Junping Wu

Bronchial artery embolization for hemoptysis: a retrospective observational study of 344 patients.

Background: Hemoptysis is a significant clinical entity with high morbidity and potential mortality. Both medical management (in terms of resuscitation and bronchoscopic interventions) and surgery have severe limitations in these patients population. Bronchial artery embolization (BAE) represents the first-line treatment for hemoptysis. This article discusses clinical analysis, embolization approach, outcomes and complications of BAE for the treatment of hemoptysis. Methods: A retrospective analysis of 344 cases, who underwent bronchial arteriography at Tianjin Haihe Hospital between 2006 and 2013. Several aspects of outcome were analyzed: Demographics, clinical presentation, radiographic studies, results, complications and follow-up of BAE. Results: Three hundred and forty-four consecutive patients underwent bronchial arteriography, 336 of 344 patients (97.7%) performed BAE; there were 1530 coils for 920 arteries embolized; the main responsible sources for bleeding were right bronchial artery (29.7%), left bronchial artery (21.6%), combined right and left bronchial trunk (18.4%), right intercostal arteries (13.3%); 61 patients (17.7%) had recurrent hemoptysis within 1 month after undergoing BAE, 74 patients (21.5%) had recurrent hemoptysis over 1 month after undergoing BAE; The common complications of BAE included subintimal dissection, arterial perforation by a guide wire, fever, chest pain, dyspnea, etc. The follow-up was completed in 248 patients, 28 patients had been dead, 21 patients still bleed, 92 patients had lost to follow-up. Conclusions: The technique of BAE is a relatively safe and effective method for controlling hemoptysis. The complications of BAE are rare. Although the long-term outcome in some patients is not good, BAE may be the only life-saving treatment option in patients who are poor surgical candidates.

Glucocorticoid dexamethasone regulates the differentiation of mouse conducting airway epithelial progenitor cells

Inhaled glucocorticoid dexamethasone is the most effective treatment of asthma currently available. Epithelial damage and shedding represents a clear manifestation of asthmatic pathologies. However it remains unknown if dexamethasone regulates functions of airway progenitor cells that are responsible for epithelial repair. In present study Secretoglobin1a1 (Scgb1a1) lineage tracing mice were injected intraperitoneally with tamoxifen to induce the expression of green fluorescence protein (GFP) in Scgb1a1-expressing conducting airway progenitor cells. Scgb1a1-expressing progenitor cells were isolated from lungs of Scgb1a1 lineage tracing mice via flow activated cell sorting. In vitro three-dimensional matrigel culture of these progenitor cells revealed that dexamethasone has little effect on the colony forming ability of airway epithelial progenitor cells, but exhibits significant effects on the differentiation of the progenitor cells. Compared to the untreated group, dexamethasone treatment inhibited the expression of forkhead box J1 (FoxJ1) and mucin subtype A & C (Muc5Ac), but promoted the expression of calcium activated chloride channel 3 (Clca3) and cystic fibrosis transmembrane conductance regulator (Cftr). Dexamethasone-induced effects on the expression of FoxJ1, Muc5Ac and Clca3 were abolished or even reversed in the presence of RU486, an antagonist of glucocorticoid receptor, indicating that glucocorticoid receptor plays a role in the regulation of airway epithelial progenitor cells by dexamethasone. These data suggested that, though effective to reduce airway inflammation, dexamethasone treatment alone fails to fully restore the mucociliary clearance function in the treatment of asthma patients.

Fatty Acid Metabolism is Associated With Disease Severity After H7N9 Infection

Background Human infections with the H7N9 virus could lead to lung damage and even multiple organ failure, which is closely associated with a high mortality rate. However, the metabolic basis of such systemic alterations remains unknown. Methods This study included hospitalized patients (n = 4) with laboratory-confirmed H7N9 infection, healthy controls (n = 9), and two disease control groups comprising patients with pneumonia (n = 9) and patients with pneumonia who received steroid treatment (n = 10). One H7N9-infected patient underwent lung biopsy for histopathological analysis and expression analysis of genes associated with lung homeostasis. H7N9-induced systemic alterations were investigated using metabolomic analysis of sera collected from the four patients by using ultra-performance liquid chromatography-mass spectrometry. Chest digital radiography and laboratory tests were also conducted. Findings Two of the four patients did not survive the clinical treatments with antiviral medication, steroids, and oxygen therapy. Biopsy revealed disrupted expression of genes associated with lung epithelial integrity. Histopathological analysis demonstrated severe lung inflammation after H7N9 infection. Metabolomic analysis indicated that fatty acid metabolism may be inhibited during H7N9 infection. Serum levels of palmitic acid, erucic acid, and phytal may negatively correlate with the extent of lung inflammation after H7N9 infection. The changes in fatty acid levels may not be due to steroid treatment or pneumonia. Interpretation Altered structural and secretory properties of the lung epithelium may be associated with the severity of H7N9-infection-induced lung disease. Moreover, fatty acid metabolism level may predict a fatal outcome after H7N9 virus infection.

Altered Lipid Metabolism in Recovered SARS Patients Twelve Years after Infection

Severe acute respiratory syndrome-coronavirus (SARS-CoV) and SARS-like coronavirus are a potential threat to global health. However, reviews of the long-term effects of clinical treatments in SARS patients are lacking. Here a total of 25 recovered SARS patients were recruited 12 years after infection. Clinical questionnaire responses and examination findings indicated that the patients had experienced various diseases, including lung susceptibility to infections, tumors, cardiovascular disorders, and abnormal glucose metabolism. As compared to healthy controls, metabolomic analyses identified significant differences in the serum metabolomes of SARS survivors. The most significant metabolic disruptions were the comprehensive increase of phosphatidylinositol and lysophospha tidylinositol levels in recovered SARS patients, which coincided with the effect of methylprednisolone administration investigated further in the steroid treated non-SARS patients with severe pneumonia. These results suggested that high-dose pulses of methylprednisolone might cause long-term systemic damage associated with serum metabolic alterations. The present study provided information for an improved understanding of coronavirus-associated pathologies, which might permit further optimization of clinical treatments.

Tsp1 promotes alveolar stem cell proliferation and its down-regulation relates to lung inflammation in intralobar pulmonary sequestration

An aberrant systemic artery supply results in recurrent infections in the abnormal lung lobe of intralobar pulmonary sequestration (ILS). The mechanisms underlying such persistent inflammation are unknown. Here, we hypothesize that alteration of an endothelial cell niche for alveolar epithelial cells results in the impaired proliferation potential of alveolar progenitor cells, leading to the defective defense mechanism in intralobar pulmonary sequestration. Paraffin sections of lung tissues from patients with intralobar pulmonary sequestration or from healthy controls were collected for analysis of alveolar epithelial alterations in intralobar pulmonary sequestration by quantitative RT-PCR or immunofluorescent staining. Differential transcripts were identified between human pulmonary artery endothelial cells and human aortic endothelial cells by microarray. Validation of microarray data by quantitative PCR analysis indicated that thrombospondin-1 expression level is low in near-lesion part but high in lesion part of ILS lobe as compared to healthy controls. In vitro 3-D matrigel culture was adopted to evaluate the regulation of alveolar progenitor cells by thrombospondin-1 and CD36. We found that the proliferative potential of alveolar type 2 stem/progenitor cells was impaired in intralobar pulmonary sequestration. Mechanistically, we discovered that endothelial thrombospondin-1 promotes alveolar type 2 cell proliferation through the interaction with CD36. These data demonstrate that alveolar stem cells are impaired in the abnormal lobe from patients with intralobar pulmonary sequestration and imply that restoring epithelial integrity can be beneficial for the future treatments of recurrent infections in lung pathologies.

The role of TGFβ‑HGF‑Smad4 axis in regulating the proliferation of mouse airway progenitor cells

The interaction between airway epithelial progenitor cells and their microenvironment is critical for maintaining lung homeostasis. This microenvironment includes fibroblast cells, which support the growth of airway progenitor cells. However, the mechanism of this support is not fully understood. In the present study, the authors observed that inhibition of transforming growth factor (TGF)-β signal with SB431542 promotes the expression of hepatocyte growth factor (HGF) in fibroblast cells. The HGF receptor, c-Met, is expressed on airway progenitor cells; HGF promotes the colony-forming ability of airway progenitor cells. The deletion of Smad4 in airway progenitor cells increases the colony-forming ability, suggesting that Smad4 plays a negative role in the regulating the proliferation of airway progenitor cells. These data demonstrated that the regulation of airway progenitor cells by TGF-β depends on TGF-βR1/2 on stromal cells, rather than on epithelial progenitor cells. These data suggested a role for the TGF-β-TGF-βR1/2-HGF-Smad4 axis in airway epithelial homeostasis and sheds new light on the interaction between airway progenitor cells and their microenvironment.

Altered gene expression of hepatic cytochrome P450 in a rat model of intermittent hypoxia with emphysema

Patients with respiratory overlap syndrome (OS), defined as concomitant chronic obstructive pulmonary disease and obstructive sleep apnea syndrome, may exhibit an increased blood concentration of ingested drugs. This poor elimination of drugs is primarily attributed to downregulated gene expression of the drug‑metabolizing cytochrome P450 enzymes (CYPs) in the liver. However, the underlying mechanisms of the decreased expression of CYPs in OS are poorly understood. In order to address this, a rat model of intermittent hypoxia with emphysema was evaluated in the present study, by analyzing liver gene expression using the reverse transcription‑quantitative polymerase chain reaction. Intermittent hypoxia and cigarette smoke exposure caused upregulation of hepatic inflammatory cytokines, while CYPs were downregulated. This downregulation of CYPs was associated with an increase in nuclear factor (NF)‑κB expression and a decrease in the expression of nuclear receptors pregnane X receptor, constitutive androstane receptor and glucocorticoid receptor, which are the upstream regulatory molecules of CYPs. The results of the present study indicated that, during the development of OS, systematic inflammatory reactions may downregulate hepatic CYP gene expression via the NF‑κB signaling pathway.

Regulation of Leukocyte Recruitment to the Spleen and Peritoneal Cavity during Pristane-Induced Inflammation

Chronic inflammation is associated with an increased number of leukocytes in the spleen, which are then redirected to the site of inflammation. However, it remains unknown how leukocyte recruitment is regulated. Herein, chronic inflammation was induced by intraperitoneal injection of pristane into mice. Leukocytes in the spleen or in the peritoneal cavity were quantified by flow cytometry. We found that the loss of IL-6 decreased macrophage recruitment to the spleen and the peritoneal cavity during pristane-induced inflammation. The loss of TNFα delayed the recruitment of neutrophils and macrophages to the spleen and inhibited the recruitment of neutrophils, macrophages, B cells, and T cells. The recruitment of neutrophils and macrophages into the spleen or peritoneal cavity was largely inhibited in the absence of LTα. The loss of TNFα receptor 1/2 resulted in reduced recruitment of neutrophils, macrophages, and dendritic cells into the spleen, but only neutrophil recruitment was inhibited in the peritoneal cavity. Similarly, a lack of B cells significantly impeded the recruitment of neutrophils, macrophages, and dendritic cells to the spleen. However, only macrophage recruitment was inhibited in the absence of T cells in the spleen. These data provide insight into the development of chronic inflammation induced by noninfectious substances.

Hepatic Cyp1a2 Expression Reduction during Inflammation Elicited in a Rat Model of Intermittent Hypoxia

Background: Intermittent hypoxia (IH) is a key element of obstructive sleep apnea (OSA) that can lead to disorders in the liver. In this study, IH was established in a rat model to examine its effects on the expression of hepatic cytochrome P450 (CYP) and CYP regulators, including nuclear receptors. Methods: Hematoxylin and eosin staining was conducted to analyze the general pathology of the liver of rats exposed to IH. The messenger RNA (mRNA) expression levels of inflammatory cytokines, CYPs, nuclear factor-&kgr;B (NF-&kgr;B), and nuclear factors in the liver were measured by quantitative reverse transcription polymerase chain reaction. Results: We found inflammatory infiltrates in the liver of rats exposed to IH. The mRNA expression level of interleukin-1beta was increased in the liver of the IH-exposed rats (0.005 ± 0.001 vs. 0.038 ± 0.008, P = 0.042), whereas the mRNA expression level of Cyp1a2 was downregulated (0.022 ± 0.002 vs. 0.0050 ± 0.0002, P = 0.029). The hepatic level of transcription factor NF-&kgr;B was also reduced in the IH group relative to that in the control group, but the difference was not statistically significant and was parallel to the expression of the pregnane X receptor and constitutive androstane receptor. However, the decreased expression of the glucocorticoid receptor upon IH treatment was statistically significant (0.056 ± 0.012 vs. 0.032 ± 0.005, P = 0.035). Conclusions: These results indicate a decrease in expression of hepatic CYPs and their regulator GR in rats exposed to IH. Therefore, this should be noted for patients on medication, especially those on drugs metabolized via the hepatic system, and close attention should be paid to the liver function of patients with OSA-associated IH.

Impaired Capacity of Fibroblasts to Support Airway Epithelial Progenitors in Bronchiolitis Obliterans Syndrome

Background: Bronchiolitis obliterans syndrome (BOS) often develops in transplant patients and results in injury to the respiratory and terminal airway epithelium. Owing to its rising incidence, the pathogenesis of BOS is currently an area of intensive research. Studies have shown that injury to the respiratory epithelium results in dysregulation of epithelial repair. Airway epithelial regeneration is supported by stromal cells, including fibroblasts. This study aimed to investigate whether the supportive role of lung fibroblasts is altered in BOS. Methods: Suspensions of lung cells were prepared by enzyme digestion. Lung progenitor cells (LPCs) were separated by fluorescence-activated cell sorting. Lung fibroblasts from patients with BOS or healthy controls were mixed with sorted mouse LPCs to compare the colony-forming efficiency of LPCs by counting the number of colonies with a diameter of ≥50 &mgr;m in each culture. Statistical analyses were performed using the SPSS 17.0 software (SPSS Inc., USA). The paired Students t-test was used to test for statistical significance. Results: LPCs were isolated with the surface phenotype of CD31- CD34- CD45- EpCAM+ Sca-1+. The colony-forming efficiency of LPCs was significantly reduced when co-cultured with fibroblasts isolated from patients with BOS. The addition of SB431542 increased the colony-forming efficiency of LPCs to 1.8%; however, it was still significantly less than that in co-culture with healthy control fibroblasts (P < 0.05). Conclusion: The epithelial-supportive capacity of fibroblasts is impaired in the development of BOS and suggest that inefficient repair of airway epithelium could contribute to persistent airway inflammation in BOS.