Prediction of requirement for mechanical ventilation in community-acquired pneumonia with acute respiratory failure: a multicenter prospective study.

Background: Several severity scoring systems for predicting mortality are established in community-acquired pneumonia (CAP).

Objectives: The predictability of the aggravation such as requirement for mechanical ventilation in addition to mortality was examined in CAP patients with acute respiratory failure by using the age, dehydration, respiratory failure, orientation disturbance and blood pressure (A-DROP) scoring system which was proposed by the Japanese Respiratory Society.

Methods: This study was a prospective, multicenter, observational cohort study.

Induction of mucin and MUC5AC expression by the protease activity of Aspergillus fumigatus in airway epithelial cells.

Allergic bronchopulmonary mycosis, characterized by excessive mucus secretion, airflow limitation, bronchiectasis, and peripheral blood eosinophilia, is predominantly caused by a fungal pathogen, Aspergillus fumigatus. Using DNA microarray analysis of NCI-H292 cells, a human bronchial epithelial cell line, stimulated with fungal extracts from A. fumigatus, Alternaria alternata, or Penicillium notatum, we identified a mucin-related MUC5AC as one of the genes, the expression of which was selectively induced by A.

Gradual increase of high mobility group protein b1 in the lungs after the onset of acute exacerbation of idiopathic pulmonary fibrosis.

The pathogenesis of acute exacerbation of idiopathic pulmonary fibrosis (IPF) remains to be elucidated. To evaluate the roles of inflammatory mediators in acute exacerbation, the concentrations of high mobility group protein B1 (HMGB1), a chief mediator of acute lung injury, and 18 inflammatory cytokines were measured in the bronchoalveolar lavage fluid, serially sampled from seven IPF patients after the onset of acute exacerbation. HMGB1 gradually increased in the alveolar fluid after the onset of acute exacerbation, in positive correlation with monocytes chemotactic protein-1 (MCP-1), a potent fibrogenic mediator.

Reevaluation of the efficacy and safety of the neutrophil elastase inhibitor, Sivelestat, for the treatment of acute lung injury associated with systemic inflammatory response syndrome; a phase IV study.

Introduction: Sivelestat, a neutrophil elastase inhibitor, has been approved in Japan for the treatment of patients with acute lung injury (ALI) associated with systemic inflammatory response syndrome (SIRS). The Pharmaceuticals and Medical Devices Agency (PMDA) has ordered to conduct a postmarket clinical study in order to reevaluate the efficacy and safety of Sivelestat in actual clinical settings in Japan.

Methods: According to the PMDA's order, we evaluated the efficacy and safety of Sivelestat in Japanese patients with ALI associated with SIRS using ventilator-free days (VFD) as the primary endpoint.

Impact of serum high-mobility group box 1 protein elevation on oxygenation impairment after thoracic aortic aneurysm repair.

High-mobility group box 1 protein (HMGB1) is a late mediator of inflammatory responses that can cause acute lung injury. We examined the significance of serum HMGB1 elevation in the development of systemic inflammatory response syndrome (SIRS) and lung oxygenation impairment (LOI) after thoracic aortic aneurysm (TAA) repair. Serial measurements of the serum HMGB1 level and SIRS score for 7 days after surgery were determined in 20 patients with TAA who underwent surgical repair.

Distinct epigenetic regulation of tumor suppressor genes in putative cancer stem cells of solid tumors.

Epigenetic gene regulation plays essential roles in differentiation of embryonic and tissue stem cells. In these benign undifferentiated cells, some polycomb targeted genes are kept in a state of DNA hypomethylation and they have a distinct chromatin signature termed bivalent chromatin structure to maintain their plasticity. We hypothesized that cancer stem cells (CSC), the malignant counterpart of these cells, are also under the control of epigenetics like benign stem cells.

Bronchoscopic microsampling is a useful complementary diagnostic tool for detecting lung cancer.

Purpose: Bronchoscopic microsampling (BMS) is a novel and direct method with which to obtain epithelial lining fluid (ELF) from the lungs. Analysis of DNA hypermethylation of tumor suppressor genes (TSGs) is expected to be a sensitive tool for the early detection of lung cancer. It has been reported that the existence of EGFR mutations and EML4-ALK gene rearrangements are related to the sensitivity of corresponding kinase inhibitors.

Evaluation of pathogen detection from clinical samples by real-time polymerase chain reaction using a sepsis pathogen DNA detection kit.

Introduction: Sepsis is a serious medical condition that requires rapidly administered, appropriate antibiotic treatment. Conventional methods take three or more days for final pathogen identification and antimicrobial susceptibility testing. We organized a prospective observational multicenter study in three study sites to evaluate the diagnostic accuracy and potential clinical utility of the SeptiFast system, a multiplex pathogen detection system used in the clinical setting to support early diagnosis of bloodstream infections.

Production and activation of matrix metalloproteinase 7 (matrilysin 1) in the lungs of patients with idiopathic pulmonary fibrosis.

Context: Idiopathic pulmonary fibrosis (IPF) is characterized by diffuse interstitial inflammation and fibroblast proliferation with accelerated remodeling of extracellular matrix, which result in irreversible destruction of the lung's architecture.

Objective: To elucidate the production levels, tissue localization, and activation of matrix metalloproteinase 7 (MMP-7) in the lungs of patients with IPF.

Design: Bronchoalveolar lavage analysis was performed in 17 IPF patients and 6 healthy volunteers.

Role of interleukin-6 in elastase-induced lung inflammatory changes in mice.

Interleukin-6 (IL-6) is known to be involved in the pathogenesis of various inflammatory diseases, but its role in the development of pulmonary emphysema remains unclear. Wild-type (WT) and IL-6-deficient mice received either phosphate-buffered saline (PBS) or porcine pancreatic elastase (PPE) intratracheally. The development of emphysema was determined by measuring the mean linear intercept (Lm).

The combination of multiple receptor tyrosine kinase inhibitor and mammalian target of rapamycin inhibitor overcomes erlotinib resistance in lung cancer cell lines through c-Met inhibition.

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) show antitumor activity in a subset of non-small cell lung cancer (NSCLC) patients. However, the initial tumor response is followed by recurrence. Several studies have suggested the importance of other receptor tyrosine kinases (RTK) and downstream kinases as potential targets in the treatment of NSCLC.

High-mobility-group box chromosomal protein 1 as a new target for modulating stress response.

Major surgical procedures induce a systemic inflammatory response syndrome (SIRS) characterized by the overproduction of proinflammatory cytokines, which induces excessive stress and may trigger postoperative complications. This has prompted the hypothesis that drugs which relieve SIRS might improve the postoperative course of major surgery. One of the most promising targets for these drugs is high-mobility-group box chromosomal protein 1 (HMGB1).

Association between beta-adrenoceptor gene polymorphisms and relative response to beta 2-agonists and anticholinergic drugs in Japanese asthmatic patients.

Background And Objective: Whether beta(2)-adrenoceptor gene (ADRB2) polymorphisms are associated with airway responsiveness to beta(2)-agonist medications remains controversial, partly due to factors that may confound pharmacogenetic associations, including age, cigarette smoking and airway remodelling. To overcome these problems, we performed an analysis using parameters that reflected the specific bronchodilator response to beta(2)-agonists.

Methods: The increases in FEV(1) after inhalation of procaterol hydrochloride (Delta FEV(1) procaterol) or oxitropium bromide (Delta FEV(1) oxitropium), and after sequential inhalation of procaterol and oxitropium (total airway reversibility), were measured in 81 Japanese patients with moderate to severe asthma.

Strain-specific phenotypes of airway inflammation and bronchial hyperresponsiveness induced by epicutaneous allergen sensitization in BALB/c and C57BL/6 mice.

Background: Allergen sensitization through a disrupted skin barrier appears to play a prominent role in the development of atopic diseases, including allergic asthma. The role of the genetic background in immunological and physiological phenotypes induced by epicutaneous sensitization is undetermined.

Methods: BALB/c and C57BL/6 mice were sensitized either epicutaneously by patch application of ovalbumin (OVA) or systemically by intraperitoneal injection of OVA with alum before exposure to aerosolized OVA.

Plasma biomarker profiles in acute exacerbation of idiopathic pulmonary fibrosis.

Little is known about the pathobiology of acute exacerbation of idiopathic pulmonary fibrosis (IPF), a condition that shares clinical and histopathological features with acute lung injury. Plasma biomarkers have been well studied in acute lung injury and have provided insight into the underlying disease mechanism. The objective of this study was to determine the plasma biomarker profile of acute exacerbation of IPF and compare this profile with that of stable IPF and acute lung injury.

[A case of miliary tuberculosis showing acute respiratory distress syndrome in rheumatoid arthritis].

A 62-year-old man, treated with corticosteroids and immunosuppressants for rheumatoid arthritis, visited hospital with high fever and dyspnea on exertion. A CT scan of the chest demonstrated bilateral diffuse ground glass opacities. On the basis of the findings of the CT scan, he was initially given a diagnosis of interstitial pneumonia.

Effect of Toll-like receptor 4 inhibitor on LPS-induced lung injury.

Objective And Design: Toll-like receptor 4 (TLR4) plays important roles in the recognition of lipopolysaccharide (LPS) and the activation of inflammatory cascade. In this study, we evaluated the effect of TAK-242, a selective TLR4 signal transduction inhibitor, on acute lung injury (ALI).

Materials And Methods: C57BL/6J mice were intravenously treated with TAK-242 15 min before the intratracheal administration of LPS or Pam3CSK4, a synthetic lipopeptide.

Acute respiratory distress syndrome after percutaneous cryotherapy for a pulmonary metastatic lesion.

Percutaneous cryotherapy (PCT) under computed tomographic guidance is minimally invasive, with satisfactory local control of primary lung cancer and pulmonary metastatic lesions. We report a case of acute respiratory distress syndrome (ARDS) in a patient who underwent PCT for lung metastasis of recurrent esophageal cancer. The patient responded to pulse steroid therapy and recovered from severe respiratory failure.

[Long-term treatment with a humanized anti-interleukin-6 receptor antibody (tocilizumab), improving interstitial pneumonia in a patient with multicentric Castleman disease].

A 46-year-old man was admitted for the evaluation of a dry cough and dyspnea on exertion. Laboratory tests revealed anemia, elevated CRP, polyclonal hyperimmunoglobulinemia, and an elevated interleukin-6 level. Radiological examination of the chest showed peribronchovascular consolidations, ground glass opacities, small nodular opacities, and interlobular septal thickenings in the lungs, accompanied with hilar and mediastinal lymphadenopathies.

[Effect of direct hemoperfusion with a polymyxin B immobilized fiber column in acute exacerbation of interstitial pneumonia and serum indicators].

Acute exacerbation of interstitial pneumonia (IP-AE) can occasionally occur and has a poor prognosis. Direct hemoperfusion with a polymyxin B immobilized fiber column (PMX-DHP) has been shown to have a beneficial effect on acute respiratory distress syndrome, which has similar pathological features to that of IP-AE. This study was aimed to investigate the effects of PMX-DHP on IP-AE and serum indicators for epithelial damage.

Neutrophil elastase inhibitor improves survival of rats with clinically relevant sepsis.

Sivelestat sodium hydrate is a selective inhibitor of neutrophil elastase, which is effective in acute lung injury associated with systemic inflammatory response syndrome. However, the effectiveness of sivelestat in sepsis has not been fully examined. In the present study, the effect of sivelestat on severe sepsis in a rat cecal ligation and puncture (CLP) model was investigated.

Laminin gamma2 fragments are increased in the circulation of patients with early phase acute lung injury.

Objective: Laminin-5, a cell adhesive molecule expressed solely by epithelium, is known to enhance epithelial cell migration and repair of injured epithelium, after its essential component gamma2-chain is processed proteolytically. Our previous study revealed circulating levels of amino-terminal fragment of laminin gamma2-chain (G2F) reflect epithelial tumor invasiveness in carcinoma patients, but its physiological role in alveolar epithelial injury remains unknown.

Design: Sampling of epithelial lining fluids or pulmonary edema fluids from patients with acute lung injury (ALI) or related diseases was performed.

Intratracheal synthetic CpG oligodeoxynucleotide causes acute lung injury with systemic inflammatory response.

Bacterial genome is characterized by frequent unmethylated cytosine-phosphate-guanine (CpG) motifs. Deleterious effects can occur when synthetic oligodeoxynucleotides (ODN) with unmethylated CpG dinucleotides (CpG-ODN) are administered in a systemic fashion. We aimed to evaluate the effect of intratracheal CpG-ODN on lung inflammation and systemic inflammatory response.