Mechanisms of pulmonary disease in F344 rats after workplace-relevant inhalation exposure to cross-linked water-soluble acrylic acid polymers.

BACKGROUND: Recently in Japan, six workers at a chemical plant that manufactures resins developed interstitial lung diseases after being involved in loading and packing cross-linked water-soluble acrylic acid polymers (CWAAPs). The present study focused on assessing lung damage in rats caused by workplace-relevant inhalation exposure to CWAAP and investigated the molecular and cellular mechanisms involved in lung lesion development. METHODS: Using a whole-body inhalation exposure system, male F344 rats were exposed once to 40 or 100 mg/m3 of CWAAP-A for 4 h or to 15 or 40 mg/m3 of CWAAP-A for 4 h per day once per week for 2 months (9 exposures). In a separate set of experiments, male F344 rats were administered 1 mg/kg CWAAP-A or CWAAP-B by intratracheal instillation once every 2 weeks for 2 months (5 doses). Lung tissues, mediastinal lymph nodes, and bronchoalveolar lavage fluid were collected and subjected to biological and histopathological analyses. RESULTS: A single 4-h exposure to CWAAP-A caused alveolar injury, and repeated exposures resulted in regenerative changes in the alveolar epithelium with activation of TGFß signaling. During the recovery period after the last exposure, some alveolar lesions were partially healed, but other lesions developed into alveolitis with fibrous thickening of the alveolar septum. Rats administered CWAAP-A by intratracheal instillation developed qualitatively similar pulmonary pathology as rats exposed to CWAAP-A by inhalation. At 2 weeks after intratracheal instillation, rats administered CWAAP-B appeared to have a slightly higher degree of lung lesions compared to rats administered CWAAP-A, however, there was no difference in pulmonary lesions in the CWAAP-A and CWAAP-B exposed rats examined 18 weeks after administration of these materials. CONCLUSIONS: The present study reports our findings on the cellular and molecular mechanisms of pulmonary disease in rats after workplace-relevant inhalation exposure to CWAAP-A. This study also demonstrates that the lung pathogenesis of rats exposed to CWAAP-A by systemic inhalation was qualitatively similar to that of rats administered CWAAP-A by intratracheal instillation.

Phase I Study of Tremelimumab Monotherapy or in Combination With Durvalumab in Japanese Patients With Advanced Solid Tumors or Malignant Mesothelioma.

BACKGROUND: The primary objective of this phase I, open-label trial was to assess safety and tolerability of tremelimumab monotherapy and combination therapy with durvalumab in Japanese patients with advanced cancer. Tremelimumab is a fully human monoclonal antibody against CTLA-4 in clinical trials; durvalumab is a monoclonal antibody against PD-L1 for the treatment of bladder and lung cancer. METHODS: In part 1, tremelimumab 3 or 10 mg/kg was given every 4 weeks (Q4W) for 6 doses, and thereafter every 12 weeks until discontinuation (n = 8); subsequently tremelimumab 10 mg/kg Q4W for 6 doses/Q12W and thereafter until discontinuation was administered in 41 patients with malignant pleural or peritoneal mesothelioma (MPM). In part 2, tremelimumab 10 mg/kg (Q4W for 6 doses followed by Q12W for 3 doses) was given in combination with durvalumab 15 mg/kg (Q4W for 13 doses) in cohort 1 (n = 4). In cohort 2 (n = 6), tremelimumab 1 mg/kg (Q4W for 4 doses) was given in combination with durvalumab 20 mg/kg (Q4W for 4 doses followed by 10 mg/kg Q2W for 22 doses), while in cohort 3 (n = 6), fixed-dose tremelimumab 75 mg Q4W for 4 doses plus durvalumab 1500 mg Q4W for 13 doses was given. RESULTS: In part 1, no dose-limiting toxicities (DLTs) for tremelimumab 3 or 10 mg/kg (Q4W for 6 doses/Q12W thereafter until discontinuation) were observed. Six (75%) patients reported treatment-related adverse events (trAEs). In the MPM dose-expansion cohort, 38 (92.7%) patients reported trAEs. In part 2, one DLT (Grade 4 myasthenia gravis) was reported for tremelimumab 10 mg/kg (Q4W for 6 doses/Q12W for 3 doses) plus durvalumab 15 mg/kg (Q4W for 13 doses). One DLT (Grade 4 hyperglycemia) was reported for tremelimumab 75 mg (Q4W for 4 doses) plus durvalumab 1500 mg (Q4W for 13 doses). Fourteen (87.5%) patients reported trAEs. Tremelimumab demonstrated low immunogenicity; 1 (16.7%) patient developed antidrug antibodies. CONCLUSION: Tremelimumab 10 mg/kg (Q4W/Q12W), tremelimumab 1 mg/kg (Q4W) plus durvalumab 20 mg/kg (Q4W/10 mg/kg Q2W), and fixed-dose tremelimumab 75 mg (Q4W) plus durvalumab 1500 mg (Q4W) were safe and tolerable.ClinicalTrials.gov Identifier: NCT02141347 (https://clinicaltrials.gov/ct2/show/NCT02141347).

Dose-response relationship of pulmonary disorders by inhalation exposure to cross-linked water-soluble acrylic acid polymers in F344 rats.

BACKGROUND: In Japan, six workers handling cross-linked water-soluble acrylic acid polymer (CWAAP) at a chemical plant suffered from lung diseases, including fibrosis, interstitial pneumonia, emphysema, and pneumothorax. We recently demonstrated that inhalation of CWAAP-A, one type of CWAAP, causes pulmonary disorders in rats. It is important to investigate dose-response relationships and recoverability from exposure to CWAAPs for establishing occupational health guidelines, such as setting threshold limit value for CWAAPs in the workplace. METHODS: Male and female F344 rats were exposed to 0.3, 1, 3, or 10 mg/m3 CWAAP-A for 6 h/day, 5 days/week for 13 weeks using a whole-body inhalation exposure system. At 1 h, 4 weeks, and 13 weeks after the last exposure the rats were euthanized and blood, bronchoalveolar lavage fluid, and all tissues including lungs and mediastinal lymph nodes were collected and subjected to biological and histopathological analyses. In a second experiment, male rats were pre-treated with clodronate liposome or polymorphonuclear leukocyte-neutralizing antibody to deplete macrophages or neutrophils, respectively, and exposed to CWAAP-A for 6 h/day for 2 days. RESULTS: CWAAP-A exposure damaged only the alveoli. The lowest observed adverse effect concentration (LOAEC) was 1 mg/m3 and the no observed adverse effect concentration (NOAEC) was 0.3 mg/m3. Rats of both sexes were able to recover from the tissue damage caused by 13 weeks exposure to 1 mg/m3 CWAAP-A. In contrast, tissue damage caused by exposure to 3 and 10 mg/m3 was irreversible due to the development of interstitial lung lesions. There was a gender difference in the recovery from CWAAP-A induced pulmonary disorders, with females recovering less than males. Finally, acute lung effects caused by CWAAP-A were significantly reduced by depletion of alveolar macrophages. CONCLUSIONS: Pulmonary damage caused by inhalation exposure to CWAAP-A was dose-dependent, specific to the lung and lymph nodes, and acute lung damage was ameliorated by depleting macrophages in the lungs. CWAAP-A had both a LOAEC and a NOAEC, and tissue damage caused by exposure to 1 mg/m3 CWAAP-A was reversible: recovery in female rats was less than for males. These findings indicate that concentration limits for CWAAPs in the workplace can be determined.

The diagnosis of early pneumoconiosis in dust-exposed workers: comparison of chest radiography and computed tomography.

BACKGROUND: Chest radiography (CR) is employed as the evaluation of pneumoconiosis; however, we sometimes encounter cases in which computed tomography (CT) is more effective in detecting subtle pathological changes or cases in which CR yields false-positive results. PURPOSE: To compare CR to CT in the diagnosis of early-stage pneumoconiosis. MATERIAL AND METHODS: CR and CT were performed for 132 workers with an occupational history of mining. We excluded 23 cases of arc-welder's lung. Five readers who were experienced chest radiologists or pulmonologists independently graded the pulmonary small opacities on CR of the remaining 109 cases. We then excluded 37 cases in which the CT data were not sufficient for grading. CT images of the remaining 72 cases were graded by the five readers. We also assessed the degree of pulmonary emphysema in those cases. RESULTS: The grade of profusion on CR (CR score) of all five readers was identical in only 5 of 109 cases (4.6%). The CR score coincided with that on CT in 40 of 72 cases (56%). The CT score was higher than that on CR in 13 cases (18%). On the other hand, the CT score was lower than that on CR in 19 cases (26%). The incidence of pulmonary emphysema was significantly higher in patients whose CR score was higher than their CT score. CONCLUSION: CT is more sensitive than CR in the evaluation of early-stage pneumoconiosis. In cases with emphysema, the CR score tends to be higher in comparison to that on CT.

Locus-Specific Isolation of the Nanog Chromatin Identifies Regulators Relevant to Pluripotency of Mouse Embryonic Stem Cells and Reprogramming of Somatic Cells.

Pluripotency is a crucial feature of pluripotent stem cells, which are regulated by the core pluripotency network consisting of key transcription factors and signaling molecules. However, relatively less is known about the molecular mechanisms that modify the core pluripotency network. Here we used the CAPTURE (CRISPR Affinity Purification in situ of Regulatory Elements) to unbiasedly isolate proteins assembled on the Nanog promoter in mouse embryonic stem cells (mESCs), and then tested their functional relevance to the maintenance of mESCs and reprogramming of somatic cells. Gene ontology analysis revealed that the identified proteins, including many RNA-binding proteins (RBPs), are enriched in RNA-related functions and gene expression. ChIP-qPCR experiments confirmed that BCLAF1, FUBP1, MSH6, PARK7, PSIP1, and THRAP3 occupy the Nanog promoter region in mESCs. Knockdown experiments of these factors show that they play varying roles in self-renewal, pluripotency gene expression, and differentiation of mESCs as well as in the reprogramming of somatic cells. Our results show the utility of unbiased identification of chromatin-associated proteins on a pluripotency gene in mESCs and reveal the functional relevance of RBPs in ESC differentiation and somatic cell reprogramming.

Physician requests by patients with malignant pleural mesothelioma in Japan.

BACKGROUND: Malignant pleural mesothelioma (MPM) is a fatal and rare disease that is caused by the inhalation of asbestos. Treatment and care requests made by MPM patients to their physicians were collected and analyzed. METHODS: This cross-sectional survey was part of a larger study (N = 133) regarding the quality of life of MPM patients. Specific responses to two open-ended questions related to patients' requests regarding treatment and care were quantified, analyzed and divided into categories based on content. RESULTS: Responses (N = 217) from MPM patients (N = 73) were categorized into 24 subcategories and then abstracted into 6 categories. The majority of requests were related to patient-physician communication. Patients wanted clear and understandable explanations about MPM and wanted their physician to deliver treatment based on the patient's perspective by accepting and empathizing with their anxiety and pain. Patients expected physicians to be dedicated to their care and establish an improved medical support system for MPM patients. CONCLUSION: Patients with MPM had a variety of unmet needs from their physicians. Physicians who provide care to MPM patients should receive training in both communication skills and stress management. A multidisciplinary care system that includes respiratory and palliative care for MPM patients should be established.

Serum levels of the chemokine CCL2 are elevated in malignant pleural mesothelioma patients.

BACKGROUND: Malignant pleural mesothelioma (MPM) is a debilitating disease of the pleural cavity. It is primarily associated with previous inhalation of asbestos fibers. These fibers initiate an oxidant coupled inflammatory response. Repeated exposure to asbestos fibers results in a prolonged inflammatory response and cycles of tissue damage and repair. The inflammation-associated cycles of tissue damage and repair are intimately involved in the development of asbestos-associated cancers. Macrophages are a key component of asbestos-associated inflammation and play essential roles in the etiology of a variety of cancers. Macrophages are also a source of C-C motif chemokine ligand 2 (CCL2), and a variety of tumor-types express CCL2. High levels of CCL2 are present in the pleural effusions of mesothelioma patients, however, CCL2 has not been examined in the serum of mesothelioma patients. METHODS: The present study was carried out with 50 MPM patients and 356 subjects who were possibly exposed to asbestos but did not have disease symptoms and 41 healthy volunteers without a history of exposure to asbestos. The levels of CCL2 in the serum of the study participants was determined using ELISA. RESULTS: Levels of CCL2 were significantly elevated in the serum of patients with advanced MPM. CONCLUSIONS: Our findings are consistent with the premise that the CCL2/CCR2 axis and myeloid-derived cells play an important role in MPM and disease progression. Therapies are being developed that target CCL2/CCR2 and tumor resident myeloid cells, and clinical trials are being pursued that use these therapies as part of the treatment regimen. The results of trials with patients with a similar serum CCL2 pattern as MPM patients will have important implications for the treatment of MPM.

Quality of life of survivors of malignant pleural mesothelioma in Japan: a cross sectional study.

BACKGROUND: Previous studies have indicated that people with malignant pleural mesothelioma (MPM) have a poor quality of life (QOL); however, information about the QOL of people with MPM in Japan is anecdotal. The aims of this study were to investigate the QOL of survivors of MPM in Japan and to determine the factors that correlate with their QOL. METHODS: This was a cross sectional study. The included patients were those diagnosed with MPM in Japan. We created a self-administered questionnaire consisting of 64 questions. The questionnaires were sent to hospitals and patient advocacy groups, distributed to the patients, completed, and sent back to the researchers by postal mail. QOL was assessed with the European Organization for Research and Treatment of Cancer 16 questionnaire (QLQ) and the short version of the core domains of the Comprehensive Quality of Life Outcome questionnaire (CoQoLo). RESULTS: In total, 133 questionnaires were collected. The QLQ assessments demonstrated that the survivors of MPM most frequently complained of fatigue, pain, sleep disturbances, and dyspnea. The symptom scales were acceptable, but the functional scales were significantly poorer for the patients with poor performance statuses (PSs). The short CoQoLo assessment was very unfavorable for 'Being free from physical pain.' Being a long-term survivor and a survivor with a poor PS were significantly correlated with poor global health status. CONCLUSIONS: Survivors of MPM have impaired function, a variety of symptoms, and lower QOL. Survivors of MPM, even those in good physical condition, need broad support.

MUC4, a novel immunohistochemical marker identified by gene expression profiling, differentiates pleural sarcomatoid mesothelioma from lung sarcomatoid carcinoma.

Sarcomatoid mesothelioma, a histological subtype of malignant pleural mesothelioma, is a very aggressive tumor with a poor prognosis. Histological diagnosis of sarcomatoid mesothelioma largely depends on the histomorphological feature of spindled tumor cells with immunohistochemical reactivity to cytokeratins. Diagnosis also requires clinico-radiological and/or macroscopic evidence of an extrapulmonary location to differentiate it from lung sarcomatoid carcinoma. Although there are promising immunohistochemical antibody panels to differentiate mesothelioma from lung carcinoma, a consensus on the immunohistochemical markers that distinguish sarcomatoid mesothelioma from lung sarcomatoid carcinoma has not been reached and requires further study. We performed whole gene expression analysis of formalin-fixed paraffin-embedded tissue from sarcomatoid mesothelioma and lung sarcomatoid carcinoma and observed significant differences in the expression of MUC4 and other genes between sarcomatoid mesothelioma and lung sarcomatoid carcinoma. Immunohistochemistry demonstrated that MUC4 was expressed in the spindled tumor cells of lung sarcomatoid carcinoma (21/29, 72%) but was not expressed in any sarcomatoid mesothelioma (0/31, 0%). To differentiate sarcomatoid mesothelioma from lung sarcomatoid carcinoma, negative MUC4 expression showed 100% sensitivity and 72% specificity and accuracy rate of 87%, which is higher than immunohistochemical markers such as calretinin, D2-40 and Claudin-4. Therefore, we recommend to include MUC4 as a novel and useful negative immunohistochemical marker for differentiating sarcomatoid mesothelioma from lung sarcomatoid carcinoma.

Utility and pitfalls of immunohistochemistry in the differential diagnosis between epithelioid mesothelioma and poorly differentiated lung squamous cell carcinoma.

AIMS: The aims of this study were to clarify the usefulness of immunohistochemistry in the differential diagnosis of epithelioid mesothelioma with a solid growth pattern [solid epithelioid mesothelioma (SEM)] and poorly differentiated squamous cell carcinoma (PDSCC), and to confirm the validity of a specific type of antibody panel. Additionally, we aimed to clarify the pitfalls of immunohistochemical analyses. METHODS AND RESULTS: Formalin-fixed paraffin-embedded specimens from 36 cases of SEM and 38 cases of PDSCC were immunohistochemically examined for calretinin, podoplanin (D2-40), Wilms' tumour gene product (WT1), cytokeratin (CK) 5/6, p40, p63, carcinoembryonic antigen (CEA), epithelial-related antigen (MOC31), claudin-4, thyroid transcription factor-1 (TTF-1), and napsin A. WT1 showed the highest diagnostic accuracy (85.1%) as a mesothelial marker, and CEA, p40 and claudin-4 showed higher diagnostic accuracies (95.9%, 94.6%, and 93.2%, respectively) as carcinoma markers. Calretinin (diagnostic accuracy: 75.7%), D2-40 (diagnostic accuracy: 67.6%), CK5/6 (diagnostic accuracy: 63.5%), TTF-1 (diagnostic accuracy: 55.4%) and napsin A (diagnostic accuracy: 52.7%) could not differentiate between SEM and PDSCC. Among these markers, the combination of calretinin and WT1 showed the highest diagnostic accuracy (86.5%) as a positive marker, and the combination of p40 and CEA showed the highest diagnostic accuracy (97.3%) as a negative marker. The combination of CEA and claudin-4 also showed relatively high diagnostic accuracy (94.6%) as a negative marker. CONCLUSIONS: We recommend the combination of WT1 and calretinin as a positive maker, and the combination of CEA and claudin-4 as a negative marker, for differential diagnoses of SEM and PDSCC.

Lung cancer in a patient with predominantly short tremolite fibers in his lung.

The carcinogenicity of short tremolite fibers in human has not been cleared and has been argued hitherto. A lung cancer patient had worked at a gabbro quarry. Particles isolated from the excised lung parenchyma of the patient were measured for asbestos bodies (ABs) and asbestos fibers (AFs). The concentrations of ABs were 3964 AB/g dry lung, and AFs were 5.60 × 106 fibers/g dry lung (>5 um in length) and 22.5 × 106 fibers/g dry lung (>1 um in length). AFs were mostly tremolite fibers and under 7 um in length (mean length 4.0 um, standard deviation 2.8 um). Almost all fibers were <10 um in length and an aspect ratio (AR) of <20:1 and ≥3:1. The patient had never smoked. His wife, who had worked with him in the quarry, had died of pleural mesothelioma. This study strongly indicates that such short tremolite fibers will induce lung cancer and possibly mesothelioma in human.

Numerical investigation of oxygen transport by hemoglobin-based carriers through microvessels.

The small size of hemoglobin-based oxygen carriers (HBOCs) may expand the realm of new treatment possibilities for various circulatory diseases. The parametric evaluation of HBOC performance for oxygen transport within tissue is essential for effectively characterizing its performance for each circulatory disease assessed. Thus, the overarching objective of this present study was to numerically investigate the reaction-diffusion phenomenon of oxygenated HBOCs and oxygen on tissues through microvessels. We considered dissociation rate coefficients, oxygen affinity, and diffusion coefficients due to Brownian motion as the biophysical parameters for estimating HBOC performance for oxygen transport. A two-dimensional computational domain, including vessel and tissue regions, was, therefore, accordingly assumed. It was observed that HBOC flows in a microvessel with a diameter of 25 µm and a length of 1 mm, and that the dissociated oxygen diffuses to the tissue region. The results indicated that oxyhemoglobin saturation and partial oxygen tension in a downstream region changed according to each biophysical parameter of HBOC. Moreover, the change in oxygen consumption rate in the tissue region had considerable influence on the oxyhemoglobin saturation level within the vessel. Comparison between simulation results and existing in vitro experimental data of actual HBOCs and RBC showed qualitatively good agreement. These results provide important information for the effective design of robust HBOCs in future.

Asbestosis and other pulmonary fibrosis in asbestos-exposed workers: high-resolution CT features with pathological correlations.

OBJECTIVE: The purpose was to identify distinguishing CT features of pathologically diagnosed asbestosis, and correlate diagnostic confidence with asbestos body burden. METHODS: Thirty-three workers (mean age at CT: 73 years) with clinical diagnoses of asbestosis, who were autopsied (n = 30) or underwent lobectomy (n = 3), were collected. Two radiologists independently scored high-resolution CT images for various CT findings and the likelihood of asbestosis was scored. Two pathologists reviewed the pathology specimens and scored the confidence of their diagnoses. Asbestos body count was correlated with CT and pathology scores. RESULTS: Pathologically, 15 cases were diagnosed as asbestosis and 18 cases with various lung fibroses other than asbestosis. On CT, only the score of the subpleural curvilinear lines was significantly higher in asbestosis (p = 0.03). Accuracy of CT diagnosis of asbestosis with a high confidence ranged from 0.73 to 0.79. Asbestos body count positively correlated with CT likelihood of asbestosis (r = 0.503, p = 0.003), and with the confidence level of pathological diagnosis (r = 0.637, p < 0.001). CONCLUSIONS: Subpleural curvilinear lines were the only clue for the diagnosis of asbestosis. However, this was complicated by other lung fibrosis, especially at low asbestos body burden. KEY POINTS: • Various patterns of pulmonary fibrosis occurred in asbestos-exposed workers. • The fibre burden in lungs paralleled confident CT diagnosis of asbestosis. • The fibre burden in lungs paralleled confident pathological diagnosis of asbestosis. • Subpleural curvilinear lines were an important CT finding favouring asbestosis.

[Clinical Pathological Diagnosis, and Treatment for Pleural Mesothelioma].

For the differential diagnosis between fibrous pleuritis and other malignancies such as lung cancer, multiple immunostaining is essential to diagnose pleural mesothelioma. For cytological diagnosis of pleural effusions, differentiation between mesothelioma cells and reactive mesothelial cells is very difficult. Therefore, histological diagnoses of tumor tissues obtained via biopsy are essential. To diagnose epthelioid mesothelioma, more than 2 positive and negative markers must be consistent with those known for mesothelioma. To diagnose sarcomatoid mesothelioma, keratin is usually positive, differentiating the diagnosis from that for real sarcoma. For surgical treatment for pleural mesothelioma, extrapleural pneumonectomy (EPP) and pleurectomy/decortication (P/D) are usually performed. The proportion of P/D increases because of the low death rates with surgery and similar survivals. However, a trimodal approach, such as EPP with chemotherapy and radiotherapy, is best for longer survival and expected to be curative. For chemotherapy, only cisplatin (CDDP) combined with pemetrexed (PEM) is effective, and no other agents have been identified for this disease. Nowadays, clinical immunotherapy trials start with phase II study.

Significant relationship between the extent of pleural plaques and pulmonary asbestos body concentration in lung cancer patients with occupational asbestos exposure.

BACKGROUND: The aim of this study was to elucidate whether there is a relationship between the extent of pleural plaques and pulmonary asbestos body concentration (PABC). METHODS: The subjects were 207 lung cancer patients with occupational asbestos exposure. We determined the plaque extent by findings on chest images using our own criteria. PABCs were measured in resected or autopsy lung specimens. RESULTS: There was a significant relationship between plaque extent and PABC. Seventy-five percent of the patients determined to have extensive plaques based on our criteria had a PABC of ≥5,000 asbestos bodies per gram of dry lung tissue, which is one of the certification criteria of lung cancer caused by asbestos for workers' compensation in Japan. CONCLUSIONS: In lung cancer patients, the plaque extent had a significant positive relationship with the PABC. The plaque extent would be useful as a proxy for PABC for lung cancer compensation purposes.

Pilot Analysis of Asbestos-induced Diffuse Pleural Thickening with Respiratory Compromise.

We investigated the clinical features of asbestos-induced diffuse pleural thickening (DPT) with severe respiratory compromise. We conducted a retrospective study of consecutive subjects with asbestos-induced DPT. Medical data such as initial symptoms, radiological findings, respiratory function test results, and clinical course were collected and analyzed. There were 24 patients between 2003 and 2012. All were men, and the median age at the development of DPT was 74 years. The top occupational category associated with asbestos exposure was dockyard workers. The median duration of asbestos exposure was 35.0 years, and the median latency from first exposure to the onset of DPT was 49.0 years. There were no significant differences in respiratory function test results between the higher and lower Brinkman index groups or between unilateral and bilateral DPT. Thirteen patients had a history of benign asbestos pleural effusion (BAPE), and the median duration from pleural fluid accumulation to DPT with severe respiratory compromise was 28.4 months. DPT with severe respiratory compromise can develop after a long latency following occupational asbestos exposure and a history of BAPE.

Asbestos-related diffuse pleural thickening.

BACKGROUND: The clinical features of asbestos-related diffuse pleural thickening (DPT) remain unclear. OBJECTIVES: To clarify the association between radiological findings of DPT and respiratory function. METHODS: Medical data from patients with asbestos-related DPT were collected, including their history of occupational or neighborhood asbestos exposure, initial symptoms, modified Medical Research Council dyspnea grade, smoking history, radiological findings, and respiratory function test results. RESULTS: There were 106 DPT patients between 2005 and 2010 [i.e. 103 men (97.2%) and 3 women (2.8%)]. The median age at diagnosis was 69 years (range 46-88). Patient occupations related to asbestos exposure included: asbestos product manufacturing (n = 17); the shipbuilding industry (n = 14); the construction industry (n = 13); heat insulation work (n = 12); plumbing, asbestos spraying, and electrical work (n = 7 each), and transportation and demolition work (n = 4 each). The median duration of asbestos exposure was 25 years (range 2-54), and the median latency period before the onset of DPT was 46 years (range 25-66). Involvement of the costophrenic angle (CPA) was also negatively correlated with the percent vital capacity (%VC; r = -0.448, p < 0.01). Pleural thickness and the craniocaudal and horizontal extension of pleural thickening, as determined by chest computed tomography (CT), were also negatively correlated with %VC (r = -0.226, p < 0.05; r = -0.409, p < 0.01, and r = -0.408, p < 0.01, respectively). CONCLUSIONS: DPT develops after a long latency period following occupational asbestos exposure and causes marked respiratory dysfunction. The extension of DPT should be evaluated by chest CT, and chest X-ray would be important for the evaluation of the involvement of the CPA.

[Asbestos-related diseases].

Asbestosis shows peribronchiolar fibrosis with numerous asbestos bodies. Subpleural dots and curvilinear lines in HRCT are good indicators for the diagnosis of asbestosis. Asbestos-related lung cancer in Japanese Compensation System means lung cancer with asbestosis. Furthermore, pleural plaques and the content of asbestos bodies in the lung tissues with the term of occupational asbestos exposure are good indicators. Mesothelioma induced also by the low dense exposure to asbestos. For the definite diagnosis of mesothelioma, we need histological examination using biopsy and immunochemical staining for positive and negative markers. Benign asbestos pleurisy is diagnosed by cytological and biochemical examinations of pleural effusions and pleural biopsy. Diffuse pleural thickening depends on the extent of radiological findings and impairment of pulmonary function with occupational asbestos exposure.