Respiratory Medicine

Our medical research library holds 53 studies published in Respiratory Medicine (1989–2021). 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. 43 have an abstract, the authors' own summary as PubMed records it: open "Abstract" to read it. For 4 studies PubMed has no abstract for, we give the abstract printed in the article or, where there is none, a summary we wrote from it, each labeled as such.

About the journal

• Publisher: Elsevier
• Published: 1989 to the present, England
• Language: English
• ISSN: 0954-6111 (print), 1532-3064 (electronic)
• Continues: British Journal of Diseases of the Chest
• Its record in the NLM Catalog

2020s

• Mesothelioma in immigrants from Turkey: Genes have a minor role. S. Metintas, M. Metintas, G. Ak, et al. 2021;186:106527. PubMed · Publisher

  Abstract

  Objective: To examine the incidence and epidemiology of malignant mesothelioma in immigrants from Karain where there is an extraordinarily high incidence of mesothelioma, Cappadocia, Turkey, to Stockholm, Sweden, and their children over 20 years of age born in Stockholm, i.e. two genetically similar populations with and without erionite exposure.

  Methods: This survey was conducted as a retrospective cohort study. Standardized average annual mesothelioma incidence rates (AAMIRs) and mesothelioma standardized incidence ratio (mSIR) were calculated. Cox regression analysis was used to determine the importance of different factors related to mesothelioma risk.

  Results: The cohort consisted of 337 people, 203 of whom were born and/or lived in Karain before immigrating to Sweden (erionite-exposed), and 134 who were born in Stockholm (erionite-unexposed). There were 69 deaths, 42 (61%) due to mesothelioma, and two patients with the disease who were still alive. Of these 44 patients, 22 were men. All mesothelioma patients were in the erionite-exposed group. In the age group 30-49 years, mesothelioma developed in 11 of 38 (29%) with erionite exposure, while there were no cases among 86 persons in the non-exposed group. For men, the AAMIR was 253.9 per 100,000 persons in the whole cohort, and for women, it was 350.9. The mSIR was 71.9 for men and 393.1 for women. Exposure to erionite exceeding 20 years and age over 40 years were associated with increased mesothelioma risk.

  Conclusion: Exposure to erionite is the leading cause of mesothelioma in Karain villagers, and genetic factors are probably of minor importance.

  Copyright © 2021 Elsevier Ltd. All rights reserved.

• The role of nitric oxide in pleural disease. O.S. Kotsiou, K.I. Gourgoulianis, S.G. Zarogiannis. 2021;179:106350. Review PubMed · Publisher

  Abstract

  Nitric oxide (NO) regulates various physiological and pathophysiological functions in the lungs. However, there is much less information about the effects of NO in the pleura. The present review aimed to explore the available evidence regarding the role of NO in pleural disease. NO, has a double-edged role in the pleural cavity. It is an essential signaling molecule mediating various physiological cell functions such as lymphatic drainage of the serous cavities, the immune response to intracellular multiplication of pathogens, and downregulation of neutrophil migration, but also induces genocytotoxic and mutagenic effects when present in excess. NO is implicated in the pathogenesis of asbestos-related or exudative pleural disease and mesothelioma. From a clinical point of view, the fraction of exhaled NO has been suggested as a potential non-invasive tool for the diagnosis of benign asbestos-related disorders. Under experimental conditions, NO-mimetics were found to attenuate hypoxia-induced therapy resistance in mesothelioma. Similarly, hybrid agents consisting of an NO donor coupled with a parent anti-inflammatory drug showed an enhancement of the anti-inflammatory activity of anti-inflammatory drugs. However, given the paucity of research work performed over the last years in this area, further research should be undertaken to establish reliable conclusions with respect to the feasibility of determining or targeting the NO signaling pathway for pleural disease diagnosis and therapeutic management.

  Copyright © 2021 Elsevier Ltd. All rights reserved.

• Aquaporins in lung health and disease: Emerging roles, regulation, and clinical implications. E. Yadav, N. Yadav, A. Hus, et al. 2020;174:106193. Review PubMed · Publisher · Free full text

  Abstract

  Aquaporins (AQPs) aka water channels are a family of conserved transmembrane proteins (~30 kDa monomers) expressed in various organ systems. Of the 13 AQPs (AQP0 through AQP12) in the human body, four (AQPs 1, 3, 4, and 5) are expressed in the respiratory system. These channels are conventionally known for mediating transcellular fluid movements. Certain AQPs (aquaglyceroporins) have the capability to transport glycerol and potentially other solutes. There is an emerging body of literature unveiling the non-conventional roles of AQPs such as in cell proliferation and migration, gas permeation, signal potentiation, etc. Initial gene knock-out studies established a physiological role for lung AQPs, particularly AQP5, in maintaining homeostasis, by mediating fluid secretion from submucosal glands onto the airway surface liquid (ASL) lining. Subsequent studies have highlighted the functional significance of AQPs, particularly AQP1 and AQP5 in lung pathophysiology and diseases, including but not limited to chronic and acute lung injury, chronic obstructive pulmonary disease (COPD), other inflammatory lung conditions, and lung cancer. AQP1 has been suggested as a potential prognostic marker for malignant mesothelioma. Recent efforts are directed toward exploiting AQPs as targets for diagnosis, prevention, intervention, and/or treatment of various lung conditions. Emerging information on regulatory pathways and directed mechanistic research are posited to unravel novel strategies for these clinical implications. Future considerations should focus on development of AQP inhibitors, blockers, and modulators for therapeutic needs, and better understanding the role of lung-specific AQPs in inter-individual susceptibility to chronic lung diseases such as COPD and cancer.

  Copyright © 2020 Elsevier Ltd. All rights reserved.

2010s

• First report of probe based confocal laser endomicroscopy during medical thoracoscopy. O. Bonhomme, B. Duysinx, V. Heinen, et al. 2019;147:72-75. Case report PubMed · Publisher

  Abstract

  Probe based confocal laser endomicroscopy (pCLE) is a new optical endoscopic technique, generating fluorescent light emission from the tissue of interest and allowing in vivo live imaging at a cellular level ("optical biopsies"). To the best of our knowledge, this article is the first to present pCLE images during medical thoracoscopy. We present here 3 different patients referred for various health problems. A precise description of pleural cavity pCLE images after intravenous fluorescein injection (a fluorophore) together with corresponding macroscopical and histological studies is performed. This led to the diagnosis of normal pleura in one case, carcinomatous pleuritis in another case and a malignant mesothelioma in the third case. We believe that optical biopsies could help clinicians to make an early diagnosis, thereby allowing rapid therapeutic intervention (talc pleurodesis for example). Furthermore, it could help to guide biopsies when affected zones are not obvious to macroscopic examination. In a near future, new fluorophores could be developed to stain some pathophysiological processes, therapeutic targets, or enzymes activities bringing new insights in endoscopic pleural disease work-up.

  Copyright © 2019. Published by Elsevier Ltd.

• The natural course of lung function decline in asbestos exposed subjects with pleural plaques and asbestosis. M. Barnikel, P.M. Million, H. Knoop, et al. 2019;154:82-85. PubMed · Publisher

  Abstract

  Unlabelled: While there is a good knowledge of the natural course of lung function in interstitial lung diseases (ILD) like idiopathic lung fibrosis (IPF), many ambiguities remain in patients with asbestosis. Therefore, we evaluated the change in lung function in asbestos exposed subjects with pleural plaques and asbestosis and analysed corresponding morphology of computer tomography of the thorax.

  Methods: 93 asbestos exposed subjects with pleural plaques and asbestosis were analysed retrospectively at the Klinikum Bergmannsheil of the Ruhr-University of Bochum. Parameters of lung function were obtained at least twice and annual changes of FVC, TLC and DLCOsb were calculated. In addition, we assessed the predominant pattern in high-resolution computer tomography of the thorax (HRCT) and differentiated three phenotypes: p (pleural) -type, f (fibrosis) -type and m (mixed) -type.

  Results: FU data are available in 56/93 (60.2%) patients. The annual deterioration (Mean ± SEM) of FVC is -31.46 ± 17.34 ml, of TLC -55.55 ± 25.67 ml, of DLCOsb -0.38 ± 0.07 mmol/min/kPa and of DLCOva -0.05 ± 0.01 mmol/min/kPa/L. A categorical change of FVC > -100 ml was found in 12/56 (21.4%) and 18/56 (32.1%) patients showed an annual loss of TLC > -100 ml. The greatest annual decline of FVC was observed in patients with the fibrotic phenotype on HRCT (-76.76 ± 66.43 ml) and the mixed phenotype (-81.52 ± 24.79 ml), while the pleural phenotype was less affected (-10.52 ± 25.07 ml).

  Conclusion: More than 20% of our cohort have a progressive disease with an annual loss of FVC > -100 ml. Patients with the fibrotic-phenotype or mixed-phenotype on HRCT are particularly at risk.

  Copyright © 2019. Published by Elsevier Ltd.

• A systematic review and meta-analysis of second-line therapies for treatment of mesothelioma. F. Petrelli, R. Ardito, B. Conti, et al. 2018;141:72-80. Meta-analysis · Systematic review PubMed · Publisher

  Abstract

  Introduction: Advanced malignant pleural mesothelioma (MPM) is generally treated with platinum/pemetrexed-based first-line therapy. Once the disease progresses, evidence for the efficacy of palliative treatments is lacking, and platinum re-challenge or single-agent chemotherapy are commonly used. To assess the effects of cytostatic or targeted therapy for treating MPM, we performed a systematic review and meta-analysis.

  Material And Methods: PubMed, the Cochrane Library, and Embase databases were searched to identify published articles on second-line treatments for recurrent or advanced mesothelioma. Inclusion criteria were publication in the English language, describing clinical trials with 20 or more patients, and evaluability for efficacy and for receiving second-line systemic therapies. Data were pooled using number of events/number of evaluable patients, median overall survival (OS) and progression-free survival (PFS), according to a fixed or random effect model. Pooled median OS was the primary endpoint.

  Results: A total of 49 eligible studies (n = 3938 patients; range, 12-400) were identified. Median progression-free survival (PFS) was 3.4 months (95%CI 2.87-3.93). Median pooled OS was 7.86 (95%CI 7.01-8.72). The pooled overall response rate (ORR) was 8.63% (95%CI 6-11.26), and the pooled disease control rate (DCR) was 54.8% (95%CI 48.9-60.6). Median pooled OS with platinum- and pemetrexed-based chemotherapy were 7.93 and 7.78 months, respectively.

  Conclusions: There remains uncertainty about the ideal second-line agent for MPM. Based on this meta-analysis, palliative chemotherapy or other experimental agents can be considered for patients with MPM who desire further treatment after their disease has progressed, during or after first-line therapy.

  Copyright © 2018. Published by Elsevier Ltd.

• Progress and challenges in Mesothelioma: From bench to bedside. K.G. Blyth, D.J. Murphy. 2018;134:31-41. Review PubMed · Publisher

  Abstract

  Malignant Pleural Mesothelioma (MPM) is currently an incurable cancer with a typical survival of 1 year from the time of diagnosis. The recent genomic and transcriptomic characterization of MPM presents new opportunities and challenges for MPM researchers. Recent advances in clinical and laboratory diagnostics, and proposals for an updated, data-driven, staging system, also present new challenges for clinicians and hospital services involved in MPM care. The aim of this review is first to introduce the reader to the topic of MPM, a disease that is causally linked to prior, typically occupational, exposure to asbestos fibres. Secondly, we will discuss MPM from the clinical and laboratory perspectives, including reviews of current and evolving therapies and our present understanding of the molecular basis of the disease. Finally, we will attempt to identify critical knowledge gaps that currently prevent more effective treatment, including the challenges involved in early detection and chemoprophylaxis.

  Copyright © 2017 Elsevier Ltd. All rights reserved.

• Focal pleural tumorlike conditions: nodules and masses beyond mesotheliomas and metastasis. M.C. de Paula, D.L. Escuissato, L.C. Belém, et al. 2015;109(10):1235-43. Review PubMed · Publisher

  Abstract

  A tumorlike condition of the pleura is any nonmalignant lesion of the pleura or within the pleural space that could be confused with a pleural tumor on initial imaging. Tumorlike conditions of the pleura are relatively rare compared with neoplastic lesions such as mesotheliomas and metastases. Imaging-based diagnosis of these conditions can be difficult due to the similarity of appearance. Thus, recognition of certain imaging patterns and interpretation of these patterns in the clinical context are important. Pleural endometriosis, thoracic splenosis, thoracolithiasis, foreign bodies, pleural pseudotumors and pleural plaques are significant examples of focal tumorlike conditions discussed in this article. Computed tomography is the mainstay imaging technique for the primary assessment of pleural disease, but other imaging methods, such as magnetic resonance imaging and positron-emission tomography, can be of great support in the diagnosis.

  Copyright © 2015 Elsevier Ltd. All rights reserved.

• Pleural neoplastic pathology. G. Karpathiou, D. Stefanou, M.E. Froudarakis. 2015;109(8):931-43. Review PubMed · Publisher

  Abstract

  Background/Purpose: Malignant pleural effusion is a frequent situation in pulmonary medicine. However, it is sometimes difficult to recognize the underlying etiology. The aim of this review is to provide the key characteristics of primary and metastatic pleural neoplasms.

  Methods: A review of the recent literature regarding pleural neoplasia is provided.

  Results: Malignant pleural mesothelioma (MPM) is the commonest primary pleural epithelial tumor showing remarkable histological heterogeneity often with prognostic significance. Various genetic alterations like changes in INK4 locus, NF2, BAP1 but also epigenetic changes are present in MPM. It should be distinguished from atypical mesothelial hyperplasia, mainly through morphological and clinical criteria, and from other rare primary and metastatic tumors, for which immunohistochemistry is rather important. Solitary fibrous tumor, the commonest primary pleural mesenchymal tumor is characterized by STAT6 overexpression. Other primary tumors, like adenomatoid tumor, well-differentiated papillary mesothelioma, synovial sarcoma, vascular tumors, various other sarcomas, thymic tumors and tumors of uncertain histogenesis are rarely encountered in the pleura. In contrast, metastatic disease is the commonest neoplasia of the pleura, and especially lung, breast and lymphoid malignancies.

  Conclusion: The basic pathological, immunohistochemical and molecular characteristics of these entities are provided in the current review, along with their differential diagnosis.

  Copyright © 2015 Elsevier Ltd. All rights reserved.

• Is living close to ophiolites related to asbestos related diseases? Cross-sectional study. I. Döngel, M. Bayram, N.D. Bakan, et al. 2013;107(6):870-4. PubMed · Publisher

  Abstract

  Objective: To determine the rate of pleural plaques and malignant mesothelioma and other factors that affect people living close to ophiolites.

  Methods: The study population was comprised of 2970 volunteers who resided <10 km from an ophiolitic unit. Control group comprised of 157 residents >25 km from ophiolites. Information gathered from the patients included presence of pleural plaques on chest X-ray, distance from ophiolites, gender, smoking status, duration of asbestos exposure, and body mass index (BMI). Mineralogical analysis of soil and rock samples was performed by X-ray diffraction.

  Results: Among the 2970 study participants, those who lived close to ophiolites, 9.8% had asbestos related disease (3 malignant mesothelioma, 289 pleural plaques). No asbestos related disease (ARD) was identified in the control group. Male gender (OR: 2.63, 95% 1.9-3.5, p < 0.001), advanced age (5% increase for every year p < 0.001), residential proximity to ophiolites (for every 1 km proximity, a 12% increase p < 0.001), and low BMI (for every 1 unit decrease, 3.6% increase p < 0.001) were associated with increased risk of ARD.

  Conclusion: The rate of ARD is higher in residents living close to ophiolites. Important risk factors for developing ARD were age, male gender, proximity to an ophiolite site, and low BMI.

  Copyright © 2013 Elsevier Ltd. All rights reserved.

• Adipokine adipsin is associated with the degree of lung fibrosis in asbestos-exposed workers. S. Leivo-Korpela, L. Lehtimäki, R. Nieminen, et al. 2012;106(10):1435-40. PubMed · Publisher

  Abstract

  Objectives: Asbestos-exposure causes an inflammatory response driven by alveolar macrophages that can lead to pulmonary fibrosis. In addition to classical inflammatory cytokines, macrophages produce adipokines which regulate the inflammatory response. We studied if adipokines are related to the degree of parenchymal fibrosis, impaired lung function and inflammation in asbestos-exposed subjects.

  Methods: Eighty-five males with moderate to heavy occupational exposure to asbestos and unexposed controls were studied. We measured plasma levels of adipokines adiponectin, adipsin, leptin and resistin, IL-6, IL-8, erythrocyte sedimentation rate (ERS), spirometry and D(L,CO). Degree of interstitial lung fibrosis (septal thickening, subpleural lines, parenchymal bands or honeycombing) was scored in classes 0-5 according to a validated scoring system. The subjects were divided into three groups: normal parenchymal finding (fibrosis class 0), borderline changes (classes 0.5-1.5) and fibrosis (i.e. asbestosis; classes 2-5).

  Results: Adipsin correlated positively with parenchymal fibrosis (rho=0.412, p<0.001) and there was a linear increasing trend of mean plasma adipsin levels among the three groups of asbestos-exposed subjects (from normal parenchymal finding to borderline changes and to fibrosis) (p<0.0001). Accordingly, plasma adipsin levels correlated positively with the extent of pleural plaques (r=0.245, p=0.043), and negatively with D(L,CO) (r=-0.246, p=0.023). Also, a positive correlation was found between adipsin and inflammatory markers ESR (r=0.315, p=0.008) and IL-6 (r=0.256, p=0.018).

  Conclusions: Adipsin was associated with the degree of parenchymal fibrosis, impairment of pulmonary diffusing capacity and with inflammatory activity in asbestos-exposed subjects suggesting that adipsin may have a role in the pathogenesis or as a biomarker in asbestos-induced lung disease.

  Copyright © 2012 Elsevier Ltd. All rights reserved.

• Factors influencing exercise performance in thoracic cancer. R. England, M. Maddocks, C. Manderson, et al. 2012;106(2):294-9. PubMed · Publisher

  Abstract

  Background: Patients with incurable thoracic cancer often complain of a reduced ability to exercise, but the cause of this has been little studied. Thus, we have explored how various physiological and psychological factors relate to exercise performance in this group.

  Methods: Inspiratory muscle strength, peripheral muscle power, lung function and mastery over breathlessness were assessed using sniff nasal inspiratory pressure, leg extensor power, simple spirometry and the mastery domain of the Chronic Respiratory Disease Questionnaire respectively. Exercise performance was assessed using the Incremental Shuttle Walking Test (ISWT) during which patients wore a K4 b(2) system permitting measurement of resting and breakpoint heart rate, minute ventilation (VE) and oxygen uptake (VO(2)). Relationships between ISWT distance and the four factors were determined using correlation and β regression coefficients.

  Results: Forty-one patients (21 male, mean (SD) age 64 (8) years) walked a median [IQR] of 320 [250-430] metres and reached a mean (SD) of 76 (10), 77 (25), and 48 (14) of their percent predicted maximum heart rate, VO(2), and VE respectively. Exercise performance was significantly associated only with inspiratory muscle strength (r = 0.42, P < 0.01) and peripheral muscle power (r = 0.39, P = 0.01). These factors were also significant determinants of exercise performance (β coefficients [95%CI] 1.77 [0.53, 3.01] and 1.22 [0.31, 2.14] respectively).

  Conclusion: Of the factors examined, only inspiratory and peripheral muscle performance were significantly related to and predictive of exercise performance. Rehabilitation interventions which include inspiratory and peripheral muscle training are worth exploring further in this group of patients with thoracic cancer.

  Copyright © 2011 Elsevier Ltd. All rights reserved.

• Outcome of patients diagnosed with fibrinous pleuritis after medical thoracoscopy. M. Metintas, G. Ak, O. Cadirci, et al. 2012;106(8):1177-83. PubMed · Publisher

  Abstract

  Background: In patients with post- medical thoracoscopy histopathological diagnoses of fibrinous pleuritis, confusion can occur concerning subsequent procedures. This issue is particularly important in regions where mesothelioma is prevalent. We aimed to identify false negatives among patients where mesothelioma was common due to asbestos exposure whose histopathological diagnosis following thoracoscopy was fibrinous pleuritis. We also determined risk factors associated with patients that required additional advanced invasive procedures for diagnosis.

  Methods: Overall, 287 patients who underwent thoracoscopy were included in the study. Patients diagnosed with fibrinous pleuritis as a result of thoracoscopy were followed for 2 years regarding this condition. More invasive procedures were performed on patients who showed no recuperation or developed pleural disease again during the follow-up period.

  Results: Fibrinous pleuritis was observed in 101 (35.2%) patients. Follow-up of these patients revealed that the false negative rate was 18% for malignant pleural diseases. The thoracoscopist's opinion regarding the pleural space, computed tomography scan findings indicating malignancy, pain and female gender were determined to be risk factors for malignant pleural diseases.

  Conclusions: In regions where mesothelioma is prevalent and one of the above-stated risk factors is present, patients whose post-thoracoscopy histopathological diagnosis is fibrinous pleuritis should be treated with a more advanced invasive diagnosis procedure.

  Copyright © 2012 Elsevier Ltd. All rights reserved.

• Pleural effusion VEGF levels as a prognostic factor of malignant pleural mesothelioma. N. Hirayama, C. Tabata, R. Tabata, et al. 2011;105(1):137-42. PubMed · Publisher

  Abstract

  Background: Malignant pleural mesothelioma (MPM) is an aggressive malignant tumor of mesothelial origin associated with asbestos exposure. MPM has a limited response to conventional chemotherapy and radiotherapy so early diagnosis of MPM is very important. Vascular endothelial growth factor (VEGF), a potent mitogen for the vascular endothelium, is also known to be an autocrine growth factor for MPM. Here, we investigated the pleural effusion VEGF levels in patients with MPM and compared them to those of a population with a non-malignant pleuritis or lung cancer involving malignant pleural effusion.

  Methods: The pleural effusion VEGF concentrations were measured in 46 MPM patients and 45 individuals with non-MPM individuals (25 individuals with non-malignant pleural effusions, and 20 individuals with lung cancer involving malignant pleural effusion).

  Results: We demonstrated that patients with MPM had significantly higher pleural effusion VEGF levels than a population with non-malignant pleuritis or lung cancer involving malignant pleural effusion, and the patients with advanced stage MPM showed higher levels of VEGF than the early stage MPM patients. The difference in overall survival between the groups with pleural effusion VEGF levels lower and higher than the assumed cut-off of 2000pg/ml was significant.

  Conclusions: Our data suggest that the pleural effusion VEGF concentration could be useful as an aid for the diagnosis of MPM and as a prognostic factor.

  Copyright © 2010 Elsevier Ltd. All rights reserved.

• Diagnostic value of soluble mesothelin-related peptides for malignant mesothelioma: a meta-analysis. L. Luo, H.Z. Shi, Q.L. Liang, et al. 2010;104(1):149-56. Meta-analysis · Systematic review PubMed · Publisher

  Abstract

  Background: Serum concentrations of soluble mesothelin-related peptides (SMRP) have been reported to be higher in patients with malignant mesothelioma than in healthy subjects and in patients with non-malignant mesothelioma diseases. The aim of the present meta-analysis was to establish the overall diagnostic accuracy of the measurement of SMRPs for diagnosing malignant mesothelioma.

  Methods: After a systematic review of English language studies, sensitivity, specificity, and other measures of accuracy of serum SMRPs in the diagnosis of malignant mesothelioma were pooled using random-effects models. Summary receiver operating characteristic curves were used to summarize overall test performance.

  Results: Eleven publications from 12 studies met our inclusion criteria. The summary estimates for SMRPs in the diagnosis of malignant mesothelioma in the studies included were sensitivity 0.64 (95% confidence interval 0.61-0.68), specificity 0.89 (0.88-0.90), positive likelihood ratio 7.10 (4.44-11.35), negative likelihood ratio 0.39 (0.31-0.48), and diagnostic odds ratio 19.35 (10.95-34.17).

  Conclusions: Serum SMRP determination plays a role in the diagnosis of malignant mesothelioma. The results of SMRP assays should be interpreted in parallel with clinical findings and the results of conventional tests.

  Copyright 2009 Elsevier Ltd. All rights reserved.

  In plain English

  This was a meta-analysis. The authors pooled results from earlier published studies rather than testing patients themselves. They asked how accurately a blood test for soluble mesothelin-related peptides (SMRP) identifies malignant mesothelioma. They searched medical databases up to March 8, 2008, and included 11 English-language publications reporting 12 studies. These covered 717 people with mesothelioma and 2851 people without it. Some comparison groups were asbestos-exposed people or patients with benign asbestos-related disease. Pooled across studies, the test was positive in 64% of mesothelioma patients (sensitivity 0.64, 95% confidence interval 0.61 to 0.68). It was negative in 89% of people without mesothelioma (specificity 0.89, 0.88 to 0.90). Results differed significantly between studies. The test did less well at telling mesothelioma apart from other lung diseases than from healthy people. The authors judged overall accuracy (area under the curve 0.82) "not as high as expected" and found signs of possible publication bias. They concluded that the test plays a role in diagnosing malignant mesothelioma, but that results should be interpreted alongside clinical findings and conventional tests.

  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.

• Pemetrexed in the treatment of malignant mesothelioma: results from an expanded access program in Germany. M. Reck, R.A. Stahel, J. von Pawel, et al. 2010;104(1):142-8. PubMed · Publisher

  Abstract

  An international expanded access program was initiated to provide access to treatment with pemetrexed prior registration and reimbursement for malignant mesothelioma (MM). Chemonaïve and pretreated patients with inoperable MM of the pleura or peritoneum were eligible. This report describes the results obtained in German centers. Investigators could choose between three treatments: Pemetrexed 500 mg/m(2) alone (P) or in combination with cisplatin 75 mg/m(2) (PC) or carboplatin AUC 5 (PCb). From November 2002 to June 2004, a total of 567 patients (554 with pleural MM; 41% pretreated) were included. Of 548 evaluable patients with pleural MM, 191 received P, 137 PC and 220 PCb. Patients in the P group were more often pretreated (70%) and had worse performance status compared with the other groups. In the P, PC, and PCb groups overall response rate (ORR) was 16%, 24% and 18%, median time to progression (TTP) was 5.5, 8.2, and 6.9 months, and median overall survival (OS) was 8.7, 11.3 and 9.7 months respectively. Efficacy outcomes were better for chemonaïve than for pretreated patients, and P was less hematotoxic than PC or PCb. Treatment of pleural MM with pemetrexed alone or in combination with platinum was safe and active as first and second-line therapy.

  Copyright 2009 Elsevier Ltd. All rights reserved.

• Pulmonary inflammation in asbestos-exposed subjects with borderline parenchymal changes on HRCT. L. Lehtimäki, P. Oksa, R. Järvenpää, et al. 2010;104(7):1042-9. PubMed · Publisher

  Abstract

  Many asbestos-exposed subjects have minor parenchymal changes on high resolution computed tomography (HRCT) that do not fulfil the diagnostic criteria for pulmonary fibrosis and asbestosis. We investigated if these borderline parenchymal changes in asbestos-exposed subjects are related to pulmonary inflammatory activity. Exhaled nitric oxide was measured, exhaled breath condensate collected and HRCT scanned in 104 subjects with moderate to high occupational asbestos exposure. Forty-one healthy unexposed subjects served as a comparison group. After excluding other pulmonary diseases, 35 asbestos-exposed subjects had normal parenchymal findings and 31 subjects had borderline parenchymal changes on HRCT. Lung function was poorer in the latter group, but there was no difference in the degree of asbestos exposure between these groups. As compared with the unexposed comparison group, asbestos-exposed subjects with borderline parenchymal changes had increased alveolar NO concentration (3.0 + or - 0.2 vs. 2.3 + or - 0.1 ppb, p = 0.008) and increased levels of leukotriene B(4) (12.2 + or - 1.1 vs. 3.3 + or - 0.8 pg/ml, p < 0.001) and 8-isoprostane (9.4 + or - 0.7 vs. 7.3 + or - 0.6 pg/ml, p = 0.021) in breath condensate. Asbestos-exposed subjects with normal parenchymal findings had only increased breath condensate levels of leukotriene B(4) (11.4 + or - 0.9, p < 0.001). Borderline parenchymal changes on HRCT in asbestos-exposed subjects are associated with increased markers of pulmonary inflammation. Such borderline parenchymal changes are likely a mild or early form of the same pathological process that leads to asbestosis.

  Copyright 2010 Elsevier Ltd. All rights reserved.

• Spontaneous regression of thoracic malignancies. T. Kumar, N. Patel, A. Talwar. 2010;104(10):1543-50. Review PubMed · Publisher

  Abstract

  Background: Clinicians are frequently questioned by patients about the possibility of spontaneous regression of tumors. Although there are many reports and a few case series documenting spontaneous regression, there is concern that these cases may not represent true regression. Using specific criteria, we attempted to determine the incidence and types of thoracic malignancy most likely to regress spontaneously.

  Methods: We used a PubMed search of the phrase "spontaneous regression of thoracic lesions" reported from 1951 to December 2008. Using a modified Everson and Cole criterion we developed to define spontaneous regression, this search was refined for true spontaneous regression of primary and metastatic thoracic malignancies.

  Results: Only 5 cases in the literature involved spontaneous regression of a primary thoracic malignancy. These include pleural mesothelioma, primary lung cancer and adenoid cystic carcinoma. 71 cases involved true spontaneous regression of metastatic thoracic neoplasms, of which 5 cases showed regression of the primary extrapulmonary tumors along with the pulmonary metastasis. Thoracic metastasis from renal cell carcinoma was the most common malignancy found to regress spontaneously.

  Conclusion: Spontaneous regression of primary thoracic malignancy is rare. Renal cell carcinoma accounts for most reported cases.

2000s

• Exhaled breath condensate biomarkers in asbestos-related lung disorders. S. Chow, C. Campbell, A. Sandrini, et al. 2009;103(8):1091-7. PubMed · Publisher

  Abstract

  Objectives: Asbestos induces generation of reactive oxygen and nitrogen species in laboratory studies. Several such species can be measured non-invasively in humans in exhaled breath condensate (EBC) but few have been evaluated. This study aimed to assess oxidative stress and lung inflammation in vivo.

  Methods: Eighty six men were studied: sixty subjects with asbestos-related disorders (asbestosis: 18, diffuse pleural thickening (DPT): 16, pleural plaques (PPs): 26) and twenty six age- and gender-matched normal individuals.

  Results: Subjects with asbestosis had raised EBC markers of oxidative stress compared with normal controls [8-isoprostane (geometric mean (95% CI) 0.51 (0.17-1.51) vs 0.07 (0.04-0.13) ng/ml, p<0.01); hydrogen peroxide (13.68 (8.63-21.68) vs 5.89 (3.99-8.69) microM, p<0.05), as well as increased EBC total protein (17.27 (10.57-28.23) vs 7.62 (5.13-11.34) microg/ml, p<0.05), and fractional exhaled nitric oxide (mean+/-SD) (9.67+/-3.26 vs 7.57+/-1.89ppb; p<0.05). EBC pH was lower in subjects with asbestosis compared with subjects with DPT (7.26+/-0.31 vs 7.53+/-0.24; p<0.05). There were no significant differences in exhaled carbon monoxide, EBC total nitrogen oxides and 3-nitrotyrosine between any of the asbestos-related disorders, or between these and controls.

  Conclusion: In asbestos-related disorders, markers of inflammation and oxidative stress are significantly elevated in subjects with asbestosis compared with healthy individuals but not in pleural diseases.

• Imaging of pleural masses: which to choose?. A.S. Bruns, J.G. Mastronarde. 2008;102(3):328-31. Case report · Review PubMed · Publisher

  Abstract

  The differential diagnosis of pleural masses is limited. Asbestos-related disease and invasive bronchogenic carcinoma make up the majority of cases. The diagnostic yield of biopsies is low, and invasive procedures are often required to achieve diagnosis. A variety of imaging techniques are available to help differentiate between benign and malignant disease to help discern which patients to biopsy. While computed tomography has a relatively good sensitivity and specificity, magnetic resonance imaging (MRI) and positron emission tomography (PET) both appear to have higher accuracy. MRI has the added benefit of being an excellent aid in determining surgical resectability of tumors. MRI and PET are limited, however, by their cost and availability in certain regions.

• The effects of secondhand smoke exposure on HRCT findings among asbestos-exposed workers. T. Vierikko, R. Järvenpää, J. Uitti, et al. 2008;102(5):658-64. PubMed · Publisher

  Abstract

  Objectives: There is evidence suggesting that secondhand smoke (SHS) exposure is causally linked to adverse respiratory effects. We examined the relations between the exposure to SHS and radiological signs in chest high-resolution computed tomography (HRCT).

  Methods: Asbestos-exposed workers (n=633) were imaged with HRCT, primarily to investigate potential occupational lung disease. After excluding current smokers, the study population included 361 ex- and 141 never-smokers. They answered a questionnaire on occupational exposures, smoking habits and SHS exposure. HRCT images were assessed for emphysema, ground-glass, irregular/linear and rounded opacities, honeycombing and several other signs. Regression analyses were adjusted for asbestos exposure, ex-smoking, age, body mass index and potential reader effect.

  Results: Due to missing data the multivariate analyses were restricted to 310 participants aged 47.5-87.0 years. Their lifetime SHS exposure ranged between 0 and 193.5 pack-years (mean 23.5), and exposure in the past 12 months 0-30 packs (0.43). Total (B=0.005, 95% confidence intervals (95% CI) 0.002-0.008, p=0.000) and workplace (B=0.006, 95% CI 0.003-0.009, p=0.001) cumulative SHS exposures were significantly related to ground-glass opacities. Total SHS exposure in the last 12 months (B=0.027, 95% CI 0.000-0.054, p=0.048) and workplace exposure (B=0.027, 95% CI 0.000-0.054, p=0.048) were also significantly related to ground-glass opacities. Positive effects of SHS were also detected on irregular/linear opacities.

  Conclusions: SHS exposure in the last 12 months and over lifetime significantly increases ground-glass opacity in HRCT, suggesting an early or subclinical desquamative interstitial pneumonia/respiratory bronchiolitis. This study further supports that SHS has adverse effects on the lungs that can be detected by X-ray methods.

• Guidelines of the French Speaking Society for Chest Medicine for management of malignant pleural mesothelioma. A. Scherpereel, French Speaking Society for Chest Medicine (SPLF) Experts Group. 2007;101(6):1265-76. Consensus statement · Guideline PubMed · Publisher

  Abstract

  Previously considered as a rare tumor, malignant pleural mesothelioma (MPM) has become a very important public health issue. In fact, MPM is a tumor with a poor survival, and its incidence is expected to continue to increase for at least the next 10 years. Asbestos exposure is the main factor involved in MPM pathogenesis. The diagnosis of MPM may be difficult because of differential diagnosis such as pleural benign disease induced by asbestos exposure or pleural metastasis of adenocarcinoma. Management of patients with MPM also remains complicated because they are often referred for evaluation late in the evolution of the disease. Moreover, MPM exhibits a high resistance to radiotherapy and chemotherapy; only few patients are candidates for radical surgery. New therapeutic strategies such as gene or cell therapy are still on clinical trial. Therefore, an optimal treatment of MPM is not clearly defined yet, despite the introduction of recent drugs. Between April 2005 and January 2006, the French Speaking Society for Chest Medicine (SPLF), in collaboration with other French scientific societies, brought together experts on mesothelioma to draw up recommendations in order to provide clinicians with clear, concise, up-to-date guidelines on management of MPM, presented in this report.

• Identification of a mesothelioma phenotype. J.A. Ohar, E.J. Ampleford, S.E. Howard, et al. 2007;101(3):503-9. PubMed · Publisher

  Abstract

  Despite the strong association of asbestos exposure to mesothelioma, only a fraction of persons exposed develop this neoplasm which is characterized by long latency and shortened survival. Familial clustering implicates both exposure and genetic predisposition as causative, but a biologically relevant mesothelioma phenotype essential to genetic analysis has not been defined. To identify a more extensive set of traits that would define a mesothelioma phenotype for the purpose of genetic analysis, we set to determine characteristics that distinguish mesothelioma patients from others exposed to asbestos and to identify factors that predict the presence of mesothelioma over other mesenchymal tumors of the peritoneum and carcinoma metastatic to the pleura. We compared demographics in four asbestos-exposed groups (controls n=347, bronchogenic cancer n=67, mesothelioma n=179 and benign asbestos-induced lung disease (BALD) n=3757). Within the mesothelioma group, we compared traits to identify characteristics associated with shortened survival. We found that compared to other asbestos-exposed groups, subjects with mesothelioma were younger at first asbestos exposure, had a greater risk of a second cancer diagnosis (odds ratio=3.29), had a longer disease latency, and had a greater risk of cancer among first-degree relatives (point estimate for risk 2.93; 95% CI 2.5-3.5). Thoracic tumor location, work exposure and male gender were consistently associated with shortened survival (1.9+/-1.3 years). We conclude that thoracic tumor location, work exposure, male gender, long latency, early age at first exposure, presence of a second cancer, and first-degree relative with cancer define a phenotype that sets mesothelioma patients with a short survival apart from other asbestos-exposed individuals. We propose that this phenotype be applied to candidate gene analysis.

• The Portsmouth thoracoscopy experience, an evaluation of service by retrospective case note analysis. S.V. Fletcher, R.J. Clark. 2007;101(5):1021-5. PubMed · Publisher

  Abstract

  Occupational asbestos exposure has been endemic in Portsmouth. A retrospective case note analysis of 50 patients who underwent thoracoscopy over a 2-year period from January 2003 was undertaken. Biopsies were taken in 47 cases, 31 of which showed malignant mesothelioma. Thirty seven percent of those without a history of direct exposure to asbestos had mesothelioma, implying that even in the absence of an exposure history a low threshold for investigation should be adopted for the local population. There was no mortality or significant morbidity associated with the procedure. Medical thoracoscopy is safe and effective in the diagnosis of benign and malignant pleural disease particularly in this high risk population.

• Malignant mesothelioma in Hong Kong. K.C. Chang, C.C. Leung, C.M. Tam, et al. 2006;100(1):75-82. PubMed · Publisher

  Abstract

  Malignant mesothelioma (mesothelioma) is rare. We conducted the first systematic study of the epidemiology of mesothelioma in Hong Kong from 1988 to May 2002 by reviewing medical records. Mesothelioma patients were identified from the database of 12 out of 20 hospitals that would have admitted mesothelioma patients territory-wide. These 12 hospitals served 73% of the total hospital bed-years of the 20 hospitals. We identified 67 mesothelioma patients. The estimated annual incidence was one per million, which was similar to the background incidence of one to two per million among Caucasians. Occupational history was available in 43 subjects. Three quarters of mesothelioma patients with available occupational history had occupational asbestos exposure. Restricting analysis to 48 patients with accessible medical records and using 67 occupational asbestosis patients for comparison, the epidemiology of mesothelioma in Hong Kong shares similarities with the literature: mean age of 63 years upon diagnosis, mean latency of 46 years, median survival of 9.5 months, male predominance, selective presentation among women, high prevalence among workers in ships and dockyards, predominantly epithelioid type, lower prevalence of asbestos bodies, and negative association with pleural plaques. Asbestos consumption in Hong Kong rose in the 1970s and peaked in early 1980s and late 1990s. Hong Kong may encounter an epidemic of mesothelioma in the 2010s if effective occupational asbestos control measures are not in place.

• Malignant pleural mesothelioma: occupational and environmental exposure. O. Yetkin. 2006;100(6):1121-2; author reply 1123-4. Comment · Letter PubMed · Publisher

• Rounded atelectasis of the lung. G.T. Stathopoulos, M.T. Karamessini, A.E. Sotiriadi, et al. 2005;99(5):615-23. PubMed · Publisher

  Abstract

  Rounded atelectasis of the lung (RA) is a lesion well described in the medical literature, yet often very difficult to diagnose. In recent years, the widespread use of high-resolution imaging modalities employed in the struggle against cancer, coinciding with the peak of the asbestos epidemic, have boosted the detection frequency of RA. However, its differential diagnosis still poses a challenge to the pulmonary specialist and the radiologist, as little is known about its pathogenesis. Furthermore, the multifactorial etiology of RA and its occasional coexistence with lung cancer make the task of confidently ruling out malignancy sometimes daunting. This article attempts to provide an update on RA's etiology, radiological evaluation, clinical management, and prognosis based on recent advances in broadly available diagnostic modalities and minimally invasive interventional procedures. An exemplary case of post-tuberculous RA is illustrated, as RA often presents as an unusual finding of a fairly common disease.

• Closed pleural needle biopsy: predicting diagnostic yield by examining pleural fluid parameters. S. Nusair, R. Breuer, G. Amir, et al. 2002;96(11):890-4. PubMed · Publisher

  Abstract

  Objective: Pleural fluid parameters that predict a diagnostic closed pleural needle biopsy were investigated.

  Design: A retrospective analysis.

  Setting: The Institute of Pulmonology, Hadassah University Hospital.

  Patients And Methods: Forty-four patients who underwent closed pleural needle biopsies were included in this study. Pleural fluid values of protein, glucose, lactate dehydrogenase (LDH), pH, and white blood cell count with differential cell counts, from patients with diagnostic and non-diagnostic pleural biopsies were compared.

  Results: Thirteen patients (29%) had diagnostic biopsies. Malignancy was identified in 10 patients (23%), of whom 70% had adenocarcinoma. Three other patients had non-malignant specific diagnosis. LDH levels in pleural fluid from patients with diagnostic pleural biopsy were higher than in patients with non-diagnostic pleural biopsies (1436 +/- 333 U l(-1) vs. 775 +/- 109 U l(-1); P < 0.05). LDH levels less than 510 U l(-1) were highly predictive of a negative biopsy (negative predictive value of 86.6%). Follow up revealed malignancy including mesothelioma and lymphoma, in 10 of 30 (33%) patients with non-diagnostic biopsies, and one patient died of unrelated cause, while the pleural effusion either resolved, remained stable or an alternative benign process was identified in 19 patients (63%).

  Conclusions: Low levels of LDH (< 510 U l(-1)) were highly predictive of a negative pleural needle biopsy. Thus, LDH may serve as a useful guide in deciding whether to perform closed pleural biopsy or to proceed to thoracoscopically guided biopsy.

• p53, p21 and metallothionein immunoreactivities in patients with malignant pleural mesothelioma: correlations with the epidemiological features and prognosis of mesotheliomas with environmental asbestos exposure. R. Isik, M. Metintas, A.R. Gibbs, et al. 2001;95(7):588-93. PubMed · Publisher

  Abstract

  The aim of this study is to investigate immunoreactivity for p53, p21 and metallothionein in diffuse malignant pleural mesothelioma (DMPM) and to determine the relationships between the age, sex, asbestos exposure time, survival of DMPM patients with environmental asbestos exposure and immunoreactivity to p53, p21 and metallothionein. Sixty-seven histopathologically-confirmed DMPMs, 38 of whom had environmental and 29 had occupational asbestos exposure, were included. The tumour tissue samples were immunostained with antibodies against p53, p21 and metallothionein. Epidemiological data and the survival times for the DMPM patients with environmental asbestos exposures were obtained from hospital records. Thirty-three per cent of the DMPMs were positive for p53, 35% for p21 and 52% for metallothionein. There was no statistical difference between the histological subtypes of DMPM in terms of immunoreactivity for p53, p21 and metallothionein. For p21 and metallothionein there was a statistically significant difference between the exposure characteristics: patients with environmental asbestos exposure had shown more immunopositivity. There were statistically significant differences between age groups and between asbestos exposure times for metallothionein, and between asbestos exposure times and p21. The patients with positive immunostaining had longer exposure times and were older than those having negative immunostaining. The differences between survival of the patients were not statistically significant in terms of the immunohistochemical results for p53, p21 and metallothionein.

• Prognostic factors in diffuse malignant pleural mesothelioma: effects of pretreatment clinical and laboratory characteristics. M. Metintas, S. Metintas, I. Ucgun, et al. 2001;95(10):829-35. PubMed · Publisher

  Abstract

  The aim of this study was to investigate the effects of various pretreatment clinical and laboratory characteristics on the survival of patients with diffuse malignant pleural mesothelioma (DMPM). One hundred histopathologically confirmed DMPM patients were evaluated. Fifty-nine were treated with chemoimmunotherapy while 41 who had refused chemoimmunotherapy received supportive therapy alone. The following pretreatment characteristics were evaluated in both univariate and multivariate Cox regression analyses: age, gender, Karnofsky performance score (KPS), histology asbestos exposure, presence of chest pain, dyspnoea, weight loss, symptom duration, smoking history, disease location, platelet count, haemoglobin, white blood cell (WBC) count, serum lactate dehydrogenase (LDH) and extent of disease (stage). Univariate analysis showed that patients with age > or = 75 years, male gender, smoking history advanced stages above stage I disease, KPS < 70, WBC count > or = 8450 and LDH level > or = 500 IU l(-1) have a worse prognosis. With multivariate Cox regression analyses, age > or = 75 years, advanced stages above stage I disease, KPS < 70 and LDH level > or = 500 IU l(-1) were found to be indicators of a poorer prognosis. In conclusion, in our study each of low performance status, older age, advanced stage disease, high LDH level and prognosis were found to be related.

• Ras oncoprotein expression in erionite- and asbestos-induced Turkish malignant pleural mesothelioma patients--a pilot study. A. Olut, P. Firat, D. Ertugrul, et al. 2001;95(8):697-8. PubMed · Publisher

  Summary

  This short report examined whether ras oncoprotein expression plays a role in malignant pleural mesothelioma caused by environmental exposure to asbestos or erionite (a fibrous zeolite) in Turkey. In some villages of rural Anatolia, this disease accounts for more than 50% of total deaths. The study included 31 patients with malignant pleural mesothelioma at Hacettepe University School of Medicine, Ankara. Diagnosis was based on histological examination of tissue obtained by percutaneous pleural biopsy, thoracoscopy or thoracotomy. Patients were grouped by the mineral to which they had been exposed, based on previously documented environmental exposure in the villages where they lived: asbestos for 16 patients and erionite for 15. The study dates were not stated. Expression of p21 ras oncoprotein was measured by immunohistochemistry on paraffin-embedded tissue sections, using a commercial antibody that detects H-, K- and N-ras products. Groups were compared with Fisher's exact test. Five of the 31 samples (16%) showed ras expression: 3 of 21 epithelial, 2 of 8 mixed-type and none of 2 fibrous mesotheliomas. Staining was only focal and cytoplasmic, and its intensity ranged from mild to moderate. Expression was found in 4 of 15 erionite-induced cases (27%) and 1 of 16 asbestos-induced cases (6%). This difference was not statistically significant. The authors concluded that ras oncoprotein expression does not seem to be significantly involved in the development of environmentally induced mesothelioma in Turkey. They described the expression in more than a quarter of erionite-induced cases as a new finding and recommended further investigation using molecular techniques.

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1990s

• Environmental asbestos exposure and malignant pleural mesothelioma. M. Metintas, N. Ozdemir, G. Hillerdal, et al. 1999;93(5):349-55. PubMed · Publisher

  Abstract

  Asbestos-related benign and malignant pleural diseases are endemic in some rural parts of central Turkey because of environmental exposure to asbestos fibres. We report here epidemiological data on 113 patients with diffuse malignant pleural mesothelioma (DMPM) diagnosed in our clinic in Eskişehir, located in central Turkey. Of the 113 patients, 59 were men and 54 women (male:female ratio = 1). Ninety-seven patients (86%) had non-occupational asbestos exposure; all were living in villages. Their mean age was 56 years. As the patients had been exposed to asbestos from birth, the latency period was equivalent to the age of the patients. Twenty-eight patients (29%) had lived in villages their entire lives. The other 69 (71%) had been born in a village but migrated to the city or had given up white-soil usage for various reasons. The mean exposure time was 55 years for those with a long exposure period and 25 years for those with a short exposure period, but there was no significant difference between the age of the disease appearance for both groups (55 and 56 years, respectively). Thus, the latency time of mesothelioma due to environmental exposure to asbestos was longer than that due to occupational exposure, but independent of the length of exposure. Soil samples from 67 villages were analysed, comprising a population of 10,120 villagers. Tremolite and some other types of asbestos were found. In conclusion, DMPM in our region is due to mainly to environmental exposure to asbestos. The risk is substantial as a large proportion of the villagers are exposed. After smoking, asbestos exposure is one of the most serious health hazards in our rural population.

• Characterization of N-acetylcysteine and ambroxol in anti-oxidant therapy. A. Gillissen, D. Nowak. 1998;92(4):609-23. Review PubMed · Publisher

  Abstract

  Reactive free oxygen radicals are known to play an important role in the pathogenesis of various lung diseases such as idiopathic pulmonary fibrosis (IPF), adult respiratory distress syndrome (ARDS) or cystic fibrosis (CF). They can originate from endogenous processes or can be part of exogenous exposures (e.g. ozone, cigarette smoke, asbestos fibres). Consequently, therapeutic enhancement of anti-oxidant defence mechanisms in these lung disorders seems a rational approach. In this regard, N-acetyl-L-cysteine (NAC) and ambroxol have both been frequently investigated. Because of its SH group, NAC scavenges H2O2 (hydrogen peroxide), .OH (hydroxol radical), and HOCl (hypochlorous acid). Furthermore, NAC can easily be deacetylated to cysteine, an important precursor of cellular glutathione synthesis, and thus stimulate the cellular glutathione system. This is most evident in pulmonary diseases characterized by low glutathione levels and high oxidant production by inflammatory cells (e.g. in IPF and ARDS). NAC is an effective drug in the treatment of paracetamol intoxication and may even be protective against side-effects of mutagenic agents. In addition NAC reduces cellular production of pro-inflammatory mediators (e.g. TNF-alpha, IL-1). Also, ambroxol [trans-4-(2-amino-3,5-dibromobenzylamino)-cyclohexane hydrochloride] scavenges oxidants (e.g. .OH, HOCl). Moreover, ambroxol reduces bronchial hyperreactivity, and it is known to stimulate cellular surfactant production. In addition, ambroxol has anti-inflammatory properties owing to its inhibitory effect on the production of cellular cytokines and arachidonic acid metabolites. For both substances effective anti-oxidant and anti-inflammatory function has been validated when used in micromolar concentrations. These levels are attainable in vivo in humans. This paper gives an up-to-date overview about the current knowledge of the hypothesis that oxidant-induced cellular damage underlies the pathogenesis of many human pulmonary diseases, and it discusses the feasibility of anti-oxidant augmentation therapy to the lung by using NAC or ambroxol.

• Finger clubbing in malignant mesothelioma and benign asbestos pleural disease. C. McGavin, P. Hughes. 1998;92(4):691-2. PubMed · Publisher

  Summary

  The authors asked whether malignant mesothelioma is itself associated with finger clubbing, or whether clubbing reported in mesothelioma might instead reflect underlying asbestosis. They compared how often finger clubbing occurred in asbestos workers with mesothelioma and in those with benign pleural disease. The subjects were 731 men with documented asbestos exposure, mainly from the Devonport naval base, seen at the Plymouth Chest Clinic in the U.K. Of these, 77 had mesothelioma, 108 had diffuse pleural fibrosis (DPF) with or without plaque, and 546 had pleural plaque alone. Mesothelioma was supported by histological or cytological evidence, and benign pleural disease was diagnosed on plain chest radiograph. Men with bronchial carcinoma were not included, and men considered to have asbestosis were excluded. A single observer, who was not blind to the diagnosis, examined all the men and recorded clubbing when there was abnormal fluctuation between the nail and its bed. Clubbing was found in 30% of the men with mesothelioma (23 of 77) and 14% of those with benign pleural disease (17% DPF, 12% plaque). The difference between mesothelioma and benign disease was highly significant (chi-squared = 16.0, P<0.0001). There was no significant difference between DPF and plaque. The authors concluded that these findings justified including malignant pleural mesothelioma as a cause of finger clubbing. They said that clubbing in an asbestos worker with an abnormal chest X-ray should alert the clinician to possible mesothelioma.

  PubMed has no abstract for this study, and the article doesn't print one. We wrote this summary from the full article with the help of AI. It is not the authors' wording.

• Medical thoracoscopy, results and complications in 146 patients: a retrospective study. M. Hansen, P. Faurschou, P. Clementsen. 1998;92(2):228-32. PubMed · Publisher

  Abstract

  In a retrospective study the results of medical thoracoscopy in 147 patients were reviewed; 136 of the patients had pleural effusion and 11 patients had diffuse pulmonary infiltration. All the pleural exudates were initially screened three times successively and found to be sterile and without tumour cells. All thoracoscopies were performed with local anaesthesia, with the 'open technique', and nine different doctors performed the thoracoscopies. The overall diagnostic sensitivity was 90.4%. The results demonstrated 62% with malignancy of the pleura, and 38% revealed benign pleural diseases, among them 2% with tuberculosis. The sensitivity for malignancy was found to be 88% and the specificity 96%. The most common primary lung cancer with involvement of the pleura was the adenocarcinoma (62%), and the most common metastatic tumour originated from the breast (28%). The sensitivity for tuberculosis was 100% and the specificity 100%. No mortality was found, and the morbidity was low at about 0.6% (empyema, pleuro-cutaneous fistula, transcutaneous growth of tumour (mesothelioma)). In 64% of the patients the thoracoscopy resulted in treatment (pleurodesis, antituberculous treatment, chemotherapy and peroral steroid therapy). The medical diagnostic thoracoscopy in local anaesthesia is a simple, low-cost investigation with a relatively high diagnostic accuracy, no mortality and a low morbidity.

• Distinction between pleural mesothelioma and pulmonary adenocarcinoma using MOC31 in an asbestos sprayer. P.J. Ryan, J.L. Oates, J. Crocker, et al. 1997;91(1):57-60. Case report PubMed · Publisher

  Abstract

  Asbestos exposure may cause asbestosis, pleural plaques and benign pleural disease, and may pre-dispose to malignant mesothelioma and other neoplasms. The occurrence to two primary tumours in the same patient is rare, and the appearance of a pleural mesothelioma and another lung tumour is exceptional. The present case report describes a patient who, by standard immunohistochemistry, was thought to have mesothelioma at pleuro-pneumonectomy, and adenocarcinoma in the other lung at post-mortem 5 months later. Subsequent investigation using the MOC31 antibody demonstrated a single pathology of adenocarcinoma of the lung. The additional use of this antibody has important histopathological and legal implications.

• Methods to improve the diagnostic accuracy of malignant mesothelioma. A. Dejmek. 1996;90(4):191-9. Review PubMed · Publisher

  Summary

  This topical review from Malmö University Hospital, Sweden, described methods intended to improve the diagnosis of diffuse malignant mesothelioma, a tumour for which asbestos was named as the most significant cause. The author noted that early diagnosis mattered for medical and medicolegal reasons. Distinguishing mesothelioma from adenocarcinoma and from benign mesothelial hyperplasia was described as difficult. Reported accuracy was close to 100% for thoracoscopy, up to 60% for closed needle biopsy, and varied widely for effusion cytology, from 4% to a sensitivity of 62%. The review then covered ancillary techniques. These were electron microscopy (for example, long, slender microvilli), histochemical stains (Alcian blue with hyaluronidase, PAS after diastase, and mucicarmine), and immunocytochemistry with markers including CEA, intermediate filaments, EMA, Leu M1, B72.3, BerEp, extracellular matrix proteins and others. Because no single antibody separated mesothelioma from adenocarcinoma, antibody panels were recommended. One panel of anti-CEA, anti-EMA and B72.3 resolved over 95% of cases. In the author's own study of 103 mesotheliomas and 43 adenocarcinomas, logistic regression selected five parameters. The review also described measuring hyaluronan in effusions. With an HPLC method, a value of 75 mg/l was reported as 100% specific for mesothelioma. The author concluded that a multimodal approach using ancillary techniques could give a correct diagnosis from small tissue samples in a considerable number of cases.

  PubMed has no abstract for this study, and the article doesn't print one. We wrote this summary from the full article with the help of AI. It is not the authors' wording.

• Lung crackle characteristics in patients with asbestosis, asbestos-related pleural disease and left ventricular failure using a time-expanded waveform analysis--a comparative study. N. al Jarad, S.W. Davies, R. Logan-Sinclair, et al. 1994;88(1):37-46. PubMed · Publisher

  Abstract

  The aim of this study is to investigate lung crackle characteristics by time-expanded waveform (TEW) analysis in patients with asbestosis (AS), asbestos-related pleural disease (ARPD) and left ventricular failure (LVF). TEW was performed on a 33 s recording from each of 40 patients (12 AS, 17 ARPD and 11 LVF). They were 38 men and two women. Crackles on TEW were counted during inspiration and expiration, and the timing of clusters of crackles with respect to inspiration and expiration was noted. A total of 1117 crackles were identified. The initial deflection width (IDW) and the two cycle duration (2CD) were calculated for all crackles within one respiratory cycle for each patient (total of 298 crackles). Crackles were detected by TEW in all patients with AS, in seven patients with ARPD and in nine patients with LVF. Crackles in AS were mainly fine, mid- to late-inspiratory. Crackles in LVF took three patterns; in the first there were repetitive mid- to late inspiratory crackles similar to those seen in AS except that the crackles in LVF tended to be medium and coarse as well as fine (three patients); in the second crackles started early in inspiration followed by a crackle-free period then by another cluster of crackles lasting to the end of inspiration and to the early third of expiration (four patients) and in the third there were repetitive expiratory crackles with no or few inspiratory crackles (two patients). Crackles in ARPD generally took the configuration of fine crackles but another type of crackle preceded by a sharp deflection followed by an M-shape oscillation then by the largest oscillation was also found. IDW and 2CD for inspiratory crackles in ARPD were shorter than those in AS and LVF (for IDW P < 0.009 and P < 0.003 compared with AS and LVF respectively and for 2CD, P < 0.006 and P < 0.003 compared with AS and LVF respectively). IDW and 2CD in AS tended to be shorter than these for LVF but these results did not reach statistical significance. It is concluded that many differences exist between crackles in AS, LVF and ARPD. Differences in nature and timing of crackles may reflect differences in the pathophysiology and mechanism giving rise to lung crackles in these conditions. TEW provides informations of diagnostic value.

• Respiratory muscle function in patients with asbestos-related pleural disease. N.A. Jarad, M.P. Carroll, C. Laroche, et al. 1994;88(2):115-20. PubMed · Publisher

  Abstract

  The effect of asbestos-related pleural disease (ARPD) on the generation of maximum respiratory pressure was investigated in 11 male patients with ARPD mean age 57 years, range 45-74, and mean duration of asbestos exposure of 9.9 years, range 5-16. There were three smokers, seven ex-smokers and one non-smoker. Breathlessness ranged from grade 1-3 on the MRC score. The extent of pleural disease was calculated using a score based on the ILO score for pleural disease. Full respiratory function tests, global respiratory muscle strength and diaphragmatic strength were assessed. Respiratory muscle strength, including diaphragm strength, was normal. Recoil pressure was high or at the upper limit of normal in four patients and correlated with chest radiograph score for pleural disease (r = 0.65, P < 0.02). There was no difference in either global respiratory muscle or diaphragmatic strength between patients with and without involvement of one or both costophrenic angles or between patients with mild or severe breathlessness. We conclude that respiratory muscle strength is not importantly reduced in ARPD, and it is unlikely that weakness contributes to breathlessness in these patients. By contrast reduced chest wall compliance is likely to be an important factor in breathlessness in some cases.

• Asbestos-related pericardial thickening detected by magnetic resonance imaging. N.A. Jarad, S.R. Underwood, R.M. Rudd. 1993;87(4):309-12. PubMed · Publisher

  Abstract

  Magnetic resonance imaging was performed in four male asbestos workers in whom the chest radiograph revealed pleural but not pulmonary or pericardial disease. Patients underwent thoracic multislice spin echo imaging, with measurement of left and right ventricular volumes at end-diastole and end-systole, and a study of the flow in the superior vena cava as an indirect measure to the filling of the right ventricle. Patients also underwent respiratory function tests and high-resolution computed tomography (HRCT). Magnetic resonance, but not HRCT, showed pericardial thickening in two patients. Magnetic resonance demonstrated reduced diastolic flow in the superior vena cava in one patient, reflecting impaired right ventricular filling. All other magnetic resonance measurements of cardiac function were normal. HRCT demonstrated mild asbestosis in three patients in which neither the chest radiograph nor magnetic resonance showed signs of parenchymal disease, and pericardiac calcification without thickening in one patient. It is concluded that magnetic resonance is superior to HRCT in identifying pericardial thickening, but that HRCT is superior to magnetic resonance in identifying asbestos-related pleural and pulmonary disease.

• Bronchoalveolar lavage and 99mTc-DTPA clearance as prognostic factors in asbestos workers with and without asbestosis. N. al Jarad, A.R. Gellert, R.M. Rudd. 1993;87(5):365-74. PubMed · Publisher

  Abstract

  The aims of this study are to investigate the change-over time of lung function and chest radiographic findings in patients with asbestosis (AS) and asbestos workers without asbestosis (AW). Secondly, to correlate these changes with broncho-alveolar lavage (BAL) profiles and with lung epithelial permeability, as detected by half-time lung-to-blood (t1/2 LB) clearance of an inhaled aerosol of diethylene triamine pentacetate labelled with technetium 99 (99mTc-DTPA) obtained a mean period of 4.2 yr (range 2.3-5.8) previously. Thirty-three patients with asbestosis and 24 asbestos workers with substantial asbestos exposure were followed-up. Nineteen healthy smokers (HS) with no asbestos exposure who were followed up for a mean period of 3.9 yr were taken as a control group for spirometric changes. Compared with AW, FEV1, FVC and TLCO were lower in AS (P < 0.0001 in each case). Smoker AS and AW had lower numbers (P < 0.03) and percentages (P < 0.004) of BAL lymphocytes and higher numbers (P < 0.04) and percentages (P < 0.02) of BAL neutrophils plus eosinophils than ex- and non-smokers. Annual declines of FEV1 (dFEV1 yr-1) and FVC (dFVC yr-1) in AS and AW were significantly greater than in HS and predicted annual declines (P < 0.002 in each case). Annual declines of TLCO (dTLCO yr-1) and KCO (dKCO yr-1) in AS and AW were significantly greater than predicted annual declines (P < 0.002 in each case). No significant differences were noted between AS and AW in annual declines in any lung function measurement. dTLCO yr-1, dKCO yr-1 were significantly greater in smokers than in ex- and non-smokers, (P < 0.05 and P < 0.04 respectively). Annual decline did not relate to base line values for any lung function measurement. Numbers and proportions of BAL lymphocyte were higher (P < 0.008 and P < 0.02, respectively) and numbers and proportions of BAL neutrophils and eosinophils were lower (P < 0.02 and P < 0.03, respectively) in patients in whom dTLCO yr-1 was less than 0.3 mmol min-1 kPa-1 than in patients in whom dTLCO yr-1 was more than 0.3 mmol min-1 kPa-1. dTLCO yr-1 inversely correlated with t1/2 LB; r = 0.51; (P < 0.008). Patients in whom the radiograph remained unchanged had higher numbers (P < 0.002) and percentages (P < 0.001) of BAL lymphocytes than patients in whom the radiograph deteriorated.(ABSTRACT TRUNCATED AT 250 WORDS)

• Toxicology of the lung. D. Dinsdale. 1993;87(4):279-84. PubMed · Publisher

• Asbestos exposure and airways obstruction. M.G. Pearson. 1991;85(4):344-6. Comment · Letter PubMed · Publisher

• Assessment of asbestos-induced pleural disease by computed tomography--correlation with chest radiograph and lung function. N. al Jarad, N. Poulakis, M.C. Pearson, et al. 1991;85(3):203-8. PubMed · Publisher

  Abstract

  We compared computed tomography (CT) scanning with chest radiography in the assessment of asbestos-induced pleural disease (AIPD) in 20 patients (17 men and 3 women, mean age 55 years, range 43-74 years). Involved pleura was scored on plain chest radiographs according to the International Labour Office (ILO) method of evaluating AIPD. A CT score was calculated from the measurement, using a digital length probe, of the circumference of the chest wall involved by pleural disease in each slice. The maximum width of pleural disease was taken into account in a way analogous to the ILO method for the chest radiograph. The CT score correlated with the chest radiograph score (r = +0.82, P less than 0.0006). CT demonstrated discrete plaques in 95% of patients but these were identified only in 59% patients on the radiograph. Diffuse pleural thickening was evident on the CT scan in all patients and in 70% on the radiograph. There was more inter-reader agreement about the type of pleural disease on the CT scans than on the chest radiographs. CT and chest radiograph scores inversely correlated with all lung function measurements except KCO. We conclude that increasingly extensive pleural disease is associated with increasingly severe impairment of lung function. CT scanning demonstrates the type of AIPD better than plain chest radiography.

• Airway obstruction in asbestos-exposed shipyard workers: with and without irregular opacities. K.H. Kilburn, R.H. Warshaw. 1990;84(6):449-55. PubMed · Publisher

  Abstract

  Airway obstruction was measured by spirometry in 296 boilermakers with 15 or more years shipyard exposure to asbestos. Percent of predicted was used to adjust each worker's pulmonary function values for height (mean 174 cm), age (mean 52.5 years) and cigarette smoking (mean 23.3 years). Mean values were significantly (P less than 0.05) below predicted for FVC 4.23 l 94.2% FEV1 3.06 l 89.3%, FEF25-75 2.51 l sec-1 82.3% and FEF75-85 0.574 l sec-1 77.8%. Corresponding values for the 106 men with pulmonary asbestosis (ILO profusion of opacities 1/0 or greater), were below these levels. Those without radiographic signs of asbestosis had intermediate values significantly below predicted. Correlation coefficients for pulmonary functions with ILO categories of asbestosis (profusion of irregular opacities) were: FVC -0.2381, FEV1 -0.2494, FEF25-75 -0.2403 and FEF75-85 -0.1629. All were significant P less than 0.05. The subgroup with radiographic asbestosis (ILO 1/0 or greater), had more functional loss. Data on this large cohort of asbestos-exposed workers establish that airway obstruction occurs after 15 years of exposure and before the slightest profusion of asbestosis scarring in the lungs of shipyard workers, and worsens progressively with greater profusions of irregular opacities.

• Ear lobe oximetry was of value for assessing disability in asbestos-related lung disease. J.E. Cotes, B. King. 1990;84(1):86. Comment · Letter PubMed · Publisher

• Investigation of pleural effusion: comparison between fibreoptic thoracoscopy, needle biopsy and cytology. W.M. Edmondstone. 1990;84(1):23-6. PubMed · Publisher

  Abstract

  Twenty-eight patients with exudative pleural effusion have been investigated by fibreoptic thoracoscopy, Abrams needle biopsy and pleural fluid cytology. Sixteen patients had previously had negative pleural biopsies and cytology. Twenty effusions were malignant (16 mesothelioma, four metastatic carcinoma), seven were due to nonspecific inflammation and in one case no abnormality was found. The diagnostic yield for all three techniques combined was 85%, for thoracoscopy alone 65%, Abrams biopsy 60% and cytology 45%. In 12 patients presenting without previous investigation all eight malignant effusions were correctly diagnosed by at least one of the techniques with individual sensitivities of 75% for thoracoscopy, 63% for Abrams and 38% for cytology. Of the 16 patients who had previously had negative investigations 12 had malignant effusions, nine (75%) of which were diagnosed by a combination of the techniques. In this group, the individual sensitivities were 58% for both thoracoscopy and Abrams and 50% for cytology. A correct diagnosis of malignancy was made by a combination of needle biopsy and cytology in 75% of patients with previous investigations and 88% of those without. Fibreoptic thoracoscopy added only two diagnoses of malignancy to those obtained by Abrams and cytology. The limitations of the technique render it unsuitable for routine investigation of pleural effusions.

• Pleural and parenchymal fibrosis mainly affecting the upper lung lobes in persons exposed to asbestos. G. Hillerdal. 1990;84(2):129-34. PubMed · Publisher

  Abstract

  From the County of Uppsala, Sweden, more than 1600 persons with pleural plaques and/or asbestos-related pleural thickening have been seen at the Uppsala University Hospital during a period of about 15 years. During the observation time, 40 patients developed lesions mainly affecting the upper lobes of the lung. They were all men, 41 to 78-years-old, and all had been occupationally exposed to asbestos. The mean latency time from the first exposure was 34 years. The mean width of the apical pleural thickening was 21 mm. In 21 patients the lesions were on the right side, in 15 they were bilateral, and in only four patients was the left side alone affected. Biopsies from the pleura were available in twelve patients and from the lung parenchyma in eight. The biopsies of the lungs all showed varying degrees of asbestosis and of the pleura nonspecific pleuritis. The lesions tended to progress and in all cases except one they were part of a diffuse pleural and parenchymal fibrosis involving the rest of the lung. Consequently, the pulmonary function was impaired, with the vital capacity reduced to an average of 62% and total lung capacity to 68% of the predicted value. In many patients there was contraction of the upper lobe and deviation of the trachea towards the same side. Upper lobe changes are a relatively rare complication of exposure to asbestos but are important to recognise. Other possible causes of upper lobe changes such as tuberculosis must always be excluded before the diagnosis is made.

• Pleural mesothelioma after asbestos exposure. A.M. Langer, R.P. Nolan. 1990;84(6):509-10. Comment · Letter PubMed · Publisher

1980s

• Advanced intravascular bronchioloalveolar tumour and review of reports in Japan. T. Shirakusa, M. Yoshida, M. Tsutsui, et al. 1989;83(2):127-32. Case report · Review PubMed · Publisher

  Abstract

  Intravascular bronchioloalveolar tumour (IVBAT) is a rare pulmonary neoplasm. We report the clinical and pathologic findings of two patients who demonstrated unusual clinical features. Both of them were young males who showed a large mass or consolidated shadow and small nodules with pleurisy on chest X-rays due to the invasive growth of tumours. In the first case the presumptive diagnosis of lung carcinoma was made from the discovery of atypical cells in pleural fluid. In the second case pleural mesothelioma was suspected. However, the histological diagnoses of these cases, including the immuno-histological and ultrastructural data, were reported and clinical features of IVBAT described previously in Japan were summarized.

• Compensation for asbestos-related diseases--the U.K. model. M. Britton. 1989;83(2):95-102. PubMed · Publisher

• Pleural mesothelioma resulting from exposure to amosite asbestos in a building. R.C. Stein, J.Y. Kitajewska, J.B. Kirkham, et al. 1989;83(3):237-9. Case report PubMed · Publisher

  Summary

  The authors reported a case of pleural mesothelioma that they attributed to amosite asbestos used as insulation in an office building, from The London Chest Hospital, U.K. A 54-year-old female office worker and lifelong non-smoker presented with six months of malaise, persistent cough and exertional dyspnoea. She had a left pleural effusion. Pleural biopsy was unhelpful, but pleural fluid cytology suggested mesothelioma. She died nine months after presentation, and post mortem examination confirmed pleural mesothelioma. Two pathologists made the diagnosis independently. No asbestos bodies were seen by light microscopy. Transmission electron microscopy of digested tissue showed 31 million fibres per gram of dry lung and 12 million fibres per gram of dry tumour. Of 500 fibres counted in the lung digest, 90% were morphologically compatible with amosite, and X-ray microanalysis of 40 of these fibres confirmed a composition compatible with amosite. She had no occupational, residential or household asbestos exposure apart from the office block, where she had worked since its construction. Its ceilings had been sprayed with soft asbestos, and a sample of this material was 70% amosite. The authors concluded that proximity to poorly maintained asbestos in buildings can result in exposure sufficient to cause serious disease.

  PubMed has no abstract for this study, and the article doesn't print one. We wrote this summary from the full article with the help of AI. It is not the authors' wording.

• The value of ear lobe oximetry in the assessment of disability in asbestos-related disease. M.G. Britton, M.C. Apps, D.L. Maxwell, et al. 1989;83(1):43-9. PubMed · Publisher

  Abstract

  Thirty-four asbestos workers, with either asbestosis, diffuse pleural thickening, calcified pleural plaques, or with comparable asbestos exposure but no evidence of asbestos-related disease and seven normal controls underwent a progressive exercise test. The subjects were categorized on the basis of lung function tests and PA chest X-rays. During the exercise test oxygen saturation was measured continuously by an ear lobe oximeter. The asbestosis and diffuse pleural thickening groups showed significant oxygen desaturation on exertion, confirming that both these conditions give rise to appreciable respiratory disability.

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