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.

Chemokine (C-C motif) ligand 3 detection in the serum of persons exposed to asbestos: A patient-based study.

Exposure to asbestos results in serious risk of developing lung and mesothelial diseases. Currently, there are no biomarkers that can be used to diagnose asbestos exposure. The purpose of the present study was to determine whether the levels or detection rate of chemokine (C-C motif) ligand 3 (CCL3) in the serum are elevated in persons exposed to asbestos. The primary study group consisted of 76 healthy subjects not exposed to asbestos and 172 healthy subjects possibly exposed to asbestos. The secondary study group consisted of 535 subjects possibly exposed to asbestos and diagnosed with pleural plaque (412), benign hydrothorax (10), asbestosis (86), lung cancer (17), and malignant mesothelioma (10). All study subjects who were possibly exposed to asbestos had a certificate of asbestos exposure issued by the Japanese Ministry of Health, Labour and Welfare. For the primary study group, levels of serum CCL3 did not differ between the two groups. However, the detection rate of CCL3 in the serum of healthy subjects possibly exposed to asbestos (30.2%) was significantly higher (P < 0.001) than for the control group (6.6%). The pleural plaque, benign hydrothorax, asbestosis, and lung cancer groups had serum CCL3 levels and detection rates similar to that of healthy subjects possibly exposed to asbestos. The CCL3 chemokine was detected in the serum of 9 of the 10 patients diagnosed with malignant mesothelioma. Three of the patients with malignant mesothelioma had exceptionally high CCL3 levels. Malignant mesothelioma cells from four biopsy cases and an autopsy case were positive for CCL3, possibly identifying the source of the CCL3 in the three malignant mesothelioma patients with exceptionally high serum CCL3 levels. In conclusion, a significantly higher percentage of healthy persons possibly exposed to asbestos had detectable levels of serum CCL3 compared to healthy unexposed control subjects.

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.

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.

COVID-19 pneumonia suspected to be co-infection with Mycoplasma pneumoniae and improved by early administration of favipiravir and ciclesonide.

A female nurse in her 40s caring for a patient with severe coronavirus disease 2019 (COVID-19) pneumonia treated with a high-flow nasal cannula (HFNC) presented with fever, cough and dyspnoea. Based on imaging findings and a positive reverse transcription-polymerase chain reaction (RT-PCR) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), COVID-19 pneumonia was diagnosed, although her cohabiting family had similar symptoms and their RT-PCR tests were negative. Laboratory results showed Mycoplasma antigen (+). She was started on ciclesonide 1200 µg/day and favipiravir (3600 mg/day on the first day and 1600 mg/day from Day 2). As Mycoplasma antigen was positive on admission and her family had similar symptoms, levofloxacin 500 mg/day was started. The patient recovered and was discharged on Day 10. The patient did not have Mycoplasma infection because the Mycoplasma antibody measured by particle agglutination (PA) method was increased only up to 80 times after 4 weeks. This case highlights that healthcare workers wearing full personal protective equipment can nevertheless acquire COVID-19 from patients treated with HFNCs.

Clinical study of asbestos-related lung cancer in Japan with special reference to occupational history.

A total of 152 patients with asbestos-related lung cancer recognized by the criteria of Japanese compensation law for asbestos-related diseases were examined and compared with 431 patients with non-asbestos-related lung cancer. Male comprised 96% of patients. Ages ranged from 50 to 91 years with a median of 72 years. Eighty-nine percent were smokers or ex-smokers. Almost all patients had occupational histories of asbestos exposure. The median duration of asbestos exposure was 31 years and the median latency period was 47 years. Thirty-four percent of patients exhibited asbestosis and 81% exhibited pleural plaques by radiography. Regarding asbestos particles in the lung for 73 operated or autopsied patients, 62% had more than 5,000 particles per gram. On the other hand, 100% of non-asbestos-related lung cancer patients had <5000 particles per gram with a median of 554 particles. The number of asbestos bodies in the lung, male gender, absence of symptoms, smoking index, and early stage of cancer were significantly much more than those of non-asbestos-related lung cancer. In this study, a diagnosis of asbestos-related lung cancer was made in 34% of patients by asbestosis, in 62% by presence of both pleural plaques and more than 10 years' occupational asbestos exposure, and in 4% by more than 5000 asbestos particles per gram of lung tissue. Occupational histories, duration of asbestos exposure, and pleural plaques are common categories for the recognition of asbestos-related lung cancer in Japan.

[Successful macrolide therapy for recurrent pneumococcal pneumonia in a man with X-linked agammaglobulinemia].

A 55-year-old man, who had not suffered from any severe or recurrent bacterial infections previously, visited our hospital because of symptoms of fever, cough, sputum, and otorrhea. Chest X-ray and computed tomography demonstrated infiltrates in the right middle lobe and lingula. Pneumococcal pneumonia and tympanitis were diagnosed based on the isolation of Streptococcus pneumoniae from sputum and otorrhea specimens. A peripheral blood analysis showed a remarkable reduction in serum IgG level and the flow cytometric analysis of his peripheral monocytes indicated a significant reduction in Bruton's tyrosine kinase expression. Thus, we diagnosed his illness as X-linked agammaglobulinemia (XLA). Although immunoglobulin replacement therapy was performed, he developed recurrent lower respiratory tract infections. Low-dose long-term erythromycin treatment resulted in decreased frequency of respiratory tract infections. These results suggest that erythromycin therapy may be useful for the control of lower respiratory tract infections in patients with XLA. Even in adults with recurrent bacterial respiratory tract infections, the presence of XLA as an underlying disease should be considered. The effect of macrolide therapy for chronic lower respiratory tract infection associated with humoral immunodeficiency has rarely been reported. This case study may provide valuable information about macrolide therapy for such an infection in patients with humoral immunodeficiency.

Clinical Investigation of Benign Asbestos Pleural Effusion.

There is no detailed information about benign asbestos pleural effusion (BAPE). The aim of the study was to clarify the clinical features of BAPE. The criteria of enrolled patients were as follows: (1) history of asbestos exposure; (2) presence of pleural effusion determined by chest X-ray, CT, and thoracentesis; and (3) the absence of other causes of effusion. Clinical information was retrospectively analysed and the radiological images were reviewed. There were 110 BAPE patients between 1991 and 2012. All were males and the median age at diagnosis was 74 years. The median duration of asbestos exposure and period of latency for disease onset of BAPE were 31 and 48 years, respectively. Mean values of hyaluronic acid, adenosine deaminase, and carcinoembryonic antigen in the pleural fluid were 39,840 ng/mL, 23.9 IU/L, and 1.8 ng/mL, respectively. Pleural plaques were detected in 98 cases (89.1%). Asbestosis was present in 6 (5.5%) cases, rounded atelectasis was detected in 41 (37.3%) cases, and diffuse pleural thickening (DPT) was detected in 30 (27.3%) cases. One case developed lung cancer (LC) before and after BAPE. None of the cases developed malignant pleural mesothelioma (MPM) during the follow-up.

Chronic necrotizing pulmonary aspergillosis in pneumoconiosis: clinical and radiologic findings in 10 patients.

STUDY OBJECTIVE: To characterize clinical, radiographic, and CT findings of chronic necrotizing pulmonary aspergillosis (CNPA) in patients with pneumoconiosis. METHODS: We studied 10 patients with pneumoconiosis who were seen at Asahi Rosai Hospital and received a clinical diagnosis of CNPA during a 15-year period, and detailed the long-term clinical and radiologic courses of four cases. RESULTS: All patients were men, ranging in age from 48 to 77 years (mean, 60.1 years). Their occupational histories included pottery making (n = 9) and coal mining (n = 1). Chest radiographic findings by the International Labor Organization profusion grading system were greater than category 2. All patients were symptomatic, with a productive cough, hemoptysis, and dyspnea. Serum findings were positive for the Aspergillus antibody in seven patients. The radiologic findings consisted of parenchymal infiltrates and cavities mostly containing mycetoma, which generally involved the upper lobes. The disease progressed slowly; in one patient, broad destruction of the lung was observed after > 10 years without antifungal administration. Most of the patients experienced clinical and radiologic improvement after receiving antifungal therapy, by oral, inhaled, or intracavitary administration. CONCLUSIONS: Chronic persistent or progressive upper-lobe infiltrates and cavities in patients with pneumoconiosis should raise the possibility of CNPA. Early diagnosis and initiation of effective therapy are recommended to achieve a better outcome.

[A case of pulmonary nocardiosis with a polypoid lesion in a bronchus].

A 62-year-old woman was admitted with fever and bloody sputum. A mass shadow in the left S3 and obstruction of the left B3 were seen on a chest radiograph and CT. Obstructive pneumonia was suspected, and cefotiam and imipenem/cilastatin were administered. However, this treatment did not show adequate efficacy. Bronchoscopy demonstrated a yellowish-white polypoid lesion in the left B3, but histopathological findings with HE staining yielded no definite diagnosis. Subsequently, Nocardia asteroides was detected in sputum test. A sulfamethoxazole-trimethoprim combination and minocycline were administered, and the clinical findings improved. Gram-positive microfilaments were confirmed retrospectively in the pathologic specimen, and a diagnosis of pulmonary nocardiosis was made.

Isolation of nontuberculous mycobacteria from patients with pneumoconiosis.

This study aimed to confirm the isolation of nontuberculous mycobacteria (NTM) from patients with pneumoconiosis. Monthly sputum examinations in 155 patients were performed from April 1998 to December 2002. When NTM were isolated, species were identified and the frequency of isolation was reviewed. We then identified the patients who satisfied the bacteriologic criteria for the diagnosis of nontuberculous mycobacterial pulmonary disease (NTM pulmonary disease) recommended by the American Thoracic Society (ATS). Symptoms and findings on computed tomography (CT) scans were evaluated. NTM were isolated from 60 patients (39%): common etiologic species defined by the ATS, i.e., Mycobacterium avium, M. intracellulare, M. abscessus, and M. kansasii, were identified in 21 patients; unusual etiologic species, i.e., M. fortuitum, M. simiae, and M. szulgai, were identified in 11 patients; and undefined species, which appeared to be nonpathogenic, were identified in 41 patients. The bacteriologic criteria were satisfied in 8 patients. NTM species isolated in conformity with the bacteriologic criteria were: M. avium in 4 patients, M. intracellulare in 2, a combination of M. intracellulare and M. kansasii in 1, and M. gordonae in 1 patient. Two patients, from whom M. avium were repeatedly isolated, satisfied the ATS diagnostic criteria for NTM pulmonary disease. It is important to note that NTM, including both pathogenic species and nonpathogenic species, were isolated from patients with pneumoconiosis.