American Journal of Respiratory and Critical Care Medicine

Our medical research library holds 78 studies published in American Journal of Respiratory and Critical Care Medicine (1994–2022). 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. 46 have an abstract, the authors' own summary as PubMed records it: open "Abstract" to read it. For 12 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: Oxford University Press
• Published: 1994 to the present, England
• Language: English
• ISSN: 1073-449X (print), 1535-4970 (electronic)
• Continues: American Review of Respiratory Disease
• Its record in the NLM Catalog

2020s

• A MUC5B Gene Polymorphism, rs35705950-T, Confers Protective Effects Against COVID-19 Hospitalization but Not Severe Disease or Mortality. A. Verma, J. Minnier, E.S. Wan, et al. 2022;206(10):1220-1229. Meta-analysis PubMed · Publisher · Free full text

  Abstract

  Rationale: A common MUC5B gene polymorphism, rs35705950-T, is associated with idiopathic pulmonary fibrosis (IPF), but its role in severe acute respiratory syndrome coronavirus 2 infection and disease severity is unclear. Objectives: To assess whether rs35705950-T confers differential risk for clinical outcomes associated with coronavirus disease (COVID-19) infection among participants in the Million Veteran Program (MVP). Methods: The MUC5B rs35705950-T allele was directly genotyped among MVP participants; clinical events and comorbidities were extracted from the electronic health records. Associations between the incidence or severity of COVID-19 and rs35705950-T were analyzed within each ancestry group in the MVP followed by transancestry meta-analysis. Replication and joint meta-analysis were conducted using summary statistics from the COVID-19 Host Genetics Initiative (HGI). Sensitivity analyses with adjustment for additional covariates (body mass index, Charlson comorbidity index, smoking, asbestosis, rheumatoid arthritis with interstitial lung disease, and IPF) and associations with post-COVID-19 pneumonia were performed in MVP subjects. Measurements and Main Results: The rs35705950-T allele was associated with fewer COVID-19 hospitalizations in transancestry meta-analyses within the MVP (Ncases = 4,325; Ncontrols = 507,640; OR = 0.89 [0.82-0.97]; P = 6.86 × 10-3) and joint meta-analyses with the HGI (Ncases = 13,320; Ncontrols = 1,508,841; OR, 0.90 [0.86-0.95]; P = 8.99 × 10-5). The rs35705950-T allele was not associated with reduced COVID-19 positivity in transancestry meta-analysis within the MVP (Ncases = 19,168/Ncontrols = 492,854; OR, 0.98 [0.95-1.01]; P = 0.06) but was nominally significant (P < 0.05) in the joint meta-analysis with the HGI (Ncases = 44,820; Ncontrols = 1,775,827; OR, 0.97 [0.95-1.00]; P = 0.03). Associations were not observed with severe outcomes or mortality. Among individuals of European ancestry in the MVP, rs35705950-T was associated with fewer post-COVID-19 pneumonia events (OR, 0.82 [0.72-0.93]; P = 0.001). Conclusions: The MUC5B variant rs35705950-T may confer protection in COVID-19 hospitalizations.

• Asbestos, Pleural Plaques, and Lung Cancer: Untangling the Relationships. P. Harber. 2020;201(1):4-6. Editorial · Comment PubMed · Publisher · Free full text

• Pleural Plaques and the Risk of Lung Cancer in Asbestos-exposed Subjects. F.J.H. Brims, K. Kong, E.J.A. Harris, et al. 2020;201(1):57-62. PubMed · Publisher

  Abstract

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

2010s

• Asbestos-related Diseases in Turkey: Caused Not Only by Naturally Occurring Fibers but Also by Industrial Exposures. M. Bayram, D. Özkan, E. Hayat, et al. 2019;199(5):656-659. Letter PubMed · Publisher

• A Significant Metabolic and Radiological Response after a Novel Targeted MicroRNA-based Treatment Approach in Malignant Pleural Mesothelioma. S.C. Kao, M. Fulham, K. Wong, et al. 2015;191(12):1467-9. Case report · Letter PubMed · Publisher

  Summary

  This letter reported one patient with malignant pleural mesothelioma (MPM) treated in MesomiR 1, an ongoing phase 1 trial in Sydney, Australia. The trial was testing intravenous, epidermal growth factor receptor (EGFR)-targeted EnGeneIC Delivery Vehicle (EDV) nanocells carrying miR-16-based mimics (TargomiRs) in patients with MPM and advanced non-small-cell lung cancer. The approach was based on the authors' earlier findings that the miR-15/16 family was down-regulated in MPM and that restoring miR-16 inhibited tumor growth in cell lines and in mice. Six patients had completed 8 weeks of weekly treatment at the first dose level. The patient described was a 51-year-old plumber with right-sided epithelial MPM diagnosed in May 2013. His disease had progressed after two courses of platinum/pemetrexed chemotherapy. Weak EGFR staining was found in 5% of his tumor cells. After 8 weeks of TargomiRs he had grade 1 toxicities and reported less chest pain. PET-CT showed a "complete" metabolic response, with peak standard uptake value falling from 17.1 to 2.7, an 84% reduction. Chest CT showed a partial response, confirmed 4 weeks later. His lung function improved, with FEV1 rising from 2.9 to 3.7 L and FVC from 3.84 to 5.22 L. Of the other five patients, four had stable disease and one had progressive disease. Most patients had shivering or rigors after infusion and transient rises in inflammatory cytokines. The authors described the results as very preliminary but called this the first report of an objective treatment response using a microRNA-based therapy.

  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.

• Ultra-low-dose chest computer tomography screening of an asbestos-exposed population in Western Australia. F.J. Brims, C.P. Murray, N. de Klerk, et al. 2015;191(1):113-6. Letter PubMed · Publisher

  Summary

  This research letter reported the results of offering ultra-low-dose chest computed tomography (LDCT) to people with past asbestos exposure in Western Australia. The authors asked whether such screening detected lung cancer and whether existing screening guidelines would have identified those at risk. Over a 12-month period, participants in the Western Australia Asbestos Review Program were offered LDCT instead of annual plain chest radiography. To be in the program, participants needed at least 3 months of occupational asbestos exposure and/or radiographically confirmed pleural plaques. Of 1,308 participants, 906 chose LDCT. Their mean age was 68.8 years, 83.6% were male, and 62.8% were ever-smokers with a mean of 17.1 pack-years. Scans were scored by thoracic radiologists using the NELSON trial method. Significant nodules were reported in 77 participants (8.4%). Seven lung cancers were found, a prevalence of 0.77%. Six were stage Ia and one stage IIa, and all were treated with surgery with curative intent. Using those who declined LDCT as a comparator, sensitivity was 100%, specificity 92.0% and positive predictive value 8.86%. Only 33 participants (3.6%) would have been eligible for screening under US Preventive Services Task Force criteria and 269 (29.7%) under NCCN guidelines. None of the seven cancer cases would have met the Task Force criteria, and two would have met the NCCN guidelines. The authors concluded that current guidelines may not adequately account for asbestos-related lung cancer risk. They called for risk prediction models that incorporate asbestos exposure.

  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.

• Asbestos exposure, pleural plaques, and the risk of death from lung cancer. J.C. Pairon, P. Andujar, M. Rinaldo, et al. 2014;190(12):1413-20. PubMed · Publisher

  Abstract

  Rationale: Although asbestos is a well-known lung carcinogen, the pleural plaque-lung cancer link remains controversial.

  Objectives: This study was designed to examine this link in asbestos-exposed workers.

  Methods: A 6-year follow-up was conducted to study lung cancer mortality in the 5,402 male subjects participating in an asbestos-related disease screening program conducted from October 2003 to December 2005 in four French regions. Chest computed tomography (CT) scan was performed in all subjects with randomized, independent, double reading of CT scans focusing on benign asbestos-related abnormalities. Cox model survival regression analysis was used to model lung cancer mortality according to the presence of pleural plaques, with age as the main time variable, adjusting for smoking and asbestos cumulative exposure index. All statistical tests were two-sided.

  Measurements And Main Results: Thirty-six deaths from lung cancer were recorded. Lung cancer mortality was significantly associated with pleural plaques in the follow-up study in terms of both the unadjusted hazard ratio of 2.91 (95% confidence interval = 1.49-5.70) and the adjusted hazard ratio of 2.41 (95% confidence interval = 1.21-4.85) after adjustment for smoking and asbestos cumulative exposure index.

  Conclusions: Pleural plaques may be an independent risk factor for lung cancer death in asbestos-exposed workers and could be used as an additional criterion in the definition of high-risk populations eligible for CT screening.

• Asbestos, asbestosis, smoking, and lung cancer: study bias and confounding issues that complicate the interpretation of the results. S.J. Geyer. 2014;189(1):115-6. Letter · Comment PubMed · Publisher

• Asbestosis, not asbestos exposure, is the primary risk factor for lung cancer. R. Ross. 2014;189(1):114-5. Letter · Comment PubMed · Publisher

• Fibroblast growth factor receptor inhibition is active against mesothelioma and synergizes with radio- and chemotherapy. K. Schelch, M.A. Hoda, T. Klikovits, et al. 2014;190(7):763-72. PubMed · Publisher

  Abstract

  Rationale: Malignant pleural mesothelioma is an aggressive malignancy characterized by frequent resistance to chemo- and radiotherapy, poor outcome, and limited therapeutic options. Fibroblast growth factors (FGFs) and their receptors are potential targets for cancer therapy, but their significance in mesothelioma has remained largely undefined.

  Objectives: To investigate the antimesothelioma potential of FGF receptor 1 (FGFR1) inhibition.

  Methods: Expression of FGFs and their receptors was analyzed in mesothelioma cell lines and tissue specimens. Several cell models were used to investigate FGFR1 inhibition in vitro and in combination with cisplatin and irradiation. Mouse intraperitoneal xenotransplant models were used for in vivo validation.

  Measurements And Main Results: FGFR1, FGF2, and FGF18 were overexpressed in mesothelioma. Stimulation with FGF2 led to increased cell proliferation, migration, and transition to a more sarcomatoid phenotype in subsets of mesothelioma cell lines. In contrast, inhibition of FGFR1 by a specific kinase inhibitor or a dominant-negative FGFR1 construct led to significantly decreased proliferation, clonogenicity, migration, spheroid formation, and G1 cell cycle arrest in several mesothelioma cell lines, accompanied by apoptosis induction and decreased mitogen-activated protein kinase pathway activity. Reduced tumor growth, proliferation, mitogenic signaling, and apoptosis induction were observed in vivo. Inhibition of FGFR1 synergistically enhanced the cytotoxic effects of ionizing radiation and cisplatin.

  Conclusions: Our data suggest that the malignant phenotype of mesothelioma cells depends on intact FGF signals, which should be considered as therapeutic targets with a promising chemo- and radiosensitizing potential.

• Reply: To PMID 23590275. S. Markowitz, A. Morabia, A. Miller. 2014;189(1):116-7. Letter · Comment PubMed · Publisher

• Asbestos and lung cancer: what we know. J.R. Balmes. 2013;188(1):8-9. Editorial · Comment PubMed · Publisher

  Summary

  This editorial commented on a study of the North American insulator cohort by Markowitz and colleagues, published in the same journal issue. The author noted continuing controversy over three questions: whether asbestos exposure increases lung cancer risk in nonsmokers, whether asbestosis is a necessary precondition for asbestos-related lung cancer, and how asbestos exposure and smoking interact. He reviewed earlier work by Irving Selikoff's group. A 1968 report on 370 New York insulators estimated more than a 90-fold increased risk of lung cancer death in those with both exposures. Later reports on 17,800 union insulators showed a greater than fourfold increased risk. These studies had been criticized for comparing insulators with the U.S. general population and for not adjusting for smoking. The new study followed 2,377 insulators with chest X-ray, spirometric, occupational and smoking data from 1981 to 1983, and compared them with 54,237 non-asbestos-exposed blue-collar workers from an American Cancer Society cohort. From 1981 to 2008, there were 18 lung cancer deaths among 468 nonsmoking insulators, a 3.6-fold increased risk. Combined asbestos exposure and smoking was associated with a 14-fold increase. Asbestosis doubled the risk in nonsmokers and was associated with a 37-fold increase in smokers. The author defended Selikoff's work. He concluded that asbestos alone can cause lung cancer, that asbestos and smoking together carry an at least additive risk, that asbestosis further increases risk, and that quitting smoking substantially lowers the risk.

  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.

• Asbestos, asbestosis, smoking, and lung cancer. New findings from the North American insulator cohort. S.B. Markowitz, S.M. Levin, A. Miller, et al. 2013;188(1):90-6. PubMed · Publisher

  Abstract

  Rationale: Asbestos, smoking, and asbestosis increase lung cancer risk in incompletely elucidated ways. Smoking cessation among asbestos-exposed cohorts has been little studied.

  Objectives: To measure the contributions of asbestos exposure, asbestosis, smoking, and their interactions to lung cancer risk in an asbestos-exposed cohort and to describe their reduction in lung cancer risk when they stop smoking.

  Methods: We examined lung cancer mortality obtained through the National Death Index for 1981 to 2008 for 2,377 male North American insulators for whom chest X-ray, spirometric, occupational, and smoking data were collected in 1981 to 1983 and for 54,243 non-asbestos-exposed blue collar male workers from Cancer Prevention Study II for whom occupational and smoking data were collected in 1982.

  Measurements And Main Results: Lung cancer caused 339 (19%) insulator deaths. Lung cancer mortality was increased by asbestos exposure alone among nonsmokers (rate ratio = 3.6 [95% confidence interval (CI), 1.7-7.6]), by asbestosis among nonsmokers (rate ratio = 7.40 [95% CI, 4.0-13.7]), and by smoking without asbestos exposure (rate ratio = 10.3 [95% CI, 8.8-12.2]). The joint effect of smoking and asbestos alone was additive (rate ratio = 14.4 [95% CI, 10.7-19.4]) and with asbestosis, supra-additive (rate ratio = 36.8 [95% CI, 30.1-45.0]). Insulator lung cancer mortality halved within 10 years of smoking cessation and converged with that of never-smokers 30 years after smoking cessation.

  Conclusions: Asbestos increases lung cancer mortality among nonsmokers. Asbestosis further increases the lung cancer risk and, considered jointly with smoking, has a supra-additive effect. Insulators benefit greatly by quitting smoking.

• No indication that mineral wool causes mesothelioma. J.P. Bonde. 2013;188(7):873. Letter · Comment PubMed · Publisher

  Summary

  This item is a letter to the editor with a reply from the author of the study it criticizes. Jens Peter Bonde of Bispebjerg University Hospital, Copenhagen, commented on a French case-control study by Lacourt and coworkers. That study concluded that occupational mineral wool exposure seemed to be associated with pleural mesothelioma and that mineral wool and asbestos might have a synergistic joint effect. Bonde wrote that this finding was surprising given previous evidence, citing a study by Kjaerheim and colleagues of lung cancer among rock and slag wool production workers. He noted that cases came from a hospital-based case-control study (1987–1996) and from the French National Mesothelioma Surveillance Program (1998–2006), while references came from two population-based samples from the French Institute for Public Health Surveillance. He argued that this violated the principle that controls must be drawn from the same study base as the cases. He also argued that the higher prevalence of blue-collar workers among cases showed that matching on socioeconomic group had failed. Finally, he said that exposures to asbestos, mineral wool and silica were too highly correlated to separate their effects, and he concluded that these concerns undermined the study's conclusions. In reply, Aude Lacourt stated that comparing mesothelioma results with a lung cancer study was irrelevant. She said cases and controls came from the same general-population source and that the two case sets did not differ significantly by socioeconomic status. She added that controls were deliberately not matched on socioeconomic status, to avoid overmatching. She said the original article had discussed exposure correlations, had not stated that mineral wool causes mesothelioma, and had called for further studies.

  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.

• Pleural mesothelioma and occupational coexposure to asbestos, mineral wool, and silica. A. Lacourt, C. Gramond, S. Audignon, et al. 2013;187(9):977-82. PubMed · Publisher

  Abstract

  Rationale: Occupational coexposure to asbestos and other fibers or particles could modify the carcinogenicity of asbestos with regard to pleural mesothelioma.

  Objectives: To estimate associations between pleural mesothelioma and occupational mineral wool and silica exposure and to study the impact of occupational coexposure on the risk of pleural mesothelioma.

  Methods: A total of 1,199 male cases and 2,379 control subjects were included in a French pooled case-control study. Complete job histories were collected, and occupational exposure to asbestos, mineral wool (MW), and silica were assessed by three French job exposure matrices. Unconditional logistic regression models adjusted for age, birth date, and occupational asbestos exposure were used to estimate odds ratios (OR) and 95% confidence intervals (CIs).

  Measurements And Main Results: A significant association between mesothelioma and MW exposure was observed after adjustment for occupational asbestos exposure. OR for subjects exposed to less than 0.01 fibers·ml(-1)·yr(-1) was 1.6 (95% CI, 1.2-2.1) and increased to 2.5 (95% CI, 1.8-3.4) for subjects exposed to more than 0.32 fibers·ml(-1)·yr(-1). All ORs for silica exposure were around the null. Coexposure to either asbestos and MW or asbestos and silica seemed to increase the risk of pleural mesothelioma. ORs were 17.6 (95% CI, 11.8-26.2) and 9.8 (95% CI, 4.2-23.2) for subjects exposed to both asbestos and MW and for subjects exposed to both asbestos and silica, respectively, compared with 4.3 (95% CI, 1.9-9.8) for occupational asbestos exposure alone.

  Conclusions: Our results are in favor of an increased risk of pleural mesothelioma for subjects exposed to both asbestos and MW or asbestos and silica.

• Reply: No indication that mineral wool causes mesothelioma. A. Lacourt. 2013;188(7):873-4. Letter · Comment PubMed · Publisher

• A₃ receptors are overexpressed in pleura from patients with mesothelioma and reduce cell growth via Akt/nuclear factor-κB pathway. K. Varani, S. Maniero, F. Vincenzi, et al. 2011;183(4):522-30. PubMed · Publisher

  Abstract

  Rationale: A strong link has been established between exposure to asbestos and increased risk for pleural malignant mesothelioma (MM). Adenosine plays a key role in inflammatory processes and cancer, where it is involved in the regulation of cell death and proliferation.

  Objectives: The primary aim of this study was to investigate the presence of adenosine receptors (ARs) in human MM pleura (MMP) and healthy mesothelial pleura (HMP). To shed some light on the interaction between adenosine and MM, the presence and functionality of ARs were explored in human healthy mesothelial cells (HMC) and in malignant mesothelioma cells (MMC).

  Methods: ARs were analyzed by using reverse transcriptase-polymerase chain reaction, Western blotting, and saturation binding assays. HMC were treated with crocidolite asbestos, which is the principal risk factor for MM. The role of A₃ ARs on these cellular models, evaluating cAMP production, Akt phosphorylation, and nuclear factor (NF)-κB activation, was investigated. The dual effect of A₃AR stimulation on healthy and cancer cell growth was studied by means of proliferation, apoptosis, and cytotoxicity assays.

  Measurements And Main Results: A₃AR was up-regulated by 2.5-fold (P < 0.01) in MMP when compared with HMP. Stimulation of A₃ARs decreased proliferation and exerted a cytotoxic and proapoptotic effect on MMC and on HMC exposed to asbestos and tumor necrosis factor-α, but not on HMC with an involvement of the deregulation of Akt/NF-κB cell survival pathway.

  Conclusions: These new findings suggest that A₃AR could represent a pharmacological target to prevent tumor development after asbestos exposure and to treat full-blown MM.

• Possible relationship between asbestos exposure and bronchial asthma: a need for clarification. M. Toyoshima, K. Chida, T. Suda, et al. 2011;183(11):1571-2; author reply 1572. Comment · Letter PubMed · Publisher

• Update in lung cancer and oncological disorders 2010. B. Halmos, C.A. Powell. 2011;184(3):297-302. PubMed · Publisher · Free full text

  Summary

  This narrative review summarized recent research on lung cancer and mesothelioma, as an update for 2010. The authors noted that lung cancer remains the leading cause of cancer death worldwide, with 157,000 U.S. deaths expected in 2010, and that tobacco smoke accounts for 90% of cases. They described studies of other exposures, including a pooled analysis of 11 case-control studies that found an odds ratio of 1.31 for occupational diesel motor exhaust exposure. They also described genetic susceptibility variants. They reported initial findings of the National Lung Screening Trial, which assigned 54,000 current and former smokers to low-dose CT or chest X-ray screening and showed a 20.3% reduction in lung cancer mortality in the CT arm. Further sections covered a new adenocarcinoma classification, mediastinal staging, mouse models of pathogenesis, treatment of early-stage disease, early palliative care, chemotherapy in the elderly, and therapies targeted to histology, EGFR mutations and ALK translocations. A section on mesothelioma stated that the disease is caused by exposure to amphibole asbestos. It reviewed serum biomarkers tested in 507 subjects (area under the curve 0.87 for soluble mesothelin and 0.85 for megakaryocyte potentiating factor), a trimodality trial with a 42% success rate, and early dendritic cell immunotherapy. The authors concluded that smoking prevention, CT screening and personalized treatment will significantly reduce lung cancer mortality.

  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.

• Diagnostic performance of soluble mesothelin and megakaryocyte potentiating factor in mesothelioma. K. Hollevoet, K. Nackaerts, J. Thimpont, et al. 2010;181(6):620-5. PubMed · Publisher

  Abstract

  Rationale: Soluble mesothelin (SM) is currently the reference serum biomarker of malignant pleural mesothelioma (MPM). Megakaryocyte potentiating factor (MPF), which originates from the same precursor protein, is potentially more sensitive, yet lacks validation.

  Objectives: To analyze the diagnostic performance of MPF as an MPM biomarker and compare this performance with SM.

  Methods: A total of 507 participants were enrolled in six cohorts: healthy control subjects (n = 101), healthy asbestos-exposed individuals (n = 89), and patients with benign asbestos-related disease (n = 123), benign respiratory disease (n = 46), lung cancer (n = 63), and MPM (n = 85). Sera were analyzed for SM and MPF levels using the Mesomark and Human MPF ELISA kit, respectively.

  Measurements And Main Results: SM and MPF levels differed significantly between patients with MPM and participants from each other cohort (P < 0.001). Receiver operating characteristics curve analysis did not reveal a significant difference between both markers in area under curve (AUC) for distinguishing MPM from all cohorts jointly (SM = 0.871, MPF = 0.849; P = 0.28). At 95% specificity, SM and MPF had a sensitivity of 64% (cutoff = 2.00 nmol/L) and 68% (cutoff = 12.38 ng/ml), respectively. Combining both markers did not improve the diagnostic performance.

  Conclusions: In this prospective multicenter study, MPF is validated as a highly performant MPM biomarker. The similar AUC values of SM and MPF, together with the limited difference in sensitivity, show that both serum biomarkers have an equivalent diagnostic performance.

• Does asbestos exposure (asbestosis) cause (clinical) airway obstruction (small airway disease)?. A. Miller, W.N. Rom. 2010;182(4):444-5. Comment · Editorial PubMed · Publisher

• Does asbestos exposure cause airway obstruction, in the absence of confirmed asbestosis?. J. Ameille, M. Letourneux, C. Paris, et al. 2010;182(4):526-30. PubMed · Publisher

  Abstract

  Rationale: Whether occupational exposure to asbestos causes airway obstruction remains controversial.

  Objectives: This study evaluated lung function in relation to cumulative exposure to asbestos in a large cohort of retired or unemployed workers exposed to asbestos.

  Methods: The study population consisted of 3,660 volunteer subjects. An individual cumulative exposure index to asbestos was calculated for each subject, and information was obtained on smoking status. Pulmonary function tests were performed in all subjects; high-resolution chest computed tomography was also performed in 3,335 subjects.

  Measurements And Main Results: Values of FEV(1)/FVC and FEF(25-75%) did not differ between five classes (quintiles) of cumulative exposure to asbestos, and no significant correlation was observed between cumulative exposure to asbestos and pulmonary function parameters, after adjustment for sex, tobacco consumption, emphysema, and body mass index. Furthermore, the proportion of abnormal pulmonary function tests did not differ between the five classes of cumulative exposure to asbestos.

  Conclusions: The results do not support a causal relationship between asbestos exposure alone and airway obstruction. However, the study sample may not be representative of all people occupationally exposed to asbestos, because a fraction of subjects with previously diagnosed asbestosis probably did not participate in this screening program.

2000s

• Airborne environmental exposure to asbestos. A. Hansell. 2008;178(6):556-7. Comment · Editorial PubMed · Publisher

• Gremlin-mediated decrease in bone morphogenetic protein signaling promotes pulmonary fibrosis. M. Myllärniemi, P. Lindholm, M.J. Ryynänen, et al. 2008;177(3):321-9. PubMed · Publisher · Free full text

  Abstract

  Rationale: Members of the transforming growth factor (TGF)-beta superfamily, including TGF-betas and bone morphogenetic proteins (BMPs), are essential for the maintenance of tissue homeostasis and regeneration after injury. We have observed that the BMP antagonist, gremlin, is highly up-regulated in idiopathic pulmonary fibrosis (IPF).

  Objectives: To investigate the role of gremlin in the regulation of BMP signaling in pulmonary fibrosis.

  Methods: Progressive asbestos-induced fibrosis in the mouse was used as a model of human IPF. TGF-beta and BMP expression and signaling activities were measured from murine and human fibrotic lungs. The mechanism of gremlin induction was analyzed in cultured lung epithelial cells. In addition, the possible therapeutic role of gremlin inhibition was tested by administration of BMP-7 to mice after asbestos exposure.

  Measurements And Main Results: Gremlin mRNA levels were up-regulated in the asbestos-exposed mouse lungs, which is in agreement with the human IPF biopsy data. Down-regulation of BMP signaling was demonstrated by reduced levels of Smad1/5/8 and enhanced Smad2 phosphorylation in asbestos-treated lungs. Accordingly, analyses of cultured human bronchial epithelial cells indicated that asbestos-induced gremlin expression could be prevented by inhibitors of the TGF-beta receptor and also by inhibitors of the mitogen-activated protein kinase kinase/extracellular signal-regulated protein kinase pathways. BMP-7 treatment significantly reduced hydroxyproline contents in the asbestos-treated mice.

  Conclusions: The TGF-beta and BMP signaling balance is important for lung regenerative events and is significantly perturbed in pulmonary fibrosis. Rescue of BMP signaling activity may represent a potential beneficial strategy for treating human pulmonary fibrosis.

• Low-level fiber-induced radiographic changes caused by Libby vermiculite: a 25-year follow-up study. A.M. Rohs, J.E. Lockey, K.K. Dunning, et al. 2008;177(6):630-7. PubMed · Publisher · Free full text

  Abstract

  Rationale: From 1921 to 1990, vermiculite ore from Libby, Montana, was shipped worldwide for commercial and residential use. A 1980 study of a manufacturing facility using Libby vermiculite was the first to demonstrate a small but significant prevalence of pleural chest radiographic changes associated with amphibole fibers contained in the ore.

  Objectives: This follow-up study of the original cohort evaluated the extent of radiographic changes and cumulative fiber exposure (CFE) 25 years after cessation of exposure.

  Methods: From the original cohort of 513 workers, 431 (84%) were living and available for participation and exposure reconstruction. Of these, 280 (65%) completed both chest radiographs and interviews. Primary outcomes were pleural and/or interstitial changes.

  Measurements And Main Results: Pleural and interstitial changes were demonstrated in 80 (28.7%) and 8 (2.9%) participants, respectively. Of those participants with low lifetime CFE of less than 2.21 fiber/cc-years, 42 (20%) had pleural changes. A significant (P < 0.001) exposure-response relationship of pleural changes with CFE was demonstrated, ranging from 7.1 to 54.3% from the lowest to highest exposure quartile. Removal of individuals with commercial asbestos exposure did not alter this trend.

  Conclusions: This study indicates that exposure within an industrial process to Libby vermiculite ore is associated with pleural thickening at low lifetime CFE levels. The propensity of the Libby amphibole fibers to dramatically increase the prevalence of pleural changes 25 years after cessation of exposure at low CFE levels is a concern in view of the wide national distribution of this ore for commercial and residential use.

• Mapping the risk of mesothelioma due to neighborhood asbestos exposure. N. Kurumatani, S. Kumagai. 2008;178(6):624-9. PubMed · Publisher

  Abstract

  Rationale: Little is known about neighborhood exposure to asbestos and mesothelioma risk among residents around an industrial source of asbestos.

  Objectives: To investigate the magnitude of the risk among residents by asbestos exposure levels and to determine the range of the area affected by asbestos.

  Methods: We calculated standardized mortality ratios of mesothelioma from 1995 to 2006 among the estimated population at risk that lived around a former large asbestos cement pipe plant in Amagasaki City, Japan, between 1957 and 1975, the time when the plant had used crocidolite and chrysotile. The distance between the plant and homes and relative asbestos concentrations obtained by diffusion equations involving meteorological conditions were used to determine asbestos exposure levels among residents.

  Measurements And Main Results: We identified 73 mesothelioma deaths of 35 men and 38 women who had no occupational exposure to asbestos. Among persons who had lived within a 300-m radius of the plant, the standardized mortality ratio of mesothelioma was 13.9 (95% confidence interval, 5.6-28.7) for men and 41.1 (95% confidence interval, 15.2-90.1) for women. When the study area was divided into five regions by relative asbestos concentration, standardized mortality ratios of mesothelioma declined, for both sexes, in a linear dose-dependent manner with concentration. The regions with a significantly elevated standardized mortality ratio reached 2,200 m from the plant in the same direction in which the wind predominantly blew.

  Conclusions: Neighborhood exposure to asbestos can pose a serious risk to residents across a wide area.

• Screening for mesothelioma: more harm than good?. J.P. van Meerbeeck, G. Hillerdal. 2008;178(8):781-2. Comment · Editorial PubMed · Publisher

  Summary

  This editorial commented on a study by Park and colleagues, published in the same journal issue, that measured soluble mesothelin-related protein (SMRP) by ELISA in people occupationally exposed to asbestos. The authors noted that malignant pleural mesothelioma (MPM) is a rare tumor mainly associated with earlier occupational asbestos exposure. Its latency is usually 3 to 5 decades, and average survival after diagnosis is less than 1 year. They reviewed earlier work. Low-dose spiral CT screening had been hindered by the low prevalence of the disease and by frequent nonmalignant nodules. A retrospective series of people exposed to crocidolite from the Wittenoom mine in Western Australia had reported a specificity of 100% and a sensitivity of 84% for SMRP in diagnosing mesothelioma. In the Park study of 538 asbestos-exposed persons, no mesothelioma was observed, although 15 (almost 3%) had elevated SMRP levels. Investigation with PET-CT detected one lung cancer and one suspected cardiac tumor. The editorialists judged the test's specificity to be low, with many false positives, and argued that screening for mesothelioma was not worthwhile. They noted there was no proof that early discovery would cure patients or improve survival, and they called for randomized treatment studies. They concluded that SMRP probably has a role in monitoring patients with MPM, but that it should be avoided for screening pending the results of ongoing large prospective studies.

  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.

• Soluble mesothelin-related protein in an asbestos-exposed population: the dust diseases board cohort study. E.K. Park, A. Sandrini, D.H. Yates, et al. 2008;178(8):832-7. PubMed · Publisher

  Abstract

  Rationale: Soluble mesothelin-related protein (SMRP) is raised in epithelial-type malignant mesothelioma (MM), but the utility of SMRP in screening for MM is unknown.

  Objectives: We aimed to evaluate SMRP in an asbestos-exposed cohort.

  Methods: A total of 538 subjects were studied. Those with elevated SMRP (> or =2.5 nM) underwent further investigation including positron emission tomography/computed tomography.

  Measurements And Main Results: Mean (+/-SD) SMRP in healthy subjects exposed to asbestos (n = 223) was 0.79 (+/-0.45) nM. Fifteen subjects had elevated SMRP, of whom one had lung cancer, which was successfully resected. Another with lung cancer was undetected by SMRP. No subjects were diagnosed with MM. Mean SMRP in healthy subjects was significantly lower than in subjects with pleural plaques alone (P < 0.01).

  Conclusions: This is the first large-scale prospective study of SMRP for screening for malignancy in asbestos-exposed individuals. A high false-positive rate was observed. SMRP seems unlikely to prove useful in screening for MM.

• Thinking longitudinally in a cross-sectional world. G.R. Wagner. 2008;177(6):565-6. Comment · Editorial PubMed · Publisher

• Engraftment of bone marrow progenitor cells in a rat model of asbestos-induced pulmonary fibrosis. J.L. Spees, D.A. Pociask, D.E. Sullivan, et al. 2007;176(4):385-94. PubMed · Publisher · Free full text

  Abstract

  Rationale: Bone marrow-derived cells have been shown to engraft during lung fibrosis. However, it is not known if similar cells engraft consequent to inhalation of asbestos fibers that cause pulmonary fibrosis, or if the cells proliferate and differentiate at sites of injury.

  Objectives: We examined whether bone marrow-derived cells participate in the pulmonary fibrosis that is produced by exposure to chrysotile asbestos fibers.

  Methods: Adult female rats were lethally irradiated and rescued by bone marrow transplant from male transgenic rats ubiquitously expressing green fluorescent protein (GFP). Three weeks later, the rats were exposed to an asbestos aerosol for 5 hours on three consecutive days. Controls were bone marrow-transplanted but not exposed to asbestos.

  Measurements And Main Results: One day and 2.5 weeks after exposure, significant numbers of GFP-labeled male cells had preferentially migrated to the bronchiolar-alveolar duct bifurcations, the specific anatomic site at which asbestos produces the initial fibrogenic lesions. GFP-positive cells were present at the lesions as monocytes and macrophages, fibroblasts, and myofibroblasts or smooth muscle cells. Staining with antibodies to PCNA demonstrated that some of the engrafted cells were proliferating in the lesions and along the bronchioles. Negative results for TUNEL at the lesions confirmed that both PCNA-positive endogenous pulmonary cells and bone marrow-derived cells were proliferating rather than undergoing apoptosis, necrosis, or DNA repair.

  Conclusions: Bone marrow-derived cells migrated into developing fibrogenic lesions, differentiated into multiple cell types, and persisted for at least 2.5 weeks after the animals were exposed to aerosolized chrysotile asbestos fibers.

• Residential proximity to naturally occurring asbestos and mesothelioma risks: further consideration of exposure misclassification and occupational confounding. M.A. Kelsh, D.W. Berman, A.M. Langer. 2006;174(12):1400; author reply 1400-1. Comment · Letter PubMed · Publisher

• Residential proximity to naturally occurring asbestos: health risk or ecologic fallacy?. C.A. Brodkin, J.R. Balmes, C.A. Redlich, et al. 2006;173(5):573; author reply 573-4. Comment · Letter PubMed · Publisher

  Summary

  This correspondence commented on a study by Pan and colleagues that used digital geologic mapping to examine residential proximity to naturally occurring asbestos (NOA) and mesothelioma risk in California. The letter writers argued that two limitations of the study design did not allow a causal association to be determined. First, the study used home address at diagnosis and did not account for the long latency of mesothelioma. They cited the CARET cohort, in which 4,060 asbestos-exposed participants, with 23 mesothelioma cases, had a mean of 35 years since first asbestos exposure. They said this was likely to cause exposure misclassification, for example a shipyard worker who retires near an NOA source. Second, distance to an NOA source was not a direct measure of exposure, so the study had the limitations of an ecologic study. They noted that ambient exposures are typically orders of magnitude below occupational levels, and that fibres must be airborne to cause disease. They concluded that the findings should be considered hypothesis generating, but that caution should also be applied to large-scale home development in NOA areas. In reply, the original authors agreed that the lack of lifetime residential history was a limitation. They reported an unpublished analysis showing no differential movement of former asbestos union members from the San Francisco Bay Area to counties with more NOA. They also suggested a prospective case-control study.

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• Soluble mesothelin-related peptides in the diagnosis of malignant pleural mesothelioma. A. Scherpereel, B. Grigoriu, M. Conti, et al. 2006;173(10):1155-60. PubMed · Publisher

  Abstract

  Background: Diagnosis of malignant pleural mesothelioma is a challenging issue. Potential markers in mesothelioma diagnosis include soluble mesothelin-related peptides (SMRPs) and osteopontin, but no subsequent validation has been published yet.

  Methods: We prospectively evaluated SMRPs in serum and pleural effusion from patients with mesothelioma (n = 74), pleural metastasis of carcinomas (n = 35), or benign pleural lesions associated with asbestos exposure (n = 28), recruited when first suspected for mesothelioma.

  Findings: Mean serum SMRP level was higher in patients with mesothelioma (2.05 +/- 2.57 nM/L [median +/- interquartile range]) than in patients with metastasis (1.02 +/- 1.79 nM/L) or benign lesions (0.55 +/- 0.59 nM/L). The area under the receiver operating characteristic curve (AUC) for serum SMRP was 0.872 for differentiating mesothelioma and benign lesions, cut-off = 0.93 nM/L (sensitivity = 80%, specificity = 82.6%). The AUC for serum SMRP differentiating metastasis and mesothelioma was 0.693, cut-off = 1.85 nM/L (sensitivity = 58.3%, specificity = 73.3%). SMRP values in pleural fluid were higher than in serum in all groups (mesothelioma: 46.1 +/- 83.2 nM/L; benign lesions: 6.4 +/- 11.1 nM/L; metastasis: 6.36 +/- 21.73 nM/L). The AUC for pleural SMRP-differentiating benign lesions and mesothelioma was 0.831, cut-off = 10.4 nM/L (sensitivity = 76.7%, specificity = 76.2%). The AUC for pleural SMRP-differentiating metastasis and mesothelioma was 0.793.

  Interpretation: We show that SMRPs may be a promising marker for mesothelioma diagnosis when measured either in serum or pleural fluid. The diagnostic value of SMRPs was similar in both types of samples, but pleural fluid SMRPs may better discriminate mesothelioma from pleural metastasis.

• 2004 asbestos disease guidelines ignore mass screening abuse. L. Martin. 2005;171(6):665; author reply 666-7. Comment · Letter PubMed · Publisher

• Can exposure to very low levels of asbestos induce pleural mesothelioma?. M. Goldberg, D. Luce. 2005;172(8):939-40. Comment · Editorial · Review PubMed · Publisher

  Summary

  In this editorial, the authors commented on a study by Pan and coworkers, in the same journal issue, of residential proximity to naturally occurring asbestos and mesothelioma risk in California. They noted that most mesotheliomas in industrialized countries were caused by occupational exposure. People could also be exposed through household contact with asbestos workers, near industrial sources, in buildings containing asbestos, and from natural geological sources. Earlier studies in rural areas of Turkey, Greece, some Mediterranean islands, China and New Caledonia had indicated that exposure from birth did not seem to affect mesothelioma latency and that susceptibility did not differ by sex. Whether low-level exposure could cause pleural mesothelioma remained controversial, because exposures in those studies may have been high and were not adequately measured. The authors considered the Pan study the first to show quite convincingly an excess risk of pleural mesothelioma even at long distances from the asbestos source. Its limitations were partial accounting for occupational exposure, no residential history, no cases under 35 years, and indirect exposure assessment. Its strengths were register-based selection of a very large number of cases, precise geocoding, and a linear distance–risk relationship that was similar in men and women. Peritoneal mesothelioma risk was not related to distance. The authors wrote that this supported the hypothesis that very low asbestos levels may cause pleural mesothelioma. They called for assessment of cumulative exposure levels in affected areas.

  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.

• Diagnosis and initial management of nonmalignant diseases related to asbestos. D. Weill, H. Weill. 2005;171(5):527-8; author reply 528-30. Comment · Letter PubMed · Publisher

  Summary

  In this letter, Weill and Weill argued that the 2004 American Thoracic Society (ATS) Statement on the diagnosis and initial management of nonmalignant asbestos-related diseases did not fully consider alternative views and the available literature. They addressed two issues. On pleural plaques, they said the Statement relied on two studies with known weaknesses. It omitted a prospective study of asbestos cement workers in which plaques without asbestosis were not associated with increased lung cancer risk, and a meta-analysis by Weiss reaching a similar view. They added that it did not address whether asbestosis is required to attribute lung cancer to asbestos. On airway disease, they said the cited studies lacked dose-response data and did not control for smoking, radiographic abnormalities and age, and that the Statement was internally inconsistent. They agreed that asbestos can cause small airway abnormalities but said these changes lack proven clinical importance. The authors disclosed consulting and testifying in occupational lung disease litigation. In reply, the Committee said the Statement updated clinical diagnostic criteria and was not a comprehensive review or a review of cancer causation. It said Weiss's 1993 review did not address the question the Statement considered, and that a review of 10 studies and later studies supported plaques as a risk marker. It said it had described the airway effect as "relatively small" and invited a point-by-point rebuttal. The reply also answered a separate letter by Ghio and Roggli on smoking and small opacities.

  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.

• Diagnosis and initial management of nonmalignant diseases related to asbestos. D.D. Smith. 2005;171(6):665-6; author reply 666-7. Comment · Letter PubMed · Publisher

  Summary

  In this letter, Dorsett D. Smith (University of Washington, Seattle) argued that the American Thoracic Society's 2004 official statement on the diagnosis and initial management of nonmalignant asbestos-related diseases contained statements not supported by the literature, many of them conflicting or inaccurate. He quoted passages on subjective symptoms and exposure histories, on pleural plaques as indicators of increased risk of future asbestosis, on asbestos and airway obstruction, and on the chest film as adequate for diagnosis. He argued that patient histories and subjective symptoms are unreliable, particularly in legal proceedings; that pleural plaques are evidence of exposure and do not indicate a greatly increased risk of asbestos-related disease compared with equally exposed workers without visible plaques; that the implication that asbestos contributes to clinically significant COPD is not supportable; and that the role of ILO B-reader chest X-ray interpretation had come into question. He disclosed that he had been an expert witness for the defense in asbestos litigation. In a reply that also answered a letter from Lawrence Martin, the ATS committee said the passages made reasonable distinctions and stood by its text on plaques. It noted that the statement described the asbestos effect on airways as possibly clinically significant in the presence of low lung function. It pointed out that the B-reader program belongs to NIOSH, not the ILO, and said the guidelines were intended for clinical diagnosis and patient care.

  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.

• Diagnosis and initial management of nonmalignant diseases related to asbestos. A.J. Ghio, V.L. Roggli. 2005;171(5):527; author reply 528-30. Letter · Comment PubMed · Publisher

• Noninvasive mechanical ventilation for asbestos-induced ventilatory failure. X. Munoz, S. Martí, J. Ferrer. 2005;172(6):785-6. Comment · Letter PubMed · Publisher

• Residential proximity to naturally occurring asbestos and mesothelioma risk in California. X.L. Pan, H.W. Day, W. Wang, et al. 2005;172(8):1019-25. PubMed · Publisher · Free full text

  Abstract

  Rationale: Little is known about environmental exposure to low levels of naturally occurring asbestos (NOA) and malignant mesothelioma (MM) risk.

  Objectives: To conduct a cancer registry-based case control study of residential proximity to NOA with MM in California.

  Methods: Incident MM cases (n = 2,908) aged 35 yr or more, diagnosed between 1988 and 1997, were selected from the California Cancer Registry and frequency matched to control subjects with pancreatic cancer (n = 2,908) by 5-yr age group and sex. Control subjects were selected by stratified random sampling from 28,123 incident pancreatic cancers in the same time period. We located 93.7% of subjects at the house or street level at initial diagnosis. Individual occupational exposure to asbestos was derived from the longest held occupation, available for 74% of MM cases and 63% of pancreatic cancers. Occupational exposure to asbestos was determined by a priori classification and confirmed by association with mesothelioma.

  Main Results: The adjusted odds ratios and 95% confidence interval for low, medium, and high probabilities of occupational exposures to asbestos were 1.71 (1.32-2.21), 2.51 (1.91-3.30), and 14.94 (8.37-26.67), respectively. Logistic regression analysis from a subset of 1,133 mesothelioma cases and 890 control subjects with pancreatic cancer showed that the odds of mesothelioma decreased approximately 6.3% for every 10 km farther from the nearest asbestos source, an odds ratio of 0.937 (95% confidence interval = 0.895-0.982), adjusted for age, sex, and occupational exposure to asbestos.

  Conclusions: These data support the hypothesis that residential proximity to NOA is significantly associated with increased risk of MM in California.

• Diagnosis and initial management of nonmalignant diseases related to asbestos. American Thoracic Society. 2004;170(6):691-715. Guideline PubMed · Publisher

• ATS, American Bar Association, and asbestos. J.J. Renn. 2003;168(11):1399-400; discussion 1400. Letter PubMed · Publisher

• Acute eosinophilic pneumonia in a New York City firefighter exposed to World Trade Center dust. W.N. Rom, M. Weiden, R. Garcia, et al. 2002;166(6):797-800. Case report PubMed · Publisher

  Abstract

  We report a sentinel case of acute eosinophilic pneumonia in a firefighter exposed to high concentrations of World Trade Center dust during the rescue effort from September 11 to 24. The firefighter presented with a Pa(O2) of 53 mm Hg and responded to oxygen and corticosteroids. Computed tomography scan showed patchy ground glass density, thickened bronchial walls, and bilateral pleural effusions. Bronchoalveolar lavage recovered 70% eosinophils, with only 1% eosinophils in peripheral blood. Eosinophils were not degranulated and increased levels of interleukin-5 were measured in bronchoalveolar lavage and serum. Mineralogic analysis counted 305 commercial asbestos fibers/10(6) macrophages including those with high aspect ratios, and significant quantities of fly ash and degraded fibrous glass. Acute eosinophilic pneumonia is a rare consequence of acute high dust exposure. World Trade Center dust consists of large particle-size silicates, but fly ash and asbestos fibers may be found in bronchoalveolar lavage cells.

• Fatal asbestosis 50 years after brief high intensity exposure in a vermiculite expansion plant. R.S. Wright, J.L. Abraham, P. Harber, et al. 2002;165(8):1145-9. Case report PubMed · Publisher

  Abstract

  The authors report the case of a 65-year-old accountant whose only asbestos exposure was during a summer job 50 years earlier in a California vermiculite expansion plant. Vermiculite is a silicate material that is useful in building and agriculture as a filler and insulating agent. He developed extensive fibrocalcific pleural plaques and end-stage pulmonary fibrosis, with rapidly progressive respiratory failure. Careful occupational and environmental history revealed no other source of asbestos exposure, and the initial clinical diagnosis was idiopathic pulmonary fibrosis; open lung biopsy shortly before his death confirmed asbestosis. Electron microscopic lung fiber burden analysis revealed over 8,000,000 asbestos fibers per gram dry lung, 68% of which were tremolite asbestos. Additional asbestiform fibers of composition not matching any of the standard asbestos varieties were also present at over 5,000,000 fibers per gram dry lung. Comparison analysis of a sample of Libby, Montana, vermiculite showed a similar mix of asbestiform fibers including tremolite asbestos. This case analysis raises several concerns: risks of vermiculite induced disease among former workers of the more than 200 expansion plants throughout the United States; health effects of brief but very high-intensity exposures to asbestos; and possible health effects in end-users of consumer products containing vermiculite.

• Occupational airborne exposure and the incidence of respiratory symptoms and asthma. T.M. Eagan, A. Gulsvik, G.E. Eide, et al. 2002;166(7):933-8. Randomized trial PubMed · Publisher

  Abstract

  Several prevalence studies have suggested an association between occupational exposure and respiratory symptoms and asthma, but there has been a lack of incidence studies to verify this. This study examined the incidence of respiratory symptoms and asthma in an 11-year Norwegian community cohort study with 2,819 subjects. Predictors examined were sex, age, educational level, lifetime exposure to quartz, asbestos, and dust or fumes, as well as smoking habits and pack-years. The prevalence of exposure to quartz, asbestos, and dust or fumes was, respectively, 3.7%, 5.0%, and 28.3% at baseline. In those exposed to dust or fumes, the odds ratios (95% confidence intervals) varied between 1.4 (1.1, 1.7) and 2.1 (1.3, 3.2) for developing respiratory symptoms or asthma after adjusting for sex, age, educational level, and smoking. Between 5.7% and 19.3% of the incidence of respiratory symptoms and 14.4% of the incidence of asthma were attributable to dust or fumes exposure after adjustment for sex, age, educational level, and smoking. In conclusion, airborne occupational exposure increases the incidence of respiratory symptoms and asthma, independent of sex, age, educational level, smoking habits, and pack-years.

• The "gold standard" for past asbestos exposure. J. Van Cleemput, H. De Raeve, J. Verschakelen, et al. 2002;165(1):134. Comment · Letter PubMed · Publisher

• Detailed occupational history: the cornerstone in diagnosis of asbestos-related lung disease. R. Bégin, J.W. Christman. 2001;163(3 Pt 1):598-9. Comment · Editorial PubMed · Publisher

  Summary

  This editorial commented on a study by Van Cleemput and colleagues published in the same issue. The authors noted that the dust burden in the lungs of exposed people cannot be measured directly and is best assessed, indirectly, by a detailed occupational history. They stated that bronchoalveolar lavage measurements of dust were less useful in asbestosis than in silicosis, and that high-resolution CT, though sensitive, was not yet a gold standard because an exposure–response relationship had not been clearly established. Van Cleemput and colleagues had used CT scanning to measure the surface area of localized pleural plaques in a group of asbestos workers and compared it with cumulative exposure calculated from workplace dust measurements. The editorialists highlighted the finding that plaque size and surface area did not correlate with the cumulative asbestos exposure index, the cumulative cigarette smoke exposure index, or lung function. They noted that pleural plaques without asbestosis have been associated with a 1.4-fold increased risk of lung carcinoma. They concluded that plaque extent should not be used as an index of cumulative asbestos exposure, although plaques remain a useful surrogate for past exposure. The gold standard remains the detailed work history. When that history is unclear, lung mineral fibre content, which requires an open lung biopsy, can help. They stated that the presence of asbestosis suggests cumulative exposure above 25 fibre·yr/cm3, but its absence does not establish lower exposure.

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• Pseudoasbestos bodies and fibers in bronchoalveolar lavage of refractory ceramic fiber users. P. Dumortier, I. Broucke, P. De Vuyst. 2001;164(3):499-503. PubMed · Publisher

  Abstract

  Refractory ceramic fibers (RCF) are widely used to replace asbestos in applications requiring high heat resistance. Ferruginous bodies mimicking asbestos bodies (ABs) have been detected in the lungs of RCF production workers. This raises the question about their presence in other occupational groups and whether "typical ABs" still reflect past asbestos exposures in all settings. An AB counting by phase-contrast light microscopy and a screening test by analytical electron microscopy were systematically performed on all bronchoalveolar lavage fluids (BALF) submitted to our laboratory in 1992 through 1997 (n = 1,800). When RCF were detected in electron microscopy, the structures considered as "typical ABs" were marked under light microscopy and prepared for further chemical and structural analysis. Pseudo-ABs on RCF were detected in samples from nine subjects (0.5%). All of them had worked either as foundry workers, steel workers, or welders. In these subjects, alumino-silicate fibers compatible with RCF accounted for 42% of the core fibers analyzed, other nonasbestos fibers for 28%, and asbestos fibers for 30%. ABs thus remain a valid marker of asbestos retention but attention must be paid to a possible occurrence of pseudo-asbestos bodies on RCF and other nonasbestos fibers in end-users of refractory fibers.

• Surface of localized pleural plaques quantitated by computed tomography scanning: no relation with cumulative asbestos exposure and no effect on lung function. J. Van Cleemput, H. De Raeve, J.A. Verschakelen, et al. 2001;163(3 Pt 1):705-10. PubMed · Publisher

  Abstract

  To evaluate if there is a relation between the size of asbestos plaques and the level of past exposure and pulmonary function, we measured the surface of localized pleural plaques found on high-resolution (HR) CT scan, using a computerized video display unit-imaging system, in 73 workers (mean age, 43.5 yr) who had worked from 23 to 27 yr in an asbestos-cement factory. Their estimated cumulative exposure to asbestos ranged from 16.4 to 98.7 fiber-years/ ml (mean, 26.3 fiber-years/ml). Lung function measurements included lung volumes, maximal expiratory flows, and diffusing capacity. A control group of 21 workers was examined by the same procedures. Plaques were detected by CT in 51 (70%) asbestos-exposed subjects and in none of the control subjects. The average calculated plaque surface was 47.9 +/- 61.7 cm2 (median, 22.1 cm2; range, 0 to 278.4 cm2). There was no relation between plaque surface and cumulative asbestos exposure (p = 0.24). In the 51 subjects with pleural plaques, the surface of the pleural lesions was not related to cumulative asbestos exposure, or to smoking history or time since first exposure. Neither the presence nor the extent of the plaques was correlated with lung function parameters.

• Chest pain in asbestos-exposed individuals with benign pleural and parenchymal disease. S. Mukherjee, N. de Klerk, L.J. Palmer, et al. 2000;162(5):1807-11. PubMed · Publisher

  Abstract

  Many asbestos-exposed individuals complain of chest pain for which there is no clear explanation. To determine whether chest pain is associated with the presence of benign pleural or parenchymal disease on chest radiograph, we studied 1,280 subjects undergoing surveillance because of prior asbestos exposure at Wittenoom, Western Australia. All subjects completed the Rose questionnaire on chest pain and this revealed 556 subjects (43%) who experienced some chest pain. A posterior-anterior chest radiograph was performed at the same clinic visit and was subsequently graded independently by two experienced readers for diffuse parenchymal disease and pleural disease. Logistic regression models adjusted for sex, age, and cumulative asbestos exposure indicated that the presence of chest pain was significantly associated with the presence of both benign pleural disease and diffuse parenchymal disease. Further analysis after stratification of chest pain into nonanginal and anginal pain showed that there was a significant association between anginal pain and the presence of pleural and parenchymal asbestos-induced radiologic abnormalities and an association of nonanginal pain with parenchymal disease. We conclude that radiographic evidence of either parenchymal or pleural disease in subjects exposed to asbestos is significantly related to the presence of chest pain, particularly anginal pain.

• Talc induces apoptosis in human malignant mesothelioma cells in vitro. N. Nasreen, K.A. Mohammed, P.A. Dowling, et al. 2000;161(2 Pt 1):595-600. PubMed · Publisher

  Abstract

  Pleurodesis with talc is an accepted method for the treatment of symptomatic pleural effusions secondary to mesotheliomas. Patients with mesothelioma who have talc-induced pleurodesis have a lower morbidity than do those who do not have pleurodesis. The mechanisms whereby talc mediated these effects were considered to be secondary to a decrease or absence of a pleural effusion. The possibility that talc may directly affect malignant cells was not considered. The present study was designed to evaluate if talc directly effects cell death of malignant mesothelioma cells (MMC) or normal pleural mesothelial cells (PMC). Three confluent MMC and PMC were exposed to talc for 24, 48, and 72 h. In parallel experiments, glass beads similar in size to talc were included as control. Apoptosis was determined by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) and DNA electrophoresis. Our results demonstrated that talc at a therapeutically achievable concentration (6 microg/cm(2)) induces significant apoptosis in MMC. Talc-induced maximum apoptosis in MMC (39.50 +/- 2.55%, 31.87 +/- 4.69%, and 15.10 +/- 3.93% in CRL-2081, CRL-5820, and CRL-5915, respectively) at 48 h, which was significantly (p < 0.05) greater than that in control cells. Electrophoresis of DNA isolated from talc-exposed MMC demonstrated the typical ladder pattern of internucleosomal DNA cleavage. Talc did not induce apoptosis in PMC, and glass beads did not cause significant apoptosis in either MMC or PMC. The present study has demonstrated that talc induces apoptosis in MMC without affecting normal mesothelial cells of the pleura.

1990s

• Effect of asbestos-related pleural fibrosis on excursion of the lower chest wall and diaphragm. B. Singh, P.R. Eastwood, K.E. Finucane, et al. 1999;160(5 Pt 1):1507-15. PubMed · Publisher

  Abstract

  To examine mechanisms responsible for reduced lung volumes (restriction) in asbestos-related pleural fibrosis (APF), we studied diaphragm function and lower rib-cage excursion in 26 subjects with previous asbestos exposure and no evidence of asbestosis. Using posteroanterior (PA) and lateral chest radiographs taken at residual volume and at 25%, 70%, and 100% vital capacity (VC) during a slow inspiratory maneuver, we measured fractional expansion of the lower rib cage (FErc), fractional shortening of the diaphragm (FSdi), and changes (Delta) in diaphragm dome height (Hdo) and subphrenic volume (Vdi). Vdi was estimated by measuring the major and minor axes of the subphrenic space at 1-cm intervals, assuming an elliptical cross-sectional shape, and correcting for the volume of spinal and paraspinal tissues. Seven subjects had no evidence of APF (control), 12 had pleural plaques (PP), and seven had diffuse pleural thickening with costophrenic obliteration (DPT). Over the range of VC, results (mean +/- SEM, normalized for height) in control subjects were VC = 101.2 +/- 4.0 % predicted and DeltaVdi = 326 +/- 8 ml/m(3), and for the right hemithorax and hemidiaphragm on the PA film, FErc = 0.07 +/- 0.02, FSdi = 0.32 +/- 0.02 and DeltaHdo = 0.8 +/- 0.2 cm/m. Relative to controls: DPT subjects had reduced VC (77.4 +/- 4.9%, p < 0.01), DeltaVdi (256 +/- 2 ml/m(3), p < 0.01), FErc (0.01 +/- 0.02, p < 0.01), FSdi (0.24 +/- 0.01, p < 0.001), and DeltaHdo (-0.9 +/- 0.06 cm/m, p < 0.01); PP subjects had reduced FSdi (0.25 +/- 0.01, p < 0.001) and DeltaVdi (233 +/- 47 ml/m(3), p < 0.01), and no difference in FErc, DeltaHdo, or VC. We conclude that restriction in DPT is due to obliteration of the zone of apposition, and that by limiting separation of the diaphragm from the rib cage during inspiration, this reduces volume contributed by motion of the diaphragm and lower rib cage. Reduction in the latter contribution was the main cause of restriction, because the reduction in volume contributed by the diaphragm was partly compensated by flattening of its dome.

• Assessment of environmental asbestos exposure in Turkey by bronchoalveolar lavage. P. Dumortier, L. Coplü, V. de Maertelaer, et al. 1998;158(6):1815-24. PubMed · Publisher

  Abstract

  Environmental or domestic exposure to asbestos fibers originating from local soil is responsible for a high incidence of diseases in large rural areas of Turkey. Bronchoalveolar lavage fluids (BALF) were obtained for 65 Turkish subjects originating from these areas and for 42 Turkish controls. Asbestos bodies (ABs) and uncovered fibers (UFs) were quantified by phase contrast light microscopy. Total fiber burden was determined by transmission electron microscopy. The main asbestos types disclosed were tremolite and to a lesser extent chrysotile. AB and fiber concentrations were higher in environmentally exposed subjects (geometric mean [geometric standard deviation]: 5.20 [6.22] AB/ml, 444 [11.6] tremolite fibers/ml) than in control subjects (0.22 [1.45] AB/ml, 12.0 [15.4] tremolite fibers/ml) (p < 0.001). In subjects environmentally exposed in Turkey, AB burdens on tremolite were in the same range as those on commercial amphiboles in subjects occupationally exposed in Belgium. In Turkish subjects, values above either 1 AB/ml, 3 uncovered fiber/ml in light microscopy, or 300 fibers/ml in electron microscopy indicated usually an abnormal alveolar retention reflecting a significant cumulative exposure from environmental or domestic origin. These observations are probably valid for other areas in the world where diseases associated with environmental exposure to soil- derived asbestos fibers occur and for immigrants originating from these areas.

• Association between diet and lung cancer location. B.W. Lee, J.C. Wain, K.T. Kelsey, et al. 1998;158(4):1197-203. PubMed · Publisher

  Abstract

  Lung cancers occur more commonly in the upper lobes than in the lower lobes, but its pathophysiologic basis is not well understood. Because numerous studies have reported a consistent inverse relationship between lung cancer risk and intake of certain vegetables and fruits, we hypothesized that the balance between diet-derived protective substances delivered via the circulation and cigarette-derived carcinogenic substances delivered via the airways would be less favorable in the upper lobes compared with the lower lobes, hence accounting for the upper lobe predominance of tumors among smokers. Thus, we examined the association between diet and tumor location in 328 patients with lung cancer. The ratio of upper to lower lobe tumors was 2.5:1.0. In univariate analysis, age, height, weight, sex, race, family history of cancer, education level, tumor histology, calories consumed per day, and intake of animal fat did not differ significantly between patients with upper versus lower lobe tumors. Predictors of tumor location in univariate analysis were family history of lung cancer; smoking history; history of asbestos exposure; and intakes of yellow-orange vegetables, alpha-carotene, beta-carotene, and vitamins A, C, and E. In multivariable logistic regression analysis, the independent predictors of upper lobe tumor location were family history of lung cancer (p = 0.03), history of asbestos exposure (p = 0.02), less intake of yellow-orange vegetables (p < 0.04), and less intake of vitamin E (p = 0.05). Our results show a strong inverse association between upper lobe location of lung cancer and intake of yellow-orange vegetables and vitamin E.

• Association of cigarette smoking and asbestos exposure with location and histology of lung cancer. B.W. Lee, J.C. Wain, K.T. Kelsey, et al. 1998;157(3 Pt 1):748-55. PubMed · Publisher

  Abstract

  Prior studies have suggested that lung cancers that arise in association with cigarette smoking favor an upper-lobe location while those associated with asbestos exposure favor a lower-lobe location. An excess of adenocarcinomas has also been reported among cases not exposed to cigarette smoke as well as among those exposed to asbestos. However, these studies typically have not adjusted adequately for potential confounders such as the patient's age, sex, race, or family history of cancer. To better examine the effects of cigarette smoking and asbestos exposure on location and histology of lung cancer, we analyzed data from a large case-control study that included 456 patients with stage I or II lung cancer. Patients with upper-lobe tumors tended to have had more exposure to tobacco as assessed by pack-years smoked (54.7 versus 46.2, p = 0.07) and less time since quitting smoking (3.0 versus 5.5 yr, p = 0.05). In contrast to some prior reports, asbestos exposure was also associated with an upper-lobe location of tumor. Among those with upper-lobe tumors, 14.6% had a history of significant asbestos exposure compared with 5.4% of those with lower-lobe tumors (p < 0.01). The relationship between asbestos exposure and upper-lobe location of tumor was also statistically significant whether stratified by smoking or analyzed by multivariable logistic regression modeling. Adenocarcinomas were more likely among those with less exposure to cigarette smoke based on fewer pack-years smoked (41.5 versus 61.8, p = 0.0001) and more time since quitting smoking (5.0 versus 3.0 yr, p = 0.02). The proportion of patients with significant exposure to asbestos was lower among those with adenocarcinomas but was not statistically significant (9.5 versus 15.3%, p = 0.09). In multivariable logistic regression analysis, longer time since smoking exposure remained a significant predictor of adenocarcinomas (p < 0.02), but history of asbestos exposure did not predict tumor histology. Thus, in patients with lung cancer, both cigarette smoking and asbestos exposure histories favor an upper-lobe location of tumor. Longer time since smoking exposure favors adenocarcinomas, but the history of asbestos exposure does not appear to influence the tumor histology.

• Cigarette smoking, asbestos exposure, lung cancer, and sample size. M.F. Petrini. 1998;158(5 Pt 1):1688. Comment · Letter PubMed · Publisher

• Environmental exposure to crocidolite and mesothelioma: exposure-response relationships. J. Hansen, N.H. de Klerk, A.W. Musk, et al. 1998;157(1):69-75. PubMed · Publisher

  Abstract

  This study aimed to estimate exposure-response relationships for mesothelioma and environmental exposure to crocidolite. All 4,659 former residents of Wittenoom, Western Australia (WA) who lived there between 1943 and 1993 for at least 1 mo and were not directly employed in the crocidolite industry, were followed-up through the WA death, cancer and mesothelioma registries, electoral rolls, and telephone books. In 1992, all subjects who should be traced were sent a questionnaire. Exposure levels were estimated from results of periodic environmental surveys and duration of residence. Incidence rates were standardized to the World Population and Cox Regression was used to estimate the effects of exposure on incidence. To the end of 1993, 27 cases of mesothelioma were diagnosed. Mesothelioma cases stayed longer at Wittenoom, had a higher average intensity of exposure, and a higher cumulative exposure to crocidolite than control subjects. The standardized incidence of mesothelioma was 260 per million person-years, and was similar for males and females. The rate increased significantly with time from first exposure, duration of exposure and cumulative exposure. At these levels of crocidolite exposure, there is a significantly increased risk of mesothelioma, which is dose-dependent.

• Mechanisms in the pathogenesis of asbestosis and silicosis. B.T. Mossman, A. Churg. 1998;157(5 Pt 1):1666-80. Review PubMed · Publisher

• Mineral dusts directly induce epithelial and interstitial fibrogenic mediators and matrix components in the airway wall. J. Dai, B. Gilks, K. Price, et al. 1998;158(6):1907-13. PubMed · Publisher

  Abstract

  Exposure to mineral dusts is associated with the development of chronic airflow obstruction, probably mediated in part by dust-induced fibrosis of the small airways. To investigate the mechanism of fibrosis, we exposed rat tracheal explants to amosite asbestos, iron oxide, or titanium dioxide. Explants were then maintained in air organ culture, and the expression of genes encoding for various mediators and matrix components assessed by reverse transcriptase-polymerase chain reaction (RT-PCR). At 7 d, all dusts produced significant increases in platelet-derived growth factor-A (PDGF-A) and transforming growth factor-beta1 (TGF-beta1) gene expression compared with control; asbestos and titanium dioxide produced increases in PDGF-B, and titanium dioxide increased TGF-alpha expression. Only asbestos caused increases in procollagen expression. No dust increased expression of tumor necrosis factor-alpha (TNF-alpha), fibronectin, or tropoelastin. Elevations in these factors coincided temporally with transport of particles into the epithelium and then to the subepithelial space. By in situ hybridization, TGF-beta gene expression was found in both the epithelium and subepithelial (interstitial) space, and PDGF-B and procollagen gene expression in the subepithelial space. Chemical analysis showed a small increase in hydroxyproline, a measure of collagen content, in asbestos-treated explants. We conclude that mineral dusts can induce airway wall fibrosis by directly upregulating proliferative and fibrogenic mediators as well as matrix components in the airway epithelium and interstitium, and that neither airspace nor circulating inflammatory cells are required for these effects. Different mineral dusts produce different patterns of reaction.

• Radiographic evidence of silicosis risk in the diatomaceous earth industry. J.M. Hughes, H. Weill, H. Checkoway, et al. 1998;158(3):807-14. PubMed · Publisher

  Abstract

  There is limited and conflicting evidence regarding the exposure-response relationship between exposure to crystalline silica and silicosis; the level of risk to current workers remains uncertain. We conducted an epidemiologic investigation of 1,809 workers in the diatomaceous earth industry, where exposures to crystalline silica are primarily to the cristobalite form. On the basis of the median of three independent readings, 81 (4.5%) workers were judged to have opacities on chest radiographs (small opacities, profusion >= 1/0, and/or large opacities). Age-adjusted relative risk of opacities increased significantly with cumulative exposure to crystalline silica. The concentration of respirable crystalline silica to which workers were exposed (highly correlated with period of hire) was an important determinant of risk after accounting for cumulative exposure. For workers with an average exposure to crystalline silica of <= 0.50 mg/m3 (or hired >= 1950), the cumulative risk of opacities for a cumulative exposure to crystalline silica of 2.0 mg/m3-yr was approximately 1.1%; for an average exposure > 0.50 mg/m3 (or hired < 1950), the corresponding cumulative risk was 3.7%. These findings indicate an exposure-response relationship between cumulative exposure to crystalline silica and radiographic opacities; moreover, the relationship was substantially steeper among workers exposed at the highest average concentrations of crystalline silica.

• Upregulation of the PDGF-alpha receptor precedes asbestos-induced lung fibrosis in rats. J.A. Lasky, B. Tonthat, J.Y. Liu, et al. 1998;157(5 Pt 1):1652-7. PubMed · Publisher

  Abstract

  Platelet-derived growth factor-AA (PDGF-AA) and its matching alpha receptor (PDGF-R alpha) are upregulated in rat lung fibroblasts (RLFs) after exposure to chrysotile asbestos fibers in vitro, which results in asbestos-induced RLF proliferation. We now report our in vivo observations, which show an increase in the expression of PDGF-R alpha mRNA, but not PDGF-beta receptor mRNA, in asbestos-exposed rat lungs when compared with RNA from air-exposed (sham) and iron-exposed lungs. Western analysis of membrane preparations confirmed the observations on mRNA expression by demonstrating an increase in PDGF-R alpha peptide expression in the asbestos-exposed rat lungs, compared with that in the air-exposed lungs. Immunohistochemistry for the PDGF-R alpha was performed on air- and asbestos-exposed rat lungs and revealed a clear increase in staining within interstitial and subepithelial compartments in the exposed animals. These observations, along with our previous report demonstrating an increase in the PDGF-AA isoform expression immediately after asbestos-exposure, suggest a scenario in which a potent lung mesenchymal cell mitogen, PDGF-AA, and its alpha-receptor are upregulated prior to the development of a fibroproliferative lung lesion, and thus may play a central role in the pathogenesis of asbestos-induced lung fibrosis.

• The protective effect of beta-carotene and retinol on ventilatory function in an asbestos-exposed cohort. P. Chuwers, S. Barnhart, P. Blanc, et al. 1997;155(3):1066-71. PubMed · Publisher

  Abstract

  The association between serum beta-carotene or retinol concentration and level of ventilatory function was investigated in a population of asbestos-exposed men with a high rate of current and former cigarette smoking. The study population consisted of 816 subjects enrolled in the pilot component of the Carotene and Retinol Efficacy Trial (CARET), a placebo-controlled trial of supplemental beta-carotene and retinyl palmitate for the chemoprevention of lung cancer. Data available for analysis included baseline questionnaire, spirometry, chest X-ray, food frequency questionnaire, and serum beta-carotene and retinol concentrations. Serum beta-carotene concentration was associated with FEV1 (p < 0.05) and FVC (p < 0.05), with an approximately 100-ml increase over predicted values associated with raising the serum concentration from the 25th to the 75th percentile of the distribution in the study population (absolute difference = 155 ng/ml), even after adjustment for the confounding effects of asbestos exposure and cigarette smoking. Raising the serum retinol concentration from the 25th to the 75th percentile (absolute difference = 211 ng/ml) was associated with an approximately 70 ml increase in FVC (p < 0.05) over the predicted value. These results provide support for the hypothesis that beta-carotene and retinol have a protective effect on loss of ventilatory function.

• Asbestos-related bilateral diffuse pleural thickening: natural history of radiographic and lung function abnormalities. D.H. Yates, K. Browne, P.N. Stidolph, et al. 1996;153(1):301-6. PubMed · Publisher

  Abstract

  Sixty-four subjects with asbestos-related diffuse pleural thickening attending the London Medical Boarding Centre for Respiratory Diseases (formerly, the Central Pneumoconiosis Panel) were studied to investigate symptomatology, lung function, and radiographic change over an average period of 8 to 9 yr. Chest pain was a common symptom, occurring in over half of the subjects. Approximately one-third of the subjects had a history of pleurisy or pleural effusion. Full long function, available in all cases, showed a highly significant decrement (p < 0.001) compared with predicted values in all variables except gas transfer coefficient (Kco) at initial presentation, consistent with a restrictive ventilatory defect. Longitudinal lung function, available over a mean period of 8.9 yr in 36 subjects, showed a significant decrement above that predicted in FEV1 and FVC only (p < 0.05). Decreases in other parameters were observed, although statistical significance was not achieved. Radiographic score increased with time but there was no correlation between change in lung function and increasing radiographic score, probably reflecting the initial severity of the disease in subjects studied. These observations confirm an initial decrement in lung function in diffuse pleural thickening which is followed by comparatively little change over time.

• Asbestos-related bilateral diffuse pleural thickening: natural history of radiographic and lung function abnormalities. A. Miller. 1996;154(6 Pt 1):1919-20. Letter · Comment PubMed · Publisher

• Black spots concentrate oncogenic asbestos fibers in the parietal pleura. Thoracoscopic and mineralogic study. C. Boutin, P. Dumortier, F. Rey, et al. 1996;153(1):444-9. PubMed · Publisher

  Abstract

  Epidemiologic and pathologic data demonstrate that malignant mesothelioma occurs preferentially after exposure to long amphibole asbestos fibers. However, mineralogic studies have rarely detected such fibers in the parietal pleura. We hypothesized that the distribution of asbestos fibers in the pleura was heterogeneous and that they might concentrate in certain areas, as does coal dust in patients showing anthracotic "black spots" of the parietal pleura during thoracoscopy. We collected thoracoscopic biopsy samples from these black spots and from normal areas of the parietal pleura and lung from 14 subjects (eight with and six without asbestos exposure). Asbestos content was determined by transmission electron microscopy. In exposed subjects, mean fiber concentrations were 12.4 +/- 9.8 x 10(6) fibers/g of dry tissue in lung, 4.1 +/- 1.9 in black spots, and 0.5 +/- 0.2 in normal pleura. In unexposed patients, concentrations were 0, 0.3 +/- 0.1, and 0, respectively. Amphiboles outnumbered chrysotile in all samples. A total of 22.5% of fibers were > or = 5 microns in length in black spots. A histologic similarity of these black spots with milky spots is suggested by conventional and electron microscopy. We conclude that the distribution of asbestos fibers is heterogeneous in the parietal pleura. Indeed, the fibers concentrate in black spots, where they can reach high concentrations. These findings could explain why the parietal pleura is the target organ for mesothelioma and plaques.

• Causes of pulmonary impairment in asbestos-exposed individuals with diffuse pleural thickening. S.T. Kee, G. Gamsu, P. Blanc. 1996;154(3 Pt 1):789-93. PubMed · Publisher

  Abstract

  To examine whether diffuse pleural thickening (DPT) causes impairment of pulmonary function independent of other manifestations of asbestos-related disease, we studied individuals selected from 1,150 men with occupational asbestos exposure who had undergone pulmonary function testing and computed tomographic (CT) scanning. The CT scans revealed 84 subjects with DPT as defined for CT. Of these 84 subjects, 53 eligible study cases were matched by age with a referent group without DPT from the same exposed group. No difference was demonstrated between cases and referents in smoking history, length of exposure, latency, or the proportion with either interstitial fibrosis or pleural plaques. Individuals with DPT demonstrated significantly reduced forced vital capacity (FVC) (p = 0.002) and diffusing capacity for carbon monoxide (DLCO) (p = 0.002) as compared with the referents. No difference was found in the two groups' FEV1 to FVC ratio (FEV1/FVC). Individuals with DPT and either interstitial fibrosis or pleural plaques showed a significantly lower FVC than did those with fibrosis or pleural plaques alone. Individuals with DPT and rounded atelectasis had similar pulmonary function to those with DPT and no rounded atelectasis. Subjects with DPT had a more frequent history of coronary bypass surgery than referents (19% versus 2%; p = 0.008). We conclude that subjects with DPT have restrictive pulmonary function and reduced diffusing capacity independent of other manifestations of asbestos-related disease.

• Mineral fiber content of lungs in patients with mesothelioma seeking compensation in Québec. A. Dufresne, R. Bégin, A. Churg, et al. 1996;153(2):711-8. PubMed · Publisher

  Abstract

  Asbestos fibers (AF) and ferruginous bodies (FB) in lung parenchyma from 50 workers seeking compensation from the Workers' Compensation Board of Québec for pleural or peritoneal mesothelioma were analyzed using transmission electron microscopy (TEM) equipped with energy-dispersive spectrometer (EDS) and phase-contrast microscopy (PCM). These workers had been occupationally exposed in mining and milling activities (12 were from Asbestos Township and 11 from Thetford Mines) and 27 were from other types of industry (asbestos factory, shipyard, etc.). For comparison, analyses of lung tissue at autopsy were done in a group of 49 subjects from a reference population. A 95% confidence interval upper limit of 540 AF < 5 microns/mg and a 95% confidence interval upper limit of 161 AF > or = 5 microns/mg dried lung tissue were found for the reference population. Similarly, a concentration of FB of 142 FB/g constituted the upper limit of detectable FB in the lungs of the reference population. Forty-eight of the 50 workers with mesothelioma had either a ferruginous body or total asbestos fiber count greater than the 95% confidence interval for the reference population; the remaining two had amosite and/or crocidolite concentrations greater than the 95% confidence interval for the reference population. The fiber types were different in the three groups, with the lungs of workers from Thetford Mines containing only chrysotile and tremolite, those from Asbestos Township containing chrysotile, tremolite, amosite, and crocidolite, and those in other industries containing largely amosite and crocidolite. We conclude that in this population of workers seeking compensation for mesothelioma, fiber analysis confirmed occupational asbestos exposure in every case. The fiber types responsible for the tumors are probably different in the three different groups.

• Ozone enhances the uptake of mineral particles by tracheobronchial epithelial cells in organ culture. A. Churg, M. Brauer, B. Keeling. 1996;153(4 Pt 1):1230-3. PubMed · Publisher

  Abstract

  We have previously shown that the basal uptake of mineral particles by tracheobronchial epithelial cells in organ culture is mediated in part by active oxygen species (AOS) and can be greatly augmented by exposure to cigarette smoke, a concentrated source of AOS, and other radicals. We hypothesized that ozone, another generator of AOS in tissues, might have the same effect. To test this hypothesis, tracheal explants were exposed to room air (control) or ozone in varying concentrations from 0.01 to 1.0 ppm for 10 min, and subsequently to a suspension of either amosite asbestos or titanium dioxide (rutile) for 1 h. Explants were then transferred to an air/CO2 incubator for 1 wk to allow particle uptake to occur, and uptake was determined by morphometry. We found that ozone exposure increased the uptake of both asbestos and titanium dioxide in a dose-response fashion; this effect appeared at lower exposure levels and was more marked with titanium dioxide than with amosite. The ozone effect could be prevented by addition of catalase but not superoxide dismutase to the particle suspension, or by preincubation of the particles with deferoxamine. These observations indicate that ozone can directly increase uptake of mineral particles by tracheobronchial epithelial cells; this effect occurs with brief exposures at very low ozone levels and appears to be mediated by hydrogen peroxide and possibly by hydroxyl radical. These findings support the general hypothesis that AOS are important mediators of epithelial particle uptake in many different settings. Enhanced uptake may be one of the mechanisms by which ozone impairs particle clearance from the lung and may play a role in the increased morbidity seen in populations with exposure to high levels of both ozone and atmospheric particulates.

• Pulmonary fibrogenesis after three consecutive inhalation exposures to chrysotile asbestos. P.G. Coin, A.R. Osornio-Vargas, V.L. Roggli, et al. 1996;154(5):1511-9. PubMed · Publisher

  Abstract

  Previously, this laboratory developed a model of asbestos-induced pulmonary fibrogenesis in rats and mice after a brief (1 to 3-h) inhalation exposure. However, typical human environmental exposures would be repeated, although at lower concentrations than those used in our animal model. Here we have extended this model to encompass repeated exposures and consequent long-term effects. Groups of rats were exposed to chrysotile aerosol (10 mg/m3) for 3- to 5-h periods over 3 consecutive days. Lung fiber burden and pathologic features were studied for as long as 6 mo after exposure. We found that many of the longest (> or = 8 microm) fibers were retained in the lung for at least 6 mo, whereas shorter fibers were cleared more rapidly. The three exposures to chrysotile caused a large increase in DNA synthesis in the epithelium of terminal bronchioles and more proximal airways. When compared with a single exposure, the triple exposure caused an enhanced inflammatory response as well as a prolonged period of increased DNA synthesis in the proximal alveolar region. Hyperplastic, fibrotic lesions subsequently developed in the same region and persisted for at least 6 mo after exposure. These findings will be valuable in directing future studies of the mechanisms of pulmonary fibrosis in this model.

• Refractory ceramic fiber exposure and pleural plaques. J. Lockey, G. Lemasters, C. Rice, et al. 1996;154(5):1405-10. PubMed · Publisher

  Abstract

  Refractory ceramic fibers (RCF) are manmade vitreous fibers (MMVF) manufactured for high-temperature applications. Between 1987 and 1992, a retrospective cohort and nested case-control study evaluated chest radiographs from 652 workers involved in the manufacture of these fibers for plausibility of a causal relationship between exposure to RCF and chest-radiographic changes. The exposure-response relationship was modeled with three variables: years since first fiber production job, years in fiber production, and cumulative fiber exposure to date of study X-ray. The case-control study used a comprehensive characterization of possible asbestos exposure to investigate asbestos as the potential causative agent of chest-radiographic changes. Chest radiographs of 20 workers (3.1%) demonstrated 19 pleural plaques and one diffuse pleural thickening. Nine of 72 workers (12.5%) with more than 20 yr since their first fiber-production job had plaques (odds ratio [OR] = 9.5; 95% confidence interval [CI] = 1.9 to 48.2). Five of 19 workers with more than 20 yr in fiber-production work (26.3%) had plaques (OR = 22.3; 95% CI = 3.6 to 137.0). Similarly, adjusted ORs demonstrated a progressive relationship between cumulative fiber-months per milliliter (fiber-mo/ml) exposure and plaques. The case-control study confirmed that asbestos exposure did not account for the observed association between fiber exposure and plaques. A validity review of historical films demonstrated biologic plausibility for the association, since sufficient latency existed from the time of first RCF exposure to the development of plaques. There was no significant increase in parenchymal changes consistent with interstitial fibrosis.

• Enhanced retention of asbestos fibers in the airways of human smokers. A. Churg, B. Stevens. 1995;151(5):1409-13. PubMed · Publisher

  Abstract

  To determine whether cigarette smoke increases the pulmonary retention of asbestos, we compared the asbestos-fiber burden in the airway mucosa of six cigarette smokers who had received heavy occupational asbestos exposure with that in a group of six subjects with similar exposure who were never smokers. The groups were matched in terms of age, sex, years of exposure, and mean parenchymal amosite burden. We found that the concentration of amosite in airway mucosa was significantly elevated (by approximately sixfold) in smokers (p < 0.02). Chrysotile parenchymal burdens were statistically similar in both groups, but the chrysotile airway burden was again higher (by approximately 50-fold) in smokers (p < 0.006). There were no differences in airway or parenchymal tremolite burdens between the two groups. Fibers of all three types of asbestos recovered from the airway mucosa or parenchyma of smokers were shorter than fibers recovered from nonsmokers, an observation in accord with experimental data suggesting that cigarette smoke leads to retention of shorter fibers. These findings indicate that cigarette smoking causes enhanced accumulation of both amosite and chrysotile in the airway mucosa. This process may play a role in potentiating the pathologic effects of asbestos.

• Asbestos fibers in bronchoalveolar lavage and lung tissue of former asbestos workers. H. Teschler, K.H. Friedrichs, G.B. Hoheisel, et al. 1994;149(3 Pt 1):641-5. PubMed · Publisher

  Abstract

  Bronchoalveolar lavage (BAL) provides a simple method of sampling inhaled particles deposited in the lower respiratory tract. We hypothesized that BAL could be used to measure the quantity and quality of lung asbestos burden. This would be true if BAL fluid asbestos fiber content reflected the total content as well as the size distribution of both uncoated and coated asbestos fibers in lung parenchyma. Therefore, we analyzed the asbestos fiber counts of 23 individual sample pairs in both BAL fluid and lung tissue samples obtained from 20 patients with occupational asbestos exposure using transmission electron microscopy (TEM). In addition, fiber type, fiber size, and aspect ratio were compared. Coated asbestos fibers were found in 10 of 23 BAL samples and 16 of 23 biopsies. The mean concentrations of coated asbestos fibers (i.e., asbestos bodies) in BAL and lung parenchyma showed a positive correlation (r = 0.75, p < 0.001). Likewise, the mean amphibole fiber concentrations correlated positively (r = 0.55, p < 0.01). However, there was no relationship between the mean chrysotile fiber counts in BAL and lung parenchyma (r = 0.18, p = 0.40). Asbestos fibers in lung tissue were significantly longer (8.2 +/- 0.5 versus 4.8 +/- 0.6 microns; p < 0.001) but had the same width (0.12 +/- 0.27 versus 0.11 +/- 0.15 microns; p = 0.24) when compared with those retrieved by BAL from the airspace compartment. The aspect ratio (dividing fiber length by width) was much higher in lung tissue than in BAL fluid (66.4 +/- 0.4 versus 42.9 +/- 0.5; p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

• Dose-responsive increases in pulmonary fibrosis after inhalation of asbestos. T.R. Quinlan, J.P. Marsh, Y.M. Janssen, et al. 1994;150(1):200-6. PubMed · Publisher

  Abstract

  We focused here on steady-state mRNA levels of genes involved in antioxidant defense, i.e., manganese superoxide dismutase and copper-zinc superoxide dismutase, and in cell proliferation, i.e., ornithine decarboxylase, c-jun, and glyceraldehyde-3-phosphate-dehydrogenase in whole-lung homogenates from Fischer 344 rats at 3 h to 20 d after exposure to crocridolite asbestos. Changes in gene expression were correlated with histopathologic findings, total and differential cell counts in bronchoalveolar lavage, and levels of hydroxyproline in lung. Dosage-dependent increases in mRNA levels of antioxidant enzymes and proliferation-related genes were observed. Differential cell counts revealed a dose-related infiltration of neutrophils that preceded elevations in gene expression. Neutrophil infiltration into lung and focal lesions of fibrosis as well as increased levels of hydroxyproline were observed only at high concentrations of asbestos. These results indicate that high airborne concentrations of asbestos cause molecular changes in lung that may be related to antioxidant defense and the triggering of cell proliferation, a feature of asbestosis and lung cancer.

• Fiber burden and asbestos-related lung disease: determinants of dose-response relationships. M.R. Becklake, B.W. Case. 1994;150(6 Pt 1):1488-92. Editorial · Review PubMed · Publisher

  Summary

  This editorial discussed what measurements of asbestos fibers retained in the lung (lung burden) show about dose-response relationships for asbestos-related lung disease. It centred on two autopsy studies by Churg and colleagues from one laboratory. The first examined 94 of 300 autopsy lungs from Quebec chrysotile miners and millers, with only six controls without asbestos-related disease. The second examined 144 of 160 lungs from Pacific Northwest shipyard workers, insulators and related tradesmen with mixed amosite and chrysotile exposure, referred mainly for medico-legal purposes, with eight controls. In the miners and millers, chrysotile and tremolite burdens were higher in cases than controls for all conditions except chrysotile with pleural plaques and with lung cancer. In the shipyard series, amosite but not chrysotile burdens were associated with asbestosis and airway fibrosis. Amosite burdens in mesothelioma were much lower than in asbestosis (0.9 versus 10.0 million fibers per g). Among chrysotile workers, mesothelioma burdens were similar to or higher than asbestosis burdens. Fiber size was related only to pleural plaques. The editorialists questioned the omission of exposure data from the analyses, the small number of controls, counting methods that favored short fibers, and the conclusion about where tremolite came from. They agreed that disease potential differs by fiber type. They concluded that lung burden can confirm past exposure, but its absence or low levels cannot rule out past occupational exposure.

  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.

• Fiber burden and patterns of asbestos-related disease in workers with heavy mixed amosite and chrysotile exposure. A. Churg, S. Vedal. 1994;150(3):663-9. PubMed · Publisher

  Abstract

  To attempt to determine the mineralogic factors that relate to the appearance of specific types of asbestos-related disease in workers with heavy mixed exposure to amphiboles and chrysotile, we analyzed the pulmonary asbestos fiber burden in a series of 144 shipyard workers and insulators from the Pacific Northwest. Amosite was found in all lungs, and tremolite and chrysotile in most lungs, but the vast majority of fibers were amosite. Tremolite and chrysotile concentrations were significantly correlated, indicating that the tremolite originated from chrysotile products, but no correlation was found between tremolite or chrysotile concentration and amosite concentration. Time since last exposure was correlated with decreasing amosite concentration and the calculated clearance half time was about 20 yr. In a multiple regression analysis that accounted for the presence of more than one disease in many subjects, a high concentration of amosite fibers was correlated with the presence of airway fibrosis and asbestosis, whereas subjects with mesothelioma, lung cancer, pleural plaques, or no asbestos-related disease had about the same, much lower, amosite concentration. No relationship was found between the concentration of chrysotile or tremolite and any disease. Analysis of fiber size measures (length, width, aspect ratio, surface, mass) showed that pleural plaques were strongly associated with high aspect ratio amosite fibers and suggested that mesotheliomas were associated with low aspect ratio amosite fibers.(ABSTRACT TRUNCATED AT 250 WORDS)

• Longitudinal changes in lung function among asbestos-exposed workers. D.A. Schwartz, C.S. Davis, J.A. Merchant, et al. 1994;150(5 Pt 1):1243-9. PubMed · Publisher

  Abstract

  To prospectively identify the determinants of persistent or accelerated loss of lung function among workers occupationally exposed to asbestos and assess the relative contribution of cigarette smoking, asbestos-induced pleural fibrosis, and specific findings from bronchoalveolar lavage and high resolution CT scans, we examined the determinants of lung function changes in 117 subjects occupationally exposed to asbestos for at least 1 yr in a high exposure setting. A minimum of 20 yr was required between the first exposure to asbestos and entry into the study. Baseline studies included an independent assessment of dyspnea, lung volumes, diffusing capacity of carbon monoxide (DLCO), a chest radiograph, a high resolution CT (HRCT) scan, and bronchoalveolar lavage (BAL). Subjects were observed for an average of 2 yr (range, 0.5 to 4.0 yr), and lung function was measured on at least two separate occasions (mean, 4.1 separate tests). During the period of observation, there was an average 1.5% decrease in the TLC and a 2.5% decrease in the DLCO. In this longitudinal data set, after controlling for age, height, pack-years of cigarette smoking, and follow-up time, persistently lower measures of TLC were independently related to moderate to severe dyspnea (p = 0.005), diffuse pleural thickening (p = 0.007), and higher concentrations of fibronectin in BAL fluid (p = 0.01). Interstitial lung disease either on the chest radiograph or HRCT scan was not independently associated with persistently lower measures of TLC during the period of observation. However, none of the clinical variables we examined were associated with an accelerated decline in TLC.(ABSTRACT TRUNCATED AT 250 WORDS)

• Oxidant stress responses in human pleural mesothelial cells exposed to asbestos. Y.M. Janssen, J.P. Marsh, M.P. Absher, et al. 1994;149(3 Pt 1):795-802. PubMed · Publisher

  Abstract

  The generation of oxidants is a proposed mechanism of cell injury by asbestos fibers. To determine whether human pleural mesothelial cells (HMC) respond to asbestos and active oxygen species (AOS) by induction of antioxidant enzymes, cells obtained from pleural effusion were exposed to crocidolite or chrysotile asbestos or xanthine/xanthine oxidase (X/XO), a chemical-generating system of AOS. Gene expression of manganese-containing superoxide dismutase (MnSOD) and heme oxygenase (HO), endogenous enzymes involved in cell defense against oxidant stresses, was then determined. Dosage-dependent increases in steady-state mRNA levels of MnSOD and HO were observed in HMC exposed to asbestos or X/XO. However, increases in gene expression of MnSOD or HO did not occur in HMC after exposure to particulates such as polystyrene beads or riebeckite, the nonfibrous analog of crocidolite asbestos. Comparative experiments with human adult lung fibroblasts (HAL) showed less striking increases in mRNA levels of MnSOD and HO in response to asbestos, but steady-state mRNA levels for HO were increased more than fivefold in response to X/XO. To determine whether increases in mRNA levels of MnSOD were translated into protein, Western blot analyses were performed on HMC and HAL cells exposed to asbestos or X/XO. Slight increases in MnSOD immunoreactive protein were observed in HMC in response to both agents. In contrast, X/XO caused striking elevations in MnSOD protein levels in HAL cells. These results suggest that certain antioxidant enzymes are inducible in HMC after exposure to asbestos and other oxidants.

• p53 protein accumulation in lung carcinomas of patients exposed to asbestos and tobacco smoke. K. Nuorva, R. Mäkitaro, E. Huhti, et al. 1994;150(2):528-33. PubMed · Publisher

  Abstract

  Primary lung carcinomas often carry mutations in the p53 tumor suppressor gene. Most of these mutations alter the conformation of the p53 protein into a more stable phenotype that makes it immunohistochemically detectable. Asbestos is a carcinogen that can cause deletions in chromosomes and possibly also gene mutations. In this study we examined 70 primary lung carcinomas for p53 protein accumulation using a polyclonal antihuman p53 antibody, CM-1. Patients were interviewed about their occupational and smoking history and classified according to their anamnestical asbestos exposure. Presence of asbestos bodies (AB) was evaluated from histologic samples of peripheral nontumorous lung tissue using both 5-microns-thick sections stained with Perls' iron and 30-microns-thick unstained sections. Abnormal accumulation of p53 protein was found in 36 tumors (51%), more often in patients exposed to asbestos than in patients without exposure (67% versus 40%, p = 0.027). Significant association was also noticed between the accumulation of p53 and the asbestos content of lung tissue: 35% of the p53-positive patients had more than one AB/cm2 compared with 14% of p53-negative cases (p = 0.046). Patients with strongly p53-positive tumors were heavier smokers (57.2 +/- 38.2 pack-years) than patients with p53-negative or lightly positive tumors (38.9 +/- 19.9 pack-years) (p = 0.017). Our findings indicate that both asbestos exposure and heavy smoking can cause abnormal p53 protein accumulation suggestive of mutated p53.

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