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.

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.

CD4+ and CD8+ T lymphocytes in lung tissue of NSIP: correlation with T lymphocytes in BALF.

BACKGROUND: Nonspecific interstitial pneumonia (NSIP) is characterized by the interstitial infiltration T lymphocytes (TLs). Bronchoalveolar lavage fluid (BALF) has been used to analyze the inflammatory cells infiltrating in lung. The controversy about whether the BALF cellular profile reflects T lymphocytes in lung tissue still persists. Some studies found a positive correlation of cell composition between BALF and lung tissue, but others gave opposite conclusion. OBJECTIVE: To investigate CD4+ and CD8+ T lymphocytes distribution in lung tissue of NSIP and the relationship with T lymphocytes in bronchoalveolar lavage. METHODS: Thirty-seven patients diagnosed as NSIP were included. The pathological and BALF date were reviewed. The characteristics of TLs infiltration in different lung regions were investigated. RESULTS: The study included 28 women. The median age was 48 years. In lung tissue, CD4+ and CD8+ lymphocytes (counts/0.1mm2) were separately accounted in lymphoid follicle region (156.51 ± 90.70 vs 85.30 ± 43.75), small blood vessel region (66.58 ± 31.99 vs 58.43 ± 30.24), interstitial region (37.60 ± 19.40 vs 47.12 ± 33.42) and small airway region (26.59 ± 17.04 vs 40.18 ± 34.02). CD4+/CD8+ ratios in lymphoid follicle and small vessel > 1, in interstitium and small airway <1. The number of CD8+ lymphocytes in BALF was correlated with CD8+ lymphocytes around small airway (r = 0.360, p = 0.029) and in interstitial region (r = 0.451, p = 0.005). CD4+/CD8+ ratio in BALF was correlated with that in small airway region (r = 0.437, p = 0.007) and interstitial region (r = 0.468, p = 0.003). CONCLUSIONS: In NSIP, T lymphocytes were distributed in different regions of lung tissue. The CD8+ T lymphocytes and CD4+/CD8+ ratio in BALF reflect those in interstitium regions and around small airway of the lung.

Defined media optimization for in vitro culture of bovine somatic cell nuclear transfer (SCNT) embryos.

The objective was to establish an efficient defined culture medium for bovine somatic cell nuclear transfer (SCNT) embryos. In this study, modified synthetic oviductal fluid (mSOF) without bovine serum albumin (BSA) was used as the basic culture medium (BCM), whereas the control medium was BCM with BSA. In Experiment 1, adding polyvinyl alcohol (PVA) to BCM supported development of SCNT embryos to blastocyst stage, but blastocyst formation rate and blastocyst cell number were both lower (P < 0.05) compared to the undefined group (6.1 vs. 32.6% and 67.3 ± 3.4 vs. 109.3 ± 4.5, respectively). In Experiment 2, myo-inositol, a combination of insulin, transferrin and selenium (ITS), and epidermal growth factor (EGF) were added separately to PVA-supplemented BCM. The blastocyst formation rate and blastocyst cell number of those three groups were dramatically improved compared with that of PVA-supplemented group in Experiment 1 (18.5, 23.0, 24.1 vs. 6.1% and 82.7 ± 2.0, 84.3 ± 4.2, 95.3 ± 3.8 vs. 67.3 ± 3.4, respectively, P < 0.05), but were still lower compared with that of undefined group (33.7% and 113.8 ± 3.4, P < 0.05). In Experiment 3, when a combination of myo-inositol, ITS and EGF were added to PVA-supplemented BCM, blastocyst formation rate and blastocyst cell number were similar to that of undefined group (30.4 vs. 31.1% and 109.3 ± 4.4 vs. 112.0 ± 3.6, P > 0.05). In Experiment 4, when blastocysts were cryopreserved and subsequently thawed, there were no significant differences between the optimized defined group (Experiment 3) and undefined group in survival rate and 24 and 48 h hatching blastocyst rates. Furthermore, there were no significant differences in expression levels of H19, HSP70 and BAX in blastocysts derived from optimized defined medium and undefined medium, although the relative expression abundance of IGF-2 was significantly decreased in the former. In conclusion, a defined culture medium containing PVA, myo-inositol, ITS, and EGF supported in vitro development of bovine SCNT embryos.

Epigenetic reprogramming of Yak iSCNT embryos after donor cell pre-treatment with oocyte extracts.

The treatment of donor cells with oocyte extracts before inter-species somatic cell nuclear transfer (iSCNT) is a novel method for cellular reprogramming. This study aims to evaluate the effect of pre-treatment donor cell with oocyte extracts on the early developmental competence of yak iSCNT embryos. Yak fibroblasts were reversibly permeabilized with streptolysin O, and then treated with yak oocyte extracts (YOE) or bovine oocyte extracts (BOE) prior to iSCNT. The 8-cell and blastocyst formation increased significantly compared with the control group (P<0.05) when donor cells pre-treated with YOE or BOE. The relative expression level of embryo-specific genes TBP1 and Mash2 were also up-regulated both in the blastocysts of the YOE and BOE groups. In addition, the methylation level of pluripotency-specific genes (Oct4 and Nanog) in the blastocysts of the YOE and BOE groups were similar to that of its IVF counterpart (53.1%, 48.8% vs. 40.1%; 24.8%, 26.5% vs. 35.9%). Our results suggested that pre-treatment of donor cells with oocyte extracts can improve nuclear-cytoplasmic reprogramming; thus representing a novel way to improve the efficiency of yak iSCNT.

[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.

Scriptaid improves in vitro development and nuclear reprogramming of somatic cell nuclear transfer bovine embryos.

The present study evaluated the effect of Scriptaid, a novel histone deacetylase inhibitor (HDACi), on the in vitro development of somatic cell nuclear transfer (SCNT) bovine embryos. Average fluorescence intensity of two epigenetic markers (H3K9ac and H3K9m2) at two-cell, eight-cell, and blastocyst stages, and the expression levels of two developmental important genes (Oct4 and IFN-t) at the blastocyst stage were also examined to assess the influence of Scriptaid on the nuclear reprogramming of bovine SCNT embryos. The results showed that treatment with 500 nM Scriptaid for 14 h after activation significantly increased the cleavage rate, blastocyst formation rate, and blastocyst hatching rate of SCNT embryos compared with those of nontreated counterparts, but the total number of blastomeres per blastocyst did not differ. Scriptaid treatment also significantly increased the immunofluorescent signal for H3K9ac in SCNT embryos at two-cell, eight-cell, and blastocyst stages, and the fluorescent signal for H3K9m2 was decreased at two-cell, eight-cell, and blastocyst stages. The expression levels of Oct4 and IFN-t were significantly higher in Scriptaid-treated SCNT blastocysts than in Scriptaid nontreated SCNT blastocysts. The results indicated that Scriptaid treatment improved the in vitro developmental capacity and the nuclear reprogramming of bovine SCNT embryos.

[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.

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.

[Concentration distribution of bioaerosol in summer and autumn in the Qingdao coastal region].

Bioaerosol samples were collected using an Andersen sampler from Jul. 2009 to Nov. 2009 in the Qingdao coastal region. Total microbe (including 'culturable microbe' and 'non-culturable microbe'), the terrigenous and marine microbe were analyzed by the counting methods of fluorescence microscope and Petri dishes containing agar media. The results showed that the proportion of non-culturable microbe to total microbe was as high as 99.58% of total on average, while the average proportion of culturable microbe to total microbe was 0.42%. The average proportions of marine bacteria/fungi did to the culturable microbe (18.99% and 45.47% respectively) were more than that of terrigenous bacteria/fungi (16.91% and 18.63% respectively), therefore marine bacteria/fungi contributed more to the microbe than terrigenous bacteria/fungi. It could be seen that the composition and concentration distribution were greatly affected by the ocean in the Qingdao coastal region. The average concentrations of total microbe were higher in Autumn (181 682.5 CFU/m3) than that in Summer (159 704.2 CFU/m3), and that of terrigenous bacteria, marine bacteria/fungi were also higher in Autumn than in Summer. The particle sizes of total microbe presented a log-normal distribution in summer and autumn, and the total microbe mainly existed in coarse particles larger than 2.1 microm. There was the highest proportion of total microbe in 3.3-4.7 microm particles, the lowest one in 0.65-1.1 microm. The terrigenous and marine bacterial particle sizes showed a skew distribution with a higher value in large particles (> 7 microm) and a lower one in fine particles (0.65-1.1 microm). The terrigenous and marine fungal particle sizes showed a log-normal distribution in summer and autumn, and the highest concentration proportion existed in particles with diameter of 2.1-3.3 microm.

[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.

[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.

[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.

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.

[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.