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PURPOSE: The aim of this study was to evaluate the relationships among [18F]fluorodeoxyglucose ([18F]-FDG) uptake, Glut-1 and HK-II expressions, and grade of inflammation in resected lung lesions. MATERIALS AND METHODS: Sixty patients had undergone preoperative 18F-FDG-PET imaging and thoracotomy. For semi-quantitative analysis of 18F-FDG uptake, partial volume effect corrected maximum standardized uptake values (pSUVs) were calculated. Immunohistochemical staining was performed in resected specimens using anti--Glut-1, anti--HK-II, and anti-proliferative cellular nuclear antigen (PCNA) antibodies, and immunoreactivities were scored as G-, H-, and P-indexes on a five-point scale (0: 0%; 1:∼20%, 2:∼40%; 3:∼60%; 4:∼80%, and 5:∼100% percentages of strongly immunoreactive cells). Grade of inflammation was also evaluated. RESULTS: The malignant lesions had higher pSUV and higher G- and H-indexes than nonmalignant lesions, pSUVs correlated with the G- (p < .001), H- (p < .01) and P-indexes (p < 0.01) in malignant lesions. In adenocarcinomas, cancers with lower differentiation showed higher expression of Glut-1 and HK-II than those with higher differentiation. A positive linear regression was observed between pSUVs and the grading of inflammation in nonmalignant lesions (p < 0.05). CONCLUSIONS: Our study indicates that 18F-FDG uptake in lung cancer correlates well with Glut-1, HK-II, and PCNA expression. For nonmalignant lesions, the presence of a higher inflammatory process correlated with 18F-FDG uptake. [ABSTRACT FROM AUTHOR]

A 71-year-old man presented with hemothorax with cough, sputa and worsening dyspnea. On chest X-ray and computed tomography(CT), a huge tumor in the right upper lobe with hematoma and small amount of gas suggesting hemopneumothorax was revealed. No apparent lymphadenopathy nor intrapulmonary metastases were observed. The tumor showed a little enhancement on the contrastenhanced CT. Then the resction of the tumor was performed, and the pathological evaluation revealed a carcionosarcoma (adenocarcinoma+osteosarcoma) pT3N0 (stage II B) G4 pl2. Sarcomatoid carcinoma such as carcinosarcoma should be considered as a possible cause of hemothorax in making a diagnosis of hemorrhagic hypovascular huge lung tumor.

Objective: The CT findings of pulmonary fibrosis in patients with pulmonary alveolar proteinosis (PAP) are not yet well defined. The objective of this study was to evaluate the CT findings of PAP with a focus on pulmonary fibrosis secondary to PAP., Materials and Methods: High-resolution CT (HRCT) scans of 44 patients with PAP were evaluated retrospectively with a focus on pulmonary fibrosis: 33 patients had autoimmune PAP, and 11 patients had secondary PAP. The intervals between the initial and last CT examinations ranged from 1 to 284 months (median, 60 months). The HRCT images were assessed by two chest radiologists independently; when the two radiologists disagreed, a final decision was made by consensus., Results: A crazy-paving pattern was a more common HRCT finding in patients with autoimmune PAP than in those with secondary PAP. Traction bronchiectasis was found in four patients (9%) on the initial scans and in 10 patients (23%) on the last scans. There was no honeycombing on the initial scans. Honeycombing developed in two patients (5%): It was detected on 2-year follow-up in one patient and on 6-year follow-up in the other patient. Among the patients with autoimmune PAP, those with fibrosis detected on HRCT during follow-up had a worse prognosis than those without fibrosis detected on HRCT (p = 0.041)., Conclusion: Fibrosis develops in approximately 20% of patients with PAP. The CT findings of parenchymal fibrosis suggest a poor outcome.

A 65-y-old Japanese man was referred to the respiratory medicine department because of abnormal radiologic findings. High-resolution chest computed tomography scans revealed a geographic distribution of ground-glass opacities and associated thickening of the interlobular septa (crazy-paving patterns) in both lower lobes. He had a habit of drinking 400-500 mL of milk and 400-800 mL of canned coffee with milk every day. A swallowing function test revealed liquid dysphagia. Bronchoalveolar lavage fluid cytology findings showed multiple lipid-laden macrophages. Taken together, these findings revealed exogenous lipoid pneumonia. We performed bronchoscopic segmental lavage therapy 3 times in the left lung. After the treatment, the radiologic findings improved in both lungs. The patient has not experienced a recurrence of lipoid pneumonia in 2 y to date. In conclusion, a case of exogenous lipoid pneumonia was successfully treated with bronchoscopic segmental lavage therapy., (Copyright © 2015 by Daedalus Enterprises.)

Aim: Thymoma is a rare neoplasm of the mediastinum, for which very few data on the efficacy and safety of chemotherapy and chemoradiotherapy are available. The objective of this pilot study was to assess the safety and efficacy of cisplatin, etoposide, and radiotherapy for thymoma., Patients and Methods: Patients with advanced, previously-untreated thymoma (Masaoka classification), measurable disease, and a performance status of 0-2 were eligible, and were treated with cisplatin-plus-etoposide, together with radiotherapy when possible., Results: One patient achieved complete response, and seven achieved partial responses. Progression-free survival was 37.7 months (95% confidence interval = 18.6-56.8 months). Ten patients had grade 4 neutropenia, and five patients had grade 3 febrile neutropenia. However, other toxicities were relatively mild. To date, only five patients (45.5%) have died, and the median survival time is 128.1 months (95% confidence interval = 51.6-204.6 months). Patients treated with chemoradiotherapy had a good response and long progression-free survival., Conclusion: The combination of cisplatin and etoposide with or without radiotherapy is effective for advanced thymoma, and has an acceptable toxicity.

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease with a poor prognosis. Recently, pirfenidone was reported to slow the rate of decline in vital capacity and improve progression-free survival in IPF. The purpose of this study was to clarify the factors that predicted a good response to pirfenidone, as well as its adverse effects., Methods: Forty-one IPF cases, treated with pirfenidone from January 2009 to January 2011, were enrolled in this investigation. Disease severity was classified into grades I-IV, as defined by the Japanese Respiratory Society (JRS). Short-term responsiveness to pirfenidone was evaluated by the modified criteria of the JRS. Predictors of nausea, anorexia, or both that represented important adverse effects were examined by multivariate Cox proportional hazard analyses. Predictors of short-time responsiveness were examined by multivariate logistic regression analyses., Results: Diagnosed by a surgical lung biopsy (SLB), the mild cases of grade I/II were predictors of good, short-term responsiveness. Patients taking acid-secretion inhibitors, including proton pump inhibitors and histamine H2-receptor antagonists, showed less anorexia, nausea, or both. Only 1 case was administered drugs to activate gastrointestinal motility., Conclusions: We concluded that IPF patients with a mild disease, diagnosis by SLB, or both showed indications of a good response to pirfenidone. In addition, acid-secretion inhibitors may reduce the frequency of anorexia, nausea, or both from pirfenidone., (© 2013 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Background: Eosinophilic pneumonia (EP) is characterized by eosinophil infiltration in the lung parenchyma. However, tracheobronchial lesions associated with the disease have been poorly described. To clarify the frequency and characteristics of cases with tracheobronchial lesions in EP, we performed a retrospective review of EP patients., Methods: We included 36 EP cases seen from January 2004 to December 2007 at the Kinki-Chuo Chest Medical Center. The incidence of tracheobronchial nodules and associated clinical features were analyzed., Results: Of these 36 patients, 29 had chronic eosinophilic pneumonia (CEP); 1, acute EP; 3, drug-induced EP; 2, allergic bronchopulmonary aspergillosis; and 1, parasite-related EP. Only 2 of the 29 CEP cases had tracheobronchial lesions. For both of these cases, bronchoscopy revealed multiple whitish nodules on the tracheobronchial mucosa. The associated histopathological findings revealed squamous metaplasia and eosinophil infiltration in the subepithelial region. In both cases, the nodules disappeared after steroid therapy. The prevalence of tracheobronchial lesions was 6.9% in CEP patients and 5.6% in EP patients overall. EP patients were divided into 3 groups: CEP with nodules (n=2), CEP without nodules (n=27), and other EP (n=7). We found that the CEP with nodules group showed a relatively higher incidence of respiratory symptoms, higher white blood cell (WBC) count, and higher levels of peripheral and bronchoalveolar eosinophilia than the other groups., Conclusions: Tracheobronchial nodules represent rare observations within the EP population, which are likely to reflect a severe disease condition., (Copyright © 2013 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

A 49-year-old man with superficial lymphadenopathy presented with symptoms of low-grade fever, general fatigue and weight loss. On examination, multiple superficial lymphadenopathies and brown macules were observed on the trunk. Laboratory studies revealed an elevation of serum C reactive protein and interleukin 6 (IL-6) in addition to polyclonal hyperimmunoglobulinaemia. High-resolution CT of the chest showed bilateral multiple nodules and patchy ground-glass opacities with interstitial thickening. Biopsy of the cervical lymph node and skin biopsy showed numerous perivascular plasma cells, which were characteristic of the plasma cell type of Castleman's disease. Surgical lung biopsy showed hyalinising granuloma, which are hyalinous nodular lesions surrounded by lymphoid cells. He was diagnosed with multicentric Castleman's disease complicated by pulmonary hyalinising granulomas; his symptoms improved by treatment with tocilizumab, which is a humanised antihuman IL-6 receptor monoclonal antibody and corticosteroid. This is the first report of a comorbid case successfully treated with tocilizumab and corticosteroid.

Background: In 2002 the American Thoracic Society/European Respiratory Society (ATS/ERS) classification of idiopathic interstitial pneumonias (IIPs) defined seven specific entities, and provided standardized terminology and diagnostic criteria. In addition, the historical "gold standard" of histologic diagnosis was replaced by a multidisciplinary approach. Since 2002 many publications have provided new information about IIPs., Purpose: The objective of this statement is to update the 2002 ATS/ERS classification of IIPs., Methods: An international multidisciplinary panel was formed and developed key questions that were addressed through a review of the literature published between 2000 and 2011., Results: Substantial progress has been made in IIPs since the previous classification. Nonspecific interstitial pneumonia is now better defined. Respiratory bronchiolitis-interstitial lung disease is now commonly diagnosed without surgical biopsy. The clinical course of idiopathic pulmonary fibrosis and nonspecific interstitial pneumonia is recognized to be heterogeneous. Acute exacerbation of IIPs is now well defined. A substantial percentage of patients with IIP are difficult to classify, often due to mixed patterns of lung injury. A classification based on observed disease behavior is proposed for patients who are difficult to classify or for entities with heterogeneity in clinical course. A group of rare entities, including pleuroparenchymal fibroelastosis and rare histologic patterns, is introduced. The rapidly evolving field of molecular markers is reviewed with the intent of promoting additional investigations that may help in determining diagnosis, and potentially prognosis and treatment., Conclusions: This update is a supplement to the previous 2002 IIP classification document. It outlines advances in the past decade and potential areas for future investigation.

Background and Objective: Despite significant recent progress in the understanding of idiopathic pulmonary fibrosis (IPF), the early phase of the disease is still poorly understood. We studied patients with IPF without pulmonary function impairment in order to determine the clinical features, natural history and key findings for physiological progression., Methods: Twenty-five patients without pulmonary function impairment were identified from among patients with previously diagnosed IPF who underwent surgical lung biopsies between January 1997 and December 2006 at our institutions. 'Without pulmonary function impairment' was defined as both forced vital capacity (FVC) and diffusing capacity for carbon monoxide (DLco) >80% predicted. Patients diagnosed with IPF through multidisciplinary discussion based on the new IPF guidelines were the subjects of this study., Results: Sixteen patients had a confirmed diagnosis of IPF. Eleven patients presented with chest X-ray abnormality found during an annual health examination. Seven patients were asymptomatic. Eleven patients showed physiological disease progression (median time; 19.9 ± 12.3 months) defined by a decline of at least 10% in FVC or at least 15% in DLco. Univariate analysis revealed that both usual interstitial pneumonia pattern and extent of honeycombing on high-resolution computed tomography (HRCT) were factors associated with disease progression (odds ratio 5.634, 95% confidence interval 1.364-23.278; odds ratio 2.371/5%, 95% confidence interval 1.042-5.395)., Conclusions: IPF patients without pulmonary function impairment have a progressive but slow clinical course. The existence and extent of honeycombing on HRCT are predictive of disease progression., (© 2013 The Authors. Respirology © 2013 Asian Pacific Society of Respirology.)

We described enlargement of intrathoracic diffuse large B-cell lymphoma (DLBCL) during treatment of pulmonary tuberculosis in a 78-year-old man. The patient had previously undergone treatment for pulmonary tuberculosis about 50 years ago and showed disease recurrence in 2010. Although after tuberculosis treatment with the standard chemotherapy regimen of isoniazid, rifampicin, ethambutol, and pyrazinamide, we observed a clear resolution of the main X-ray shadows, a nodular shadow in the right upper lung field was observed to have increased in size. After evaluation by transbronchial biopsy of the upper right lung lobe, we diagnosed DLBCL with subepithelial infiltration of an airway. This is a rare case of coexistence of active pulmonary tuberculosis and intrathoracic DLBCL.

Rationale: Idiopathic pulmonary fibrosis (IPF) is a chronic pulmonary disorder of unknown etiology with few treatment options. Although tetraspanins are involved in various diseases, their roles in fibrosis have not been determined., Objectives: To investigate the role of tetraspanin CD151 in pulmonary fibrosis., Methods: CD151 knockout (KO) mice were studied by histological, biochemical, and physiological analyses and compared with wild-type mice and CD9 KO mice. Further mechanistic analyses were performed in vitro, in vivo, and on samples from patients with IPF., Measurements and Main Results: A microarray study identified an enrichment of genes involved in connective tissue disorders in the lungs of CD151 KO mice, but not in CD9 KO mice. Consistent with this, CD151 KO mice spontaneously exhibited age-related pulmonary fibrosis. Deletion of CD151 did not affect pulmonary fibroblast functions but instead degraded epithelial integrity via attenuated adhesion strength on the basement membrane; CD151-deleted alveolar epithelial cells exhibited increased α-SMA expression with activation of p-Smad2, leading to fibrotic changes in the lungs. This loss of epithelial integrity in CD151 KO lungs was further exacerbated by intratracheal bleomycin exposure, resulting in severe fibrosis with increased mortality. We also observed decreased numbers of CD151-positive alveolar epithelial cells in patients with IPF., Conclusions: CD151 is essential for normal function of alveolar epithelial cells; loss of CD151 causes pulmonary fibrosis as a result of epithelial disintegrity. Given that CD151 may protect against fibrosis, this protein represents a novel target for the treatment of fibrotic diseases.

Background: Relationships among clinical, physiological, imaging and pathological findings of small airway disease associated with Sjögren's syndrome have remained unclear., Subjects and Methods: We retrospectively studied 14 patients who underwent surgical lung biopsy and who were diagnosed with small airway disease associated with primary or secondary Sjögren's syndrome. We compared clinical, bronchoalveolar lavage, physiological, imaging and pathological findings between primary and secondary Sjögren's syndrome. We scored HRCT and pathological abnormalities and investigated correlations among physiological, HRCT and pathological data, changes in physiological parameters and in HRCT scores after two years of treatment, as well as correlations between these values and pathological scores., Results: Bronchoalveolar lavage fluid, physiological, imaging and pathological findings of the airways did not significantly differ between primary and secondary Sjögren's syndrome. Air trapping on HRCT negatively correlated with MEF50 and MEF25. Although lymphoid cell infiltration and peribronchiolar fibrosis were the most common pathologies, constrictive change scores correlated negatively with MEF50 and MEF25, positively with air trapping scores and negatively with improvements after therapy in MEF(50), MEF(25) and air trapping., Conclusions: Constrictive change was the most significant determinant of physiological and imaging presentations and of changes in these factors after therapy for small airway disease associated with Sjögren's syndrome., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

A 49-year-old man consulted our hospital several days after the onset of dyspnea and was admitted because it rapidly exacerbated 9 days after presentation. Diffuse centrilobular micronodular shadows and diffuse opacities in all lung fields were noted on high-resolution computed tomography of the chest. Severe pulmonary hypertension and dilatation of the right ventricle was observed on echocardiography. Although there was no evidence of thrombus in the central portion of the pulmonary artery or deep veins of the lower limbs, the patient's respiratory insufficiency rapidly progressed and he died about 14 hours after admission. A postmortem examination revealed widespread gastric cancer and tumor emboli in the pulmonary arterioles, complicated with intraluminal organization, which is consistent with pulmonary-tumor thrombotic microangiopathy (PTTM). His serum level of vascular endothelial growth factor-D (VEGF-D) was elevated, but VEGF-D was not detected by immunohistological staining. A possible pathophysiological association with PTTM and VEGF-D should be examined in future studies.

The 1999 WHO classification of adenocarcinoma of the lung and pleural tumors listed five rare variants of adenocarcinoma of the lung: well-differentiated fetal adenocarcinoma, colloid 'mucinous' adenocarcinoma, mucinous cystadenocarcinoma, signet ring adenocarcinoma and clear-cell adenocarcinoma. The International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society developed a multidisciplinary, international classification of lung adenocarcinoma that was published in the February 2011 issue of the journal of Thoracic Oncology. This most current classification lists four rare variants of invasive adenocarcinoma of the lung: invasive mucinous adenocarcinoma (formerly mucinous bronchioloalveolar carcinoma), colloid adenocarcinoma (retained and expanded), fetal adenocarcinoma (retained) and enteric adenocarcinoma (new). Signet ring adenocarcinoma and clear-cell adenocarcinoma were removed from the list of variants of adenocarcinoma of the lung. Mucinous cystadenocarcinoma was merged into colloid adenocarcinoma. The new 2011 classification also takes into consideration of the amount of tissue sample available according to the two major methods how the tumor is procured: resection specimens versus small biopsy/cytology. Rare variants of invasive adenocarcinoma of the lung will only now be classified from resection specimens where adequate architecture of tumor can be identified.

We treated 8 cases of autoimmune pulmonary alveolar proteinosis (APAP) with whole lung lavage (WLL) in our hospital and evaluated the disease severity of APAP before and after WLL, adverse events (AEs) and recurrence-free survival in those cases who improved. In all cases, unilateral WLL was performed in both lungs. The median of total lavage volume in unilateral WLL was 17.9 L, and the median procedure time of unilateral WLL was 105 min. Fever was the most frequently observed AE (87.5% of all procedures). Pulmonary function tests (percentage of predicted value of VC, FEV1 and diffusing capacity of carbon monoxide), serum markers (KL-6, surfactant apoprotein (SP)-D, SP-A and carcinoembryonic antigens), arterial blood gas analyses (PaO2, AaDO2) and disease severity score all significantly improved after WLL. The serum levels of anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) antibody temporarily decreased after unilateral WLL, but returned to previous levels (before WLL) in 7 cases. The radiological findings improved in 6 cases. In the 7 improved cases in whom AaDO2 decreased more than 10 Torr, the median recurrence-free survival of APAP after WLL was 17.5 months. We concluded that WLL is an effective and safe method for the treatment of APAP, and all parameters except for anti GM-CSF antibody are useful to evaluate the effect of WLL.

Cryptococcal empyema is a rare disease which usually occurs in immunocompromised patients. We describe a 57-year-old man with diabetes mellitus with a mass-like shadow in the right middle lung field. Transbronchial lung biopsy of the right lung revealed numerous yeast-like fungi in fibrotic and necrotic lesions. These findings, together with positive serum cryptococcal antigen yielded a diagnosis of pulmonary cryptococcosis secondary to diabetes mellitus. Despite treatment with several anti-fungal drugs, and dyspnea and pleural effusion developed. He was referred to our hospital for further examination and therapy. The presence of positive cryptococcal antigen and numerous yeast-like fungi were confirmed cytologically in the pleural effusion. Therefore, we suspected that pulmonary cryptococcosis had perforated into the thoracic space and empyema had developed. Because antifungal drugs were ineffective, debridement of the fibrinopurulent material by medical thoracoscopy and chest drainage were performed. The clinical symptoms of this patient improved with antifungal treatment for 1 year, and we successfully treated the cryptococcal empyema without recurrence. Debridement by medical thoracoscopy and chest drainage were useful for this case of cryptococcal empyema.

Unlabelled: Clinical and other features, as well as prognostic factors for survival, were examined in patients with rapidly progressive interstitial pneumonia. The disease entity included different histological patterns with diverse outcomes, and distinctions were not possible from baseline data. Histological diagnosis was the only significant prognostic determinant., Background and Objective: The aim of the present study was to examine clinical and other features that might allow prognostic distinctions between histological patterns in presentations with rapidly progressive interstitial pneumonia (RPIP), and to assess prognostic factors for survival., Methods: Patients with RPIP among 425 consecutive patients with diffuse lung disease, who underwent surgical lung biopsy, were studied retrospectively. The discriminatory value of clinical and investigative features for identifying disease with a better outcome was evaluated. An a priori comparison was made between diffuse alveolar damage (DAD)/usual interstitial pneumonia with DAD pattern (Group A), and organizing pneumonia/non-specific interstitial pneumonia pattern (Group B)., Results: Twenty-eight patients (6.6%) fulfilled the criteria for RPIP. The diagnosis was Group A disease in 15 (DAD in 10, usual interstitial pneumonia with DAD in 5), and Group B disease in 13 (organizing pneumonia in 8, non-specific interstitial pneumonia in 5). There were no significant differences in initial findings between the groups. Prognosis was significantly better for Group B patients than for Group A patients (P=0.021). Neither BAL nor parenchymal high-resolution CT score was indicative of therapeutic responsiveness or outcome. Distinction between Group A and Group B on the basis of disease pattern was the only significant determinant of prognosis., Conclusions: RPIP included varied histological patterns with different outcomes, and in many cases these could not be predicted using baseline clinical data. Histology was the only significant predictor of ultimate prognosis.

Previous studies on the mammary carcinoma cell line have shown that the pre B cell leukemia transcription factor 1 (PBX1) was a transcription factor for valosin-containing protein (VCP), which is involved in invasion and metastasis of cancers. The roles of PBX1 and PBX2, a highly homologous transcription factor to PBX1, for expression of VCP were examined in the cell lines from non-small cell lung cancer (NSCLC). The effects of PBX1 and PBX2 on VCP expression were examined with siRNA in A549 and PC14 NSCLC cell lines. Expression levels of PBX2 and VCP were immunohistochemically examined and compared with each other in 206 NSCLC cases. Subsequently, significance of PBX expression in clinical behavior of NSCLC patients was evaluated. Expression levels of VCP mRNA significantly decreased when PBX2 but not PBX1 expression was knocked down in NSCLC cell lines. Immunohistochemically, staining intensity of PBX2 was correlated with that of VCP in clinical samples. Then correlation of PBX2 expression and clinical behavior of NSCLC patients was evaluated. Univariate analysis revealed high expression levels of PBX2 and VCP to be poor prognosticators for overall and disease-free survival. Multivariate analysis revealed that high expression of VCP but not PBX2 to be an independent prognostic factor. PBX2 is a transcription factor for VCP in NSCLC. Because high levels of PBX2 expression correlated with prognosis of NSCLC, PBX2 could be a target molecule for treatment of NSCLC.

Objective: The objective of this study was to evaluate the efficacy and safety of cisplatin-based chemotherapy followed by surgery for patients with a malignant nonseminomatous germ cell tumor (NSGCT) of the mediastinum., Methods: Ten patients with malignant NSGCTs received cisplatin-based induction chemotherapy and then underwent surgery. The clinicopathological characteristics of these 10 patients were examined retrospectively., Results: A partial response to induction chemotherapy was noted in eight patients and no response in two. The induction chemotherapy was tolerated well by all the patients. Each patient underwent complete surgical resection of the residual tumor following chemotherapy. A yolk sac tumor was detected in one patient and malignant teratoma along with a yolk sac tumor in one patient postoperatively. The overall survival of the 10 patients was 67% at 60 months of follow-up. The survival rate at 60 months was poorer for the patients whose resected specimens exhibited the presence of viable cells than for those whose specimens were free of viable cells., Conclusion: Postchemotherapy surgical resection of the residual tumor plays an integral role in the management of patients with NSGCT. The presence of viable tumor cells in the resected specimens is associated with poor survival.

Rationale: The 2002 American Thoracic Society/European Respiratory Society classification of idiopathic interstitial pneumonias identified nonspecific interstitial pneumonia (NSIP) as a provisional diagnosis. Concern was expressed that NSIP was a "wastebasket" category, difficult to distinguish from other idiopathic interstitial pneumonias., Objectives: The following questions were addressed: (1) Is idiopathic NSIP a distinct entity? 2) If so, what are its clinical, radiologic and pathologic characteristics? (3) What is the role of radiology and pathology in establishing the diagnosis? (4) To make a diagnosis of idiopathic NSIP, what other disorders need to be excluded and how should this be done?, Methods: Investigators who had previously reported cases of idiopathic NSIP were invited to submit cases for review (n = 305). After initial review, cases with complete clinical, radiologic, and pathologic information (n = 193) were reviewed in a series of workshops., Measurements and Main Results: Sixty-seven cases were identified as NSIP. Mean age was 52 years, 67% were women, 69% were never-smokers, and 46% were from Asian countries. The most common symptoms were dyspnea (96%) and cough (87%); 69% had restriction. By high-resolution computed tomography, the lower lung zones were predominantly involved in 92% of cases; 46% had a peripheral distribution; 47% were diffuse. Most showed a reticular pattern (87%) with traction bronchiectasis (82%) and volume loss (77%). Lung biopsies showed uniform thickening of alveolar walls with a spectrum of cellular to fibrosing patterns. Five-year survival was 82.3%., Conclusions: Idiopathic NSIP is a distinct clinical entity that occurs mostly in middle-aged women who are never-smokers. The prognosis of NSIP is very good.

A 31-year-old man was referred to our hospital for further investigation of a pulmonary shadow in July, 2004. Chest X-ray and CT films revealed an ill-defined nodule in the right middle lung field. Because the specimens of transbronchial lung biopsy were not diagnostic, video-assisted thoracoscopic surgery was performed. The pathologic diagnosis of the resected lung was lymphomatoid granulomatosis/angiocentric immunoproliferative lesion (LYG/AIL), grade I. Adjuvant therapy was not performed. There has been no evidence of recurrence during the 2-year postoperative follow-up period.

Background: Angiotensin II, a potent vasoconstrictor, has been considered to be involved in various fibrotic disorders including idiopathic interstitial pneumonias. To clarify whether this agent contributes to the development and progression of usual interstitial pneumonia, a major entity of idiopathic interstitial pneumonias, we immunohistochemically examined expression of its specific receptor, angiotensin II type 1 receptor, in human normal and diseased lung tissues., Methods: Video-assisted thoracoscopic lung biopsy specimens obtained from patients with usual interstitial pneumonia (n=8) were sectioned and stained using single or double immunostaining techniques with specific antibodies against angiotensin II type 1 receptor and smooth muscle actin. Lung tissues of desquamative interstitial pneumonia (n=2) and normal lung tissues (n=6) were also examined for comparative analyses., Results: Expression of angiotensin II type 1 receptor was limited in vascular and bronchial smooth muscle cells in normal lungs. In contrast, the receptor-positive mesenchymal cells, most of which were also positive for smooth muscle actin and arranged like a bundle, were markedly increased in association with dense collagen deposition in thickened alveolar walls of usual interstitial pneumonia. In desquamative interstitial pneumonia, the fibroproliferative change, including angiotensin II type 1 receptor-positive mesenchymal cell proliferation, was milder than that in usual interstitial pneumonia., Conclusions: These findings suggest that angiotensin II and its type 1 receptor play a profibrogenic role in idiopathic interstitial pneumonias, particularly in usual interstitial pneumonia. Furthermore, angiotensin II type 1 receptor-positive smooth muscle cells increased in diseased lung tissues may be contractile and may contribute to reduction of airspaces in usual interstitial pneumonia.

A 56-year-old female non-smoker complained of general fatigue and pyrexia. Laboratory examination revealed elevation of white blood cells (WBC) 10200/microl and C-reactive protein (CRP) 13.3mg/dl. Chest radiograph showed bilateral patchy and ring-shaped consolidations in both lungs. Chest computed tomography (CT) revealed multiple round ground glass opacities fringed with consolidation, namely the "reversed halo sign". Transbronchial lung biopsy specimens showed polypoid granulation tissue in terminal air spaces, consistent with an organizing pneumonia pattern. Clinical findings suggesting collagen vascular diseases and drug induced lung diseases were not recognized, thus cryptogenic organizing pneumonia (COP) was diagnosed. High dose methylprednisolone therapy improved her condition, and the ring-shaped opacities on chest CT resolved. She relapsed twice during approximately five years after the disease onset. Chest CT at the recurrences revealed subpleural patchy consolidations without formation of the "reversed halo sign". The sign was originally supposed to be specific for cryptogenic organizing pneumonia. However, other diseases like sarcoidosis and paracoccidioidomycosis have been reported to show this sign. The meaning of the "reversed halo sign" should be examined based on the accumulation of more cases.

Background: To investigate whether the better prognosis of interstitial pneumonias associated with collagen vascular disease (CVD) compared with idiopathic interstitial pneumonia (IIP) is due to higher frequency of the nonspecific interstitial pneumonia (NSIP) pattern in CVD, we compared the outcomes of patients from these two groups with the same histopathologic pattern., Subjects: The clinical features and survival of 362 patients (269 with IIP and 93 with CVD) diagnosed using surgical lung biopsy were analyzed., Results: The mean survival of the CVD group (131.0 mo) was longer than that of the IIP group (80.5 mo) (p<0.0001). The patients with usual interstitial pneumonia pattern among the CVD group (n=36) was younger, female, and predominantly nonsmoking compared with the IIP group (n=203). Although baseline lung functions were not significantly different, the CVD group survived longer (mean, 177.0 mo) than the IIP group (mean, 66.9 +/- 6.5 mo; p=0.001). By multivariate analysis, younger age, better pulmonary function, and the presence of a CVD were independent prognostic factors. In NSIP pattern, no significant differences in survival, clinical features, or lung function were found between the two groups., Conclusion: Our data suggest that the better prognosis of patients in the CVD group is not solely due to the predominance of the NSIP pattern. The prognosis of patients with the usual interstitial pneumonia pattern in CVD is better than in those with idiopathic pulmonary fibrosis, despite the same pathologic pattern. In contrast, in those with an NSIP pattern, the prognosis is similar in both groups.

Study Objectives: To evaluate the long-term clinical course of patients with idiopathic pulmonary fibrosis (IPF) complicated with pulmonary arterial hypertension., Design: Prospective analysis of consecutive IPF patients undergoing initial workup with right-heart catheterization (RHC) and pulmonary function testing (PFT). Pulmonary arterial pressure (PAP) and diffusion capacity of the lung for carbon monoxide (Dlco) were focused on., Setting: University hospital., Patients: Seventy-eight patients with IPF (67 men, 11 women; diagnosis by pathology, n = 59; clinical diagnosis, n = 19) had been followed up after initial workup for a maximum of 14 years., Measurements and Results: RHC data on 61 patients and PFT data on 52 patients were available. Five-year survival rates were 62.2% in the normal-PAP group (mean PAP < 17 mm Hg, n = 37) and 16.7% in the high-PAP group (mean PAP > 17 mm Hg, n = 24) [p < 0.001]; 70.4% in the preserved-Dlco group (percentage of predicted > 40%, n = 27) and 20.0% in the low-Dlco group (percentage of predicted < 40%, n = 25) [p < 0.001]; and 82.6% in group 1 (normal PAP and preserved Dlco, n = 23) and 15.6% in group 2 (high PAP, low Dlco, or both, n = 32) [p < 0.0001]. The relative risks of mortality within 5 years after RHC were 2.20 (95% confidence interval [CI], 1.40 to 3.45) in the high-PAP group, 2.70 (95% CI, 1.46 to 4.99) in the low-Dlco group, and 4.85 (95% CI, 1.97 to 11.97) in group 2., Conclusion: Dlco was a critical factor for evaluating disease status and prognosis, and PAP status provided feasible information in the initial workup of IPF patients.

We report two cases of bilateral diffuse bronchiectasis in which early recurrence of the original lung disease occurred after bilateral lung transplantation (LT). Patient 1 underwent cadaveric LT. Recurrent bronchiectasis occurred 4 months later, and he died 6 years after LT. Patient 2 underwent living-related lobar LT, bronchiectasis relapsed 4 months later, and he died 13 months after LT. Both cases were finally diagnosed as bilateral diffuse bronchiectasis by the pathological features of the explanted lungs: infiltration of inflammatory cells predominantly in the conducting airways with dilation of the bronchi of bilateral lungs and scarcity of foamy macrophages in the wall of the respiratory bronchioles. Similar pathological features were seen in autopsy specimens from patient 1 and a transbronchial biopsy specimen from patient 2. LT should be carried out with caution in patients with bilateral diffuse bronchiectasis. When performing LT in such patients, it is suggested that sinusitis should be controlled perioperatively.

Study Objectives: To report on our experience with acute interstitial pneumonia (AIP) in which patients underwent early diagnostic procedures and received mechanical ventilation with a "lung-protective" strategy and early institution of immunosuppressive therapy., Design: A retrospective chart review., Setting: A tertiary referral hospital., Participants: Ten patients with AIP who presented with idiopathic ARDS and showed diffuse alveolar damage on surgical lung biopsy specimens from July 1995 to March 2004., Measurements and Results: The median age of patients was 65.5 years (age range, 38 to 73 years). Patients presented with a median duration of severe dyspnea of 9.5 days (range, 2 to 34 days) at the hospital visit. All patients required mechanical ventilation beginning at median time of hospital day 1 (range, hospital day 0 to 5), which continued for a median duration of 9.5 days (range, 4 to 98 days). Patients received ventilation in the pressure assist-control mode with a median tidal volume of 6.97 mL/kg (range, 6.05 to 8.86 mL/kg) and median positive end-expiratory pressure of 11 cm H(2)O (range, 8 to 16 cm H(2)O). An aggressive diagnostic workup for respiratory infection, including BAL at a median time of hospital day 2 (range, hospital day 1 to 5) was performed. High-dose steroid pulse therapy was initiated on median hospital day 3.5 (range, hospital day 1 to 8), while surgical lung biopsy was performed on median hospital day 4 (range, hospital day 2 to 7). Eight patients (80%) survived to hospital discharge., Conclusion: Earlier intervention, such as an aggressive diagnostic approach, mechanical ventilation with lung-protective strategy, and the early institution of immunosuppressive may improve clinical outcome in patients with AIP.

A 52-year-old woman presented with low grade fever and fatigue. She had diffuse micronodules in both lung fields on chest X-ray. Chest CT showed diffuse multiple small nodules. Laboratory examination revealed high values for C-reactive protein, together with anemia and polyclonal hyper-immunoglobulinemia and an elevated interleukin-6 level. Although we suspected multicentric Castleman's disease, thoracoscopic lung biopsy revealed primary pulmonary MALT lymphoma by immunohistochemical analysis of tissue specimens. After COP and rituximab therapy, partial remission was obtained.

Study Objectives: To investigate the histopathologic pattern and clinical features of patients with rheumatoid arthritis (RA)-associated interstitial lung disease (ILD) according to the American Thoracic Society (ATS)/European Respiratory Society consensus classification of idiopathic interstitial pneumonia., Design: Retrospective review., Setting: Two thousand-bed, university-affiliated, tertiary referral center., Patients: Eighteen patients with RA who underwent surgical lung biopsy (SLBx) for suspected ILD., Method: SLBx specimens were reviewed and reclassified by three lung pathologists according to the ATS/European Respiratory Society classification. Clinical features and follow-up courses for the usual interstitial pneumonia (UIP) pattern and the nonspecific interstitial pneumonia (NSIP) pattern were compared., Results: The histopathologic patterns were diverse: 10 patients with the UIP pattern, 6 patients with the NSIP pattern, and 2 patients with inflammatory airway disease with the organizing pneumonia pattern. RA preceded ILD in the majority of patients (n = 12). In three patients, ILD preceded RA; in three patients, both conditions were diagnosed simultaneously. The majority (n = 13) of patients had a restrictive defect with or without low diffusion capacity of the lung for carbon monoxide (D(LCO)) on pulmonary function testing; 2 patients had only low (D(LCO)). The UIP and NSIP groups were significantly different in their male/female ratios (8/2 vs 0/6, respectively; p = 0.007) and smoking history (current/former or nonsmokers, 8/2 vs 0/6; p = 0.007). Many of the patients with the UIP pattern had typical high-resolution CT features of UIP. Five patients with the UIP pattern died, whereas no deaths occurred among patients with the NSIP pattern during median follow-up durations of 4.2 years and 3.7 years, respectively., Conclusions: The histopathologic type of RA-ILD was diverse; in our study population, the UIP pattern seemed to be more prevalent than the NSIP pattern.

Background: B7 proteins (CD80, CD86) are costimulatory molecules expressed on antigen-presenting cells and are essential factors for T cell activation., Objectives: The aim of this study is to investigate the relationship of B7 gene polymorphisms either to disease susceptibility or to cell profile of bronchoalveolar lavage (BAL) fluid in Japanese sarcoidosis patients., Methods: Gene polymorphisms located in CD80 promoter, CD80 exon 3 and exon 8 of CD86 were examined in 146 Japanese sarcoidosis patients and 157 healthy controls using single-strand conformation polymorphism and direct sequencing. The distribution of genotypes was compared between the two groups. BAL fluid cell profiles were compared for the various genotypes of the different polymorphisms for the 62 patients who underwent BAL., Results: There were no significant differences in the distribution of genotypes or allele frequencies for all polymorphisms between sarcoidosis and controls. There were no significant differences in BAL fluid cell profiles among the different genotype groups of the various polymorphisms studied., Conclusions: There was no relationship between the B7 gene polymorphisms studied and disease susceptibility or BAL fluid cell profiles in Japanese sarcoidosis patients., (Copyright 2005 S. Karger AG, Basel)

We report a case of a patient with anti PL-12 antibody accompanied by interstitial pneumonia and severe pulmonary hypertension. At first presentation, hyperkeratotic skin lesions were found, although the diagnosis of CVD was not conclusive. Lung histology showed diffuse fibrosing interstitial pneumonia predominantly in the subpleural regions. During the seven-year follow-up period, severe pulmonary hypertension developed, although the progression of lung fibrosis was relatively limited. Anti-PL12 antibody was detected, and therefore the patient was diagnosed as having antisynthetase syndrome. Lung histology and pulmonary arteriogram suggested that vascular involvement of the disease contributed to the development of severe pulmonary hypertension.

The histopathologic pattern provides the most important prognostic marker for idiopathic interstitial pneumonia; however, studies have suggested that short-term changes in lung function may be more important. We investigated the prognostic factors for fibrotic interstitial pneumonia. The clinical features and follow-up course of 179 patients (131 with idiopathic pulmonary fibrosis and 48 with nonspecific interstitial pneumonia; 41 fibrotic types and 7 cellular) were analyzed retrospectively. The lung function indices improved or stabilized in most patients with fibrotic nonspecific interstitial pneumonia in contrast to the deterioration or stable condition of most patients with idiopathic pulmonary fibrosis. The 5-year survival of patients with fibrotic nonspecific interstitial pneumonia (76.2%) was better than for those with idiopathic pulmonary fibrosis (43.8%) (p = 0.007). Multivariate analysis at the time of presentation revealed that pathologic pattern, age, and diffusion capacity had important prognostic implications. However, after 6 months of follow-up, changes in FVC, initial diffusion capacity, and sex were the only independent prognostic factors, with no additional prognostic information conferred by the histologic diagnosis. Our data confirmed the importance of physiological parameters including short-term change in FVC. However, at the time of diagnosis, histopathology was important for the prediction of prognosis and future change in lung function.

Rationale: Clinicopathologic pulmonary manifestations associated with primary Sjogren's syndrome have yet to be reviewed in a large series since the recognition of nonspecific interstitial pneumonia (NSIP) as a distinct histologic pattern., Objectives: To determine clinical presentations, high-resolution computed tomographic (HRCT) and histologic findings of the lung disease associated with primary Sjogren's syndrome in the light of NSIP, and to analyze prognosis of the disease., Methods: On the basis of 33 cases (31 surgical lung biopsies and 2 autopsies) collected consecutively from multiple centers, we have retrospectively evaluated clinical, radiologic, and pathologic manifestations of the disease. Prognostic factors were identified by univariate and multivariate analysis., Measurements and Main Results: We found that NSIP was the most frequently seen histologic pattern (20 of 33 cases [61%], 19 fibrosing and 1 cellular). Bronchiolar diseases and amyloid and malignant lymphoma were seen less frequently. HRCT-pathologic correlation resulted in a 94% positive predictive value of CT-NSIP pattern for pathologic diagnosis of NSIP, whereas the diagnostic value of HRCT was low (15%) with an HRCT pattern other than NSIP, data that may influence the decision to biopsy. The 5-year survival rate was 84% overall and 83% in patients with NSIP. Multivariate analysis on all patients showed that low Pa(O(2)) (p = 0.02) and presence of microscopic honeycombing (p = 0.04) were independently associated with survival. Patients with NSIP showed lower vital capacity (mean +/- SD: 68.5 +/- 16.6%pred) than patients without NSIP (92.5 +/- 18.6%pred; p < 0.001)., Conclusion: Among a diversity of pulmonary lesions in primary Sjogren's syndrome, NSIP was the commonest histologic pattern and had a favorable prognosis.

A 53-year-old woman visited our hospital in July 2002 with complaints of skin eruptions on the face and extremities, dry cough and dyspnea. A diagnosis of amyopathic dermatomyositis (ADM) was made on the basis of characteristic skin lesions and skin biopsy findings with slight muscle symptoms and mild elevation of muscle enzymes. Interstitial shadows were observed in both lower lung fields on chest radiographs, and thoracoscopic lung biopsy specimens revealed a diffuse alveolar damage (DAD) pattern. After induction of chemotherapy with prednisolone (50 mg/day) and cyclosporin A (150 mg/day), the respiratory symptoms and interstitial shadows were gradually reduced. Although it is known that interstitial pneumonia has an acute course and poor prognosis in ADM, the present case responded well to the chemotherapy with prednisolone and cyclosporin A.

Objective: SR-PSOX/CXCL16 is a transmembrane chemokine and is implicated in activated CD8+ T cell trafficking. In the present study, we examined the expression pattern of SR-PSOX/CXCL16 in the heart and investigated a potential role of SR-PSOX/CXCL16 in inflammatory valvular heart disease., Methods and Results: Initial expression of SR-PSOX/CXCL16 in murine embryos was detected in endothelial cells lining endocardial cushions in the forming heart at E11.5. From mid-gestation to adult, expression of this gene in the heart was exclusively observed in valvular endothelial cells. Examination of SR-PSOX/CXCL16 expression in human cardiac valves demonstrated that SR-PSOX/CXCL16 was strongly expressed in valvular and neocapillary endothelial cells in patients with infective endocarditis. SR-PSOX/CXCL16 expression in neocapillary endothelial cells was also observed in patients with rheumatic and atherosclerotic valvular disease. Moreover, CD8+ T cells were distributed closely to endothelial cells expressing SR-PSOX/CXCL16. In vitro adhesion assays showed that SR-PSOX/CXCL16 induced adhesion of activated CD8+ T cells to vascular cell adhesion molecule-1 (VCAM-1) through very late antigen-4 (VLA-4) activation. Furthermore, SR-PSOX/CXCL16 stimulated interferon-gamma (IFN-gamma) production by CD8+ T cells., Conclusions: SR-PSOX/CXCL16 may be involved in CD8+ T cell recruitment through VLA-4 activation and stimulation of IFN-gamma production by CD8+ T cells during inflammatory valvular heart disease.

Background: Sarcoidosis is a systemic disease characterized by T-cell activation and subsequent granuloma formation at the site of involvement. Genetic susceptibility is a key factor in the pathogenesis of this disease, and genes involved in T-cell regulation are potential candidates. Cytotoxic T-lymphocyte antigen-4 (CTLA-4) is a negative regulator of T-cell activation expressed on activated T-cells. The G allele of the CTLA-4 exon 1 polymorphism has previously been described to be associated with disease susceptibility in several autoimmune diseases. We investigated the relationship of CTLA-4 to disease susceptibility and cell profiles in bronchoalveolar lavage (BAL) in Japanese sarcoidosis patients., Methods: Japanese sarcoidosis patients (n = 135) and controls (n = 97) were typed for an A/G bi-allelic polymorphism in exon 1 of CTLA-4 using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and the distribution of genotypes was compared between both groups. Sixty-seven patients underwent BAL, and cell profiles in BAL fluid were compared between patients with G/G genotype and those with A/A genotype., Results: No significant differences in the distribution of genotype and allele frequencies were found between sarcoidosis (GG: 46%, AG: 39%, AA: 15%) and controls (GG: 42%, AG: 49%, AA: 8%). Patients with G/G genotype had significantly increased lymphocyte ratios, lymphocyte counts, and CD4(+) cell counts in BAL fluid compared with patients with A/A genotype (p < 0.05)., Conclusions: CTLA-4 exonl polymorphism might affect BAL fluid lymphocyte profiles in Japanese sarcoidosis patients.

Objective: The aim of this study was to determine whether the presence of lung shrinkage on CXR can predict diminished survival in patients with idiopathic pulmonary fibrosis (IPF)/usual interstitial pneumonia (UIP)., Methodology: In a hospital-based cohort study 68 subjects diagnosed with IPF/UIP by surgical lung biopsy or at autopsy were observed for a mean of 7.6 years. The radiographic scores from Cherniack's method, pulmonary function tests, arterial blood gas, and haematological data were obtained at initial presentation. Longitudinal radiographic changes over a mean interval of 2.7 years were measured. Survival analysis was performed using Kaplan-Meier and Cox's proportional hazards regression analysis., Results: At some point during the observation period 36 (53%) of 68 patients did not exhibit lung shrinkage and 32 (47%) of 68 patients showed lung shrinkage. Patients with lung shrinkage were more likely to have a diminished survival than those with lung preservation; median survival was 4.4 vs 7.8 years, respectively. Lung shrinkage during the observation period (hazard ratio, 3.89; 95% CI = 1.68-9.01; P= 0.001) was associated with lower rates of survival., Conclusion: In patients with IPF/UIP, lung shrinkage on CXR during the observation period was a poor prognostic factor.

We report here a case of solitary atypical adenomatous hyperplasia (AAH). A 17-year-old non-smoker man developed spontaneous pneumothorax, and computed tomogram scanning of his chest revealed a ground-glass opacity measuring 5 x 5 mm in the right lung with no change in its size for the next 7 months. To exclude the possibility of pulmonary neoplasia, he underwent partial pulmonary resection. The postoperative pathologic diagnosis was AAH. The present case is very exceptional for AAH because of the patient's young age and non-association with pulmonary carcinoma. The postoperative 23-month follow-up was uneventful., (Copyright 2003 S. Karger AG, Basel)

Respiratory bronchiolitis-associated interstitial lung disease (RB-ILD) is a clinicopathologic entity occurring rarely in smokers. We report three cases of RB-ILD diagnosed pathologically by surgical lung biopsy. Cough was observed in all cases, sputum in one case and dyspnea on exertion in another. Reduction of diffusing capacity was observed in all three cases. No abnormality was found in the chest radiographs of any case. However, in high-resolution computed tomography (HRCT), ground-glass opacities and centrilobular nodules were observed in all three cases, emphysema in one case, intralobular linear or reticular opacities in two cases, small subpleural cysts in two and emphysema in one. Histologic examination of lung biopsy specimens taken by thoracoscopy showed peribronchiolar fibrosis and centrilobular intraluminal accumulation of macrophages in all three cases, centrilobular emphysema, membranous bronchioles filled with mucus and macrophages, and focal microscopic honeycombing in subpleural lesions in one case each. RB-ILD should be included in the differential diagnosis of interstitial lung disease in smokers.