Asbestosis Patients Research Articles

Expression of microRNAs in leukocytes and serum of asbestosis patients

BackgroundAlthough asbestos use is banned in many countries, long latency of asbestos-related diseases like pleural plaques or asbestosis mean it is still a public health issue. People suffering from these diseases have a higher risk of developing mesothelioma or lung cancer, which can progress quickly and aggressively. MicroRNAs were suggested as potential biomarkers in several diseases. However, in asbestosis, blood microRNAs are less explored. Since miR-32-5p, miR-143-3p, miR-145-5p, miR-146b-5p, miR-204-5p and miR-451a are involved in fibrotic processes and in cancer, expression of these microRNAs was analyzed in leukocytes and serum of asbestosis patients.MethodsMicroRNA expression was analyzed in leukocytes and serum of 36 patients (26 affected by pleural plaques and 10 by asbestosis) and 15 healthy controls by real-time RT-PCR. Additionally, data analyses were performed regarding disease severity based on ILO classification.ResultsMicroRNA miR-146b-5p was significantly down-regulated in leukocytes of patients suffering from pleural plaques with a large effect indicated by η2p = 0.150 and Cohen’s f = 0.42, a value of difference of 0.725 and a 95% confidence interval of 0.070–1.381. In patients suffering from asbestosis miR-146b-5p was not significantly regulated. However, data analyses considering disease severity only, revealed that miR-146b-5p was significantly down-regulated in leukocytes of mildly diseased patients compared to controls with a large effect indicated by η2p = 0.178 and Cohen’s f = 0.465, a value of difference of 0.848 and a 95% confidence interval of 0.097–1.599. Receiver operating characteristic (ROC) curve and an area under the ROC curve value of 0.757 for miR-146b-5p indicated acceptable discrimination ability between patients suffering from pleural plaques and healthy controls. Less microRNAs were detectable in serum than in leukocytes, showing no significant expression differences in all participants of this study. Moreover, miR-145-5p was regulated significantly differently in leukocytes and serum. An R2 value of 0.004 for miR-145-5p indicated no correlation in microRNA expression between leukocytes and serum.ConclusionLeukocytes seem more suitable than serum for microRNA analyses regarding disease and potentially cancer risk assessment of patients suffering from asbestos-related pleural plaques or asbestosis. Long-term studies may reveal whether down-regulation of miR-146b-5p in leukocytes might be an early indicator for an increased cancer risk.

Comorbidities and Causes of Death of Patients With Asbestosis.

Comorbidities are common and affect the prognosis of patients with interstitial lung diseases, but few previous studies have investigated patients with asbestosis. We collected comorbidities and death causes of 116 patients with asbestosis treated in Oulu University Hospital. Causes of death were confirmed by autopsy in 68% of the cases. The most common comorbidities of asbestosis patients were pleural plaques (96%) and coronary artery disease (CAD; 67%). The prevalence of rheumatoid arthritis was 8.6%. The most common underlying causes of death were asbestosis (36%), CAD (24%), and lung cancer (LC) (10%). CAD and LC were associated with shorter survival in adjusted analyses. Patients with asbestosis have multiple comorbidities. Prevention and treatment of CAD and LC may influence the prognosis of asbestosis patients.

Safety and tolerability of pirfenidone in asbestosis: a prospective multicenter study

BackgroundPirfenidone slows down disease progression in idiopathic pulmonary fibrosis (IPF). Recent studies suggest a treatment effect in progressive pulmonary fibrosis other than IPF. However, the safety and effectiveness of pirfenidone in asbestosis patients remain unclear. In this study, we aimed to investigate the safety, tolerability and efficacy of pirfenidone in asbestosis patients with a progressive phenotype.MethodsThis was a multicenter prospective study in asbestosis patients with progressive lung function decline. After a 12-week observational period, patients were treated with pirfenidone 801 mg three times a day. Symptoms and adverse events were evaluated weekly and patients completed online patient-reported outcomes measures. At baseline, start of therapy, 12 and 24 weeks, in hospital measurement of lung function and a 6 min walking test were performed. Additionally, patients performed daily home spirometry measurements.ResultsIn total, 10 patients were included of whom 6 patients (66.7%) experienced any adverse events during the study period. Most frequently reported adverse events were fatigue, rash, anorexia and cough, which mostly occurred intermittently and were reported as not very bothersome. No significant changes in hospital pulmonary function (forced vital capacity (FVC), diffusion capacity of the lung for carbon monoxide (DLCO), 6 min walking test or patient-reported outcomes measures before and after start of pirfenidone were found. Home spirometry demonstrated a FVC decline in 12 weeks before start of pirfenidone, while FVC did not decline during the 24 week treatment phase, but this difference was not statistically significant.ConclusionsTreatment with pirfenidone in asbestosis has an acceptable safety and tolerability profile and home spirometry data suggest this antifibrotic treatment might attenuate FVC decline in progressive asbestosis.Trial registration MEC-2018-1392; EudraCT number: 2018-001781-41

Integrated approach to bronchoalveolar lavage cytology to distinguish interstitial lung diseases

BackgroundBroncho-alveolar lavage (BAL) is a safe diagnostic procedure, useful for differentiating fibrotic lung disorders and for excluding malignancy and infection. A recent multicenter study demonstrated a new, relatively sensitive, and specific index called Bronchoalveolar Cytology Threshold (BCT), useful for distinguishing healthy individuals from patients with lung diseases. ObjectivesIn our study, BCT was applied for the first time to the analysis of interstitial lung diseases (ILDs), investigating its potential for differential diagnosis. Combinations of BAL cells that improve diagnostic accuracy for ILDs were studied and are proposed. MethodsA retrospective analysis of BAL samples was performed. We considered more than 1000 BAL samples from patients investigated for ILD, performed at Siena University Hospital.The samples enrolled for the study included 468 patients: 413 with and 55 without ILD. BAL was performed for diagnostic purposes in line with international guidelines. BCT were calculated according to available literature. ResultsAmong ILDs, patients with fibrotic hypersensitivity pneumonitis, idiopathic pulmonary fibrosis (IPF) and sarcoidosis showed significantly lower BCTs than unclassified ILD. Asbestosis patients showed significantly lower BCTs than nonspecific interstitial pneumonia (NSIP), cryptogenic organizing pneumonia (COP), connective tissue disease related ILD (CTD-ILD), sarcoidosis and unclassified ILD patients. COP patients showed significantly higher BCT than IPF, f-HP and sarcoidosis. Moreover, COP patients were best distinguished by BCT. ConclusionThe analysis of BAL features is currently included in the diagnostic algorithm of ILDs. BAL cell patterns and BCT index can provide useful information for distinguishing ILDs, reducing the need for invasive procedures. Integrated approaches to BAL analysis can improve the interpretation of results without further cost or loss of time.

Exploration of identifying novel serum biomarkers for malignant mesothelioma using iTRAQ combined with 2D-LC-MS/MS

Malignant mesothelioma (MM) is an aggressive cancer linked to asbestos exposure. Its poor prognosis makes early diagnosis extremely important, which would provide an opportunity for early treatment and potentially changing outcomes. This study aimed to explore the underlying mechanisms of MM and discover novel noninvasive biomarkers for the diagnosis of malignant mesothelioma. Using Isobaric tags for relative and absolute quantitation (iTRAQ) combined with two-dimensional liquid chromatography/tandem mass spectrometry (2D LC-MS/MS), a total of 145 differentially expressed serum proteins were identified between MM patients and healthy controls. The identified proteins were further analyzed by bioinformatics, out of which three candidate biomarkers (Filamin A (FLNA), Fibulin 1 (FBLN1) and Thrombospondin-1 (TSP-1)) were validated in large cohorts of patients with asbestos-related diseases including MM patients by ELISA assay. Receiver operating characteristic (ROC) curve analysis showed that serum FLNA, FBLN1 and TSP-1 had high diagnostic values in distinguishing MM patients from healthy controls, individuals with asbestos exposure (AE), and patients with pleural plaques (PP) or asbestosis. Meanwhile, serum FBLN1 and TSP-1 possessed good diagnostic values in distinguishing asbestosis patients from healthy controls and individuals with AE. The combination of FLNA, FBLN1, and TSP-1 proteins had higher sensitivity and specificity in discriminating patients with MM, PP and asbestosis. Our findings indicated that analysis of serum proteome using iTRAQ is a feasible strategy for biomarker discovery, and serum FLNA, FBLN1 and TSP-1 may be promising candidates for diagnosis of malignant mesothelioma and screening of at-risk individuals.

Risk factors for development of community-acquired pneumonia in workers of main occupations in production of chrysotile asbestos

Inpatient examination covered 46 workers of main occupations in chrysotile asbestos production, with diagnosed occupational disease “asbestosis”, and reference group comprising 20 healthy workers of the same enterprise. Th e results present comparative analysis of clinical and anamnesis data in dependence on the past pneumonia, studies of immune state in the asbestosis patients and the healthy workers, data on high occurrence of pneumonia in the workers, comparative analysis of respiratory infections occurrence and concomitant diseases according to the outpatients records and medical examinations. Findings are reliable diff erences and earlier respiratory manifestations in the past-pneumonia workers exposed to chrysotile asbestos, higher occurrence (1.3-fold) of chronic bronchitis and severe disorders of bronchial patency. Immune response factors were characterized as pathogenetic links of pneumococcus infectious invasion. Additional risk factors of pneumonia appeared to be frequent respiratory infections, chronic diseases of upper respiratory tract and middle ear, lower functional state of neutrophils, increased auto-reactivity. To evaluate signifi cance of risk factors infl uence, the authors used fi tt ing criterion X2 (chi-square). Intensity of relationships between the risk factor and outcome was evaluated by contingency coeffi cient of Pearson. Signifi cance level (p) for all the calculation was accepted less than 0.05.

Occupational conditionality of cardiovascular diseases in workers exposed to fibrogenic dust

Using single-factor analysis, the study covered prevalence and occupational conditionality of cardiovascular diseases in workers exposed to fibrogenic dust. The findings are higher prevalence of arterial hypertension, left ventricle myocardium hypertrophy, sinus tachycardia, obesity, hypertriglyceridemia, fasting hyperglycemia in silicosis and asbestosis patients if compared to refractory and asbestos-enrichment production workers with long length of service. Based on calculated relative risk and etiologic fraction, the authors revealed average occupational conditionality of arterial hypertension (etiologic fraction 45%), high occupational conditionality of left ventricle myocardium hypertrophy (etiologic share 59.7%), sinus tachycardia syndrome and obesity, and extremely high occupational dependence of carbohydrate metabolism (etiologic fraction 77.2%) on fibrogenic dust — that helps to assign this metabolic and cardiovascular disorders to occupationally-conditioned diseases.

Differences of CT pulmonary function indexes in asbestosis patients engaged in different types of work

Objective To evaluate the changes and characteristics of pulmonary function in asbestosis patients engaged in different types of work by multi-slice spiral CT imaging. Methods Total 30 asbestosis patients were equally divided into three groups, who engaged in the work of raw asbestos processing, fiber combing and pressure molding, respectively. The pulmonary volume, pulmonary density and pulmonary small airway indexes were measured by a whole lung scanning at maximum inspiratory and maximum expiratory efforts. The pulmonary volume indexes include maximum inspiratory volume, maximum expiratory volume, pulmonary volume difference and pulmonary volume ratio. The mean pulmonary density indexes include the mean pulmonary densities after inspiratory and expiratory activities, pulmonary density difference and pulmonary density ratio. The small airway indexes include the diameter ratios of the wall after inspiratory and expiratory activities and the percentage of bronchial wall area after inspiratory activity. Results The differences of the gender, age, stage, and contact history of the patients are not statistically significant for all the groups (all P>0.05). The differences of the mean pulmonary densities after expiratory activity, the left and right pulmonary densities after expiratory activities, pulmonary density ratio, diameter ratios of the wall after inspiratory and expiratory activities, and the percentage of bronchial wall area after inspiratory activity are statistically significant among the three groups (all P 0.05). The differences among the three groups in other indexes are not statistically significant (all P>0.05). Conclusions The emphysema with fibrous thickening in the alveolar septum and small airway wall is more severe in the workers who engaged in asbestos fiber combing comparing with in raw asbestos processing and asbestos pressure molding. Therefore, the medical protection of these groups of patients should be strengthened. Key words: Asbestosis; Respiratory dysfunction; Occupation

Evaluation of respiratory dysfunction in patients with asbestos lung based on pulmonary function indexes utilizing CT

Objective To evaluate the changes and characteristics of respiratory function and pulmonary function in patients with asbestosis by multi-slice spiral CT imaging. Methods 61 asbestosis patents and 30 healthy subjects were enrolled and divided into normal respiratory function group, mild injury group and moderate/severe injury group according to forced vital capacity and forced expiratory volume in one second. The lungs were scanned at the end of inspiratory and expiratory phase, and the lung volume, lung density and small airway index were measured. Results There were significant differences in lung volume (inspiratory and expiratory volume, volume difference, and volume ratio) among the normal group, the mild injury group and the moderate/severe injury group (all P<0.05). There were statistically significant differences in the mean lung density (lung density at the end of inspiratory and expiratory phase, lung density difference, lung density ratio) among the three groups (all P<0.05). There were significant differences in the small airway indexes (tracheal wall thickness ratio at the end of inspiratory and expiratory phase, bronchial wall area ratio) among the three groups (all P<0.05). Conclusions CT lung function imaging techniques can be used to assess the degree of respiratory dysfunction in asbestosis patients. With the development of pulmonary respiratory dysfunction, the total lung volume decreased, the amount of lungs gradually increased, emphysema gradually increased, and the thickness of small airway wall and alveolar fibrous hypertrophy gradually increased. Key words: Asbestosis; Pulmonary respiratory dysfunction; Pulmonary function

Cancer Incidence in Asbestos-Exposed Workers: An Update on Four Finnish Cohorts.

BackgroundWe assessed the cancer risks of four different Finnish asbestos-exposed cohorts. We also explored if the cohorts with varying profiles of asbestos exposure exhibited varying relative risks of cancer.MethodsThe incident cancer cases for the asbestos-exposed worker cohorts were updated to the end of 2012 using the files of the Finnish Cancer Registry. The previously formed cohorts consisted of asbestos mine workers, asbestosis patients, asbestos sprayers, and workers who had taken part in a screening study based on asbestos exposure at work.ResultsThe standardized incidence ratio (SIR) for mesothelioma varied from about threefold to > 100-fold in the different cohorts. In the screening cohort the SIR for mesothelioma was highest in 2003–2007, In other cohorts it was more constant in 5-year period inspection. The SIR for lung cancer was about twofold to tenfold in all except the screening cohort. Asbestos sprayers were at the highest risk of mesothelioma and lung cancer.ConclusionThe SIR for mesothelioma is high in all of the cohorts that represent different kinds of asbestos exposure. The smaller SIR for mesothelioma in the screening cohort with lowest level of asbestos exposure might suggest dose-responsiveness between asbestos exposure and mesothelioma. It does seem that the highest risk of lung cancer in these cohorts except in the youngest of the cohorts, the screening cohort, is over. The highest SIR for lung cancer of the asbestosis patient and sprayers cohort is explained by their heavy asbestos exposure.

Characteristics of lung function in patients with asbestosis of different stages

Objective: To investigate the characteristics of lung function in the patients with asbestosis of different stages, and analyze the correlations between the pulmonary function values and imaging score of chest X-ray. Methods: A cohort of newly diagnosed 249 asbestosis patients over a period of eight years in a single center were evaluated. Clinical data were collected from clinical charts. Radiographs were reviewed by the experts blinded to clinical data. The asbestosis patients were classified into I to III stages by chest X-ray according to the guideline. The correlations between the pulmonary function values and imaging score of chest X-ray were analyzed. Results: The prevalence of stage I to III in this asbestosis cohort was 73.5%, 19.3% and 7.2% respectively. With the stages increasing, the patients' forced vital capacity (FVC) , total lung capacity (TLC) , total carbon monoxide diffusion capacity (DLCO) predicted values were all reduced showing the restrictive ventilation impairment and/or gas exchange barrier. The obstruction of the small respiratory tracts was detected in the asbestosis of all the different stages. According to the small shadow density of each lung area, chest small shadow density score had a significant negative correlation with FVC, TLC or DLCO predicted values respectively (all P<0.01). Conclusion: The patients with asbestosis of different stages had varying degrees of gas exchange impairment, small airway dysfunction with or without ventilation dysfunction. The decreasing of DLCO was earlier than lung volume change. Chest X-ray image score paralleled the decline of lung function values, reflecting the severity of the disease.

The incidence of asbestos-related diseases about on asbestos enterprises in Qingdao from 1988 to 2014

It can provide statistics reference for the prevention and treatment by analysising the status and characteristics related to the asbestos disease of an asbestos products enterprises from 1988 to 2014. We have collected the data concerning the case of asbestos-related disease between 1988 and 2014, then the data were arranged, collecteted and analyzed using statistical method. The total of patients is 625 (male: 225, female: 400). Diagnosis of asbestosis is 617 cases, Accordingly, stage Ⅰis 500, stage Ⅱis 112 and stage Ⅲ is 5. Average age of morbidity is 64.84±9.87 and working age is 24.45±7.40 years; The patients of lung cancer caused by asbestos are 12 people, and average age of morbidity is 66.25±11.20 years, and the working age is 29.18±7.77years; The patients of mesothelioma are 4 people, average age of morbidity is 49-78 (M=60) and working age is 27years. Asbestosis patients with complications of pleural plaque is 37.44%, complications of pulmonary tuberculosis is 5.19%., and there are 239 patients lose their lives, motality is 38.74%. There is a high incidence of a disease about asbestos related disease in the asbestos products factory, it has close relationship with asbestos exposure time, the dust concentration of workplace and type of work et al. Asbestos related diseases are still the main problem in Qingdao.

Asbestosis and environmental causes of usual interstitial pneumonia.

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. 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. 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.

Iron and Iron-Related Proteins in Asbestosis.

We tested the postulate that iron homeostasis is altered among patients diagnosed to have asbestosis. Lung tissue from six individuals diagnosed to have had asbestosis at autopsy was stained for iron, ferritin, divalent metal transporter 1 (DMT1), and ferroportin 1 (FPN1). Slides from six individuals having pneumonectomy for lung cancer were employed as controls. Lung tissue from those patients with asbestosis demonstrated stainable iron, whereas control lung tissue did not. Staining for this metal was observed predominantly in airway and alveolar macrophages. Expression of the iron-related proteins ferritin, DMT1, and FPN1 was elevated in lung tissue from the six asbestosis patients relative to controls. This increased expression of iron-transport and iron-storage proteins was evident in both airway and alveolar epithelial cells. Asbestos bodies were abundant in lung tissue from patients diagnosed to have had asbestosis. While staining for iron, ferruginous bodies did not demonstrate uptake of antibodies for ferritin, DMT1, and FPN1. We conclude that iron homeostasis is altered in lung disease among those diagnosed to have asbestosis with an accumulation of the metal and a modified expression of iron-related proteins being evident.

Asbestos-induced Disruption of Calcium Homeostasis Induces Endoplasmic Reticulum Stress in Macrophages

Although the mechanisms for fibrosis development remain largely unknown, recent evidence indicates that endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR) may act as an important fibrotic stimulus in diseased lungs. ER stress is observed in lungs of patients with idiopathic pulmonary fibrosis. In this study we evaluated if ER stress and the UPR was present in macrophages exposed to chrysotile asbestos and if ER stress in macrophages was associated with asbestos-induced pulmonary fibrosis. Macrophages exposed to chrysotile had elevated transcript levels of several ER stress genes. Macrophages loaded with the Ca(2+)-sensitive dye Fura2-AM showed that cytosolic Ca(2+) increased significantly within minutes after chrysotile exposure and remained elevated for a prolonged time. Chrysotile-induced increases in cytosolic Ca(2+) were partially inhibited by either anisomycin, an inhibitor of passive Ca(2+) leak from the ER, or 1,2-bis(2-aminophenoxyl)ethane-N,N,N',N'-tetraacetic acid (BAPTA-AM), an intracellular Ca(2+) chelator known to deplete ER Ca(2+) stores. Anisomycin inhibited X-box-binding protein 1 (XBP1) mRNA splicing and reduced immunoglobulin-binding protein (BiP) levels, whereas BAPTA-AM increased XBP1 splicing and BiP expression, suggesting that ER calcium depletion may be one factor contributing to ER stress in cells exposed to chrysotile. To evaluate ER stress in vivo, asbestos-exposed mice showed fibrosis development, and alveolar macrophages from fibrotic mice showed increased expression of BiP. Bronchoalveolar macrophages from asbestosis patients showed increased expression of several ER stress genes compared with normal subjects. These findings suggest that alveolar macrophages undergo ER stress, which is associated with fibrosis development.

Spiroergometric parameters at maximal exercise testing assessed functional respiratory impairment in asbestos‐induced fibrosis

Exercise intolerance is typical for asbestosis. We examined the correlation of spiroergometric parameters with severity of asbestosis according to the International Labour Office (ILO) classification. Patients were compared to a healthy control group. Nineteen consecutive male patients with compensated asbestosis and 24 healthy subjects were examined. All participants underwent pulmonary functional testing including maximal cardiopulmonary exercise testing (CPET). Results were compared to those of healthy subjects; the correlation to disease status was investigated. Significantly lower VCin , FVC, FEV1 , MEF50 , TLC and PaO2 at rest (P<0.001) were observed in asbestosis patients. Lower peak (weight-related) work rate (WR, WR/kg), (weight-related) oxygen uptake (V'O2 , V'O2 /kg), oxygen pulse (V'O2 /hr), ventilation volume (V'E ), carbon dioxide output (V'CO2 ) and blood lactate was associated (P<0.001) with more severe asbestosis according to the ILO-classification. Significant positive correlations (P<0.001) were seen for alveolar-arterial oxygen difference [P(A-a)O2 ] and PaCO2 . Multiple regression analysis revealed that asbestosis was the only significant factor associated with the spiroergometric parameters (P<0.001). A reduction of V'O2 , V'O2 /kg, V'O2 /hr, V'E , or V'CO2 at identical submaximal workload could neither be detected among the asbestosis severity nor in comparison to healthy subjects. Only the respiratory frequency was depending on severity of asbestosis. The severity of asbestosis correlates with maximal WR, V'O2 , V'O2 /hr, V'E and gas exchange. At identical workload the discrimination between patients and controls was only possible concerning the respiratory frequency. For detection of limitations in asbestosis patients, maximal CPET is recommended.

Een patiënt met asbestose, chorea en neuropsychiatrische symptomen

A patient with known asbestosis and a recent chorea was admitted for analysis of increasing disturbances of mobility, memory and social unacceptable behavior. At physical examination only minor neurological signs were seen. Additional investigations (among others CT-brain and PET-scan) suggested early M. Alzheimer. Two months later, the patient was readmitted with pneumonia and delirium. A literature review revealed some reports of vague neurological symptoms. An association between asbestos and the disorders in this patient was considered unlikely . An approach is proposed for asbestosis patients with vague neurological and/or psychiatric symptoms.

Is an Individual Prediction of Maximal Work Rate by 6-Minute Walk Distance and Further Measurements Reliable in Male Patients with Different Lung Diseases?

Background: In patients with chronic lung diseases, the work rate for endurance training is calculated by the maximal work rate (W_max). Because the assessment bears side effects, a prediction by easier accessible tests would be of practical use. Objective: We addressed the reliability of predicting W_max on the basis of the 6-min walk distance (6MWD) test and a set of further parameters in patients with different lung diseases. Methods: Baseline data of a longitudinal study including 6MWD, W_max, peripheral muscle force, lung function, fat-free mass and dyspnea (Modified Medical Research Council score) of 255 men with occupational lung diseases (104 asthma, 69 asbestosis, 42 silicosis, 40 chronic obstructive pulmonary disease) were evaluated. Results: 6MWD correlated with W_max (r = 0.51, p < 0.05). The product of 6MWD and body weight, in particular fat-free mass, led to an improvement in the correlation of W_max with 6MWD. Muscle force, lung function and Modified Medical Research Council score correlated moderately but significantly with W_max (p < 0.05 each). The maximum correlation gained by including 6MWD and further parameters in the prediction equations was r = 0.76 in patients with obstructive lung function impairment and r = 0.61 in asbestosis patients. The residual standard deviations of W_max predicted by the calculated equations ranged between 20 and 28 W, and the 95% prediction intervals of W_max ranged between ±47 and ±65 W. Conclusions: A reliable prediction of individual W_max by 6MWD or related measures and therefore a replacement by other tests is not possible. Nevertheless, it may be useful for the comparison of average values in epidemiological and clinical studies.

MARCO modulates asbestos‐induced Rac1 mitochondrial import and H2O2 production

Rac1 is a second messenger involved in many cellular processes, including the production of H2O2. Our previous observations demonstrate that macrophage Rac1 activation is crucial for the development of pulmonary fibrosis, and Rac1 localizes to the mitochondria in asbestosis patients. Asbestos induced Rac1 translocation to the mitochondria and mediated H2O2 production. The mechanism by which asbestos activates Rac1 is not known. The macrophage receptor with collagenous structure (MARCO) has been shown to provide innate immune defense against inhaled particles and pathogens. We, therefore, hypothesized that MARCO binds asbestos and modulates Rac1 import into the mitochondria and mitochondrial H2O2 production. Both the total and cell surface expression of MARCO was greater in macrophages from asbestosis patients compared to normal subjects. To address if MARCO modulated Rac1 import, we silenced MARCO and found that it resulted in reduced Rac1 mitochondrial localization. Furthermore, inhibition of ligand binding of MARCO dramatically decreased chrysotile‐induced mitochondrial H2O2. These results suggest that MARCO binds asbestos and, together with Rac1, is involved in upstream signaling events leading to asbestos‐induced mitochondrial H2O2 production. This work was supported by NIH grants ES015981 and ES014871 and Merit Review from Department of Veterans Affairs.

Lung and pleural fibrosis in asbestos-exposed workers: a risk factor for pneumonia mortality

Lungs exposed to occupational dust may be especially vulnerable to fatal infections. We followed up asbestos-exposed workers (n=590) originally screened for lung cancer with computed tomography and scored for pleuropulmonary fibrosis. We checked these workers' influenza and pneumonia mortality data (ICD-10 codes J10-J18) in the national register. In total, 191 deaths, including 43 deaths from infectious pneumonia, occurred in 6158 person-years of follow-up (mean follow-up time 10·44 years). 'Some interstitial fibrosis' [hazard ratio (HR) 2·26, 95% confidence interval (CI) 0·98-5·19, P=0·06] and 'definite interstitial fibrosis' (HR 3·70, 95% CI 1·22-11·23, P=0·02) were associated with an increased risk of death from pneumonia compared to no fibrosis. Asbestosis patients, i.e. those with both asbestos exposure and lung fibrosis, therefore appear to be particularly at risk for death from pneumonia. These patients should be vaccinated against influenza and Pneumococcus.