Lung

Our medical research library holds 28 studies published in Lung (1987–2022). Each entry links to the study's record on PubMed and, where there is one, to the publisher's page and a free full text. 27 have an abstract, the authors' own summary as PubMed records it: open "Abstract" to read it.

About the journal

• Publisher: Springer Verlag
• Published: 1976 to the present, United States
• Language: English, German
• ISSN: 0341-2040 (print), 1432-1750 (electronic)
• Continues: Pneumonologie
• Its record in the NLM Catalog

2020s

• Sulfated Glycans Recognized by S1 Monoclonal Antibody can Serve as a Diagnostic Marker for Malignant Pleural Mesothelioma. K. Nakashima, Y. Sakai, H. Hoshino, et al. 2022;200(3):339-346. PubMed · Publisher

  Abstract

  Purpose: Malignant pleural mesothelioma (MPM) is a malignant neoplasm of the pleura caused by asbestos exposure. For diagnosis of MPM, immunohistochemistry using multiple markers is recommended to rule out differential diagnoses, such as pulmonary adenocarcinoma. However, the specificity of currently used markers is not fully satisfactory. We previously developed a monoclonal antibody named S1, which recognizes 6-sulfo sialyl Lewis x, an L-selectin ligand expressed on high endothelial venules. During the screening process, we discovered that this antibody stained normal pleural mesothelium. This finding prompted us to hypothesize that the epitope recognized by S1 might serve as a new diagnostic marker for MPM.

  Methods: To test this hypothesis, we immunostained human MPM (n = 22) and lung adenocarcinoma (n = 25) tissues using S1 antibody.

  Results: 77.3% of MPM were S1 positive, and if limited to epithelioid type, the positivity rate was 100%, while that of lung adenocarcinoma was only 36.0%. Statistical analysis revealed a significant difference in the S1 positivity rate between each disease. Furthermore, immunohistochemistry using a series of anti-carbohydrate antibodies combined with glycosidase digestion revealed the structure of sulfated glycans expressed in MPM to be 6-sulfo sialyl N-acetyllactosamine attached to core 2-branched O-glycans.

  Conclusion: We propose that the S1 glycoepitope could serve as a new diagnostic marker for MPM.

  © 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

2010s

• Mesothelin, Calretinin, and Megakaryocyte Potentiating Factor as Biomarkers of Malignant Pleural Mesothelioma. C. Jiménez-Ramírez, S. Casjens, C.A. Juárez-Pérez, et al. 2019;197(5):641-649. PubMed · Publisher

  Abstract

  Purpose: Malignant pleural mesothelioma (MPM) is a highly lethal cancer caused by exposure to asbestos. Currently, the diagnosis is a challenge, carried out by means of invasive methods of limited sensitivity. This is a case-control study to evaluate the individual and combined performance of minimally invasive biomarkers for the diagnosis of MPM.

  Method: A study of 166 incident cases of MPM and 378 population controls of Mestizo-Mexican ethnicity was conducted. Mesothelin, calretinin, and megakaryocyte potentiating factor (MPF) were quantified in plasma by ELISA. The samples were collected from 2011 to 2016.

  Results: Based on ROC analysis and a preset specificity of 95%, the combination of the three biomarkers reached an AUC of 0.944 and a sensitivity of 82% in men. In women, an AUC of 0.937 and a sensitivity of 87% were reached. In nonconditional logistic regression models, the adjusted ORs in men were 7.92 (95% CI 3.02-20.78) for mesothelin, 20.44 (95% CI 8.90-46.94) for calretinin, and 4.37 (95% CI 1.60-11.94) for MPF. The ORs for women were 28.89 (95% CI 7.32-113.99), 17.89 (95% CI 3.93-81.49), and 2.77 (95% CI 0.47-16.21), respectively.

  Conclusions: To our knowledge, this is the first study evaluating a combination of mesothelin, calretinin, and MPF, and demonstrating a sex effect for calretinin. The biomarker panel showed a good performance in a Mestizo-Mexican population, with high sensitivity and specificity for the diagnosis of MPM.

• Thoracic Hyper-IgG4-Related Disease Mimicking Malignant Pleural Mesothelioma. F. Lococo, T. Di Stefano, C. Rapicetta, et al. 2019;197(3):387-390. Case report PubMed · Publisher

  Abstract

  We report a rare case of a IgG4-related disease presenting with recurrent pleural effusion, pleural thickness and multiple mediastinal lymphadenopathies and no involvement of other extrathoracic organs. A 65-year-old man with a previous asbestos exposure presented with cough and pain discomfort. A large right pleural effusion was detected and evacuated (siero-haematic liquid). With the suspicious of a pleural mesothelioma, a CT-scan before and a 18F-FDG PET/CT-scan later were performed revealing multiple pleural thickenings and multiple mediastinal lymphadenopathies with radiotracer uptake. EBUS-TBNA EBUS-TBNA did not result in a formal pathological diagnosis; thus, multiple pleural biopsy were performed via right thoracoscopy. At pathology the pleura was markedly thickened by a chronic fibroinflammatory process with scattered lymphoid follicles and a large number of mature plasma cells. Immunohistochemistry shows a mixed B (CD20+) and T (CD3+) population of lymphocytes, without light chain restriction and an increased number of IgG4-positive plasma cells. A presumptive diagnosis of IgG4-related disease was formulated. Total body CT-scan excluded other organ involvement. Blood test showed elevated serum IgG4 concentrations (253 mg/dL) and mild elevation of acute-phase reactants (C-reactive protein 10.7 mg/L). Autoimmune profile was negative. A diagnosis of definite IgG4-related disease was made, and treatment with prednisone 50 mg/day was started.

• Electronic Nose Technology in Respiratory Diseases. S. Dragonieri, G. Pennazza, P. Carratu, et al. 2017;195(2):157-165. Review PubMed · Publisher

  Abstract

  Electronic noses (e-noses) are based on arrays of different sensor types that respond to specific features of an odorant molecule, mostly volatile organic compounds (VOCs). Differently from gas chromatography and mass spectrometry, e-noses can distinguish VOCs spectrum by pattern recognition. E-nose technology has successfully been used in commercial applications, including military, environmental, and food industry. Human-exhaled breath contains a mixture of over 3000 VOCs, which offers the postulate that e-nose technology can have medical applications. Based on the above hypothesis, an increasing number of studies have shown that breath profiling by e-nose could play a role in the diagnosis and/or screening of various respiratory and systemic diseases. The aim of the present study was to review the principal literature on the application of e-nose technology in respiratory diseases.

• First Identification of Pulmonary Asbestos Fibres in a Spanish Population. M.I. Velasco-García, M.J. Cruz, C. Diego, et al. 2017;195(5):671-677. PubMed · Publisher

  Abstract

  Introduction: This study aimed to characterize, for the first time in Spain, the type of asbestos fibres (AF) in the lungs of exposed and non-exposed populations.

  Materials And Methods: Lung samples from 38 subjects living in Barcelona and Ferrol, Spain, were studied, which were divided into three groups: Group A-five subjects without known respiratory disease; Group B-20 ex-shipyard workers and Group C-13 patients with lung cancer. After eliminating the organic material, the inorganic residue was analysed using electronic microscopy (EM). To identify the type of fibre, the samples were analysed by scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDX).

  Results: All the fibres identified corresponded to amphiboles (crocidolite 45%, anthophyllite 22%, tremolite 16%, amosite 15% and actinolite 3%). In 14 patients (37%), a single type of asbestos was found in the lungs (amosite in two, actinolite in one, anthophyllite in four, crocidolite in five and tremolite in two). Forty-six percent of the AF analysed had a length > 5 µm and a diameter < 0.2 µm.

  Conclusions: The results of this study provide the first data on the type of asbestos retained in the lung of Spanish population. A particularly striking finding is the exclusive retention of amphiboles, which suggests that chrysotile is eliminated after inhalation. Our findings support estimations considering Spain and other southern European countries with similar asbestos imports and consumption at a high risk to develop asbestos-related diseases in the years to come.

• Predicting Malignant and Paramalignant Pleural Effusions by Combining Clinical, Radiological and Pleural Fluid Analytical Parameters. S. Herrera Lara, E. Fernández-Fabrellas, G. Juan Samper, et al. 2017;195(5):653-660. PubMed · Publisher

  Abstract

  Background: The usefulness of clinical, radiological and pleural fluid analytical parameters for diagnosing malignant and paramalignant pleural effusion is not clearly stated. Hence this study aimed to identify possible predictor variables of diagnosing malignancy in pleural effusion of unknown aetiology.

  Methods: Clinical, radiological and pleural fluid analytical parameters were obtained from consecutive patients who had suffered pleural effusion of unknown aetiology. They were classified into three groups according to their final diagnosis: malignant, paramalignant and benign pleural effusion. The CHAID (Chi-square automatic interaction detector) methodology was used to estimate the implication of the clinical, radiological and analytical variables in daily practice through decision trees.

  Results: Of 71 patients, malignant (n = 31), paramalignant (n = 15) and benign (n = 25), smoking habit, dyspnoea, weight loss, radiological characteristics (mass, node, adenopathies and pleural thickening) and pleural fluid analytical parameters (pH and glucose) distinguished malignant and paramalignant pleural effusions (all with a p < 0.05). Decision tree 1 classified 77.8% of malignant and paramalignant pleural effusions in step 2. Decision tree 2 classified 83.3% of malignant pleural effusions in step 2, 73.3% of paramalignant pleural effusions and 91.7% of benign ones.

  Conclusions: The data herein suggest that the identified predictor values applied to tree diagrams, which required no extraordinary measures, have a higher rate of correct identification of malignant, paramalignant and benign effusions when compared to techniques available today and proved most useful for usual clinical practice. Future studies are still needed to further improve the classification of patients.

• Prognosis of Cancer with Synchronous or Metachronous Malignant Pleural Effusion. J.M. Porcel, C. Solé, A. Salud, et al. 2017;195(6):775-779. PubMed · Publisher

  Abstract

  Purpose: Malignant pleural effusions (MPE) may either coincide with or follow the diagnosis of a primary tumor. Whether this circumstance influences prognosis has not been well substantiated.

  Methods: Retrospective review of all consecutive patients who were cared for at a Spanish university hospital during an 11-year period and received a diagnosis of MPE.

  Results: Of 401 patients, the MPE was the first evidence of cancer in 265 (66%), and it followed a previously diagnosed neoplasm in 136 (34%). Lung cancer predominated in the former group (131, 50%), and breast cancer in the latter (55, 40%). MPE that were the presenting manifestation of hematological and ovarian tumors had a statistically significant survival advantage as compared to those which developed in patients from a previously known cancer (respective absolute differences of 41 and 20 months; p < 0.005).

  Conclusions: In hematological and ovarian malignancies, the synchronous or metachronous diagnosis of MPE may have prognostic implications.

• Applications of Magnetic Resonance Imaging of the Thorax in Pleural Diseases: A State-of-the-Art Review. F.M. Pessôa, A.S. de Melo, A.S. Souza, et al. 2016;194(4):501-9. Review PubMed · Publisher

  Abstract

  The aim of this review was to present the main aspects of pleural diseases seen with conventional and advanced magnetic resonance imaging (MRI) techniques. This modality is considered to be the gold standard for the evaluation of the pleural interface, characterization of complex pleural effusion, and identification of exudate and hemorrhage, as well as in the analysis of superior sulcus tumors, as it enables more accurate staging. The indication for MRI of the thorax in the identification of these conditions is increasing in comparison to computerized tomography, and it can also be used to support the diagnosis of pulmonary illnesses. This literature review describes the morphological and functional aspects of the main benign and malignant pleural diseases assessed with MRI, including mesothelioma, metastasis, lymphoma, fibroma, lipoma, endometriosis, asbestos-related pleural disease, empyema, textiloma, and splenosis.

• Driver Gene and Novel Mutations in Asbestos-Exposed Lung Adenocarcinoma and Malignant Mesothelioma Detected by Exome Sequencing. S. Mäki-Nevala, V.K. Sarhadi, A. Knuuttila, et al. 2016;194(1):125-35. PubMed · Publisher

  Abstract

  Background: Asbestos is a carcinogen linked to malignant mesothelioma (MM) and lung cancer. Some gene aberrations related to asbestos exposure are recognized, but many associated mutations remain obscure. We performed exome sequencing to determine the association of previously known mutations (driver gene mutations) with asbestos and to identify novel mutations related to asbestos exposure in lung adenocarcinoma (LAC) and MM.

  Methods: Exome sequencing was performed on DNA from 47 tumor tissues of MM (21) and LAC (26) patients, 27 of whom had been asbestos-exposed (18 MM, 9 LAC). In addition, 9 normal lung/blood samples of LAC were sequenced. Novel mutations identified from exome data were validated by amplicon-based deep sequencing. Driver gene mutations in BRAF, EGFR, ERBB2, HRAS, KRAS, MET, NRAS, PIK3CA, STK11, and ephrin receptor genes (EPHA1-8, 10 and EPHB1-4, 6) were studied for both LAC and MM, and in BAP1, CUL1, CDKN2A, and NF2 for MM.

  Results: In asbestos-exposed MM patients, previously non-described NF2 frameshift mutation (one) and BAP1 mutations (four) were detected. Exome data mining revealed some genes potentially associated with asbestos exposure, such as MRPL1 and SDK1. BAP1 and COPG1 mutations were seen exclusively in MM. Pathogenic KRAS mutations were common in LAC patients (42 %), both in non-exposed (n = 5) and exposed patients (n = 6). Pathogenic BRAF mutations were found in two LACs.

  Conclusion: BAP1 mutations occurred in asbestos-exposed MM. MRPL1, SDK1, SEMA5B, and INPP4A could possibly serve as candidate genes for alterations associated with asbestos exposure. KRAS mutations in LAC were not associated with asbestos exposure.

• Evaluation of New Biomarkers in the Prediction of Malignant Mesothelioma in Subjects with Environmental Asbestos Exposure. M. Demir, H. Kaya, M. Taylan, et al. 2016;194(3):409-17. PubMed · Publisher

  Abstract

  Introduction: The purpose of this study was to investigate the potential value of certain biomarkers in predicting the presence of malignant pleural mesothelioma (MPM) in individuals environmentally exposed to asbestos.

  Methods: This prospective study investigated three groups; a control group composed of 41 healthy subjects, an asbestos exposure group consisting of 48 individuals, and a MPM group consisting of 42 patients. Serum levels of soluble mesothelin-related peptide (SMRP), thioredoxin-1 (TRX), epidermal growth factor receptor (EGFR), fibulin-3, syndecan-1 (SDC-1), and mesothelin were determined.

  Results: Benign pleural plaques were present in 27 (58.3 %) of the individuals in the asbestos exposure group. The asbestos exposure group had significantly higher mean TRX, SMRP, and mesothelin levels compared to the control group (p = 0.023, p = 0.011, and p < 0.001, respectively). Compared to the asbestos exposure group, the MPM group had significantly higher mean EGFR, TRX, SMRP, and fibulin-3 levels (p = 0.041, p = 0.023, p = 0.002, and p = 0.001, respectively), and significantly lower mean SDC-1 levels (p = 0.002). Unlike the other biomarkers, SMRP and TRX levels increased in a graded fashion among the control, asbestos exposure, and MPM groups, respectively. Area under the curve values for SMRP and TRX were 0.86 and 0.72, respectively (95 % CI 0.79-0.92 and p < 0.001 for SMRP, and 95 % CI 0.62-0.81 and p < 0.001 for TRX). The cut-off value for SMRP was 0.62 nmol/l (sensitivity: 97.6 %, specificity: 68.9 %, positive predictive value (PPV): 56.2 %, and negative predictive value (NPV): 98.3 %) and for TRX was 156.67 ng/ml (sensitivity: 92.9 %, specificity: 77.6 %, PPV: 41.4 %, and NPV: 92.1 %). The combination of the biomarkers reached a sensitivity of 100 %, but had lower specificity (as high as 27.7 %).

  Conclusions: Serum biomarkers may be helpful for early diagnosis of MPM in asbestos-exposed cases. SMRP and TRX increased in a graded fashion from the controls to asbestos exposure and MPM groups. These two seem to be the most valuable biomarkers for the diagnosis of MPM, both individually and in combination.

• Expression Profiles of Cytokine mRNAs in the Pleural Fluid Reveal Differences Among Tuberculosis, Malignancies, and Pneumonia-Exudative Pleural Effusions. D.L. Espósito, V.R. Bollela, A.L. Feitosa, et al. 2015;193(6):1001-7. PubMed · Publisher

  Abstract

  Introduction: Tuberculosis (TB) and malignant diseases are the most common causes of lymphocytic pleural effusion in adults. Serum and pleural fluid cytokine levels have been analyzed to help in the differential diagnosis, but with limited results.

  Purpose: This study investigates transcription levels of selected cytokine genes in pleural effusion of patients under investigation for TB.

  Methods: This was a prospective study that included adult patients under investigation for pleural effusion in Brazil. The expression of 19 cytokine genes was analyzed by RT-qPCR.

  Results: The majority of cytokine-related genes expressed in pleural fluid of TB patients were similar in non-TB patients, except for RORA and RORC genes, which showed a statistically higher level in TB. All cytokines in the Th17 pattern were induced in TB patients' pleural fluid. Patients with malignant pleural effusion expressed higher levels of IFN-α1, IFN-β1, TNF-α, IL-4 and IL-6, and suppression of TGFβ-1.

  Conclusion: There is still a lot to understand about the cytokine roles in the pro- and anti-inflammatory environment of exudative pleural effusions. The data presented here showed an increased expression of Th17 pattern cytokines genes in TB patients that could be used as markers to differentiate tuberculous pleuritis from other common causes of exudative pleural effusion.

• Inflammatory Cytokines Contribute to Asbestos-Induced Injury of Mesothelial Cells. M.M. Acencio, B. Soares, E. Marchi, et al. 2015;193(5):831-7. PubMed · Publisher

  Abstract

  Background: Several diseases have been related to asbestos exposure, including the pleural tumor mesothelioma. The mechanism of pleural injury by asbestos fibers is not yet fully understood. The inflammatory response with release of mediators leading to a dysregulation of apoptosis may play a pivotal role in the pathophysiology of asbestos-induced pleural disease.

  Objective: To determine whether pro-inflammatory cytokines produced by asbestos-exposed pleural mesothelial cells modify the injury induced by the asbestos.

  Methods: Mouse pleural mesothelial cells (PMC) were exposed to crocidolite or chrysotile asbestos fibers (3.0 μg/cm(2)) for 4, 24, or 48 h and assessed for viability, necrosis and apoptosis, and the production of cytokines IL-1β, IL-6 and macrophage inflammatory protein-2 (MIP-2). Cells exposed to fibers were also treated with antibodies anti-IL-1β, anti-IL-6, anti- IL-1β+anti-IL-6 or anti-MIP-2 or their irrelevant isotypes, and assessed for apoptosis and necrosis. Non-exposed cells and cells treated with wollastonite, an inert particle, were used as controls.

  Results: Mesothelial cells exposed to either crocidolite or chrysotile underwent both apoptosis and necrosis and released cytokines IL-1β, IL-6 and MIP-2. In the crocidolite group, apoptosis and the levels of all cytokines were higher than in the chrysotile group, at comparable concentrations. Neutralization of IL-1β andIL-6, but not MIP-2, inhibited apoptosis and necrosis, especially in the cells exposed to crocidolite fibers.

  Conclusions: Both crocidolite and chrysotile asbestos fibers induced apoptosis and produced an acute inflammatory response characterized by elevated levels of IL-1β, IL-6 and MIP-2 in cultured mouse PMC. IL-1β and IL-6, but not MIP-2, were shown to contribute to asbestos-induced injury, especially in the crocidolite group.

• Radiological characteristics, histological features and clinical outcomes of lung cancer patients with coexistent idiopathic pulmonary fibrosis. K.A. Khan, M.P. Kennedy, E. Moore, et al. 2015;193(1):71-7. PubMed · Publisher

  Abstract

  Introduction: Despite advances in diagnosis and management, the outcomes for both lung cancer and idiopathic pulmonary fibrosis (IPF) are still unfavourable. The pathophysiology and outcomes for patients with concomitant lung cancer and IPF remains unclear.

  Methodology: A retrospective analysis was performed of all patients presenting with concomitant IPF and lung cancer to our centre over a 3-year period. Patients with connective tissue disease, asbestos exposure, sarcoidosis, previous thoracic radiation, radiological evidence of fibrosis but no histological confirmation of lung cancer, or the use of medications known to cause pulmonary fibrosis were excluded. We describe clinical, radiological and pathological characteristics of this group. We also report the response to standardized lung cancer therapy in this cohort.

  Results: Of 637 lung cancer patients, 34 were identified with concomitant IPF (5.3 %) and all were smokers. 85 % had non-small cell lung cancer, 41 % were squamous cell cancers. The majority of tumours were located in the lower lobes, peripheral and present in an area of honeycombing. Despite the fact that approximately 2/3rds of the patients had localised or locally advanced lung cancer, the outcome of therapy for lung cancer was extremely poor regardless of tumour stage or severity of IPF.

  Conclusions: At our centre, 1/20 patients with lung cancer have concomitant IPF. The majority of these tumours are small in size, peripheral in location and squamous cell carcinoma; in an area of honey combing. The outcome for concomitant lung cancer and IPF regardless of stage or therapy is poor.

• Which is the Role of Pneumonectomy in the Era of Parenchymal-Sparing Procedures? Early/Long-Term Survival and Functional Results of a Single-Center Experience. A. Janet-Vendroux, M. Loi, A. Bobbio, et al. 2015;193(6):965-73. PubMed · Publisher

  Abstract

  Aim: Despite the increasing adoption of parenchymal-sparing procedures, pneumonectomy is still necessary in several pleural and pulmonary (benign or malignant) diseases. We reviewed clinical data of a large cohort of patients treated by pneumonectomy with the aim of better define its impact on early and long-term results.

  Methods: Clinical and pathological characteristics of all consecutive patients treated by pneumonectomy between January 2005 and May 2012 were retrospectively reviewed. Thirty- and 90-day mortality, as well as long-term survival was assessed. Factors associated to long-term survival were analyzed by univariate and multivariate analyses. Evaluation of quality of life was carried out by a standard questionnaire (SF-12) administrated by phone to patients surviving beyond 1 year.

  Results: A total of 398 patients (293 men; mean age 61 ± 10.9 years) were operated on in the study period. Indication was malignancy in 380 patients (350 primary lung cancers). Thirty-day mortality was 9 % (right: 12.6 % vs. left: 6.3 %, p = 0.013), significantly correlating with age (p = 0.021), comorbidities (p = 0.034), PS > 1 (p = 0.018), preoperative dyspnea (p = 0.0013), and FEV1 (p = 0.0071). Overall 1-, 3-, 5-, and 7-year survival rates were 76.6, 46.6, 34.4, and 29.2 %. In case of primary lung cancer, these figures were 76.8, 46.4, 34.5, and 29.7 %. At univariate analysis, a less favorable survival was associated to PS > 1 (p = 0.0078), right side (p = 0.044), occurrence of postoperative complications (p = 0.00079), and T3-4 status (p = 0.013). At multivariate analysis, PS > 1, right side, and occurrence of postoperative complications were identified as independent worse prognostic factors. SF12 physical score was 39.1 ± 9.0 and was correlated to the presence of preoperative symptoms (p = 0.013). Mental score was 50.68 ± 9.63 and was correlated to preoperative FEV1/FVC ratio (p = 0.023) and side of disease (p = 0.023).

  Conclusion: In current practice, pneumonectomy is still performed for malignancy, sometimes after induction treatment. High postoperative morbidity and mortality are observed; however, at a farer interval time point, long-term survival with preserved quality of life can be observed.

• Serum biomarkers in patients with mesothelioma and pleural plaques and healthy subjects exposed to naturally occurring asbestos. M. Bayram, I. Dongel, A. Akbaş, et al. 2014;192(1):197-203. PubMed · Publisher

  Abstract

  Purpose: This study investigated the diagnostic accuracy of the serum biomarkers osteopontin and mesothelin in discriminating mesothelioma patients from those with other, benign conditions and whether levels of the biomarkers differed in subjects who had inhaled naturally occurring asbestos compared with a non-exposed control group.

  Methods: This cross-sectional study studied 24 subjects with mesothelioma, 279 subjects with pleural plaques, 123 "healthy exposed," and 120 control subjects. The Kruskal-Wallis test was performed to compare mesothelin and osteopontin levels of the groups, and receiver operating characteristics curves were generated to determine diagnostic yields of both biomarkers. Multiple linear regression analyses were used to identify associated covariates with osteopontin and mesothelin levels.

  Results: Serum osteopontin and mesothelin levels were higher in mesothelioma than in benign asbestos-related diseases and healthy exposed subjects. Both biomarker levels were independently associated with mesothelioma, age and smoking pack years. Mesothelin levels were also associated with body mass index. The sensitivity and specificity of osteopontin in distinguishing mesothelioma from the three other groups were 75 and 86 %, respectively; those of mesothelin were 58 and 83 %, respectively. The sensitivity and specificity to discriminate mesothelioma from pleural plaques and healthy subjects were 93 and 73 %, respectively, if osteopontin and mesothelin levels were higher than their optimal cut off levels.

  Conclusions: The combination of serum osteopontin and mesothelin levels can help to distinguish mesothelioma from benign asbestos-related diseases and asbestos-exposed subjects.

• Stratification of malignant pleural mesothelioma prognosis using recursive partitioning analysis. H. Suzuki, K. Asami, T. Hirashima, et al. 2014;192(1):191-5. PubMed · Publisher

  Abstract

  Purpose: Prognostic factors and complicated prognostic models have been proposed for malignant pleural mesothelioma (MPM). This study was designed to stratify MPM prognosis by using a simple model.

  Methods: Patients diagnosed with MPM in the past 10 years (n = 122) were examined retrospectively. Data on the presence of chest pain, performance status (PS), asbestos exposure, smoking status, white blood cell count (WBC), haemoglobin (Hb) concentration, platelet count (PLT), lactate dehydronate (LD), histology, stage, and date of death or censored status were collected. After the factors were examined in the univariate analysis, recursive partitioning analysis was performed.

  Results: Statistically significant factors related to survival were the type of histology, stage, PS, WBC, PLT, Hb concentration, and LD. Histology, stage, PS, and Hb concentration were used in multivariate analysis. Stage and Hb concentration showed good statistical significance, whereas PS was borderline significant. The survival analyses were stratified into five groups by PS, stage, Hb concentration, and chest pain using recursive partitioning analysis. Group A comprised patients showing the most favourable prognoses (PS 0-2 and Hb concentration >12.1 g dL(-1) or PS 0-2 and Hb concentration ≤12.1 g dL(-1) without pain), and group B comprised the remaining patients. The median overall survival in groups A and B was 563 days (95 % confidence interval [CI] 502-779) and 157 days (95 % CI 115-224), respectively (hazard ratio of 5.44 [3.46-8.53, P < 0.0001]).

  Conclusions: The MPM patients with PS 0-2 and Hb concentration >12.1 or ≤12.1 g dL(-1) without chest pain had favourable prognoses.

• Heme oxygenase-1 promoter polymorphism is associated with risk of malignant mesothelioma. A. Murakami, Y. Fujimori, Y. Yoshikawa, et al. 2012;190(3):333-7. PubMed · Publisher

  Abstract

  Background: Malignant mesothelioma is an aggressive tumor of serosal surfaces that is closely associated with asbestos exposure which induces oxidative stress. Heme oxygenase (HO)-1, a rate-limiting enzyme of heme degradation, plays a protective role against oxidative stress. The HO-1 gene promoter carries (GT)n repeats whose number is inversely related to transcriptional activity of the HO-1 gene.

  Methods: To investigate the relationship between the length polymorphism of (GT)n repeats and mesothelioma susceptibility, we analyzed the HO-1 promoter in 44 asbestos-exposed subjects without mesothelioma and 78 asbestos-exposed subjects with mesothelioma using PCR-based genotyping.

  Results: The number of repeats ranged from 16 to 38, with two peaks at 23 and 30 repeats. Polymorphisms of (GT)n repeats were grouped into two classes of alleles, short (S) (<24) and long (L) (≥24), and three genotypes: L/L, L/S, and S/S. The proportions of allele frequencies in class L as well as genotypic frequencies of L allele carriers (L/L and L/S) were significantly higher in the asbestos-exposed subjects with mesothelioma than in those without mesothelioma.

  Conclusion: The findings of this study suggest that long (GT)n repeats in the HO-1 gene promoter are associated with a higher risk of malignant mesothelioma in the Japanese population.

• The validity of static lung compliance in asbestos-induced diseases. J. Schneider, R. Arhelger, W. Raab, et al. 2012;190(4):441-9. PubMed · Publisher

  Abstract

  Background: Pulmonary compliance can be viewed as an indicator of distensibility of the lungs, not only in asbestos-induced pulmonary disorders but also in visceral pleural fibrosis extending into the lung parenchyma. In this study we evaluated static compliance measurements in asbestos-derived diseases, especially in patients with parietal pleura plaques. Lung function analyses, especially static lung compliance, were correlated with high-resolution computer tomography examinations.

  Methods: Sixty-three patients with parietal pleural plaques, 10 with visceral pleural fibrosis, 39 with parenchymal pulmonary asbestosis together with parietal pleural plaques, and 42 with parenchymal pulmonary asbestosis together with visceral pleural fibrosis were enrolled in the study.

  Results: In comparison with patients having only parietal pleural plaques, those having asbestosis and visceral pleural fibrosis showed significant decreases in static lung compliance, diffusing capacity, and vital capacity. Visceral pleural thickening was also associated with significantly reduced FEV(1), MEF(50), and FEV(1)/FVC ratios. Multiple regression analyses indicated that the existence of visceral pleural fibrosis (p = 0.017) is the most important factor accounting for a decrease in static compliance. Reference values of static lung compliance differ notably. In comparison with mean reference values, the sensitivity of detecting reduced lung compliance was calculated to be between 9.7 and 45.5 %. Other respiratory function variables failed to show any significant differences.

  Conclusion: Our data indicate that the measurement of static compliance is not sufficient for early detection of pulmonary function impairment in patients with parietal pleural plaques.

• Tumor type influences the effectiveness of pleurodesis in malignant effusions. S. Bielsa, P. Hernández, F. Rodriguez-Panadero, et al. 2011;189(2):151-5. PubMed · Publisher

  Abstract

  Pleurodesis is commonly indicated for symptom relief in patients with malignant pleural effusions. A number of factors may influence pleurodesis outcome, but whether tumor type is one of them is a matter of debate. This study investigates the impact of tumor type on the efficacy of bedside doxycycline and thoracoscopic talc poudrage pleurodesis in order to determine which patients may benefit most from these procedures. A retrospective study of 138 and 450 doxycycline and talc poudrage pleurodesis procedures, respectively, evaluated their overall successes and failures, according to primary tumor types. In addition, a logistic regression model addressed whether the pleurodesis outcome in different tumor types was influenced by or attributable to pleural tumor burden. In the talc group, patients with lung cancer and mesothelioma had significantly lower complete response rates (63 and 61%, respectively) as compared with breast (77%) and other metastatic effusions (74%, p = 0.012). In the doxycycline group, the data followed the same trend in that complete response rates were lower in patients with lung carcinomas (31%) than in those with breast cancer (54%) or metastases from other primary sites (74%, p = 0.001). The regression analysis showed pleural burden and tumor type as independent predictors of pleurodesis failure in the talc group. The tumor type involving the pleural surfaces influences the success of a pleurodesis, regardless of the sclerosing agent used. Malignant effusions due to mesothelioma and lung cancer are particularly prone to a failed procedure.

  In plain English

  This retrospective study at two Spanish hospitals asked whether cancer type affects pleurodesis success. Pleurodesis seals the space around the lung to stop fluid returning. It covered 126 patients given doxycycline in Lleida and 447 given talc during thoracoscopy in Sevilla. Asbestos was not studied; mesothelioma was one cancer type. With talc, failure rates were 24% for mesothelioma and 15% for lung cancer, versus 7.5% for breast cancer and 9% for other cancers spread to the pleura (p = 0.012). With doxycycline, complete response rates were 31% for lung cancer, 54% for breast cancer and 74% for cancers spread from sites other than lung or breast (p = 0.001). Only one doxycycline patient had mesothelioma. After allowing for the amount of pleural tumor, breast cancer and cancers spread from sites other than lung or breast still did better with talc than mesothelioma. Lung cancer did not differ significantly from mesothelioma, and more pleural tumor was linked to more failures. The authors concluded that tumor type influences pleurodesis success but should not alone be used to deny the procedure. They noted possible bias from the retrospective design.

  We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

• Combined pulmonary fibrosis and emphysema alters physiology but has similar mortality to pulmonary fibrosis without emphysema. M.D. Jankowich, S. Rounds. 2010;188(5):365-73. PubMed · Publisher · Free full text

  Abstract

  Studies have described individuals with combined pulmonary fibrosis and emphysema (CPFE), with preserved lung volumes, significant reductions in gas exchange, and high prevalence of pulmonary hypertension. While physiologic changes in CPFE are well documented, there is little mortality data in the CPFE population compared to appropriate controls. A study was performed to determine the features and outcomes of a group of individuals with imaging and/or pathologic evidence of CPFE to determine if individuals with combined pulmonary fibrosis and emphysema have different features and survival than individuals with pulmonary fibrosis alone. We conducted a retrospective study at a Veterans Affairs Medical Center. Included in the study were individuals hospitalized over a 5-year period who were given a clinical diagnosis of pulmonary fibrosis. Individuals with confirmed imaging or pathologic evidence of pulmonary fibrosis were divided into a study group with concomitant emphysema (CPFE group, n = 20) and a control group without emphysema (isolated pulmonary fibrosis (PF) group, n = 24). The CPFE group, all current or former cigarette smokers, had significantly larger lung volumes, more expiratory airflow obstruction, and worse gas exchange than the isolated pulmonary fibrosis group. Mortality did not differ between the groups. Combined pulmonary fibrosis and emphysema results in unique physiologic features but no difference in survival compared with a group with pulmonary fibrosis alone.

• Crocidolite induces prostaglandin I(2) release mediated by vitronectin receptor and cyclooxygenase-2 in lung cells. F.J. Leyva, K. Roberts. 2010;188(2):133-41. PubMed · Publisher · Free full text

  Abstract

  Interstitial lung disease (ILD) produces disruption of alveolar walls with loss of functionality and scar tissue accumulation. Asbestosis is the ILD produced by the inhalation of asbestos fibers. This study attempts to elucidate the role of lung epithelial cells in the generation of asbestos-induced ILD. When exposed to crocidolite LA-4 cells had a decrease in viability and an increase in the release of lactate dehydrogenase (LDH) and 6-keto PGF(1alpha), a PGI(2) metabolite. PGI(2) release was mediated by cyclooxygenase-2 (COX-2) and vitronectin receptor (VNR). When LA-4 cells were treated with VNR inhibitors, either RGD (Arg-Gly-Asp) peptide or VNR blocking antibody, a statistically significant decrease in PGI(2) metabolite production was observed, but crocidolite-induced cytotoxicity was not prevented. These findings propose that crocidolite is coated by an RGD protein and binds VNR-inducing COX-2 expression and PGI(2) release. Moreover, when LA-4 cells were exposed to crocidolite in the presence of reduced serum culture media, PGI(2) production was prevented, and when bronchoalveolar lavage fluid (BALF) was added, PGI(2) production was rescued. Cytotoxicity did not occur, either in reduced serum culture media or when BALF was added. In conclusion, crocidolite requires the presence of an RGD protein coating the fibers to induce inflammation (PGI(2) production) and crocidolite alone cannot induce cytotoxicity in lung cells.

2000s

• Asbestos induces tissue factor in Beas-2B human lung bronchial epithelial cells in vitro. A. Iakhiaev, U. Pendurthi, S. Idell. 2004;182(4):251-64. PubMed · Publisher

  Abstract

  Asbestos has been implicated in the pathogenesis of interstitial lung diseases including asbestosis. Tissue factor (TF) initiates blood coagulation in vivo contributing to inflammation and tissue remodeling via extravascular fibrin deposition and signaling for profibrogenic mediators. We hypothesized that asbestos could induce TF expression by lung epithelial cells. We found that TF mRNA and TF-dependent procoagulant activity were induced in asbestos-treated Beas-2B human airway epithelial cells, which we used as a model system. The effect was increased by crocidolite and chrysotile versus control particulates, including titanium dioxide (TiO2) and Wollastonite (W). Transcription factors that bind the TF gene promoter, including NF-kappaB, AP1 and Sp1, were induced by asbestos while TF mRNA was unstable. TF mRNA was inhibited by mithramycin in asbestos-treated as well as control cells suggesting that Sp1 contributes to TF maintenance in Beas-2B cells. Sp1 knockdown with specific siRNA decreased TF antigen, which is consistent with Sp1-mediated control of TF in Beas-2B cells. The results demonstrate that asbestos induces TF expression in lung epithelial cells in vitro, representing a newly recognized potential mechanism by which asbestos may modulate epithelial cell responses germane to lung remodeling. The mechanism involves alterations in steady-state TF mRNA that do not involve posttranscriptional regulation, implicating control of TF gene expression at the transcriptional level through Sp1 or other transcription factors.

• [(18)F]-FDG PET and localized fibrous mesothelioma. J. Cortes, J. Rodriguez, M.J. Garcia-Velloso, et al. 2003;181(1):49-54. Case report · Review PubMed · Publisher

  Abstract

  The aim of this article is to present our experience with positron emission tomography (PET) and localized fibrous mesothelioma and to review the literature on this issue. During the past five years we found three patients with a complete clinical history who underwent a CT scan of the thorax and (18)F-fluorodeoxyglucose positron emission tomography ([(18)F]-FDG-PET) and were diagnosed with localized fibrous mesothelioma. Two of the patients were asymptomatic men and the third was a woman with chest pain. The standardized uptake value was 2.1 in one case, and in the other two an absence of FDG uptake was seen. All three had complete resection of the tumor, and in one case the presurgery diagnosis was adenocarcinoma. In one patient the tumor relapsed twice, and the other two patients are alive without any evidence of disease. The value of FDG-PET in the differential diagnosis of pulmonary and pleural abnormalities has gained ground during the last few years. As in most benign tumors, the FDG uptake is usually low (< 2.5) in the localized fibrous mesothelioma. However, more studies are necessary to define the role of FDG-PET in assessing this tumor.

• The pleura in health and disease. J.S. Jones. 2001;179(6):397-413. Review PubMed · Publisher

  Abstract

  The normal structure and function of the pleura are discussed here in addition to how physiological abnormalities and various pathological processes can upset the finely balanced situation between the visceral and parietal pleural surfaces, leading to effusion formation, and/or adhesions. The various inflammatory and reactive processes that affect the pleura, together with primary and secondary tumor formations are described. Particular emphasis is placed on those conditions of the pleura that are associated with asbestos exposure because this group of diseases will increase over the next few decades due to the large number of workers who have been exposed to asbestos. They will therefore be of increasing importance to the clinician, radiologist, and pathologist in future years.

1990s

• Indoor air pollutants stimulate interleukin-8-specific mRNA expression and protein secretion of alveolar macrophages. K. Drumm, H. Schindler, R. Buhl, et al. 1999;177(1):9-19. PubMed · Publisher

  Abstract

  Indoor air pollutants may cause inflammatory changes of the airways and adjacent pulmonary tissue. After phagocytosis of inhaled particles alveolar macrophages (AM) release chemotactic mediators capable of attracting inflammatory cells into the lung tissue. To evaluate these mechanisms further peripheral blood mononuclear cells (PBMNC) and human AM (freshly recovered from the lower respiratory tract) were exposed to the indoor particles Soot FR 101 and Printex 90, the asbestos fiber Chrysotile B, and titanium dioxide (TiO2) at concentrations of 10 or 50 microg/10(6) cells for up to 8 h. The migration of granulocytes into the conditioned supernatants of AM and PBMNC was quantified by chemotaxis assay in a Boyden chamber. Granulocyte migration increased by 42.3 +/- 25.8% (Chrysotile B), 64. 6 +/- 18.3% (FR 101), 74.2 +/- 16.5% (P 90), and 86.7 +/- 25.6% (TiO2) in AM-conditioned supernatants (p < 0.05). Qualitative, Interleukin (IL)-8 specific reverse transcriptase-polymerase chain reaction was performed after exposure of AM or PBMNC to Chrysotile B, FR 101, P 90, and TiO2 at concentrations of 10 and 50 microg/10(6) cells for 90 min. Each of the tested particles caused an increase in IL-8-specific mRNA expression of AM or PBMNC after particle exposure compared with the unexposed control. To find out if IL-8, the most powerful granulocyte chemokine, is involved, supernatants were preincubated with anti-IL-8. Granulocyte migration decreased by up to 35 +/- 15% (50 ng/ml anti-IL-8) and 41.5 +/- 16% (100 ng/ml anti-IL-8) (p < 0.0625) in AM-conditioned supernatants. Pretreatment of the granulocytes with human IL-8 decreased by up to 59 +/- 18% (10 ng/ml) (p < 0.0625) in AM-conditioned supernatants. Similar reaction patterns were observed using anti-IL-8-pretreated supernatants of particle-exposed PBMNC. In conclusion, indoor air pollutants may promote inflammatory changes in the lung via IL-8 release by alveolar macrophages.

• Production of reactive oxygen intermediates by human macrophages exposed to soot particles and asbestos fibers and increase in NF-kappa B p50/p105 mRNA. R. Oettinger, K. Drumm, M. Knorst, et al. 1999;177(6):343-54. PubMed · Publisher

  Abstract

  Alveolar macrophages (AM) play a decisive role in the immunologic defense system of the lung and in inflammatory pulmonary pathomechanisms. AM and blood monocytes (BM) were exposed to chrysotile B, soot FR 101, and Printex 90 (P 90). We evaluated the reactive oxygen intermediate (ROI) release of AM and BM after particle exposure. ROI release was measured by chemiluminescence. Thirty-minute exposure caused a significant (up to 2.5-fold) increase in ROI release of AM (100 micrograms/10(6) cells) compared with control experiments (p < 0.01). Identical exposure conditions for BM resulted in a similar reaction pattern (maximum 2.2-fold increase in ROI release; p < 0.05). After a 90-min particle exposure at concentrations of 10 and 100 micrograms/10(6) cells, we investigated the steady-state level of p50/p105 mRNA encoding for the precursor protein of the p50 subunit of nuclear factor kappa B (NF-kappa B) by semiquantitative reverse transcription-polymerase chain reaction. One hundred micrograms Chrysotile B, FR 101, or P 90 induced a significant maximum 4.0-fold up-regulation of NF-kappa B gene expression in AM and a 3.3-fold up-regulation in BM (p < 0.05). The addition of superoxide dismutase (200 U/ml) to particle- and fiber-exposed macrophages resulted in inhibition of ROI release and a decrease in NF-kappa B mRNA expression (70%). NF-kappa B is an important transcription factor involved in the regulation of numerous genes (e.g., for inflammatory cytokines, and cytokine receptors). These cytokines are supposed to be involved in inflammatory pathomechanisms in bronchial epithelial cells, which result, for example, in chronic obstructive pulmonary disease. Our results suggest that particle-induced ROI release is associated with an increase in NF-kappa B (p50/p105) mRNA steady-state level.

• Induction of manganese superoxide dismutase gene expression in bronchoepithelial cells after rockwool exposure. J. Marks-Konczalik, A. Gillissen, M. Jaworska, et al. 1998;176(3):165-80. PubMed · Publisher

  Abstract

  Superoxide dismutases play an important protective role in the lung defense against the pro-oxidative effect of fibrous dusts (e.g. crocidolite fibers). Particularly crocidolite, but also other asbestos fibers, are known to induce cellular antioxidant defense. Although rockwool, a man-made fiber made from rock, is used widely for insulation purposes, its effects on the superoxide dismutases in bronchoepithelial cells have not been investigated. Thus, the purpose of this study was to determine whether human bronchoepithelial cells (BEAS 2B) respond to rockwool fibers (115-4 experimental rockwool fiber) by induction of MnSOD mRNA and an increase of MnSOD activity levels. The results were compared with BEAS 2B cells exposed to silica (alpha-quartz: DQ12; SiO2) and UICC (Union Internationale Contre le Cancer) crocidolite (concentrations of all dusts: 0, 2, 5, 10, 25, 50 micrograms/cm2 = 0, 2.4, 6, 12, 30, 60 micrograms/ml; 24-h exposure) as control fibers. Scanning electron microscopy confirmed close dust cell contact under all experimental settings. Very low MnSOD mRNA baseline levels rose significantly (p < 0.001) in BEAS 2B cells exposed to all three dusts at 2 micrograms/cm2. However, at > 25 micrograms/cm2 MnSOD mRNA levels in silica- and crocidolite- but not in rockwool-exposed cells decreased. Slight (no significance) increases of MnSOD activity were observed which decreased at higher dust (> 5 micrograms/cm2) concentrations. These results suggest that: (1) like crocidolite and silica, rockwool accelerates MnSOD gene expression in bronchoepithelial cells; (2) an increase of MnSOD mRNA levels is not accompanied by MnSOD activity elevation; (3) in contrast to rockwool, high concentrations (> or = 25 micrograms/cm2) of crocidolite and silica reduced MnSOD activity and MnSOD mRNA levels. Because oxidants (H2O2) and crocidolite fibers were shown to reduce SOD activity, lack of active MnSOD protein may be caused by inactivation on a post-translational level. Furthermore, the decline of MnSOD mRNA and MnSOD activity levels coincides with increasing cytotoxicity. In conclusion, rockwool was demonstrated to induce MnSOD gene expression, perhaps because of its pro-oxidative effect in bronchoepithelial cells. In contrast to crocidolite and silica, rockwool fibers are not cytotoxic in this experimental setting.

1980s

• Mechanisms affecting exercise performance in subjects with asbestos-related pleural fibrosis. C. Picado, D. Laporta, A. Grassino, et al. 1987;165(1):45-57. PubMed · Publisher

Browse every journal in the library or the library by type of article, or return to medical research.