sRAGE alleviates neutrophilic asthma by blocking HMGB1/RAGE signalling in airway dendritic cells.

Receptor for advanced glycation end products (RAGE) plays a role in inflammatory reactions. The soluble form of RAGE (sRAGE) acts as a decoy to inhibit interactions of RAGE with advanced glycation end products such as High mobility group box 1 (HMGB1). We have demonstrated that HMGB1 directs Th17 skewing by regulating dendritic cell (DC) functions in a previous study. However, the protective effects of HMGB1 blockade with sRAGE in the development of neutrophilic asthma remain unclear. Here, we showed that allergen challenge decreased expression of sRAGE in a murine model of neutrophilic asthma, correlating well with neutrophil counts and interleukin (IL)-17 production. When HMGB1 signalling was blocked by intratracheal administration of sRAGE before sensitisation, HMGB1 expression, neutrophilic inflammation, and Th17-type responses were reduced significantly. Anti-asthma effects of sRAGE were achieved by inhibition of RAGE and IL-23 expression in airway CD11c+ antigen-presenting cells. Finally, we showed that sRAGE inhibited Th17 polarisation induced by recombinant HMGB1 (rHMGB1)-activated dendritic cells (DCs) in vitro. Adoptive transfer of rHMGB1-activated DCs was sufficient to restore airway inflammation, whereas transfer of rHMGB1 plus sRAGE-activated DCs significantly reduced neutrophilic inflammation. Thus, sRAGE prevents Th17-mediated airway inflammation in neutrophilic asthma at least partly by blocking HMGB1/RAGE signalling in DCs.

Adenosine Triphosphate Promotes Allergen-Induced Airway Inflammation and Th17 Cell Polarization in Neutrophilic Asthma.

Adenosine triphosphate (ATP) is a key mediator to alert the immune dysfunction by acting on P2 receptors. Here, we found that allergen challenge caused an increase of ATP secretion in a murine model of neutrophilic asthma, which correlated well with neutrophil counts and interleukin-17 production. When ATP signaling was blocked by intratracheal administration of the ATP receptor antagonist suramin before challenge, neutrophilic airway inflammation, airway hyperresponsiveness, and Th17-type responses were reduced significantly. Also, neutrophilic inflammation was abrogated when airway ATP levels were locally neutralized using apyrase. Furthermore, ATP promoted the Th17 polarization of splenic CD4+ T cells from DO11.10 mice in vitro. In addition, ovalbumin (OVA) challenge induced neutrophilic inflammation and Th17 polarization in DO11.10 mice, whereas administration of suramin before challenge alleviated these parameters. Thus, ATP may serve as a marker of neutrophilic asthma, and local blockade of ATP signaling might provide an alternative method to prevent Th17-mediated airway inflammation in neutrophilic asthma.

The pulmonary nodule "discovered" by pneumonia: a case report.

The number of patients diagnosed with pulmonary nodules increased as more patients with high risk of lung cancer choose low-dose computed tomography (CT) scans for the screening of cancer. Clinicians might get two questions from the patients: what is the definite diagnosis of the nodule? What should we do? We have already got many guidelines trying to solve these problems. There are also several prediction models for pulmonary nodules. However, guidelines are not suitable for all types of patients, and the reality of patients is more complicated. Here we reported a 58-year-old man with a lung nodule in the right upper lobe, which was occasionally found during a period of pneumonia. We suggested two periods of follow-up, and the patient was also admitted to a clinical trial about circulating tumor cells (CTCs). He finally accepted surgical excision with a pathologic diagnosis of adenocarcinoma. This case suggests that: we might suggest CT surveillance for patients with solid nodules about 8 mm maximum diameter; three-dimensional reconstruction of CT scans could provide more information about the details of nodules; CTCs counts of peripheral blood could be considered as a potential clue for malignancy.

Recurrent "pneumonia" in left lower lobe lasting for 8 years: a case report.

Bronchioloalveolar carcinoma (BAC) is a unique lung neoplasm with variable forms, such as single nodular, multifocal and lobar pneumonic types. The pneumonic type BAC is often difficult to differentiate from pneumonia. Here we present a case of 63-year-old Chinese male, who had recurrent cough, white sputum with pneumonic lesions in left lower lobe. He suffered from lung biopsies for three times, and finally diagnosed as high differentiated adenocarcinoma 8 years later. He was treated with four cycles of pemetrexed and cisplatin, and four cycles of docetaxel and nedaplatin. However, he did not achieve disease stabilization and is still under follow up. This case suggests that, pneumonic type adenocarcinoma may radiographically and clinically resemble infectious pneumonia. Lack of fever and leukocytosis, no response to antibiotics, air bronchogram, and accompanied nodules or patches in computed tomography (CT) scans should raise suspicion about the diagnosis of pneumonia. Lung biopsy might be the only means of ruling in a diagnosis of BAC.

Anti-HMGB1 neutralizing antibody ameliorates neutrophilic airway inflammation by suppressing dendritic cell-mediated Th17 polarization.

We demonstrate that high mobility group box 1 protein (HMGB1) directs Th17 skewing by regulating dendritic cell (DC) function. First, our in vitro studies reveal that recombinant HMGB1 (rHMGB1) activates myeloid DCs to produce IL-23 in vitro, and rHMGB1-activated DCs prime naïve lymphocytes to produce the Th17 cytokine IL-17A. Second, we demonstrate that anti-HMGB1 neutralizing antibody attenuates HMGB1 expression, neutrophilic inflammation, airway hyperresponsiveness, and Th17-related cytokine secretion in vivo by using a murine model of neutrophilic asthma induced by ovalbumin (OVA) plus lipopolysaccharide (LPS). Furthermore, anti-HMGB1 neutralizing antibody decreases the number of Th17 cells in lung cells and suppresses the production of IL-23 by lung CD11C(+) APCs. Finally, we show that intranasal adoptive transfer of rHMGB1-activated DCs was sufficient to restore lung neutrophilic inflammation and the Th17 response in a DC-driven model of asthma, whereas the transfer of rHMGB1 plus anti-HMGB1-treated mDCs significantly reduced these inflammation phenotypes. These data suggest, for the first time, that HMGB1 drives the DC-polarized Th17-type response in allergic lung inflammation and that blocking HMGB1 may benefit the attenuation of neutrophilic airway inflammation in asthma.

[Invasive aspergillosis after near-drowning: case reports and review of the literature].

OBJECTIVE: The purpose of this study was to analyze the clinical presentations and disease courses of invasive aspergillosis (IA) in patients after near-drowning. METHODS: The clinical data of 3 cases of invasive aspergillosis after near-drowning from Oct. 2005 to Aug. 2010 in this hospital were retrospectively analyzed, and the related literature was reviewed. RESULTS: There were 1 male and 2 female patients, aged from 18 to 72 years. All of them had been immunocompetent before drowning. Two patients drowned because of traffic accident, and 1 fell in sewage by accident. All of the 3 patients were intubated because of acute respiratory failure, and received broad-spectrum antibiotic therapy. One had transient leucopenia, and 2 patients received glucocorticoid therapy. The condition of the 3 cases deteriorated 9 to 11 days after near-drowning. Aspergillus was isolated from sputum samples of 2 patients at the same time. Thoracic CT findings included multiple nodules, consolidation and cavity formation. Multiple abscesses in cerebral parenchyma were found in 1 patient with invasive cerebral aspergillosis. One patient died, whose lungs, cerebral parenchyma, myocardium and kidney were all infected by aspergillus. The other 2 patients, whose infection limited to the lungs, had a positive prognosis. Using the terms "aspergillosis" and "near-drowning" a PUBMED search yielded 7 articles, published between 1984 and 2010. Using the terms "invasive pulmonary aspergillosis" and "near-drowning", searching Wangfang data and CHED data, encompass 1 article, published in 2009. In all of the 8 articles, there are 5 final diagnosis cases and 3 clinical diagnosis cases. CONCLUSIONS: IA was very rare in immunocompetent hosts but had been reported in previously healthy individuals after near-drowning. Aspergillosis might develop 1 to 2 weeks after near-drowning, and the prognosis was poor in patients with central nervous system involvement.

Diagnostic efficiency and complication rate of CT-guided lung biopsy: a single center experience of the procedures conducted over a 10-year period.

BACKGROUND: Computed tomography (CT)-guided transthoracic lung biopsy is a well-established technique for the diagnosis of pulmonary lesions. The objective of this study was to evaluate the diagnostic efficiency and complication rate of CT-guided lung biopsy in a Chinese population. METHODS: CT-guided cutting needle lung biopsies were performed in our institution on 1014 patients between January 2000 and October 2010. A chest radiograph was taken after the biopsy. Data about basic patient information, final diagnosis, and complications secondary to biopsy procedure (pneumothorax and bleeding) were extracted. RESULTS: The diagnostic efficiency of CT-guided lung biopsy was 94.8%; only 53 patients did not get a final diagnosis from lung biopsy. Final diagnoses found 639 malignant lesions (63.0%) and 322 benign lesions (31.8%). Pneumothorax occurred in 131 patients and 15 required insertion of an intercostal drain. Small hemoptysis occurred in 41 patients and mild parenchymal hemorrhage occurred in 16 patients. The overall complication rate was 18.5%. CONCLUSIONS: CT-guided cutting needle biopsy of pulmonary lesions is a relatively safe technique with a high diagnostic accuracy. It can be safely performed in clinical trials.