Persistent diffuse pulmonary interstitial emphysema mimicking pulmonary emphysema.

A 69-year-old male non-smoker with a history of atopic asthma presented with symptoms suggestive of chronic obstructive pulmonary disease and this appeared to be corroborated by lung function testing and a chest radiograph. However, a chest CT showed no evidence of pulmonary emphysema and instead demonstrated free air along the bronchovascular sheaths indicative of pulmonary interstistial emphysema, possibly caused by repeated prior exacerbations of asthma. His lung function tests and symptoms improved within months of being treated for his airways disease but the CT findings were unchanged after 2 years.

[Intentional limited resection for lung adenocarcinoma of 2 cm in size or less according to intraoperative frozen section and high-resolution computed tomography].

One hundred twenty-six cases of resected lung adenocarcinoma of 2 cm in size or less were studied about intra and postoperative Noguchi's classification, high-resolution computed tomography (HRCT) findings and lymph node metastases in cases of lobectomy. Intentional limited resection for lung adenocarcinoma of 2 cm in size or less was recommended for selected patients with tumors of type A of Noguchi's classification diagnosed by intraoperative frozen diagnosis or tumors of intraoperative type B of 0.5 in ground-glass opacity (GGO) diameter ratio or more of HRCT. These patients are almost equal to patients of 0.5 in GGO diameter ratio or more with any type of Noguchi's classification. This GGO diameter ratio of 0.5 is easily available as a criteria of intentional limited resection for lung adenocarcinoma of 2 cm in size or less.

Changes in HRCT findings in patients with respiratory bronchiolitis-associated interstitial lung disease after smoking cessation.

High-resolution computed tomography (HRCT) findings in patients with respiratory bronchiolitis-associated interstitial lung disease (RB-ILD) are varied and nonspecific. There is no known report of changes in HRCT findings and respiratory function test results for RB-ILD patients following the cessation of smoking. Five patients with RB-ILD, confirmed by surgical lung biopsy, were retrospectively studied. Each stopped cigarette smoking and did not receive corticosteroid therapy after diagnosis. The clinical symptoms, respiratory function test results and HRCT findings obtained at the final observation were compared with those from the time of diagnosis. Ground-glass opacity and centrilobular nodules corresponding to pathological respiratory bronchiolitis, as well as intralobular fine linear-reticular opacity corresponding to fibrosis involving the subpleural alveolar septa, showed computed tomography-pathological correlations. Both clinical symptoms and the diffusing capacity of the lungs for carbon monoxide improved significantly following smoking cessation, as did ground-glass opacity and centrilobular nodules seen during the initial HRCT examination. Centrilobular nodules and ground-glass opacity, which are the main features of high-resolution computed tomography of respiratory bronchiolitis-associated interstitial lung disease patients and represent pathological respiratory bronchiolitis, can be improved by smoking cessation. The diffusing capacity of the lung for carbon monoxide in respiratory function tests can be also improved.

[HRCT findings for four cases of measles pneumonia].

Although, in Western countries, adult-onset pneumonia that is associated with measles is not rare, reports of its incidence in Japan have been sparse. Among eight adolescent and adult (16-34-year-old) measles patients hospitalized in National Sanatorium Tsuruga Hospital, we found four in whom chest radiography and CT revealed pneumonia. The high-resolution lung CTs of these patients revealed features differing from those characteristic of bacterial pneumonia: bronchial wall thickness, centrilobular nodules in ground glass opacity, interstitial lesions (interlobular septal thickening, fissure thickening, pleural effusion) and lymphadenopathy. Of these findings, the centrilobular nodules in ground glass opacity were marked in these cases, and so this may be the most prominent finding in measles pneumonia; and furthermore, since interlobular septal thickening has not been reported in mycoplasma pneumonia or other atypical pneumonias, it may indicate a measles-specific, virus-induced pneumonia.

[Acute eosinophilic pneumonia with positive response to smoking challenge test, suggesting the involvement of health food].

A 17-year-old girl was admitted to our hospital because of acute febrile illness, progressive dyspnea and severe hypoxemia. Chest radiography and HRCT showed bilateral diffuse ground-glass opacities, consolidation, Kerley lines and pleural effusion. Analysis of bronchoalveolar lavage fluid showed 41.9% eosinophils, and a transbronchial lung biopsy revealed infiltration of eosinophils into the alveolar septa and mild alveolar septal edema. The patient's condition was improved immediately by corticosteroid therapy. She had begun smoking and taking health food (chitosan) 3 months before the admission. A smoking challenge test was positive and a drug-induced lymphocyte stimulation test for chitosan was positive. These findings suggested acute eosinophilic pneumonia caused by smoking and health food. The concentration of interleukin-5 (IL-5) in the serum and BALF/granulocyte colony-stimulating factor (G-CSF) in the serum on admission were very high, but decreased after the improvement. Therefore, it is likely that IL-5 and G-CSF are important in the onset of acute eosinophilic pneumonia.

[Clinical significance of sialyl SSEA-1 (SLX) in patients with idiopathic interstitial pneumonia].

Serum SLX levels were measured in 29 patients with idiopathic interstitial pneumonia (IIP) to evaluate its clinical significance. Serum SLX had positive correlations with the BALF neutrophil ratio but not with the severity or the disease activity in patients with IIP, and bronchoalveolar lavage fluid (BALF) SLX had positive correlations with the BALF neutrophil count. Epithelial lining fluid (ELF) SLX levels showed positive correlations with serum SLX, but were much higher. These results suggest that increases of serum SLX may reflect increases of SLX in the lung tissues. Thus, we speculate that increases of the serum SLX level may represent increases of the BALF neutrophil count. Patients with higher SLX showed poor therapeutic responses and poor prognoses in comparison with those with normal SLX for the reason that serum SLX level represents BALF neutrophil level.

[A case of pulmonary thromboembolism with heparin-induced thrombocytopenia].

In February 2000, a 70-year-old man was admitted to our hospital complaining of back pain and dyspnea on exertion. Pulmonary thromboembolism was diagnosed, and he was treated with intravenous urokinase and heparin. The pulmonary thromboembolism improved, though heparin-induced thrombocytopenia (HIT) was subsequently observed. The thrombocytopenia was then improved by withdrawing the intravenous heparin, but thrombosis appeared extending from both femoral veins to the inferior vena cava. The thrombosis was dispersed by catheter-directed thrombolysis. There have been few reports of HIT in Japan. Heparin is frequently used for the treatment of pulmonary thromboembolism, but special care must be taken, since severe thrombotic complications are associated with HIT.

[A case of radiologically negative small-cell lung carcinoma successfully detected early by whole-body FDG-PET].

A 68-year-old man was referred to our hospital after being treated for early gastric cancer to investigate the causative malignancy, as his serum carcinoembryonic antigen (CEA) level was increased. Chest radiography showed no abnormal opacities. Subsequently, a whole-body FDG-PET was performed, which detected some tiny lesions in the mediastinum and the right lower lung field. A diagnosis of small-cell lung carcinoma was made after mediastinoscopic and bronchoscopic examinations. After chemoradiotherapy, the previously abnormal uptake of FDG was attenuated and the bronchoscopic appearance was improved, while the serum CEA and NSE levels returned to normal. Our findings demonstrated that whole-body scanning by FDG-PET could be useful for early detection of lung cancer, especially in cases of small-cell lung cancer.

[The effect of O2 therapy on mixed venous concentration of endothelin-1 in chronic obstructive pulmonary disease].

Pulmonary hypertension (PH) is an important factor in the prognosis of cases of chronic obstructive pulmonary disease (COPD), and endothelin-1 (ET-1) is a major factor in the development of PH in COPD. Oxygen (O2) therapy improves the prognosis of COPD by suppressing the development of PH. We therefore assessed the correlation of PH and ET-1, and the effect of O2 therapy on the plasma ET-1 concentration. In COPD patients, the plasma ET-1 level in mixed venous blood, but not in arterial blood, was negatively correlated with mixed venous O2 tension and positively correlated with pulmonary vascular resistance. No such correlation, however, was observed in the case of plasma HANP or plasma BNP. O2 administration significantly suppressed the plasma ET-1 level. This level in mixed venous blood was thought to serve as a marker of PH in COPD. and O2 administration decreased the plasma ET-1 level in mixed venous blood. It consequently attenuated PH.

[A case of lymphocytic interstitial pneumonia with Sjögren's syndrome and systemic lupus erythematosus in which human herpes virus-6 infection was the suspected pathogen].

A 47-year-old-woman was admitted to our hospital complaining of thirst and dry cough after catching cold. Sjögren's syndrome (SjS) and systemic lupus erythematosus (SLE) were diagnosed. Chest X-P and CT findings suggested strongly that she had interstitial pneumonia. Thoracoscopic lung biopsy was therefore performed, and the biopsy specimens showed marked infiltration of small lymphocytes and of plasma cells into the alveolar walls and interlobular septa. Since the infiltrating cells were not atypical and gene analysis did not show mono-clonality, we made a diagnosis of lymphocytic interstitial pneumonia (LIP). Because the patient's symptoms appeared only after she caught cold, we suspected that virus infections were somewhat involved in the etiology of these diseases. The level of human herpesvirus-6 (HHV-6) antibody was high, and furthermore, HHV-6 was detected using the polymerase chain reaction from lung biopsy specimens. We suspected in this case that LIP, SjS, and SLE had appeared concomitantly after an active HHV-6 infection.

[Evaluation of fluorine-18-fluorodeoxyglucose whole body positron emission tomography imaging in the clinical diagnosis of lung cancer].

In recent years the use of positron emission tomography (PET) with fluorine-18-fluorodeoxyglucose (FDG) has become a valuable tool in the detection of a variety of tumors including lung cancer. To determine its role in the diagnosis of patients with suspected lung cancer, we compared the results of FDG-PET with those of the other scintigraphic imaging techniques (67Ga-planar image, 201Tl-SPECT and 99mTc-bone scintigraphy) used worldwide in patients with lung cancer. The analysis group consists of 178 patients, 159 malignant pulmonary diseases and 19 benign pulmonary diseases. FDG-PET was performed in 65 patients (51 malignant pulmonary diseases, 14 benign pulmonary diseases). FDG-PET had a sensitivity, specificity and accuracy of 98.0%, 78.6% and 93.8%, respectively, in detecting malignant pulmonary nodules. In N staging, sensitivity, specificity and accuracy were 66.7%, 81.3% and 76.0%, respectively. In M staging, the accuracy was 100%. Thus, FDG-PET imaging was more accurate than the other types of scintigraphic imaging. In our observations, whole-body 18FDG-PET images improved diagnostic accuracy in the evaluation of lung lesions and the staging of lung cancer.

Increased secretory leukoprotease inhibitor in patients with nonsmall cell lung carcinoma.

BACKGROUND: It is well known that acute pulmonary inflammation, such as that observed in pneumonia, elevates secretory leukoprotease inhibitor (SLPI) levels in serum. A previous report indicated that serum SLPI levels in lung carcinoma patients with concurrent pneumonia were significantly higher than in those in patients whose disease was unaccompanied by pneumonia or in healthy subjects. The authors hypothesized that serum SLPI may increase in patients with lung carcinoma, even carcinoma occurring without pneumonia, and that cells in lung carcinoma might produce SLPI. METHODS: Serum SLPI levels in 58 patients with primary lung carcinoma unaccompanied by pneumonia and in 42 healthy subjects were measured by an enzyme immunoassay. Twenty-four specimens from 24 of the patients with primary lung carcinoma also were examined immunohistochemically using the rabbit antihuman SLPI antibody. RESULTS: The results of the current study confirmed that the serum levels of SLPI in patients with primary lung carcinoma were higher than those in healthy subjects, and further found there was no significant correlation between serum SLPI levels and C-reactive protein in lung carcinoma patients without pneumonia. When classifying primary lung carcinoma by its histology, SLPI levels in patients with adenocarcinoma and squamous cell carcinoma were significantly higher than in those in patients with small cell lung carcinoma (SCLC). In patients with nonsmall cell lung carcinoma (NSCLC), the SLPI levels in the advanced group (International Union Against Cancer Stages III and IV disease; n = 35) were significantly elevated compared with the nonadvanced group (Stages I and II disease; n = 12), and such elevated SLPI levels were reduced in some cases by an efficient response to surgical therapy or chemotherapy. Immunohistochemical studies showed that all the NSCLC tissues were stained with anti-human SLPI antibody, whereas staining was not noted in any of the SCLC tissues. CONCLUSIONS: The authors believe that the findings of the current study demonstrate that cells of NSCLC produce SLPI. Furthermore, they suggest that serum SLPI levels in serum may be a helpful marker in patients with NSCLC unaccompanied by pneumonia, and that SLPI also could be used as an immunohistochemical marker to distinguish between NSCLC and SCLC.

[The usefulness of serum KL-6 levels for the diagnosis of disease activity in idiopathic interstitial pneumonia].

Serum KL-6 levels were measured in 29 patients with idiopathic interstitial pneumonia (IIP) as a means of evaluating disease activity. Levels of serum KL-6 were significantly higher in patients with active IIP (n = 11) than in those with inactive IIP (n = 18). The levels of serum KL-6 were 2,546 +/- 1,703 U/ml in patients with active IIP and 795 +/- 385 U/ml in patients with inactive IIP, respectively. The levels of serum LDH, CEA, P-III-P, and 7 S collagen in patients with active IIP did not differ significantly from those in patients with inactive IIP. For the diagnosis of active IIP, the sensitivity of serum KL-6 (cut off value of 1,500 U/ml) was 81.8% and the specificity, 94.4%. These results were almost identical to findings obtained with chest Ga-67 scintigraphy. Furthermore, they suggested that serum KL-6 levels may be a useful marker for the diagnosis of disease activity in IIP, as well as a useful indicator for the administration of steroid therapy to patients with IIP.

[Neurally mediated syncope in association with small cell lung carcinoma].

A 66-year-old woman was admitted to our hospital because of frequent syncopal episodes and for treatment of small cell lung carcinoma. Neurally mediated syncope was diagnosed by the head-up tilt test, which evoked early severe hypotension (after 12 min at the 80-degree tilt position). Treatment of carcinoma by chemotherapy and radiotherapy promptly eliminated the syncopal episodes. This was an unusual case of neurally mediated syncope associated with small cell lung carcinoma.

Leukotoxin, 9,10-epoxy-12-octadecenoate, causes pulmonary vasodilation by stimulation of vascular eNOS and iNOS.

We have previously reported that leukotoxin, 9,10-epoxy-12-octadecenoate (Lx) dilates rat pulmonary arteries by means of nitric oxide synthase (NOS) activation. In this study, we investigated if Lx stimulates constitutive and/or inducible NOS. We studied the effect of the NOS inhibitors, N(G)-monomethyl-L-arginine and aminoguanidine, as well as endothelium denudation on Lx-induced rat pulmonary arterial dilation and that of aminoguanidine on Lx-induced endothelium denuded lipopolysaccharide (LPS)-treated rat pulmonary arterial dilation and tissue cGMP content. Furthermore, we assessed the effect of aminoguanidine, an inducible NOS (iNOS) inhibitor, on the cGMP content increase induced by Lx in LPS-treated human pulmonary artery smooth muscle cells (HPASMC). The NOS inhibitors and endothelium denudation significantly attenuated Lx-induced vasodilation. Aminoguanidine also significantly attenuated Lx-induced vasodilation in LPS-treated rat denuded pulmonary arteries, and attenuated Lx-induced cGMP content increase in denuded pulmonary arterial rings from LPS-treated rats and in LPS-treated HPASMC. These results suggest that Lx causes pulmonary vasodilation by stimulation of vascular endothelial NOS (eNOS) and iNOS.

[Two cases of lung metastasis of malignant melanoma].

We report 2 cases of lung metastasis of malignant melanoma. Patient 1 was a 71-year-old woman who had undergone an operation for enucleation of her left eye 13 years earlier. Chest magnetic resonance imaging (MRI) demonstrated intermediate intensity including partially high intensity on T 1 weighted images, and high intensity including partially low intensity on T 2 weighted images. Microscopic findings from a transbronchial lung biopsy specimen disclosed melanotic melanoma. Patient 2 was a 54-year-old man who had undergone surgery for malignant melanoma in the left upper arm 4 years earlier. Chest MRI films demonstrated low intensity on T 1 weighted images, and high intensity on T 2 weighted images. Microscopic findings from specimens of the primary lesion in the left upper arm revealed melanotic melanoma, but the findings from the lower right lobectomy disclosed amelanotic melanoma. It has been reported that MRI is useful in the diagnosis of malignant melanoma, and that melanin content reflects MRI signal intensity. The MRI findings were consistent with the histopathologic findings in each of the 2 cases we reported.

[Silicosis characterized by increasing serum CA 19-9 in parallel with progression of lung fibrosis].

In November 1997, a 61-year-old man was admitted to our hospital complaining of dyspnea. He had worked as a miner for 10 years and had received medical treatment based on a diagnosis of idiopathic interstitial pneumonia at our hospital since 1984. In conjunction with the progression of interstitial pneumonia, the patient's serum CA 19-9 had gradually increased since 1992, reaching 9,920 U/ml in 1997. Though cancer of the pancreas or other organs was suspected, an extensive examination revealed no malignancy. In April 1998, the patient died of bacterial pneumonia. Lung autopsy specimens disclosed severe interstitial fibrosis with prominent silicotic nodules. Based on these findings, silicosis was diagnosed. In immunohistochemical staining for CA 19-9, the lumina of severely fibrotic lesions covered with epithelial cells stained positively with anti-CA 19-9 antibody. These findings suggested that serum CA 19-9 may have been produced in the epithelial cells. We speculated that increased serum CA 19-9 levels in patients with interstitial pneumonia may occasionally be more indicative of the magnitude of destruction of lung architecture than the degree of disease activity.