BAG3-Related Myofibrillar Myopathy Presenting as Hypercapnia: A Case Report and Literature Review.

Objective BAG3-related myopathy is a rare condition so far reported in twenty patients worldwide. The purpose of this study was to draw attention to this rare disease and to the fact that BAG3-related myopathy should be considered as a rare differential diagnosis of hypercapnia. Methods We report a sporadic case of a 14-year-old Chinese girl with a de novo p.Pro209Leu mutation in BAG3 and reviewed the literatures for reported cases related to this mutation. Results We described a 14-year-old Chinese girl who presented with gradually appearing symptoms of hypercapnia that required assisted ventilation. The muscle biopsy and the blood whole-exome sequencing results confirmed the diagnosis of myofibrillar myopathy with a de novo p.Pro209Leu mutation in BAG3. Totally twenty-one patients from twenty families with a confirmed diagnosis of BAG3-related myopathy were reported to date, including this patient and literature review. The male to female ratio was 11:10 and most showed initial symptoms in the first decade of life. Most patients presented toe/clumsy walking or running as the onset symptom, followed by muscle weakness or atrophy. Creatine kinase levels were elevated in fourteen patients and were normal in three. Eighteen patients developed respiratory insufficiency during the disease course and thirteen (one could not tolerate non-invasive assisted ventilation) required non-invasive assisted ventilation for treatment. Except for one not reported, heart involvement was found in seventeen patients during the disease course and seven underwent heart transplantation. Z-disk streaming and aggregation could be observed in most of the patients' muscle histology. In the long-term follow-up, five patients died of cardiac or respiratory failure. Conclusion BAG3-associated myopathy is a rare type of myofibrillar myopathy. It should be considered as a rare differential diagnosis of hypercapnia.

PHD/HIF-1 upregulates CA12 to protect against degenerative disc disease: a human sample, in vitro and ex vivo study.

Intervertebral disc degeneration is a major cause of low back pain. The nucleus pulposus (NP) is an important intervertebral disc component. Recent studies have shown that carbonic anhydrase 12 (CA12) is a novel NP marker. However, the mechanism by which CA12 is regulated and its physiological function are unclear. In our study, CA12, hypoxia-inducible factor 1α (HIF-1α) and HIF-2α expression levels were examined in 81 human degenerated NP samples using real-time RT-PCR, immunohistochemistry and western blot. Rat NP cells were cultured in a hypoxic environment, and hypoxia-induced CA12 expression was examined. Rat NP cells were treated with HIF-1α siRNA or the prolyl hydroxylase (PHD) inhibitor dimethyloxalylglycine (DMOG) to evaluate the role of PHD/HIF-1 in regulating CA12 expression. Rat NP cells were treated with CA12 siRNA to determine the function of CA12. A rat ex vivo model was established to confirm that PHD, HIF-1, and CA12 have important roles in disc degeneration. We found that CA12 was significantly downregulated in degenerated human NP samples at the mRNA and protein levels. CA12 expression sharply increased by ~30-fold in response to hypoxia. The expression of HIF-1α, but not HIF-2α, also decreased in degenerated human NP samples and was positively correlated with CA12 expression. HIF-1α knockdown under hypoxia reduced the CA12 mRNA and protein expression levels. DMOG treatment increased HIF-1α and CA12 expression. CA12 knockdown significantly inhibited anabolic protein expression, whereas catabolic enzymes remained unchanged. The ex vivo experiments supported our in vitro studies of the role of PHD/HIF-1/CA12. In conclusion, CA12 is downregulated in degenerated NPs, and its expression may be regulated by the PHD/HIF-1 axis. Decreased CA12 expression may lead to decreased extracellular matrix synthesis, which contributes to degenerative disc disease progression.

Role of bronchoalveolar lavage for diagnosing pulmonary infection in patients with rheumatic autoimmune diseases and lung infiltrates.

OBJECTIVES: The aims of the study were to evaluate the effectiveness of bronchoalveolar lavage (BAL) for diagnosing pulmonary infection in patients with rheumatic autoimmune diseases and lung infiltrates and to evaluate factors that affect the diagnostic yield. METHODS: A retrospective study was performed in patients with rheumatic autoimmune diseases and lung infiltrates whose BALs were sent for microbial assays at Peking Union Medical College Hospital from January 2009 to June 2013. Patient characteristics, clinical symptoms, medication history, laboratory parameters, radiographic findings, lung lobe lavaged, and diagnostic yield were retrieved. RESULTS: Seventy BALs were performed in 69 patients. The overall diagnostic yield of BAL for pulmonary infection was 17.1% (12/70), sensitivity was 35.5%, and specificity was 97.4%. Twelve microorganisms were isolated from 12 different BALs conforming to diagnostic criteria, including 4 Aspergillus, 3 Pneumocystis jirovecii, 3 gram-negative bacilli, 1 gram-positive coccus, and 1 mycobacterium. Patients with clinical symptoms of fever, cough, or expectoration had a higher diagnostic yield than patients without either symptom (25.6% vs 3.7%, P = 0.042). Patients with ground-glass opacity, mass, or consolidation radiographically had a higher yield than did patients with reticular or nodular infiltrates (20.3% vs 0, P < 0.001). CONCLUSIONS: Bronchoalveolar lavage is a useful tool for patients with rheumatic autoimmune diseases and lung infiltrates, especially in cases where initial antimicrobial therapy is ineffective. Opportunistic pathogens are important in patients with rheumatic autoimmune diseases and lung infiltrates and should be considered when antibacterial treatment is ineffective.

[Clinical characteristic analysis of 96 cases of hypersensitivity pneumonitis].

OBJECTIVE: To improve understanding of the clinical characteristics and diagnosis of hypersensitivity pneumonitis (HP). METHODS: We retrospectively analyzed the clinical data, including clinical symptoms, laboratory tests, exposure, pulmonary function tests, chest CT imaging and cytological classification of bronchoalveolar lavage (BAL) of 96 patients with HP from Jan 2001 to Jun 2011 in Peking Union Medical College Hospital. We divided the patients into 2 groups: a pathologically-confirmed group and a clinically-suspected group. RESULTS: There were 58 females and 41 males. The median age at the diagnosis was 53 years. The most common exposures were low-molecular-weight chemicals (42.7%) and animal proteins (37.5%). Common clinical symptoms included dyspnea on exertion (90.6%) and cough (76.0%). Pulmonary function test showed diffusion abnormality (73.5%) and restrictive ventilatory impairment (59.7%). Chest CT scan revealed patchy or diffuse bilateral ground-glass opacities (64.6%), centrilobular nodules (21.9%), and air trapping (15.6%). Reticulation (45.8%), traction bronchiectasis (21.9%) and honeycombing(9.4%) were present in chronic HP. BAL lymphocyte counts > 0.2 and CD4/CD8 < 0.9 were more commonly seen in patients with a disease course of less than 1 year. The pathologically-confirmed group and the clinically-suspected group shared many similar characteristics including age at diagnosis, gender, clinical manifestation, pulmonary function impairments and imaging findings, but significant differences existed in certain parameters. In the pathologically- confirmed group, the duration of disease was longer (24 months vs 6 months, Z = -2.492, P = 0.013) and clubbed fingers were more common (23.4% vs 8.2%, χ(2) = 4.227, P = 0.040). Diffusion abnormality was present in more patients of this group (90.7% vs 44.0%, χ(2) = 35.219, P < 0.01). By CT scan, reticulation, traction bronchiectasis and honeycombing (57.5% vs 26.5%, χ(2) = 9.434, P < 0.01) were more evident as compared to the clinically-suspected group. The value of transbronchial lung biopsy for diagnosing HP was limited, with a positive result of only 8.2%. Surgical lung biopsy was needed in uncertain cases. CONCLUSION: The diagnosis of HP was difficult. In some cases a clinical diagnosis can be made by combination of history of exposure, CT manifestations and cell classification of BAL. For atypical cases a multi-disciplinary approach including pathologists, radiologists and pulmonologists is needed.

[The diagnostic value of CT-guided percutaneous needle lung biopsy in diffuse parenchymal lung diseases].

OBJECTIVE: This study was to evaluate the efficacy and limitation of CT-guided percutaneous cutting needle lung biopsy in the diagnosis of diffuse parenchymal lung diseases (DPLD). METHODS: A total of 481 patients admitted in Peking Union Medical College Hospital from January 2000 to December 2008 underwent CT-guided percutaneous cutting needle lung biopsy. The patients were evaluated by clinical history, physical examination and lung HRCT. Those with localized opacity or lesions in a single lung in the CT scan were excluded. Finally, 248 patients with DPLD in HRCT were enrolled for this study. RESULTS: The study patients included 114 males and 134 females, and the mean (± SD) age at diagnosis was 50 ± 16 (range from 13 - 78) years. Confirmed diagnosis by percutaneous needle lung biopsy was obtained in 130 patients (52.4%), including pulmonary infection (35.4%, 46/130), pulmonary malignant diseases (25.4%, 33/130), bronchiolitis obliterans organizing pneumonia/organizing pneumonia (22.3%, 29/130), pulmonary vasculitis (6.2%, 8/130), granulomatous lesions (4.6%, 6/130), pulmonary sarcoidosis (2.3%, 3/130), acute interstitial pneumonia (1.5%, 2/130), pulmonary amyloidosis (1.5%, 2/130), and pulmonary alveolar proteinosis (0.8%, 1/130). Open lung biopsy/video-assisted thoracoscopic surgery was performed in 37 out of 118 cases for which the diagnosis was undetermined by percutaneous lung biopsy. Confirmed diagnosis was obtained in 36 patients, including non-specific interstitial pneumonia (NSIP, 33.3%, 12/36), usual interstitial pneumonia (UIP, 8.3%, 3/36), pulmonary infection (16.7%, 6/36), neoplasm (8.3%, 3/36), lymphoid interstitial pneumonia, pulmonary vasculitis (5.6% 2/36), hypersensitivity pneumonitis (5.6%, 2/36), and pulmonary sarcoidosis, allergic bronchopulmonary aspergillosis, pulmonary hyalinizing granuloma, pneumoconiosis, Castleman's disease, and lymphoproliferative disorder (1 case respectively). CONCLUSION: CT-guided percutaneous cutting needle lung biopsy can provide confirmed diagnosis in half of patients with DPLD, and has a high diagnostic yield in patients with infectious or neoplastic diseases, but it is not a good method for diagnosis of interstitial lung diseases such as NSIP and UIP.

Pathological and high resolution CT findings in Churg-Strauss syndrome.

OBJECTIVE: To investigate the Churg-Strauss syndrome (CSS) associated lung involvement, concentrating on clinical characteristics, pathological findings of lung involvements, response to treatment, and prognosis. METHODS: We retrospectively analyzed the characters of the clinical manifestations, thin-section CT and pathological findings of CSS. The study involved 16 patients. Clinical data were obtained by chart review. All patients underwent transbronchial lung biopsy (TBLB). Six of them underwent surgical lung biopsy as well. RESULTS: The patients included 7 men and 9 women, aged from 14 to 61 years (median, 47.5 years). Extrathoracic organs involved included nervous system (7/16) and skin (5/16). Respiratory symptoms included cough (12/16), exertional dyspnea (11/16), hemoptysis (4/16), and chest pain (3/16). CT findings included bilateral ground-glass opacities (12/16), bilateral patchy opacities (12/16), and centrilobular nodules (6/16). The pathological findings of TBLB demonstrated increased eosinophils (3/16), vasculitis (3/16), and interstitial pneumonia (16/16). The pathological findings of surgical lung biopsy of 6 cases showed necrotizing vasculitis in 4 cases, capillaries in 5, eosinophilic pneumonia in 3, granulomas in 2, and airway abnormalities in 3. All patients improved in symptoms after therapy during the study period (range, 3 to 51 months; median, 15 months). CONCLUSIONS: Asthma may be present in CSS patient when there is bronchial involvement. Ground-glass opacities and consolidation seen on high-resolution CT reflect the presence of eosinophilic pneumonia, vasculitis, and pulmonary alveolar hemorrhage. TBLB has significant limitations for the diagnosis of CSS. Early diagnosis and therapy can result in satisfactory prognosis.

[The methylation status of PEG10 in placentas of cloned transgenic calves].

The low efficiency of somatic cell nuclear transfer (SCNT) is a significant barrier to the production of highly valuable transgenic livestock. It is generally believed that the principal cause of the low SCNT efficiency is the aberrant nuclear epigenetic reprogramming of donor somatic cell. DNA methylation is a major epigenetic modification of the genome and plays a crucial role in nuclear reprogramming during SCNT. In order to assess whether the abnormal epigenetic modifications of the imprinted gene in placenta are correlated with the development abnormality and death of the cloned transgenic calves, the DNA methylation patterns of PEG10 were compared in the placentas from different kinds of cattle. This comparison included transgenic cloned calves died during perinatal stage and showed developmental defects (Death group), transgenic cloned calves survived and lived on healthily (Live group) and the normal reproduced calves (N group) used as the control group analyzed by Bisulfite Sequencing PCR (BSP) method and Combined Bisulfite Restriction Analy-sis (COBRA). Comparing to the control group, PEG10 gene in the Death group showed abnormal hypermethylation, but was not significant different in methylation level from the Live group. It can be postulated from the results that the incom-plete or abnormal DNA methylation epigenetic reprogramming of imprinting gene in placenta may be one of the main causes of the abnormal development and death of the transgenic cloned cattle.

Phosphorylcholine-Primed Dendritic Cells Aggravate the Development of Atherosclerosis in ApoE-/- Mice.

Background: Atherosclerosis is an inflammatory disease involving activation of adaptive and innate immune responses to antigens, including oxidized low-density lipoprotein (oxLDL) and phosphorylcholine (PC). Dendritic cells (DCs), which are antigen-presenting cells that activate T cells, are present in atherosclerotic lesions and are activated in immune organs. However, the mechanism by which PC promotes atherosclerosis is unclear. Methods and Results: To evaluate whether PC promotes atherosclerosis via DCs, 2×105 DCs activated by PC-keyhole limpet hemocyanin (DCs+PC-KLH) were injected into ApoE-/- mice and the features of the plaques and the effects of the DCs on cellular and humoral immunity against PC-KLH were determined. Mice injected with DCs+PC-KLH had significantly larger atherosclerotic lesions than controls, with increased inflammation in the lesions and plaque instability. Furthermore, DCs+PC-KLH were characterized using flow cytometry after coculture of bone marrow-derived DCs and naïve T cells. DCs+PC-KLH showed an inflammatory phenotype, with increased CD86, CD40, and major histocompatibility complex Class II molecules (MHC-II), which promoted PC-specific T helper (Th) 1 and Th17 cell differentiation in vivo and in vitro. Moreover, 2 weeks after the administration of DCs+PC-KLH to mice, these mice produced PC- and oxLDL-specific IgG2a, compared with no production in the controls. Conclusions: These findings suggest that DCs presenting PC promote specific immunity to PC, increase lesion inflammation, and accelerate atherosclerosis, which may explain how PC promotes atherosclerosis.

[Clinical analysis of four cases of primary ciliary dyskinesia and literature review].

OBJECTIVE: To study the clinical characteristics and diagnosis of primary ciliary dyskinesia (PCD). METHODS: Four cases diagnosed as PCD by cilia electron microscopy examination from Jan. 2007 to Aug. 2009 in this hospital were retrospectively analyzed, and the related literature was reviewed. RESULTS: In the 4 patients, there were 1 male and 3 females. The age at disease onset was 0 - 10 years, and the age at diagnosis was 15 - 53 years. The most common symptoms were productive cough (4/4), sinusitis (3/4), and shortness of breath (3/4). Other manifestations included situs inversus (2/4), infertility (1/4), and tympanitis (1/4). Hypoxemia was found in 3 cases. Obstructive ventilatory impairment accompanied with diffusion dysfunction was observed in 2 cases, while the pulmonary function tests were normal in the other 2 cases. All 4 cases received chest CT scan, and bronchiectasis was present in all of them. Bilateral diffuse micronodules and patchy infiltrates were found in 3 and 2 cases respectively. Electron microscopic examination of the endobronchial biopsy specimen showed lack of dynein arms in 4, lack of muco-cilia in 2, and abnormal arrangement of microtubules in 2 cases. CONCLUSIONS: The Kartagener syndrome is relatively easy to be diagnosed, because it is characterized by the triad of sinusitis, bronchiectasis and situs inversus. However, PCD without situs inversus often goes unrecognized. PCD should be considered in patients with childhood onset disease, bronchiectasis, centrilobular micronodules or tree-in-bud signs in CT scan. Examination of the ciliary ultrastructure is essential to the confirmation of the diagnosis.

Pulmonary manifestations of Sjögren's syndrome.

BACKGROUND: Primary Sjögren's syndrome (PSS) is associated with various histological patterns of interstitial lung disease. Although chest images and lung function studies showed that lung involvement predominantly occurs in small airways, pathological findings were not consistent with the results of high-resolution CT (HRCT) and lung function tests. OBJECTIVES: To investigate the pathological characteristics of PSS-associated interstitial lung disease (PSS-ILD) and their relationship with HRCT lung function tests. METHODS: Fourteen patients diagnosed as PSS who underwent surgical lung biopsy in Peking Union Medical College Hospital from October 2000 to October 2006 were reviewed. Histopathologic findings, radiologic findings and lung function tests were analyzed. RESULTS: The study included 13 women. The median age was 46 years. Most patients presented with dyspnea and cough. CT scans revealed bilateral ground-glass, consolidative, reticular and nodular opacities and cyst lesions. The histological patterns included nonspecific interstitial pneumonia (NSIP) cellular pattern associated with organizing pneumonia (OP), NSIP mixed pattern associated with OP, noncaseating granulomas, chronic bronchiolitis, follicular bronchiolitis, constrictive bronchiolitis, lymphocytic interstitial pneumonia associated with follicular bronchiolitis, NSIP mixed pattern associated with follicular bronchiolitis, NSIP mixed pattern coexisting with chronic bronchiolitis, OP associated with chronic bronchiolitis, and noncaseating granulomas coexisting with OP. Treatment included prednisone and cyclophosphamide. During the follow-up period (median 38 months), most patients improved or remained stable. The patient with constrictive bronchiolitis died from progression of primary disease. CONCLUSIONS: The histopathologic patterns of PSS-ILD included lung interstitial involvement and small airway involvement or both. Corticosteroid therapy combined with cyclophosphamide was administered with a favorable response in the majority of patients.

Clinical features and prognosis in 21 patients with extrinsic allergic alveolitis.

OBJECTIVE: To assess the spectrum of causes, clinical features, differences between disease phases, and prognosis of extrinsic allergic alveolitis (EAA). METHODS: Patients with EAA diagnosed at Peking Union Medical College Hospital from August 1983 to May 2007 were analyzed retrospectively. Their medical records were examined to gather clinical, laboratorial, radiological, and histopathological data. Patients were divided to three phases (acute, subacute, and chronic) according to clinical presentations. Follow-up data regarding treatment response, subsequent radiological and pulmonary function studies, and clinical outcomes were collected. RESULTS: A total of 21 cases were enrolled. Among them, 11 were subacute, 10 were chronic. The most common exposure was pet birds (6 cases, 28.6%). The primary abnormality of pulmonary function was restriction and/or reduction in diffusing capacity (12 cases, 63.2%). The most common findings on high-resolution computed tomography (HRCT) were ground-glass opacities (13 cases, 68.4%) and centrilobular nodules (8 cases, 42.1%). Airway obstruction in pulmonary function test, emphysema, lung cysts, and fibrosis on HRCT were more frequently seen in chronic than in subacute patients, though the differences were not statistically significant. Bronchoalveolar lavage fluid (BALF) showed lymphocytosis. The total cell count and the percentage of neutrophils were significantly higher in subacute than in chronic patients (P<0.05). Nonnecrotizing granulomas were seen in 8 (47.1%) cases. Improvement or normalization in symptoms, radiography, and pulmonary function test after treatment were seen in all 18 patients with available follow-up data. Five patients recurred. CONCLUSIONS: The characteristic abnormalities of pulmonary function, findings on HRCT, and pathology are essential for all phases of EAA, and the atypical manifestations such as obstruction and fibrosis can also be present frequently, particularly in chronic cases. Differential cell counts of BALF are related to the phase of the disease. The treatment response and prognosis of EAA are good.

[Churg-Strauss syndrome: clinical features and long-term follow-up of 16 patients].

OBJECTIVE: To enhance the knowledge about Churg-Strauss syndrome (CSS). METHODS: The clinical data of 16 CSS patients were analyzed. Follow-up was conducted for 42 (14 - 76) months. RESULTS: All patients had the symptom of asthma. As in other case series, the lung, peripheral nervous system, and skin were the most commonly involved organs. During the active stage of the disease, most of the patients exhibited peripheral blood eosinophilia and elevated serum total IgE level. Two patients were treated with pulse treatment of methylprednisolone followed by prednisone with tapering dose and cyclophosphamide, nine patients were treated with corticosteroids and cyclophosphamide, and the others were treated with corticosteroids alone. Several patients were treated with the following drugs in combination: methotrexate, hydroxychloroquine, azathioprine, ciclosporin, common Threewingnut root, and intravenous injection of IgG. Symptom relief was seen in all patients after treatment. Two patients were lost to follow-up. Seven patients showed sustained remission, of which 3 had discontinued the medication, 3 were treated with low-dose corticosteroids and immunity inhibitors, and 1 continued to be treated with low-dose corticosteroids. Six patients suffered from relapse 1.7 times due to withdrawal of corticosteroid treatment or tapering of corticosteroid dose and they regained remission once more after increasing the corticosteroid dose and combination of cyclophosphamide. Four of these 6 patients were treated with corticosteroids of low or medium dose as maintenance doses, and the other 2 with medium-dose corticosteroids and cyclophosphamide. One patient committed suicide because of family dissension 1 year after treatment. CONCLUSIONS: The clinical manifestations and course of CSS vary considerably. Its clinical manifestations may range from mild symptoms to life-threatening conditions. Corticosteroids and cyclophosphamide are both effective remedies. Despite relapses in several cases, the general prognosis is good.

[Diffuse alveolar hemorrhage in systemic lupus erythematosus].

OBJECTIVE: To determine the clinical features of systemic lupus erythematosus (SLE) patients with diffuse alveolar hemorrhage (DAH). METHODS: The medical records of seventeen SLE patients with DAH were reviewed. RESULTS: Hypoxemia (100%), dyspnea (88%), cough (88%) and fever (82%) were the most common symptoms instead of hemoptysis (71%). The most common extrapulmonary presentation was renal involvement (94%). About 60% patients were complicated with lung infection. The mean drop in hemoglobin was (32 +/- 11.3) g/L. Mean SLEDAI was (17 +/- 10). All received high-dose steroids and most also were given cyclophosphamide. Ratio of mechanical ventilation in non-survivors was higher than that of survivors (P < 0.05). CONCLUSIONS: DAH is a rare and catastrophic event in SLE. DAH can occur in any course, which suggests active SLE, and frequently complicated with lupus nephritis. Some patients may have no hemoptysis.

[Diagnostic specificity of dynamic assessment and monitoring of spirometry in asthma].

OBJECTIVE: To evaluate the diagnostic specificity of dynamic assessment and monitoring using a portable spirometer in diagnosis and differential diagnosis of asthma. METHODS: We retrospectively reviewed the results of dynamic monitoring of spirometry in 145 symptomatic patients with physician-diagnosed asthma. Flow-volume curve and simultaneous symptoms and mood were measured in a fixed-time thrice-daily assessment schedule for 2 weeks. Patients were allowed to make additional measurements in case of symptom exacerbations. RESULTS: The clinical data of 51 males and 94 females with a mean age of (39.1 +/- 13.0) years (ranged from 10 to 65 years) were analyzed. Duration of asthma before study was (6.7 +/- 9.9) years. Of 145 patients with physician-diagnosed asthma, 126 (87%) could be conclusively confirmed for a diagnosis of asthma. Asthma was misdiagnosed in 14 patients (9.7%). Overdiagnosis of asthma was observed in 5 patients (3.4%). CONCLUSION: Dynamic assessment and monitoring using a portable spirometer by revealing variability and reversibility of airway obstruction may provide an additional tool for diagnosis and differential diagnosis of asthma.

[Clinical and radiological features of pulmonary tuberculosis manifested as interstitial lung diseases.].

OBJECTIVE: The purpose of this paper was to investigate the clinical and radiological features of pulmonary tuberculosis presenting as interstitial lung diseases (ILD). METHODS: We analyzed the data of cases suspected of diffuse parenchyma lung diseases at this hospital between October 2003 and October 2007. The diagnosis of active pulmonary tuberculosis was based on epithelioid granuloma or positive acid-fast bacilli in lung biopsy and changes on serial radiographs obtained during treatment. RESULTS: The data of a series of 230 consecutive patients with suspected ILD were retrospectively analyzed. The diagnosis was confirmed by lung biopsy. Twelve patients were confirmed to have pulmonary tuberculosis. There were 5 males and 7 females with a mean age of 38 +/- 11 years (range, 17 - 68). The median course of disease in these patients was 3 months (range, 0.5 - 18 months). Patients with pulmonary tuberculosis presented with fever (11/12), cough (9/12), weight loss (7/12), dyspnea (7/12), lymphadenopathy (4/12), and splenohepatomegaly (2/12). On chest CT scan, ground-glass attenuation was identified in 4, bilateral patchy infiltration in 5, tree-in-bud appearance 1, and centrilobular lesions in 2 of the 12 patients. During the follow-up period (median, 9 month, range from 3 to 12 month), 11 patients improved, but 1 died of diabetic ketoacidosis. CONCLUSION: The diagnosis of pulmonary tuberculosis should be considered in suspected ILD patients presenting with fever, splenohepatomegaly and lymphadenopathy.

[Primary pulmonary lymphoma: analysis of 18 cases].

OBJECTIVE: To study the clinical characteristics, pathology, diagnosis and treatment of primary pulmonary lymphoma. METHODS: Eighteen cases of primary pulmonary lymphoma diagnosed from Jan 1989 to Feb 2007 were retrospectively analyzed. RESULTS: There were 6 males and 12 females, with a median age of 47.5 years (17-71 years). Fifteen cases were diagnosed by surgical lung biopsy; 1 by percutaneous needle lung biopsy (1/6), 1 by percutaneous needle lung biopsy and bronchoscopic examination at the same time, the other 1 by bronchoscopic examination (1/10). Histological diagnosis showed that 2 cases were Hodgkin lymphoma, 9 mucosa-associated lymphoid tissue lymphoma, 1 follicular lymphoma, 2 diffuse large B cell lymphoma 2 anaplastic large cell lymphoma, 2 non-Hodgkin lymphoma whichcould not be classified because the slides were from other hospitals. The most common symptoms were cough (9/18) and fever (6/18). ESR elevation was common (10/12). CT features included solitary or multiple nodules (14/18), patchy opacities (11/18), consolidations (5/18), pleural effusions (5/18), atelectasis (5/18), and cavities (1/18). Misdiagnosis was found in 11 patients. Treatment modalities included surgical resection, radiotherapy and chemotherapy. Median follow-up time was 11 months (10 d to 205 mon). Thirteen patients were still alive, 4 patients were lost, and 1 patient died. The prognosis was associated with the level of [25.1 x 10(9)/L(18.1 - 39. -1) x 10(9)/L in poor prognosis group, 6.7 x 10(9)/L (5.48 - 8.41) x 10(9)/L in good prognosis group, u = 0.000, P <0.05] leukocytosis (3/3 vs 1/10, P <0.05). CONCLUSIONS: The clinical manifestations of primary pulmonary lymphoma are nonspecific. Misdiagnosis is common. Surgical lung biopsy is necessary for early diagnosis.

[Predictive value of single and combined indexes in the diagnosis of sarcoidosis].

OBJECTIVE: To evaluate the predictive value of single and combined indexes in the diagnosis of sarcoidosis. METHODS: Eighty-eight patients suspected of having sarcoidosis were retrospectively investigated. The diagnostic predictive value of lymphocyte percentage and CD4/CD8 ratio in bronchoalveolar lavage (BAL), angiotensin converting enzyme (ACE) and their combination was evaluated by ROC curve method and Bayes' rule. RESULTS: Final diagnosis of sarcoidosis by biopsy was available in 59 patients (67%), 16 were males (27%), 43 were females (73%), with a mean age of (48 +/- 10) years. The diagnosis of non-sarcoidosis was available in 29 patients (33%), 12 were males (41%), 17 were females (59%), with a mean age of (49 +/- 13) years. The ROC curve area of lymphocyte percentage, CD4/CD8 ratio and ACE were 0.64, 0.74 and 0.69 respectively; CD4/CD8 ratio had the best diagnostic efficiency. The optimized cut-offs of the three single indexes, lymphocyte percentage > or = 30%, CD4/CD8 ratio > or = 4.0 and ACE > or = 40 U/L, were determined by the tangential points and coordinates of the ROC curve. The positive predictive values were 76.7%, 80.4% and 76.8% respectively; CD4/CD8 ratio had the best predictive value. The ROC curve area of the combined CD4/CD8 ratio and ACE was 0.81, and the combination of lymphocyte percentage, CD4/CD8 ratio and ACE was 0.78. They were both higher than those of the respective single indexes. The combination of CD4/CD8 ratio and ACE had the best diagnostic efficiency. On the other hand, it had the best positive predictive value of 90.5% in all the diagnostic indexes. CONCLUSION: CD4/CD8 ratio in BAL is still a useful index in the auxiliary diagnosis of sarcoidosis. The combination of CD4/CD8 ratio and ACE can improve the diagnostic efficiency and predictive value of sarcoidosis.

[The diagnostic value of transbronchial lung biopsy in diffuse parenchymal lung diseases].

OBJECTIVE: This study was to evaluate the efficacy and limitations of transbronchial lung biopsy (TBLB) in the diagnosis of diffuse parenchymal lung diseases (DPLD). METHODS: TBLB was performed in 416 patients with diffuse lung diseases from January 2001 to October 2006 in Peking Union Medical College Hospital. The results of clinical data and pathologic diagnosis were retrospectively analyzed. RESULTS: Confirmed diagnosis by TBLB was obtained in 124 patients, the total positive diagnostic rate was 29.8%. The diseases included pulmonary sarcoidosis (52/124, 41.9%), bronchiolitis obliterans organizing pneumonia/organizing pneumonia (BOOP/OP) (28/124, 22.6%), pulmonary alveolar proteinosis (19/124, 15.3%), lung cancer (12/124, 9.7%), pulmonary vasculitis (5/124, 4.0%), pulmonary tuberculosis (3/124, 2.4%), and pneumocystis carinii pneumonia, lung fungal infection, lymphangiomyomatosis, and pulmonary amyloidosis (each 1/124, 0.8%). Open lung or thoracoscopic biopsy was performed in 104 cases in whom the diagnosis was undetermined by TBLB. Confirmed diagnosis was obtained in 109 patients, including nonspecific interstitial pneumonia (37/104, 37.7%), usual interstitial pneumonia (18/104, 18.4%), pulmonary sarcoidosis (11/104, 11.2%), BOOP/OP (6/104, 6.1%), and lung cancer (5/104, 5.1%). CONCLUSIONS: Pathologic diagnosis can be obtained by TBLB in about 30% of the cases with DPLD, and therefore it should be considered to be a routine diagnostic procedure before open lung or thoracoscopic biopsy.

[Clinico-pathological manifestations in interstitial lung diseases associated with polymyositis-dermatomyositis].

OBJECTIVE: Polymyositis-dermatomyositis has been associated with various histological patterns of interstitial lung disease (ILD). This study was to investigate the clinico-pathologic features of interstitial lung diseases associated with polymyositis-dermatomyositis. METHODS: We retrospectively identified 26 patients with polymyositis-dermatomyositis associated ILD who underwent lung biopsies (6 autopsies, 5 surgical lung biopsies and 15 percutaneous lung biopsies) at our hospital during a 27-year period from January 1980 through October 2007. Histopathologic findings were analyzed and correlated with radiological features and outcome. RESULTS: Median age was 48 years (range, 19 to 65 years), and 16 patients were women. Chest X-ray imaging revealed bilateral infiltrates including ground-glass attenuation, patchy infiltration, and reticular opacities. The major histopathologic patterns included diffuse alveolar damage (DAD) (n = 5), lymphocytic interstitial pneumonia (n = 2), nonspecific interstitial pneumonia (NSIP) (cellular pattern, n = 6; mixed pattern, n = 8), organizing pneumonia (n = 4), usual interstitial pneumonia (UIP) (n = 1). Treatment commonly included prednisone with immunosuppressive agent. During the follow-up period (median, 15 month,range from 6 to 108 month), 18 patients improved or remained stable. Eight patients died, including 5 deaths from DAD, 2 from NSIP mixed pattern, 1 from UIP. CONCLUSIONS: A variety of histological patterns can be seen in patients with polymyositis-dermatomyositis-associated ILD. Those with DAD tended to have poor prognosis.

[Acute exacerbation of usual interstitial pneumonia and nonspecific interstitial pneumonia: analysis of 6 cases].

OBJECTIVE: Acute exacerbation of diffuse parenchymal lung disease (DPLD) is a condition in which patients with usual interstitial pneumonia (UIP), and other forms of interstitial lung disease, develops rapid respiratory failure, accompanied by extensive radiological infiltrates, and had no evidence of infection. The pathologic features of this condition are usually diffuse alveolar damage (DAD) and the outcome is poor. Our study was to define the clinicopathologic features and outcome of acute exacerbation in 3 patients with UIP and 3 with nonspecific interstitial pneumonia (NSIP). METHOD: The clinical data of the 6 patients from April 1999 to Jun 2007 were analyzed retrospectively. RESULTS: In the 6 patients, 2 were males. The median age was 51 yrs (29 -57 yrs). Three case had UIP [1 UIP/idiopathic pulmonary fibrosis (IPF), 1 UIP/dermatomyositis (DM), 1 UIP/UCTD], 2 had NSIP (1 idiopathic NSIP, 1 NSIP/DM), and 1 was diagnosed as DAD (the basic pathology was NSIP/DM) by autopsy. Four of the patients underwent video-assisted thoracoscopic surgery (VATS) for diagnosis, and 1 underwent CT-guided transthoracic needle biopsy. Two of them underwent surgical lung biopsy 1 week before acute exacerbation. Five cases had fever. Computed tomography data were available in all cases and showed the presence of extensive bilateral ground-glass opacities (5/6), sometimes accompanied by focal consolidation (2/6), superimposed on underlying fibrosis. The median oxygenation index was 200 (quartile range: 158-237) mm Hg (1 mm Hg = 0.133 kPa). Five patients were treated with corticosteroids, and in some combined with cyclophosphamide or intravenous immunoglobulin. Two patients survived the acute episode and were discharged from hospital. All 3 patients using mechanical ventilation died. CONCLUSIONS: Both UIP and NSIP can develop acute exacerbations. The trigger of acute exacerbation was unclear, but in some cases it maybe related to VATS. The clinical features include rapid respiratory failure, accompanied by extensive radiological infiltrates. The fatality is high. Corticosteroids or intravenous immunoglobulin may be helpful in the treatment of the condition.