Kazunori Tobino

Characteristics of pulmonary cysts in Birt–Hogg–Dubé syndrome: Thin-section CT findings of the chest in 12 patients

PURPOSE To describe in detail the characteristic chest computed tomography (CT) findings of Birt-Hogg-Dubé (BHD) syndrome. MATERIALS AND METHODS Thin-section chest CT scans of consecutive 12 patients with genetically diagnosed BHD syndrome were retrospectively evaluated by two observers, especially about the characteristics (distribution, number, size, shape and relation to pleura) of pulmonary cysts. Interobserver agreement in the identification of abnormalities on the CT images was achieved using the κ statistic, and the degree of interobserver correlation for the characterization of pulmonary cysts was assessed using the Spearman rank correlation coefficient. RESULTS Multiple pulmonary cysts were seen in all patients. The number of cysts in each patient was various (range, 29-407), and cysts of various sizes (from a few mm to 2 cm or more) were seen in all patient. 76.6% (mean) of cysts were irregular-shaped, and 40.5% (mean) of cysts were located along the pleura. The mean extent score of cysts was 13% of the whole lung, and the distribution of cysts was predominantly in the lower medial zone. Finally, cysts abutting or including the proximal portions of lower pulmonary arteries or veins were also seen in all patients. CONCLUSION Multiple, irregular-shaped cysts of various sizes with lower medial lung zone predominance are characteristic CT findings of BHD syndrome. Cysts abutting or including the proximal portions of lower pulmonary arteries or veins may also exist in this syndrome in a high probability.

Differentiation between Birt–Hogg–Dubé syndrome and lymphangioleiomyomatosis: Quantitative analysis of pulmonary cysts on computed tomography of the chest in 66 females

BACKGROUNDS Since Birt-Hogg-Dubé syndrome (BHDS) and lymphangioleiomyomatosis (LAM) share some clinical manifestations (multiple pulmonary cysts with pneumothorax, renal tumors, and sometimes skin lesions), the differential diagnosis of the two diseases becomes problem especially in female patients. This study aims to quantify pulmonary cysts in computed tomography (CT) of females with BHDS and those with LAM and also to identify the independent parameters for differentiating the two diseases. METHODS Fourteen patients with BHDS and 52 with LAM were studied. In CT scans, lung fields were defined as areas with fewer than -200 Hounsfield units (HU) and pulmonary cysts as areas consisting of 10 or more consecutive pixels with fewer than -960 HU. The extent, number, size and circularity of cysts were calculated by using hand-made software and compared between the two diseases. Moreover, the lung fields were divided into six zones and analyzed for the distribution of cysts. Finally, a stepwise discriminant analysis employing quantitative measurements of cysts and clinical features was performed. RESULTS The two diseases were significantly different in all quantitative measurements of cysts. Stepwise discriminant analysis accepted the following four variables: the family history of pneumothorax within the second degree relatives, lower-medial zone predominance of cysts, diffusing capacity and mean size of cysts in this order. CONCLUSION The quantitative characteristics of pulmonary cysts are significantly different between BHDS and LAM. The independent parameters for differentiating the two diseases are the family history of pneumothorax, zonal predominance of cysts, diffusing capacity and size of cysts.

Complete lack of vitamin C intake generates pulmonary emphysema in senescence marker protein-30 knockout mice

Vitamin C (VC) is a potent antioxidant and plays an essential role in collagen synthesis. As we previously reported, senescence marker protein-30 (SMP30) knockout (KO) mice cannot synthesize VC due to the genetic disruption of gluconolactonase (i.e., SMP30). Here, we utilized SMP30 KO mice deprived of VC and found that VC depletion caused pulmonary emphysema due to oxidative stress and a decrease of collagen synthesis by the third month of age. We grew SMP30 KO mice and wild-type (WT) mice on VC-free chow and either VC water [VC(+)] or plain water [VC(-)] after weaning at 4 wk of age. Morphometric findings and reactive oxygen species (ROS) in the lungs were evaluated at 3 mo of age. No VC was detected in the lungs of SMP30 KO VC(-) mice, but their ROS increased 50.9% over that of the VC(+) group. Moreover, their collagen content in the lungs markedly decreased, and their collagen I mRNA decreased 82.2% compared with that of the WT VC(-) group. In the SMP30 KO VC(-) mice, emphysema developed [21.6% increase of mean linear intercepts (MLI) and 42.7% increase of destructive index compared with VC(+) groups], and the levels of sirtuin 1 (Sirt1) decreased 16.8%. However, VC intake increased the MLI 16.2% and thiobarbituric acid reactive substances 22.2% in WT mice, suggesting that an excess of VC can generate oxidative stress and may be harmful during this period of lung development. These results suggest that VC plays an important role in lung development through affecting oxidant-antioxidant balance and collagen synthesis.

Characterization of pulmonary cysts in Birt–Hogg–Dubé syndrome: histopathological and morphometric analysis of 229 pulmonary cysts from 50 unrelated patients

To characterize the pathological features of pulmonary cysts, and to elucidate the possible mechanism of cyst formation in the lungs of patients with Birt–Hogg–Dubé syndrome (BHDS), a tumour suppressor gene syndrome, using histological and morphometric analyses.

Vitamin C Prevents Cigarette Smoke–Induced Pulmonary Emphysema in Mice and Provides Pulmonary Restoration

Vitamin C (VC) is a potent antioxidant and is essential for collagen synthesis. We investigated whether VC treatment prevents and cures smoke-induced emphysema in senescence marker protein-30 knockout (SMP30-KO) mice, which cannot synthesize VC. Two smoke-exposure experiments using SMP30-KO mice were conducted. In the first one (a preventive study), 4-month-old mice received minimal VC (0.0375 g/l) [VC(L)] or physiologically sufficient VC (1.5 g/l) [VC(S)] and exposed to cigarette smoke or smoke-free air for 2 months. Pulmonary evaluations followed when the mice were 6 months of age. The second study began after the establishment of smoke-induced emphysema (a treatment study). These mice no longer underwent smoke exposure but received VC(S) or VC(L) treatment for 2 months. Morphometric analysis was performed, and measurements of oxidative stress, collagen synthesis, and vascular endothelial growth factor in the lungs were evaluated. Chronic smoke exposure caused emphysema (29.6% increases of mean linear intercepts [MLI] and 106.5% increases of destructive index compared with the air-only group) in 6-month-old SMP30-KO mice, and this emphysema closely resembled human chronic obstructive pulmonary disease. Smoke-induced emphysema persisted in the VC(L) group after smoking cessation, whereas VC treatment provided pulmonary restoration (18.5% decrease of MLI and 41.3% decrease of destructive index compared with VC(L) group). VC treatment diminished oxidative stress, increased collagen synthesis, and improved vascular endothelial growth factor levels in the lungs. Our results suggest that VC not only prevents smoke-induced emphysema in SMP30-KO mice but also restores emphysematous lungs. Therefore, VC may provide a new therapeutic strategy for treating chronic obstructive pulmonary disease in humans.

Multidetector CT of the Lung: Image Quality with Garnet-based Detectors

PURPOSE To evaluate the image quality of both standard- and reduced-dose computed tomography (CT) by comparing multidetector CT with garnet-based detectors with multidetector CT with conventional detectors. MATERIALS AND METHODS The study was approved by the internal ethics review board. Informed consent was obtained. Eleven cadaveric lungs inflated and fixed by using the Heitzman method were scanned by using both CT with garnet-based detectors and CT with conventional detectors. Tube current was 400 mA for standard-dose and 10 mA for reduced-dose CT, and voltage was 120 kVp. Either normal scan mode with 984 views (conventional and garnet-based detectors) or high-resolution mode with 2496 views was used. Image quality at conventional-detector CT and garnet-based-detector CT in all modes was graded by two independent observers with a five-point scale. The evaluation items included normal lung structures, subjective visual noise, and abnormal CT findings. Quantitative image noise measurements were calculated by measuring the standard deviations in a circular region of interest on each selected image. RESULTS At standard-dose CT, image quality at CT with garnet-based detectors (high-resolution mode) was significantly improved (P < .001, Tukey-Kramer). However, there was no significant difference between quantitative image noise measurements (P > or = .24). At reduced-dose CT, only noise differed significantly, with both subjective visual noise and quantitative image noise measurements significantly greater at CT with garnet-based detectors (high-resolution mode) (P < or = .01). There was no significant difference in image quality except for noise between conventional-detector CT and garnet-based-detector CT (P > or = .06). CONCLUSION The image quality of standard-dose garnet-based-detector CT (high-resolution) was significantly improved. Although highly reduced-dose garnet-based-detector CT (high-resolution mode) provided more image noise, overall image quality was not different between conventional-detector CT and garnet-based-detector CT.

Comparison of chest computed tomography features in the acute phase of cardiogenic pulmonary edema and acute respiratory distress syndrome on arrival at the emergency department.

Purpose: Discriminating cardiogenic pulmonary edema (CPE) from acute respiratory distress syndrome (ARDS) is a serious problem in emergency departments, and the ability of chest radiographs to differentiate between these 2 entities is limited. We compared the chest computed tomography (CT) findings in the acute phase of CPE with those of ARDS. Materials and Methods: Outpatients with acute respiratory failure presenting to emergency departments with bilateral pulmonary opacities were enrolled. The patients included not only those who visited our hospital first but also those referred from other hospitals. Two intensivists who were blinded to the results of the chest imaging studies reviewed the patients’ clinical records independently in order to determine a diagnosis of CPE or ARDS, and the chest CT findings were independently evaluated by 2 radiologists who were unaware of the patients’ clinical information. The positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy of the statistically different findings were calculated using standard definitions. Results: Forty-one patients with CPE and 20 patients with ARDS were assessed. Upper-lobe–predominant ground-glass attenuation, central-predominant ground-glass attenuation, and central airspace consolidation were associated with high PPVs (95.2%, 92.3%, and 92.0%, respectively) and moderate NPVs (47.5%, 51.4%, and 50.0%, respectively) to diagnose as CPE. Left-dominant pleural effusion and small ill-defined opacities revealed relatively high PPVs (71.4% and 58.3%, respectively) and NPVs (72.2% and 73.5%, respectively) to diagnose as ARDS. The overall accuracy of the diagnosis by chest CT was 88.5% (54/61). Conclusions: Chest CT may be a useful tool for differentiating CPE from ARDS in the emergency department setting.

Computed tomographic features of lymphangioleiomyomatosis: Evaluation in 138 patients

PURPOSE The aim was to characterize the computed tomographic (CT) findings from Japanese patients with lymphangioleiomyomatosis (LAM). MATERIALS AND METHODS CT scans of the chest, abdomen, and pelvis from 124 patients with sporadic LAM (S-LAM, mean age, 37.4 years) and 14 patients with tuberous sclerosis complex (TSC)-LAM (mean age, 35.6 years) were analyzed. RESULTS Pulmonary nodules (18.8%) and hepatic angiomyolipoma (AML, 24.3%) were more common in our patients than those in previous reports. Compared with TSC-LAM, S-LAM group had a higher frequency of pulmonary nodules (28.6% vs 32.3%, P<0.01) and lower frequencies of air-space consolidation (21.4% vs 2.4%, P<0.01), pneumothorax (28.6% vs 8.1%, P=0.02), pulmonary hilar lymphadenopathy (14.3% vs 0.8%, P<0.01), renal AML (85.7% vs 17.4%, P<0.01), hepatic AML (71.4% vs 17.4%, P<0.01), and retrocrural lymphadenopathy (14.3% vs 1.4%, P=0.04). Axial lymphatic abnormalities (i.e., thoracic duct dilatation, lymphadenopathy, and lymphangioleiomyoma) were most common in the pelvis and tended to decrease in incidence with increased distance from the pelvis. CONCLUSION The incidence of some CT findings in Japanese patients differed from those in previous reports. Axial lymphatic abnormalities noted here suggest that the origin of LAM cells may be the pelvis.

Quantitative CT analysis of small pulmonary vessels in lymphangioleiomyomatosis

BACKGROUNDS Lymphangioleiomyomatosis (LAM) is a destructive lung disease that share clinical, physiologic, and radiologic features with chronic obstructive pulmonary disease (COPD). This study aims to identify those features that are unique to LAM by using quantitative CT analysis. METHODS We measured total cross-sectional areas of small pulmonary vessels (CSA) less than 5mm(2) and 5-10mm(2) and calculated percentages of those lung areas (%CSA), respectively, in 50 LAM and 42 COPD patients. The extent of cystic destruction (LAA%) and mean parenchymal CT value were also calculated and correlated with pulmonary function. RESULTS The diffusing capacity for carbon monoxide/alveolar volume (DL(CO)/VA %predicted) was similar for both groups (LAM, 44.4 ± 19.8% vs. COPD, 45.7 ± 16.0%, p=0.763), but less tissue damage occurred in LAM than COPD (LAA% 21.7 ± 16.3% vs. 29.3 ± 17.0; p<0.05). Pulmonary function correlated negatively with LAA% (p<0.001) in both groups, yet the correlation with %CSA was significant only in COPD (p<0.001). When the same analysis was conducted in two groups with equal levels of LAA% and DL(CO)/VA %predicted, %CSA and mean parenchymal CT value were still greater for LAM than COPD (p<0.05). CONCLUSIONS Quantitative CT analysis revealing a correlation between cystic destruction and CSA in COPD but not LAM indicates that this approach successfully reflects different mechanisms governing the two pathologic courses. Such determinations of small pulmonary vessel density may serve to differentiate LAM from COPD even in patients with severe lung destruction.

A Community-acquired Lung Abscess Attributable to Streptococcus pneumoniae which Extended Directly into the Chest Wall

We herein report the case of 75-year-old Japanese female with a community-acquired lung abscess attributable to Streptococcus pneumoniae (S. penumoniae) which extended into the chest wall. The patient was admitted to our hospital with a painful mass on the left anterior chest wall. A contrast-enhanced chest computed tomography scan showed a lung abscess in the left upper lobe which extended into the chest wall. Surgical debridement of the chest wall abscess and percutaneous transthoracic tube drainage of the lung abscess were performed. A culture of the drainage specimen yielded S. pneumoniae. The patient showed a remarkable improvement after the initiation of intravenous antibiotic therapy.