Endobronchial ultrasound-guided transbronchial needle aspiration of undiagnosed mediastinal lymphadenopathy

Background Endobronchial ultrasound-guided transbronchial needle aspiration （EBUS-TBNA） can sample the enlarged mediastinal lymph nodes which are unreachable by conventional bronchoscopy.It is a relatively simple and safe method to see beyond the bronchial tree.We describe and discuss its initial application and our experience.Methods From July 2009 to December 2009, 52 patients with undiagnosed enlarged mediastinal lymph nodes were accessed with EBUS-TBNA in the People＇s Liberation Army General Hospital.Conventional bronchoscopy was performed before EBUS-TBNA, and patients with endobronchial lesions were excluded from this study.Smears fixed in 95% alcohol and histological specimens fixed in formalin were sent to Department of Pathology.Results EBUS-TBNA was diagnostic in 33 （63%） patients, with diagnosis of lung cancer in 23 patients （14 patients of small cell lung cancer, eight patients with adenocarcinoma, and one patient of squamous carcinoma）.Four patients, who had negative EBUS-TBNA results, were later diagnosed with malignancy at thoracotomy.One patient with negative EBUS-TBNA results died of cancer cachexia.The sensitivity, specificity, and positive and negative predictive value of EBUS-TBNA for the diagnosis of neoplastic disease were 85%, 100%, 100%, and 50% respectively.Among the 16sarcoidosis patients, who were diagnosed by a combination of the clinical and radiological information as well as pathological results obtained by EBUS-TBNA, nine of them had granulomas and benign lymphoid cells detected by EBUS-TBNA.The sensitivity, specificity, and positive and negative predictive value of EBUS-TBNA for the diagnosis of sarcoidosis were 56%, 100%, 100%, and 13%, respectively.Five patients with no definite diagnosis from EBUS-TNBA examination are under close follow-up.Conclusions EBUS-TBNA can provide a safe and effective method to sample mediastinal leisions suspected of malignancy.It also adds pathological information needed to make the diagnosis of sarcoidosis.

Bone marrow-derived mesenchymal stem cells protect rats from endotoxin-induced acute lung injury

Background Acute lung injury （ALl） is a serious and common condition for which there are currently no specific strategies for treatment. Recent studies have suggested that bone marrow-derived multipotent mesenchymal stem cells （MSCs） may have therapeutic applications in multiple clinical disorders. We explored the biological effects of MSCs during endotoxin-induced ALl and the mechanisms involved. Methods MSCs were isolated from male rat bone marrow and the ALl model was induced by intravenous endotoxin injection. Female rats were sacrificed at 6 hours, 24 hours, 4 days, 1 week and 3 weeks post-injection of MSCs or saline and the lung tissue, bronchoalveolar lavage fluid, and serum were harvested for analysis. We further evaluated the survival of the rats and examined the effects of endotoxin-induced injury on the interaction between alveolar macrophages （AMs） and MSCs in ex vivo. Results There was a significant decrease in numbers of neutrophils in bronchoalveolar lavage fluid （P 〈0.05）, and myeloperoxidase activity in the lung （P 〈0.01）, and of TNF-α and IL-1β in serum （P 〈0.05） in the MSC treated rats at 4 days. Furthermore, MSC treated rats exhibited improved survival, lower lung injury score, higher concentration of IL-10 in the serum and a reduced hydroxyproline content, but these differences were not statistically significant. Moreover, co-cultures of MSCs and AMs had significantly reduced levels of TNF-α, IL-1β and macrophage inflammatory protein （MIP）-1α and significantly increased levels of IL-10 （P〈0.05） in the culture supernatants. Conclusions Treatment with intravenous injection of bone marrow-derived MSCs have beneficial effects on endotoxin-induced ALl in rats. The beneficial effect might be achieved through the engraftment of differentiated MSCs in the lungs and appears derive more from their capacity to secrete soluble factors that modulate immune responses.

Perfluorocarbon attenuates lipopolysaccharide-mediated inflammatory responses of alveolar epithelial cells in vitro

Background Toll-like receptor-4 （TLR-4） is integrally involved in lipopolysaccharide （LPS） signaling and has a requisite role in the activation of nuclear factor-κB （NF-κB）. The exact mechanisms that lend perfluorocarbon （PFC） liquids a cytoprotective effect have yet to be elucidated. Therefore we examined in an in vitro model the cytoprotective effect of PFC on LPS-stimulated alveolar epithelial cellls （AECs）. Methods AECs （A549 cells, human lung adenocarcinoma cell line） were divided into four groups： control, PFC, LPS and LPS ＋ PFC （coculture group） groups. Intercellular adhesion molecule-1 （ICAM-1） was detected by ELISA, tumor necrosis factor-g （TNF-a） and interleukin-8 （IL-8） were detected by radioimmunological methods. The expression of TLR-4 mRNA and protein was detected by real time PCR and Western blotting, respectively. The activation of NF-κB was detected by Western blotting （proteins of I-κBa and NF-κB p65）. Results ICAM-1, TNF-a and IL-8 were significantly increased in LPS-stimulated AECs groups. The expression of TLR-4 mRNA and protein in LPS-stimulated groups was markedly increased. Meanwhile, NF-κB was activated as indicated by the significant degradation of IKB-a and the significant release of NF-κB P65 and its subsequent translocation into the nucleus. There were no significant effects of PFC alone on any of the factors studied while the coculture group showed significant downregulation of the secretion of ICAM-1, TNF-a and IL-8, the expression of TLR-4 rn^NA and the activity of NF-κB. Conclusions Taken together, our results demonstrate that LPS can induce AEC-related inflammatory injury via the activation of TLR-4 and subsequent activation of NF-κB. PFC is able to protect AECs from LPS-induced inflammatory injury by blocking the initiation of the LPS signaling pathway, which is indicated by the significant decrease of TLR-4 expression and NF-κB activation.

Gemifloxacin for the treatment of community-acquired pneumonia and acute exacerbation of chronic bronchitis： a meta-analysis of randomized controlled trials

Background Gemifloxacin is a fluoroquinolone antibiotic with broad spectrum of antibacterial activity.The aim of the study was to evaluate the comparative effectiveness and safety of gemifloxacin for the treatment of patients with community-acquired pneumonia （CAP） or acute exacerbation of chronic bronchitis （AECB）.Methods We performed a meta-analysis of randomized controlled trials （RCTs） comparing gemifloxacin with other approved antibiotics.The PubMed,EMBASE,Chinese Biomedical Literature Database and the Cochrane Central Register of Controlled Trials were searched,with no language restrictions.Results Ten RCTs,comparing gemifloxacin with other quinolones （in 5 RCTs） and β-lactams and/or macrolides （in 5 RCTs）,involving 3940 patients,were included in this meta-analysis.Overall,the treatment success was higher for gemifloxacin when compared with other antibiotics （odds ratio 1.39,95% confidence interval 1.15-1.68 in intention-to-treat patients,and 1.33,1.02-1.73 in clinically evaluable patients）.There was no significant difference between the compared antibiotics regarding microbiological success （1.19,0.84-1.68） or all-cause mortality （0.82,0.41-1.63）.The total drug related adverse events were similar for gemifloxacin when compared with other quinolones （0.89,0.56-1.41）,while lower when compared with β-lactams and/or macrolides （0.71,0.57-0.89）.In subgroup analyses,administration of gemifloxacin was associated with fewer cases of diarrhoea and more rashes compared with other antibiotics （0.66,0.48-0.91,and 2.36,1.18-4.74,respectively）.Conclusions The available evidence suggests that gemifloxacin 320 mg oral daily is equivalent or superior to other approved antibiotics in effectiveness and safety for CAP and AECB.The development of rash represents potential limitation of gemifloxacin.

Gefitinib attenuates murine pulmonary fibrosis induced by bleomycin

Background Gefitinib, an inhibitor of epidermal growth factor receptor （EGFR） tyrosine kinase, is an effective treatment for epithelial tumors, including non-small cell lung cancer （NSCLC）, and is generally well tolerated.However, some clinical trials revealed that gefitinib exposure caused lung fibrosis, a severe adverse reaction.This study investigated the effect of gefitinib on lung fibrosis in mice.Methods We generated a mouse model of lung fibrosis induced by bleomycin to investigate the fibrotic effect of gefitinib.C57BL/6 mice were injected intratracheally with bleomycin or saline, with intragastric administration of gefitinib or saline.Lung tissues were harvested on day 14 or 21 for histology and genetic analysis.Results The histological results showed that bleomycin successfully induced lung fibrosis in mice, and gefitinib prevented lung fibrosis and suppressed the proliferation of S100A4-positive fibroblast cells.In addition, Western blotting analysis revealed that gefitinib decreased the expression of phosphorylated EGFR （p-EGFR）.Furthermore, quantitative real-time PCR （qRT-PCR） demonstrated that gefitinib inhibited the accumulation of collagens Ⅰ and Ⅲ.Conclusions These results reveal that gefitinib reduces pulmonary fibrosis induced by bleomycin in mice and suggest that administration of small molecule EGFR tyrosine kinase inhibitors has the potential to prevent pulmonary fibrosis by inhibiting the proliferation of mesenchymal cells, and that targeting tyrosine kinase receptors might be useful for the treatment of pulmonary fibrosis in humans.

Blastomycosis in China： a case report and literature review

Blastomycosis is a fungal disease that is endemic in parts of North America. It is very rare in China and also commonly misdiagnosed, often as cancer or other infectious diseases. The clinical profile of a case of disseminated blastomycosis with pulmonary changes and skin ulcers was described. He had been misdiagnosed with tuberculosis, after adequate therapy with a lipid formulation of amphotericin B, followed by itraconazole, the lung and skin lesions improved. Then the five cases reported in China and literatures were reviewed. The aim of this report was to improve the knowledge regarding blastomycosis for physicians in China to avoid delaying adequate therapy.

Secondary pulmonary alveolar proteinosis associated with myelodysplastic syndrome

Pulmonary alveolar proteinosis （PAP） IS an uncommon disease first reported by Rosen et al^1 in 1958, and characterized by the accumulation of surtactant proteins and phospholipids within the alveolar spaces. Acquired PAP is divided into two forms based on clinical features： idiopathic PAP and secondary PAE Secondary PAP is reported to be associated with haematological malignancies, Pneumocystis carinii pneumonia and inhalation of silica or titanium, and the most frequent underlying disease of secondary PAP is haematological malignancy. The exact incidence of PAP in haematological malignancies is still obscure, since there have been only sporadic reports of secondary PAP.^ 2, 3