Evaluation of chest radiography and low-dose computed tomography as valuable screening tools for thoracic diseases.

BACKGROUND: Recent studies have shown that low-dose computed tomography (LDCT) is effective for the early detection of lung cancer. However, the utility of chest radiography (CR) and LDCT for other thoracic diseases has not been as well investigated as it has been for lung cancer. This study aimed to clarify the usefulness of the veridical method in the screening of various thoracic diseases. METHODS: Among individuals who had received general health checkups over a 10-year period, those who had undergone both CR and LDCT were selected for analysis. The present study included 4317 individuals (3146 men and 1171 women). We investigated cases in which abnormal opacity was detected on CR and/or LDCT. RESULTS: A total of 47 and 124 cases had abnormal opacity on CR and LDCT, respectively. Among these, 41 cases in which the abnormal opacity was identified by both methods contained 20 treated cases. Six cases had abnormalities only on CR, and none of the cases required further treatment. Eighty-three cases were identified using LDCT alone. Of these, many cases, especially those over the age of 50 years, were diagnosed with thoracic tumors and chronic obstructive pulmonary disease, which required early treatment. In contrast, many cases of pulmonary infections have improved spontaneously, without any treatment. CONCLUSION: These results revealed that LDCT allowed early detection of thoracic tumors and chronic obstructive pulmonary disease, especially in individuals over the age of 50 years. CR is still a useful imaging modality for other thoracic diseases, especially in individuals under the age of 49 years.

Role of genetic susceptibility to latent adenoviral infection and decreased lung function.

BACKGROUND: Latent adenoviral infection may amplify cigarette smoke-induced lung inflammation and therefore play an important role in the development of chronic obstructive pulmonary disease (COPD). Adenoviruses can evade the human immune response via their 19-kDa protein (19K) which delays the expression of class I human leukocyte antigen (HLA) proteins. The 19K protein shows higher affinity to HLA-B7 and A2 compared with HLA-A1 and A3. The receptor for adenovirus (CXADR) and integrin beta(5) (ITGB5) are host factors which might affect adenovirus infection. Therefore, we investigated the contribution of HLA, CXADR, and ITGB5 genetic variants to the presence of the E1A gene and to level of lung function. METHODS: Study subjects were assayed for HLA-B7, A1, A2 and A3 by PCR-based assays using allele-specific primers. Polymorphisms of the CXADR and ITGB5 genes were genotyped by PCR-based restriction fragment length polymorphism assays. Detection of adenoviral E1A gene was performed by a real-time PCR TaqMan assay. RESULTS: E1A positive individuals had a lower FEV(1) compared with E1A negative individuals. However, there was no significant difference in E1A positivity rate between the high (HLA-B7 and A2) and low (HLA-A1 and A3) 19K affinity groups. There was also no significant difference in FEV(1) level between each affinity group. There was no significant difference in E1A positivity rate or lung function among the CXADR and ITGB5 genotypes. CONCLUSIONS: Genetic variants in HLA, CXADR and ITGB5 do not influence latent adenoviral infections and are not associated with COPD.

Specific genotyping of human leukocyte antigen-A*01 by polymerase chain reaction using allele group-specific primers

We established a specific genotyping assay for HLA-A*01, which is one of the most frequently found HLA-A alleles in the Caucasian population. This assay uses the polymerase chain reaction (PCR) with allele group-specific primers (ASP). HLA-A*01 group-specific primers were designed for exon 3 of the HLA-A gene, based on the recent HLA-sequence alignment. Both sense and anti-sense primers were designed with completely matched sequences to each specific HLA-A*01 allele, but mismatched by at least 1 nucleotide to all other known class I HLA alleles. By the use of these primers and stringent PCR conditions, we successfully genotyped the HLA-A*01 group alleles and achieved greater accuracy than previous methods.

Lack of association of human leukocyte antigen-B7 with COPD and rate of decline in lung function.

BACKGROUND: Although variation in the human leukocyte antigen (HLA) locus is associated with various diseases, there have been a limited number of studies that have examined the possible role of HLA in chronic obstructive pulmonary disease (COPD). Only HLA-B7 has been shown to be correlated with low forced expiratory volume in 1s (FEV1) in Caucasians; however, this finding has not been replicated. The aim of this study was to investigate the contribution of the HLA-B7 allele to COPD and to rate of decline of lung function. METHODS: We determined the prevalence of HLA-B7 in a group of COPD patients and a non-obstructed control group of smokers by using a polymerase chain reaction-based genotyping assay. We also determined the prevalence of HLA-B7 in smokers selected from the National Heart Lung and Blood Institute, Lung Health Study for having the fastest and slowest decline of lung function. RESULTS: No significant difference was found in the frequency of HLA-B7 between the COPD and non-obstructed groups. There was also no significant association of HLA-B7 with rate of decline of lung function. CONCLUSION: These data indicate that HLA-B7 does not contribute to COPD or rate of decline of FEV1 in smokers.

[A case of arc welder's lung with ground-glass opacities and progressive massive fibrosis].

A 62-year-old man who had worked as a welder for 35 years was admitted with abnormal chest radiograph shadows. Chest CT scan showed ground-glass opacities (GGO) and nodular shadows (progressive massive fibrosis: PMF) with spiculation in both lung fields. Transbronchial lung biopsy (TBLB) findings of a nodule (left segment 8) revealed many iron particles in the alveoli and positive staining for Fe (Berlin blue stain). Moreover, bronchoalveolar lavage (BAL) fluid of a GGO (left segment 4) revealed many iron particles and positive staining for Fe (Berlin blue stain) in macrophages. Serum ferritin was extremely high (6.352 ng/ml) and ferritin in the BAL fluid was 210 ng/ml. Taking the clinical course and pathological findings together, pneumoconiosis (arc welder's lung) was diagnosed. The most common chest CT pattern in arc welder's lung is ill-defined micronodules diffusely distributed in the lung like hypersensitivity pneumonitis. Arc welder's lung rarely presents as PMF. We report a case of arc welder's lung accompanied with PMF.

[A suspected case of Wegener granulomatosis accompanied with pachymeningitis and white matter lesions].

A 53-year-old woman was admitted to our hospital because of high fever and abnormal chest radiograph shadows. Chest X-ray on admission showed a nodular shadow in the right upper lung field and a mass shadow with a cavity in the left middle lung field. Laboratory data indicated leukocytosis and elevation of C-reactive protein. Pulmonary suppuration was suspected, panipenem/betamipron was prescribed, but a mass and consolidation developed, and the medication was changed to ciprofloxacin. Convulsive seizures with loss of consciousness appeared after the change to ciprofloxacin. Lumbar puncture revealed pleocytosis with a predominance of mononuclear cells (198/3) and elevated protein(83 mg/dl). Brain CT showed no abnormal image, and acute aseptic meningitis was diagnosed and was treated with cefotaxime, clindamycin, fluconazole, acicrovir and sulfamethoxazole/trimethoprim. However, the treatment did not result in symptomatic improvement, and brain MRI showed intracranial disorders. Serum PR3-ANCA was elevated to 15 U/ml. Taken together with chest X-ray, sinusitis and clinical course, a generalized form of Wegener's granulomatosis was diagnosed. She was given 60 mg/day of prednisolone, 100 mg/day of cyclophosphamide and 9 g/day of sulfamethoxazole-trimethoprim and progressively improved. In this process, enhanced MR images showed thickened dural enhancement of the falx and bilateral anterior regions, which showed improvement on brain MRI at 8 months after starting treatment. We report a rare case of Wegener's granulomatosis accompanied with pachymeningitis and white matter lesions.

[A case of pulmonary intravascular lymphoma treated with CHOP chemotherapy plus rituximab].

We report a case of pulmonary intravascular lymphoma of large B cell type in a 72-year-old woman. She had a one-month history of fever and dry cough before admission. Chest X-ray revealed ground glass shadow in both lung fields, and the high-resolution CT disclosed centrilobular distribution of ground glass opacities. Transbronchial lung biopsy demonstrated large lymphoid cells in the capillaries of alveolar septa. The tumor cells showed strong immunohistochemical reactivity to CD 20. After combined treatment with CHOP and rituximab, clinical symptoms, laboratory and radiological findings were improved. As with diffuse large B cell lymphoma, CHOP chemotherapy plus rituximab may prove useful as a standard regimen for pulmonary intravascular lymphoma.

Apoptosis induction of vitamin K2 in lung carcinoma cell lines: the possibility of vitamin K2 therapy for lung cancer.

Vitamin K2 (menaquinone-4: VK2) has been reported to show apoptosis and differentiation-inducing effects on leukemia cells. Furthermore, the clinical benefits of using VK2 have been demonstrated for the treatment of the patients with acute leukemia and myelodysplastic syndromes. In the present study, we examined the in vitro effects of VK2 on lung carcinoma cell lines LU-139 and LU-130 for small cell carcinomas, PC-14 and CCL-185 for adenocarcinomas, LC-AI and LC-1/sq for squamous cell carcinomas, and IA-LM for large cell carcinoma, respectively. Treatment with VK2 for 48 to 96 h resulted in cell growth suppression in a dose-dependent manner in all cell lines tested. IC50 (50% inhibitory concentration) for VK2 ranged from 7.5 to 75 micro M, and there was no relation between the efficacy of growth suppression by VK2 and tissue type of lung carcinoma cell lines. Morphologic features of the cells treated with VK2 were typical for apoptosis along with caspase-3 activation and becoming positive for APO2.7 monoclonal antibody, an antibody which specifically detects the cell undergoing apoptosis. In addition to the leukemia cell line, LU-139 cells accumulated into G0/G1 phase during 72-h exposure to VK2. Combined treatment of cisplatin plus VK2 resulted in enhanced cytocidal effect compared to the cells treated with either cisplatin or VK2 alone. Since VK2 is a safe medicine without prominent adverse effects including bone marrow suppression, our data strongly suggest the therapeutic possibility of using VK2 for the treatment of patients with lung carcinoma.

[A case of spinal sarcoidosis complaining of chest and back pain as a first manifestation and mimicking syringomyelia on MRI].

The patient was a 24-year-old female complaining of bell-shaped chest and back pain with visual disturbance. Chest X-ray showed bilateral hilar lymphadenopathy without the presence of pleural effusion. Bronchoalveolar fluid showed lymphocytosis with an elevated CD 4/CD 8 ratio. Transbronchial lung biopsy demonstrated a non-caserous granulomatous lesion with an accumulation of epitheloid cells, suggesting lung sarcoidosis. No abnormality of electrocardiogram was detectable, and spinal tap for examination of chest and back pain demonstrated on elevated level of beta 2-microglobulin, and a normal angiotensin converting enzyme level. Spinal MRI showed a lineal lesion mimicking syringomyelia on T 2-weighted image. Steroid administration was started for the chest and back pain, since the spinal lesion was suspected due to spinal sarcoidosis. All clinical and laboratory findings, without the presence of pleural effusion or cardiac fluid, supported the diagnosis of spinal sarcoidosis causing chest and back pain. In the literature, patients with spinal sarcoidosis manifesting chest and back pain and with a MRI finding mimicking syringomyelia have been rarely reported. This case might be important in considering spinal cord sarcoidosis as a differential diagnosis of chest and back pain.

Direct demonstration of the productive capability of cytokines at the single cell level in lung sarcoidosis using multicolor cytometry.

BACKGROUND: Sarcoidosis is a chronic systemic disorder of unknown etiology characterized by noncaseating epithelioid cell granulomatous lesions, around which an increasing number of CD4+ T cells infiltrate. These CD4+ T cells may release interferon-gamma (IFN-gamma) and interleukin-2 (IL-2). These cytokines are considered to play an important role in pathogenesis of sarcoidosis. METHODS: We employed a modification of Jung's method using multicolor flow cytometry to assess the capability of single cells obtained from bronchoalveolar lavage (BAL) fluid to produce various cytokines. BAL CD4+ T cell production of IFN-gamma, IL-2 and IL-4 after phorbol ester and ionomycin stimulation were studied. RESULTS: The percentage of IFN-gamma- and IL-2-producing CD4+ T cells was significantly higher in patients with sarcoidosis compared to healthy volunteers [84.7 +/- 7.5 vs. 51.2 +/- 14.8% (p < 0.005), and 75.3 +/- 8.7 vs. 39.8 +/-11.0% (p < 0.001), respectively]. No significant difference in the percentage of IL-4-producing CD4+ T cells was noted (1.2 +/- 0.6 vs. 3.5 +/- 2.6%; not significant), whereas the absolute number of IL-4-producing CD4+ T cells was significantly higher in patients with sarcoidosis compared to healthy volunteers (563.6 +/- 330.2 vs. 50.9 +/- 66.9/ml; p < 0.005). In the IL-4-producing CD4+ T cells, about 80% of cells concomitantly produced IFN-gamma and more than 60% of cells also produced IL-2. CONCLUSION: We demonstrate that Th1-like-producing cells are predominant in the CD4+ as well as in the CD8+ T cell subset of patients with sarcoidosis. We for the first time demonstrated concomitant capabilities of BAL CD4+ T cells to produce Th1 and Th2 cytokines at the single cell level by multicolor flow cytometry.