Demographic, exposure and clinical characteristics in a multinational registry of engineered stone workers with silicosis.

OBJECTIVES: To investigate differences in workplace exposure, demographic and clinical findings in engineered stone (ES) workers from a multinational consortium using the Engineered Stone Silicosis Investigators (ESSI) Global Silicosis Registry. METHODS: With ethics board approval in Israel, Spain, Australia and the USA, ES workers ages 18+ with a physician diagnosis of work-related silicosis were enrolled. Demographic, occupational, radiologic, pulmonary function and silica-related comorbidity data were compared cross-sectionally among countries using analysis of variance, Fisher's exact tests and logistic regression. RESULTS: Among 169 ES workers with silicosis, most were men, with mean age 51.7 (±11.4) years. Mean work tenure in stone fabrication or masonry was 19.9 (±9.8) years. Different methods of case ascertainment explained some inter-country differences, for example, workers in Queensland, Australia with a state-based surveillance program were likely to be identified earlier and with shorter work tenure. Overall, 32.5% of workers had progressive massive fibrosis, the most severe form of dust-related pneumoconiosis, of whom 18.5% reported ≤10 years of work tenure. Lung function impairment including restriction, reduced diffusion capacity and hypoxaemia was common, as was autoimmunity. CONCLUSIONS: Findings from a multinational registry represent a unique effort to compare demographic, exposure and clinical information from ES workers with silicosis, and suggest a substantial emerging population of workers worldwide with severe and irreversible silica-associated diseases. This younger worker population is at high risk for disease progression, multiple comorbidities and severe disability. The ESSI registry provides an ongoing framework for investigating epidemiological trends and developing prospective studies for prevention and treatment of these workers.

Current global perspectives on silicosis-Convergence of old and newly emergent hazards.

Silicosis not a disease of the past. It is an irreversible, fibrotic lung disease specifically caused by exposure to respirable crystalline silica (RCS) dust. Over 20,000 incident cases of silicosis were identified in 2017 and millions of workers continue to be exposed to RCS. Identified case numbers are however a substantial underestimation due to deficiencies in reporting systems and occupational respiratory health surveillance programmes in many countries. Insecure workers, immigrants and workers in small businesses are at particular risk of more intense RCS exposure. Much of the focus of research and prevention activities has been on the mining sector. Hazardous RCS exposure however occurs in a wide range of occupational setting which receive less attention, in particular the construction industry. Recent outbreaks of silicosis associated with the fabrication of domestic kitchen benchtops from high-silica content artificial stone have been particularly notable because of the young age of affected workers, short duration of RCS exposure and often rapid disease progression. Developments in nanotechnology and hydraulic fracking provide further examples of how rapid changes in technology and industrial processes require governments to maintain constant vigilance to identify and control potential sources of RCS exposure. Despite countries around the world dealing with similar issues related to RCS exposure, there is an absence of sustained global public health response including lack of consensus of an occupational exposure limit that would provide protection to workers. Although there are complex challenges, global elimination of silicosis must remain the goal.

Association between elevated serum bilirubin levels with preserved lung function under conditions of exposure to air pollution.

BACKGROUND: High serum bilirubin levels have been shown to be associated with an improved pulmonary function test results. Their potential ability to similarly benefit pulmonary function in an environment of polluted air has not been tested. We retrospectively analyzed data of 15,605 apparently healthy individuals in order to evaluate the effect of serum bilirubin levels on forced expiratory volume in 1 s (FEV1). METHODS: Individuals attended the Tel-Aviv Medical Center Inflammatory Survey for a routine annual health check between February, 2002 and June, 2009 and were divided into low, medium and high serum bilirubin levels. Their FEV1 results were compared under various levels of air pollution. Air pollution and weather data were obtained from air pollution monitoring stations of the Israeli Ministry of Environmental Protection. RESULTS: The elevated serum bilirubin concentrations on FEV1 were evaluated under moderate and high pollution levels FEV1 and were significantly higher in participants with high blood bilirubin levels compared to medium or low levels (p < 0.001 and p = 0.018, respectively). Participants with high levels of bilirubin had preserved FEV1 under exposure to high and medium pollution levels of both Nitrogen Oxide (NOx) and Carbon Monoxide (CO) pollutants (p = 0.003 and p = 0.022, respectively). The multivariate regression analysis revealed that the influence of bilirubin under conditions of air pollution remained significant even after adjustment for FEV1 confounders, but the interaction was not significant. CONCLUSIONS: Elevated serum bilirubin concentrations are associated with preserved lung function in healthy individuals in Israel exposed to high levels of air pollution.

Eosinophil cell count in bronchoalveolar lavage fluid in early childhood wheezing: is it predictive of future asthma?

Objective: Increased eosinophil level in bronchoalveolar lavage fluid (BALF) characterizes asthma in school-age children and adults and has been suggested as a marker for disease severity and response to treatment. We aimed to investigate the occurrence and yield of BALF eosinophil cell count in preschool children with recurrent wheezing and its possible relation to future diagnosis of asthma. Methods: BALF was retrospectively studied in young wheezy children and its relation to asthma at age 6 years was evaluated. BALF from children aged 1-48 months (mean = 20.4) was analyzed in preschool wheezy children. Children with anatomical airway obstruction and other lower airway/lung diseases who underwent BALF served as controls. Assessment of asthma was accomplished at 6 years. Results: Eighty-two children were included. The mean age during bronchoscopy and BAL was 20.4 ± 14.4 months (range: 1-48 months). Twenty-six patients had recurrent preschool wheezing, 13 anatomical airway obstruction and 43 had other lower airways/lung diseases. Groups were comparable for age during bronchoscopy and gender. No difference was found between groups for any of the BALF cell types. Eosinophils were very low in all three groups [mean (interquartile range): 0 (0-0.4), 0 (0-0.8), and 0.4 (0-1), respectively, p = 0.25]. No difference in eosinophil levels during bronchoscopy was found between asthmatic children to non-asthmatic as defined at age 6 years. Conclusions: Wheezing in preschool children is not associated with increased BALF eosinophils; hence, at this age, the diagnostic yield of BALF for cell count analysis for diagnosing asthma is limited and is not routinely indicated.

Functional, inflammatory and interstitial impairment due to artificial stone dust ultrafine particles exposure.

OBJECTIVE: Artificial stone dust (ASD) contains high levels of ultrafine particles (UFP <1 µm) which penetrate deeply into the lungs. This study aimed to demonstrate the direct effect of UFP in the lungs of ASD-exposed workers on functional inflammatory and imaging parameters. METHODS: 68 workers with up to 20 years of ASD exposure at the workplace were recruited from small enterprises throughout the country and compared with 48 non-exposed individuals. Pulmonary function test (PFT), CT, induced sputum (IS) and cytokine analyses were performed by conventional methods. The CT scans were evaluated for features indicative of silicosis in three zones of each lung. UFP were quantitated by the NanoSight LM20 system (NanoSight, Salisbury) using the Nanoparticle Tracking Analysis. Interleukin (IL)-6, IL-8 and tumour necrosis factor alpha (TNF-α) levels were measured by Luminex (R&D Systems). RESULTS: Thirty-four patients had CT scores between 0 and 42, and 29 of them were diagnosed with silicosis. Content of the UFP retrieved from IS supernatants correlated negatively with the PFT results (total lung capacity r=-0.347, p=0.011; forced expiratory volume in 1 s r=-0.299, p=0.046; diffusion lung carbon monoxide in a single breath r=-0.425, p=0.004) and with the CT score (r=0.378, p=0.023), and with the inflammatory cytokines IL-8 (r=0.336, p=0.024), IL-6 (r=0.294, p=0.065) and TNF-α (r=0.409, p=0.007). Raw material of ASD was left to sedimentate in water for <15 min, and 50% of the floating particles were UFP. A cut-off of 8×106 UFP/mL in IS samples had a sensitivity of 77% to predict pulmonary disease. CONCLUSIONS: This is the first demonstration of an association between UFP-related decreased PFT results, worsening of CT findings and elevation of inflammatory cytokines, which may be attributed to high-dose inhalation of UFP of ASD at the workplace.

Sputum Anticitrullinated Protein Antibodies in Patients With Long-standing Rheumatoid Arthritis.

OBJECTIVE: The aim of this study was to evaluate the presence of autoantibodies to cyclic citrullinated synthetic peptides (ACPAs) in the sputum of patients with long-standing rheumatoid arthritis (RA). METHODS: Nineteen consecutive RA patients and 16 age- and sex-matched control subjects participated in this cross-sectional study. All underwent complete lung function tests and provided induced sputum. Antibodies to citrullinated (CitP) and the corresponding norleucine-containing (NorP) peptides in the sputum of the RA patients and control subjects, as well as in the serum of the RA patients, were determined by enzyme-linked immunosorbent assay. RESULTS: Patients with RA had the following characteristics: mean disease duration of 12 years, Disease Activity Score for 28 joints of 3.44, and Sharp-van der Heijde score of 57.5. Ten of the 19 RA patients showed high titers of ACPAs in their sera. Four of the seropositive (40%), none of the seronegative RA patients, and only 1 of the control subjects showed detectable levels of ACPAs in their sputum. The ratio between the reactivity with CitP and NorP peptides in the sputum was significantly higher in RA sputum than in control sputum (1.33 ± 1.2 vs. 0.64 ± 0.14, P = 0.02). A positive correlation was found between sputum ACPAs and age, serum ACPAs, sputum anti-NorP, serum anti-CitP/NorP reactivity ratio, and the proportion of neutrophils and lymphocytes in the sputum. No significant correlation was found between sputum ACPAs and disease severity, history of smoking, lung function tests, or treatment for RA. CONCLUSIONS: Anticitrullinated protein/peptide antibodies can be detected in the sputum of RA patients and are correlated with the presence in the serum.

Survival following lung transplantation for artificial stone silicosis relative to idiopathic pulmonary fibrosis.

BACKGROUND: Silicosis is a progressive lung disease resulting from the inhalation of respirable crystalline silica. Lung transplantation is the only treatment for end-stage silicosis. The aim of this study was to analyze the survival experience following lung transplantation among patients with silicosis. METHODS: We reviewed data for all patients who underwent lung transplantation for silicosis and a matched group undergoing lung transplantation for idiopathic pulmonary fibrosis (IPF) at a single medical center between March 2006 and the end of December 2013. Survival was followed through 2015. RESULTS: A total of 17 lung transplantations were performed for silicosis among 342 lung transplantations (4.9%) during the study period. We observed non-statistically significant survival advantage (hazard ratio 0.6; 95%CI 0.24-1.55) for those undergoing lung transplantation for silicosis relative to IPF patients undergoing lung transplantation during the same period. CONCLUSIONS: Within the limits of a small sample, survival in silicosis patients following lung transplantation was not reduced compared to IPF. Am. J. Ind. Med. 60:248-254, 2017. © 2017 Wiley Periodicals, Inc.

Radiological Evaluation of Artificial Stone Silicosis Outbreak: Emphasizing Findings in Lung Transplant Recipients.

OBJECTIVE: The aim of this study was to describe the computed tomography (CT) findings and correlate pulmonary function tests (PFTs) of silicosis patients with emphasis on the findings in lung transplantation (LTX) recipients. METHODS: We studied the chest CT scans from 82 marble workers exposed to artificial stone dust and who had a diagnosis of silicosis, of whom 13 patients underwent LTX. Silicosis-associated findings were graded and correlated to concomitant PFT. RESULTS: A statistically significant inverse relationship was found between chest CT scores and PFT including forced expired volume in the first second (r = -0.54, P < 0.0001), total lung capacity (r = -0.4, P < 0.0001), and diffusion capacity for carbon monoxide single breath % (r = -0.6, P < 0.0001) parameters. Progressive massive fibrosis indicating advanced and complicated silicosis was found in 85% of LTX patients, as compared with 40% in patients with maintained pulmonary function. Ground-glass opacities were seen in some LTX patients with or without signs of progressive massive fibrosis. Two of these patients had silicoproteinosis diagnosed within the resected lung, indicating an acute or accelerated form of silicosis. CONCLUSIONS: This silicosis current outbreak is important because of the worldwide use of this and similar high-silica-content, artificial stone products, which can cause progressive severe forms of silicosis. Along with standard clinical assessment and PFT, CT parameters are indicative measures of the disease severity.

Mapping air pollution by biological monitoring in the metropolitan Tel Aviv area.

Conventional environmental monitoring is not surrogate of personal exposure. In contrast, biomonitoring provides information on the presence of substances in the human body, making it highly relevant to the assessment of exposure to toxic substances. Induced sputum (IS) is a noninvasive technique for detecting inflammation and reflecting particulate matter content in the airways. In this study, we mapped particulate matter dispersion in metropolitan Tel Aviv by both biomonitoring techniques employing IS samples and by environmental monitoring. All adults referred to the Pulmonary Lab for respiratory symptom evaluation in 2007 and in 2009 were enrolled. Pulmonary function tests were performed by conventional methods. Particulate size distribution in IS was analyzed, and maps of air pollution were created. Biomonitoring was more informative and enabled mapping of wider areas. Integration of biomonitoring and environmental monitoring should be considered in forming public health policy on containment of airborne particles of toxic substances.

Fingerprint of Lung Fluid Ultrafine Particles, a Novel Marker of Acute Lung Inflammation.

BACKGROUND: Acute lung inflammation can be monitored by various biochemical readouts of bronchoalveolar lavage fluid (BALF). OBJECTIVE: To analyze the BALF content of ultrafine particles (UFP; <100 nm) as an inflammatory biomarker in early diagnosis of acute and chronic lung diseases. METHODS: Mice were exposed to different stress conditions and inflammatory insults (acute lipopolysaccharide inhalation, tobacco smoke and lethal dose of total body irradiation, i.e. 950 rad). After centrifugation, the cellular pellet was assessed while cytokines and ultrafine particles were measured in the soluble fraction of the BALF. RESULTS: A characteristic UFP distribution with a D50 (i.e. the dimension of the 50th UFP percentile) was shared by all tested mouse strains in the BALF of resting lungs. All tested inflammatory insults similarly shifted this size distribution, resulting in a unique UFP fingerprint with an averaged D50 of 58.6 nm, compared with the mean UFP D50 of 23.7 nm for resting BALF (p < 0.0001). This UFP profile was highly reproducible and independent of the intensity or duration of the inflammatory trigger. It returned to baseline after resolution of the inflammation. Neither total body irradiation nor induction of acute cough induced this fingerprint. CONCLUSIONS: The UFP fingerprint in the BALF of resting and inflamed lungs can serve as a binary biomarker of healthy and acutely inflamed lungs. This marker can be used as a novel readout for the onset of inflammatory lung diseases and for complete lung recovery from different insults.

An official American Thoracic Society statement: diagnosis and management of beryllium sensitivity and chronic beryllium disease.

RATIONALE: Beryllium continues to have a wide range of industrial applications. Exposure to beryllium can lead to sensitization (BeS) and chronic beryllium disease (CBD). OBJECTIVES: The purpose of this statement is to increase awareness and knowledge about beryllium exposure, BeS, and CBD. METHODS: Evidence was identified by a search of MEDLINE. The committee then summarized the evidence, drew conclusions, and described their approach to diagnosis and management. MAIN RESULTS: The beryllium lymphocyte proliferation test is the cornerstone of both medical surveillance and the diagnosis of BeS and CBD. A confirmed abnormal beryllium lymphocyte proliferation test without evidence of lung disease is diagnostic of BeS. BeS with evidence of a granulomatous inflammatory response in the lung is diagnostic of CBD. The determinants of progression from BeS to CBD are uncertain, but higher exposures and the presence of a genetic variant in the HLA-DP ß chain appear to increase the risk. Periodic evaluation of affected individuals can detect disease progression (from BeS to CBD, or from mild CBD to more severe CBD). Corticosteroid therapy is typically administered when a patient with CBD exhibits evidence of significant lung function abnormality or decline. CONCLUSIONS: Medical surveillance in workplaces that use beryllium-containing materials can identify individuals with BeS and at-risk groups of workers, which can help prioritize efforts to reduce inhalational and dermal exposures.

Biological monitoring of particulate matter accumulated in the lungs of urban asthmatic children in the Tel-Aviv area.

PURPOSE: Lung inflammation from exposure to airborne particulate matter (PM) may be responsible for morbidity in asthma, but several studies using environmental monitoring data showed inconsistent results. Thus, the aim of this study was to evaluate the capability of induced sputum (IS) technology in order to biologically monitor PM in the lungs of urban asthmatic children. METHODS: We collected clinical, demographic, biological and environmental monitoring data on 136 children referred for asthma evaluations. The study participants were divided into two groups according to IS eosinophil counts of <3% (non-eosinophilic inflammation, n = 52) and ≥3% (eosinophilic inflammation, n = 84). RESULTS: The eosinophilic group displays significantly higher levels of fractional exhaled nitric oxide than the non-eosinophilic one (58.8 ± 47.5 vs 28.9 ± 34.2 ppm, p = 0.007). Particles (0-2.5 and 0-5 µm) comprised a strong risk factor for eosinophilic inflammation in IS (≥3%). Children with >80% of particles (0-2.5 µm) out of the total PM accumulated in the airways displayed the highest OR 10.7 (CI 2.052-56.4 p = 0.005) for an existing eosinophilic inflammation. Heme oxygenase-1 (HO-1) enzyme levels in IS positively correlated with % eosinophils and with particles in IS ranging between 2 and 3 µm. The level of HO-1 enzyme activity and FEV1/FVC in children with <3% eosinophils, but not ≥3%, was positively and significantly correlated, showing a protective effect of HO-1. CONCLUSION: Accumulation of PM involves oxidative stress pathways and is a risk factor for developing eosinophilic inflammation in asthmatic children. IS can biologically monitor this process.

Interferon Gamma Release Assay-Guided Latent Tuberculosis Prophylaxis in Israel.

BACKGROUND: Determining the accuracy of interferon gamma-release assays (IGRAs) is difficult due to the lack of a gold standard test for diagnosing latent tuberculosis (LTB). OBJECTIVES: To analyze the guidelines used for interpreting IGRAs in determining prophylactic treatment management for latent tuberculosis (LTB) in Israel. METHODS: We analyzed the retrospective data of 367 subjects who were referred to our laboratory during the period 2007-2011 for QuantiFERON Test-Gold In Tube (QFT-GIT) tests because of suspected LTB. Demographics and clinical data were retrieved from a questionnaire at enrollment, and 166/367 (45%) were further interviewed by phone in order to complete follow-up information on prophylactic TB treatment. RESULTS: The majority of subjects (116/166, 69.9%, P (P < 0.0001) were spared prophylactic treatment subsequent to QFT-GIT testing. Subjects with negative QFT-GIT and positive tuberculin skin test (TST) results who were BCG-vaccinated had the lowest treatment rates (6/68, 8.8%, P < 0.0001). Most BCG-vaccinated subjects with positive TST and negative QFT-GIT test results received treatment with anti-tumor necrosis factor-alpha (TNFα) (17/19, 89.5%, P = 0.004). We found more negative QFT-GIT test results in subjects who were receiving anti-TNFα or steroid and other immunosuppressive treatment prior to testing (11/11, 100%, P = 0.029; 22/26, 84.6%, P = 0.06; 15/17, 88%, P = 0.06, respectively). CONCLUSIONS: Deciding on LTB prophylactic treatment in Israel is highly influenced by QFT-GIT test results. QFT-GIT findings contribute to clinical decisions, but their interpretation must also consider the patient's medical history and clinical characteristics.

Man-made mineral fibers and interstitial lung diseases.

PURPOSE OF REVIEW: Manufactured (artificial) fibers represent an important and continuously growing volume among substitutes to natural fibers. A major proportion of the population in an industrialized society has been, is, or will be in contact with these fibers. The fibrous configuration of asbestos is well recognized as being an important parameter in toxicity, and now that of synthetic fibers is also suspected of inducing serious health effects on the respiratory system. There is an ongoing debate about the actual fibrogenic effect of these man-made mineral fibers (MMMFs) in humans. RECENT FINDINGS: Several case reports have demonstrated the biopersistance of MMMFs in the lung of workers who were exposed to rock wool or fiberglass for long periods of time and were diagnosed with interstitial pulmonary fibrosis. A 20-year follow up also identified refractory ceramic fibers in workers' lung tissue, with significant association between cumulative fiber exposure and radiographic pleural changes. Newly emerging man-made fiber industries appear to induce new types of occupational diseases. SUMMARY: Exposure of workers in MMMFs production plants is correlated to high risk for developing pneumoconiosis. Large epidemiological studies are needed in order to determine dose metrics for risk assessment and management.

A novel alternative to environmental monitoring to detect workers at risk for beryllium exposure-related health effects.

The purpose of this study was to describe a methodology for surveillance and monitoring of beryllium exposure using biological monitoring to complement environmental monitoring. Eighty-three Israeli dental technicians (mean age 41.6 ± 1.36 years) and 80 American nuclear machining workers (54.9 ± 1.21 years) were enrolled. Biological monitoring was carried out by analyzing particle size (laser technique) and shape (image analysis) in 131/163 (80.3%) induced sputum samples (Dipa Analyser, Donner Tech, Or Aquiva, Israel). Environmental monitoring was carried out only in the United States (Sioutas impactor, SKC, Inc., Eighty Four, Pa.). Pulmonary function testing performance and induced sputum retrieval were done by conventional methods. Sixty-three Israeli workers and 37 American workers were followed up for at least 2 years. Biological monitoring by induced sputum indicated that a >92% accumulation of <5 µm particles correlated significantly to a positive beryllium lymphocyte proliferation test result (OR 3.8, 95% CI 1.2-11.4, p = 0.015) among all participants. Environmental monitoring showed that beryllium particles were <1 µm, and this small fraction (0.1-1 µ) was significantly more highly accumulated in nuclear machining workers compared to dental technicians. The small fractions positively correlated with induced sputum macrophages (r = 0.21 p = 0.01) and negatively correlated with diffusion lung carbon monoxide single breath (DLCO-SB r = 0.180 p = 0.04) in all subjects. Years of exposure were positively correlated to the number of accumulated particles 2-3 µ in diameter (r = 0.2, p = 0.02) and negatively correlated to forced expiratory volume in one second/forced vital capacity findings (r = -0.18, p = 0.02). DLCO was decreased in both groups after two years of monitoring. Biological monitoring is more informative than environmental monitoring in the surveillance and monitoring of workers in beryllium industries. Induced sputum is a feasible and promising biomonitoring method that should be included in the surveillance of exposed workers.

Association between silicosis and autoimmune disease.

PURPOSE OF REVIEW: There is a well established association between silica inhalational exposure and autoimmune disease, particularly in the context of intense exposure. We will provide in this article an update overview of new sources of silica dust exposure, with evidences of mechanisms from human and animal studies for association between silica and autoimmune diseases, their early detection of silicosis and new options for treatment. RECENT FINDINGS: New industries such as jewelry polishing, denim jean production, fabrication of artificial stone benchtops, glass manufacturing and glassware has led to re-emergence of silicosis around the world. Silicosis with long term exposure to dust containing crystalline silica has been examined as a possible risk factor with respect to several autoimmune diseases as scleroderma, rheumatoid arthritis, lupus erythematosus, and some types of small vessel vasculitis with renal involvement. The dust may act to promote or accelerate disease development, requiring some other factors to break immune tolerance or initiate autoimmunity. Autophagy, apoptosis, or pyroptosis-related signaling pathways have also been suggested to contribute to the formation of those pathways with coordination of environmental co-exposure that can magnify autoimmune vulnerability. SUMMARY: Better understanding the mechanisms that involve silica -induced autoimmune diseases may contribute to early diagnosis.

Nanoparticles in induced sputum - a window to airway inflammation among active smokers.

Aims: To evaluate the role of nanoparticles (NP) in sputum samples of active smokers as markers of inflammation and disease. Materials & methods: 29 active smokers were included (14 with chronic obstructive pulmonary disease [COPD]) and underwent clinical assessment, pulmonary function tests, sputum induction (with NP analysis) and blood sampling. Results: Higher particle and NP concentrations and smaller mean size directly correlated with clinical parameters such as the COPD Assessment Test score and impulse oscillometry results. Similar correlations were found between NPs and increased sputum IL-1ß, IL-6 and TNF-α. Among COPD patients, higher IL-8 and lower IL-10 serum levels also correlated with NP concentrations. Conclusion: This proof-of-concept study shows the potential of sputum NPs as markers of airway inflammation and disease.

What is this article about? Identifying markers of lung inflammation and diseases could offer early diagnosis and treatment. In this study, we questioned whether nanoparticles in the sputum of active smokers correlate with lung inflammation and disease. What were the results? We found that higher nanoparticle concentration in the sputum and lower mean nanoparticle size correlated with different clinical parameters and inflammatory markers. What do the results mean? This proof-of-concept study suggests that nanoparticle analysis in the sputum of active smokers has potential as a marker that correlates with lung inflammation and disease. Our results should encourage additional research in this field to better understand the role of nanoparticles in the diagnosis, prognosis and treatment of active smokers.

Contribution of T cell subset analysis in induced sputum in diagnosing ocular sarcoidosis.

OBJECTIVE: The aim of this study was to establish a correlation between the diagnosis of ocular sarcoidosis and the presence of an elevated CD4/CD8 ratio in the induced sputum(IS) of patients with uveitis and no other systemic symptoms. METHODS: This retrospective chart review study included all newly diagnosed uveitis patients treated between 1998-2006. IS examinations and determination of angiotensin-converting enzyme (ACE) levels were carried out. A CD4/CD8 ratio > 2.5 and an ACE level > 145 Cd/ml/min were considered abnormal. The etiology of uveitis was retrieved from the medical records. RESULTS: Twenty males and 26 females (mean age 47 +/- 16.1 years) were enrolled. The CD4/CD8 ratio was elevated in 26 (56.5%) patients, and five (10.9%) were diagnosed as having sarcoidosis by the end of follow-up. The sensitivity and specificity of the T lymphocytes CD4/CD8 ratio in diagnosing sarcoidosis were 100% and 48.8%, respectively. CD4/CD8 ratios were not significantly different between the sarcoid and non-sarcoid groups (p > 0.05), but the former tended to have higher levels (p = 0.0991). The mean ACE level of the sarcoid patients was significantly higher than that of the non-sarcoid patients (p < 0.001). CONCLUSION: CD4/CD8 lymphocytes ratios obtained by IS were sensitive in uveitis patients with concomitant sarcoidosis, suggesting that analysis of T cells subsets in IS may rule out an etiology of sarcoidosis in newly diagnosed uveitis patients.

Ultrafine and nanoparticles-induced oxidative stress: the role of heme oxygenase-1 and carbon monoxide as anti-inflammatory pathways.

INTRODUCTION: Particulate matter (PM) is an environmental factor that has been associated with increased respiratory morbidity and mortality. The major effect of ambient PM on the pulmonary system is that it promotes inflammation in susceptible people. One of the mechanisms by which ambient PM exerts its proinflammatory effects is by generating increased oxidative stress induced by chemical compounds and metal constituents. Cellular responses to PM-induced oxidative stress include activation of antioxidant defense. OBJECTIVE. To investigate the anti-inflammatory and anti-apoptotic roles of heme oxygenase-1 (HO-1) and carbon monoxide (CO) in the PM-induced oxidative stress arm, inflammation, and toxicity. Methods. Particle size analyses were performed according to a laser technique based on the time of transition theory using an Eyetech Analyzer (Donner Technologies Ltd., Israel). HO-1 was analyzed by quantitative reverse transcriptase polymerase chain reaction (RT-PCR) in induced sputum (IS) samples. RESULTS: We demonstrate the feasibility of measuring micro- and nanoparticles in IS samples of exposed individuals in and out of the workplace to determine the protective role of HO-1 and CO. CONCLUSIONS: Ongoing studies will further elucidate the protective role of HO-1 and CO in the PM-induced oxidative stress model.