activity (PA) in people with dust-related pleural and interstitial lung diseases and to compare these levels of PA to a healthy population. There is limited data on PA in this patient population and no previous studies have compared PA in people with dust-related respiratory diseases to a healthy control group. Participants with a diagnosis of a dust-related respiratory disease including asbestosis and asbestos related pleural disease (ARPD) and a healthy age- and gender-matched population wore the SenseWear(®) Pro3 armband for 9 days. Six-minute walk distance, Medical Outcomes Study 36-item short-form health survey and the Hospital Anxiety and Depression Scale were also measured. Fifty participants were recruited and 46 completed the study; 22 with ARPD, 10 with dust-related interstitial lung disease (ILD) and 14 healthy age-matched participants. The mean (standard deviation) steps/day were 6097 (1939) steps/day for dust-related ILD, 9150 (3392) steps/day for ARPD and 10,630 (3465) steps/day for healthy participants. Compared with the healthy participants, dust-related ILD participants were significantly less active as measured by steps/day ((mean difference 4533 steps/day (95% confidence interval (CI): 1888-7178)) and energy expenditure, ((mean difference 512 calories (95% CI: 196-827)) and spent significantly less time engaging in moderate, vigorous or very vigorous activities (i.e. >3 metabolic equivalents; mean difference 1.2 hours/day (95% CI: 0.4-2.0)). There were no differences in levels of PA between healthy participants and those with ARPD. PA was reduced in people with dust-related ILD but not those with ARPD when compared with healthy age and gender-matched individuals.

Asbestosis and environmental causes of usual interstitial pneumonia.

PURPOSE OF REVIEW: Recent epidemiologic investigations suggest that occupational and environmental exposures contribute to the overall burden of idiopathic pulmonary fibrosis (IPF). This article explores the epidemiologic and clinical challenges to establishing exposure associations, the current literature regarding exposure disease relationships and the diagnostic work-up of IPF and asbestosis patients. RECENT FINDINGS: IPF patients demonstrate a histopathologic pattern of usual interstitial pneumonia. In the absence of a known cause or association, a usual interstitial pneumonia pattern leads to an IPF diagnosis, which is a progressive and often terminal fibrotic lung disease. It has long been recognized that asbestos exposure can cause pathologic and radiographic changes indistinguishable from IPF. Several epidemiologic studies, primarily case control in design, have found that a number of other exposures that can increase risk of developing IPF include cigarette smoke, wood dust, metal dust, sand/silica and agricultural exposures. Lung mineralogic analyses have provided additional support to causal associations. Genetic variation may explain differences in disease susceptibility among the population. SUMMARY: An accumulating body of literature suggests that occupational and environmental exposure can contribute to the development of IPF. The impact of exposure on the pathogenesis and clinical course of disease requires further study.

Asbestos-related lung disease: a pictorial review.

Asbestos exposure can lead to a variety of adverse effects in the thorax. Although currently in the western world, levels of exposure are kept in check by strict regulations, history of previous asbestos exposure continues to have an effect on many, owing to the latent nature of the pathophysiological response of the body to the inhaled fibers. The adverse effects of asbestos generally fall under 3 categories: pleural disease, lung parenchymal disease, and neoplastic disease. Effects on the pleura include pleural effusions, plaques, and diffuse pleural thickening. In the parenchyma, rounded atelectasis, fibrotic bands, and asbestosis are observed. Differentiating asbestosis from other forms of interstitial lung diseases, such as idiopathic pulmonary fibrosis, usual interstitial pneumonia, smoking-related lung disease, and mixed interstitial lung diseases, is important because the prognosis, course of disease, and management of the patient should be tailored based on the specific etiology of the disease. In this review, imaging findings specific to asbestosis are discussed. Finally, exposure to asbestos can lead to neoplastic disease such as pleural mesothelioma, peritoneal mesothelioma, and bronchogenic carcinoma. The purpose of this article is to review the effects of asbestos exposure in the thorax, pathophysiology of these responses, and disease course. Particular emphasis is placed on the radiographic appearance of the disease, discussion of various imaging modalities and their utility, and the role of imaging in the management of patients with previous asbestos exposure and asbestos-related pulmonary disease.

Exercise training for asbestos-related and other dust-related respiratory diseases: a randomised controlled trial.

BACKGROUND: The study aimed to determine the short and long-term effects of exercise training on exercise capacity and health-related quality of life (HRQoL) compared to usual care in people with dust-related pleural and interstitial respiratory diseases. No previous studies have specifically evaluated exercise training in this patient population. METHODS: Participants with a diagnosis of a dust-related respiratory disease including asbestosis and asbestos related pleural disease were recruited and randomised to an eight-week exercise training group (EG) or a control group (CG) of usual care. Six-minute walk distance (6MWD), St George's Respiratory Questionnaire (SGRQ) and Chronic Respiratory Disease Questionnaire (CRQ) were measured at baseline, eight weeks and 26 weeks by an assessor blinded to group allocation. RESULTS: Thirty-three of 35 male participants completed the study. Sixty-nine percent of participants had asbestos related pleural disease. At eight weeks, compared to the CG, the EG showed a significantly increased 6MWD (mean difference (95%CI)) 53 metres (32 to 74), improved SGRQ total score, -7 points (-13 to -1) and increased CRQ total score, 6.4 points (2.1 to 10.7). At 26 weeks significant between-group differences were maintained in 6MWD, 45 metres (17 to 73) and CRQ total score, 13.1 points (5.2 to 20.9). CONCLUSION: Exercise training improved short and long-term exercise capacity and HRQoL in people with dust-related pleural and interstitial respiratory diseases. CLINICAL TRIAL REGISTRATION NUMBER: ANZCTR12608000147381. Date trial registered: 27.03.2008.

Diffusing capacity and forced vital capacity in 5,003 asbestos-exposed workers: relationships to interstitial fibrosis (ILO profusion score) and pleural thickening.

BACKGROUND: Asbestosis is an interstitial lung disease whose radiographic severity has long been graded by the International Labour Office (ILO) profusion score. Its effect on pulmonary function is further impacted by asbestos related pleural thickening. OBJECTIVES: This report aims to describe the relationships between radiographic grading of interstitial and pleural fibrosis and a key test of pulmonary function, the diffusing capacity, which measures gas exchange and has rarely been assessed in large groups, and to confirm the relationship to an independent test of pulmonary function, the vital capacity, which measures a mechanical property of the lungs. METHODS: The data were derived from a survey during the period 1997-2004 of 5,003 workers (all white males) exposed to asbestos in various trades. Tests included chest radiographs read by a certified expert ("B") reader, forced vital capacity (FVC), and carbon monoxide diffusing capacity (DLco). Cigarette smoking was adjusted for in the predictive equation for DLCO . Workers were evaluated at a mobile facility at work sites in four southern states. RESULTS: Both diffusing capacity and vital capacity were negatively correlated with profusion score over the full spectrum of radiographic severity. ILO profusion scores 0/1 (conventionally classified as normal) and 1/0 (conventionally classified as abnormal) were associated with similar diffusing capacity and vital capacity values. The highest profusion scores were associated with a greater proportionate decrease in diffusing capacity than in FVC. Both tests showed an effect of pleural fibrosis. CONCLUSIONS: Both radiographic severity graded by the profusion score and pleural thickening are correlated with two independent measures of pulmonary function. FVC (which had been reported in smaller work forces) and DLCO (which has not been reported). Both measures show a decrease from normal to intermediate (0/1, 1/0) scores and a further decrease with greater scores, demonstrating the consistency of radiographic and functional assessments.

Functional exercise capacity and health-related quality of life in people with asbestos related pleural disease: an observational study.

BACKGROUND: Functional exercise capacity in people with asbestos related pleural disease (ARPD) is unknown and there are no data on health-related quality of life (HRQoL). The primary aims were to determine whether functional exercise capacity and HRQoL were reduced in people with ARPD. The secondary aim was to determine whether functional exercise capacity was related to peak exercise capacity, HRQoL, physical activity or respiratory function. METHODS: In participants with ARPD, exercise capacity was measured by the six-minute walk test (6MWT) and incremental cycle test (ICT); HRQoL by the St George's Respiratory Questionnaire and physical activity by an activity monitor worn for one week. Participants also underwent lung function testing. RESULTS: 25 males completed the study with a mean (SD) age of 71 (6) years, FVC 82 (19)% predicted, FEV1/FVC 66 (11)%, TLC 80 (19)% predicted and DLCO 59 (13)% predicted. Participants had reduced exercise capacity demonstrated by six-minute walk distance (6MWD) of 76 (11)% predicted and peak work rate of 71 (21)% predicted. HRQoL was also reduced. The 6MWD correlated with peak work rate (r=0.58, p=0.002), St George's Respiratory Questionnaire Total score (r=-0.57, p=0.003), metabolic equivalents from the activity monitor (r=0.45, p<0.05), and FVC % predicted (r=0.52, p<0.01). CONCLUSIONS: People with ARPD have reduced exercise capacity and HRQoL. The 6MWT may be a useful surrogate measure of peak exercise capacity and physical activity levels in the absence of cardiopulmonary exercise testing and activity monitors. TRIAL REGISTRATION: ANZCTR12608000147381.

Longitudinal decline in lung function in former asbestos exposed workers.

BACKGROUND: This study was designed to assess the effect of asbestos exposure on longitudinal lung function decline. METHODS: A group of 502 former asbestos-cement workers with at least two spirometry tests 4 years apart. Repeated evaluations included respiratory symptoms questionnaire, spirometry and chest imaging. Asbestos exposure was ascertained as years of exposure, an index of cumulative exposure and latency time. The mixed effects model was used to evaluate the effect of exposure on the level and rate of change in forced expiratory volume in 1 s (FEV(1)) and forced vital capacity (FVC). RESULTS: Mean age at entry was 51 (SD 9.9) years, mean latency time 25.6 (SD 10.0) years, mean follow-up time 9.1 (SD 2.8) years and mean number of spirometry tests 3.5. The FEV(1) level was significantly related to pack-years of smoking at entry and during the follow-up, the index of cumulative asbestos exposure at entry, and the presence of asbestosis at follow-up. The FVC level was significantly related to pack-years of smoking during the follow-up, cumulative asbestos exposure at entry, asbestosis and pleural thickening at follow-up, and body mass index at entry. Asbestos exposure was not associated with increasing rates of FEV(1) and FVC decline. However, FEV(1) regression slopes with age, estimated by terciles of cumulative exposure, showed significant differences. Combined effects of smoking and exposure conferred further acceleration in lung function decline. CONCLUSIONS: Occupational exposure in asbestos-cement industry was a risk factor for increased lung function decline. The effect seems to be mostly concentrated during the working period. Smoking and exposure had synergic effects.

Asbestos-related diseases in Thailand and review literature.

Asbestos is a harmful substance that can cause both malignancy and non-malignancy in humans. Although it has been used in Thailand for several years, few cases of asbestos-related diseases were reported. Concerning about high consumption and long exposure of asbestos in the country, the incurable but preventable diseases caused by asbestos will be the health problem in the near future. The authors presented 2 cases with asbestos-related diseases, one diagnosed as malignant mesothelioma and the other as asbestosis.

Continued progression of asbestos-related respiratory disease after more than 15 years of non-exposure.

BACKGROUND: Most studies on asbestos-related diseases describe the associations between exposure and disease and the factors influencing that association. It is recognized that there is a long latency period between exposure and disease, but the health status of affected individuals after long-term non-exposure is uncertain. OBJECTIVES: To describe the changes in pulmonary function tests (PFTs) and computed tomographic imaging of the thorax over a 15 year period after cessation of exposure to asbestos in a cohort of Israeli power plant workers. METHODS: Israeli power plant workers whose PFTs and thoracic CT imaging between 1993 and 1998 revealed asbestos-related disease underwent a second clinical, functional and imaging evaluation up to 15 years later. The two sets of results were compared. RESULTS: Of the original cohort of 59 males, 35 were still alive and 18 of them agreed to take part in the current study. The mean length of their exposure was 30 +/- 10.06 years (range 7-43 years). Comparison of the initial and follow-up examination findings revealed a significant increase in calcification of the pleural plaques (from 37% to 66%, P = 0.008) and a deterioration in PFT results (P= 0.04). Of the 24 men who died, malignant disease was the cause of death in 53%, mostly in sites other than the respiratory system. CONCLUSIONS: PFTs declined and CT findings worsened in subjects who were formerly exposed to asbestos and had not been exposed to it for over a decade. Continued monitoring of individuals exposed to asbestos, even decades after the cessation of exposure, is recommended.

Mortality from asbestosis and mesothelioma in Britain by birth cohort.

BACKGROUND: Analysis of occupational mortality in England and Wales during 1991-2000 showed no decline in work-attributable deaths from asbestosis. AIMS: To explore why there was no decline in mortality from asbestosis despite stricter controls on asbestos exposure over recent decades. METHODS: Using data from registers of all deaths in Great Britain with mention of mesothelioma or asbestosis on the death certificate, we plotted death rates by 5 year age group within 5 year birth cohorts for(a) mesothelioma and (b) asbestosis without mention of mesothelioma. RESULTS: Analysis was based on a total of 33,751 deaths from mesothelioma and 5396 deaths from asbestosis. For both diseases, mortality showed a clear cohort effect; within birth cohorts, death rates increased progressively with age through to 85 years and older. However, highest mortality from mesothelioma was in men born during 1939-43, whereas, mortality from asbestosis peaked in men born during 1924-38. CONCLUSIONS: Our findings suggest that mortality, in Britain, from asbestosis has been determined mainly by cumulative exposure to asbestos before 45 years of age and that the effect of such exposure continues through to old age. That mortality from asbestosis peaked in earlier birth cohorts than mortality from mesothelioma may reflect a difference in exposure-response relationships for the two diseases. The discrepancy could be explained if risk of asbestosis increased more steeply than that of mesothelioma at higher levels of exposure to asbestos and if the highest prevalence of heavy exposure occurred in earlier birth cohorts than the highest prevalence of less intense exposures.