Toshiya Inui

Calcium oxalate crystal deposition in a patient with Aspergilloma due to Aspergillus niger

Discrimination between aspergilloma and chronic necrotizing pulmonary aspergillosis (CNPA) based on radiological findings can difficult. We describe a patient with aspergilloma and organizing pneumonia that was possibly caused by Aspergillus niger infection and radiologically mimicked CNPA. A postmortem histological analysis showed diffuse alveolar damage that had originated in peri-cavitary lung parenchyma. Calcium oxalate or Aspergillus niger was located inside, but not outside the cavity in the right upper lobe. Calcium oxalate or other unknown hyphal bioactive components might provoke severe lung inflammation not only adjacent to the cavity, but also on the contralateral side.

IL-17A synergistically stimulates TNF-α-induced IL-8 production in human airway epithelial cells: A potential role in amplifying airway inflammation

ABSTRACT Background: Recent reports have suggested an involvement of neutrophilic inflammation driven by interleukin (IL)-17 from Th17 cells, especially in severe, refractory asthma. It remains unknown about the possible interactions of this cytokine and other proinflammatory cytokines to direct neutrophilic airway inflammation. Materials and Methods: We evaluated the effects of IL-17A, IL-17E, and IL-17F in combination with other stimuli such as tumor necrosis factor (TNF) –α on the production and expression of IL-8 in human bronchial epithelial cells. We also studied their effects on other cytokine production. The possible role of mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) signaling pathways was evaluated by specific inhibitors. We examined the effects of anti-asthma drugs, such as steroids or salmeterol. Results: IL-17A alone induced only a minimal effect on IL-8 expression. IL-17A, but not IL-17E or IL-17F, in combination with TNF-α showed a synergistic effect on IL-8 expression. Similar findings were found when combination with IL-1β and IL-17A were used, but such was not the case with lipopolysaccharide (LPS). In addition, we further found such synergy on GM-CSF production. The synergy with TNF-α and IL-17A was significantly inhibited by MAPKs inhibitors. Corticosteroids such as fluticasone propionate and dexamethasone, but not salmeterol, partially suppressed the IL-17A and TNF-α-induced IL-8 production. Conclusions: IL-17A in the combination with TNF-α or IL-1β showed a synergistic augmenting effect on IL-8 and GM-CSF production in human airway epithelial cells.

Clarithromycin ameliorates pulmonary inflammation induced by short term cigarette smoke exposure in mice

BACKGROUND Cigarette smoking is considered to be one of major causes of acute worsening of asthma as well as chronic obstructive pulmonary disease (COPD). Macrolide antibiotics have been reported to reduce the risk of exacerbations of COPD, and possibly neutrophilic asthma. However, the effect of clarithromycin (CAM) on pulmonary inflammation caused by short term exposure to cigarette smoke still remains to be investigated. METHODS C57BL/6J female mice were daily exposed to tobacco smoke using a tobacco smoke exposure system, or clean air for 8 days, while simultaneously treated with either oral CAM or vehicles. Twenty four hours after the last exposure, mice were anaesthetized and sacrificed, and bronchoalveolar lavage (BAL) fluids were collected. Cellular responses in BAL fluids were evaluated. Levels of cytokine mRNA in the lung tissues were measured by quantitative RT-PCR. Paraffin-embedded lung tissues were evaluated to quantitate degree of neutrophil infiltration. RESULTS The numbers of total cells, macrophages and neutrophils in the BAL fluid of smoke-exposed mice were significantly increased as compared to clean air group. These changes were significantly ameliorated in CAM-treated mice. The lung morphological analysis confirmed decrease of neutrophils by CAM treatment. Studies by quantitative PCR demonstrated CAM treatment significantly reduced lung expression levels of IL-17A, keratinocyte-derived chemokine (KC), granulocyte-macrophage colony stimulating factor (GM-CSF) and MMP-9 induced by cigarette smoke. CONCLUSION We demonstrate that CAM administration resolves enhanced pulmonary inflammation induced by short term cigarette smoke exposure in mice.

Serum Reactive Oxygen Metabolite Levels Predict Severe Exacerbations of Asthma

Background and Purpose Bronchial asthma (BA) is a chronic airway disease characterized by airway hyperresponsiveness and remodeling, which are intimately linked to chronic airway inflammation. Reactive oxygen species (ROS) such as hydrogen peroxide are generated by inflammatory cells that are involved in the pathogenesis of BA. However, the role of ROS in the management of BA patients is not yet clear. We attempted to determine the role of ROS as a biomarker in the clinical setting of BA. Subjects and Methods We enrolled patients with BA from 2013 through 2015 and studied the degrees of asthma control, anti-asthma treatment, pulmonary function test results, fractional exhaled nitric oxide (FeNO), serum reactive oxygen metabolite (ROM) levels, and serum levels of interleukin (IL)-6 and IL-8. Results We recruited 110 patients with BA. Serum ROM levels correlated with white blood cell (WBC) count (rs = 0.273, p = 0.004), neutrophil count (rs = 0.235, p = 0.014), CRP (rs = 0.403, p < 0.001), and IL-6 (rs = 0.339, p < 0.001). Serum ROM levels and IL-8 and CRP levels negatively correlated with %FEV1 (rs = -0.240, p = 0.012, rs = -0.362, p < 0.001, rs = -0.197, p = 0.039, respectively). Serum ROM levels were significantly higher in patients who experienced severe exacerbation within 3 months than in patients who did not (339 [302–381] vs. 376 [352–414] CARR U, p < 0.025). Receiver-operating characteristics analysis showed that ROM levels correlated significantly with the occurrence of severe exacerbation (area under the curve: 0.699, 95% CI: 0.597–0.801, p = 0.025). Conclusions Serum levels of ROM were significantly associated with the degrees of airway obstruction, WBC counts, neutrophil counts, IL-6, and severe exacerbations. This biomarker may be useful in predicting severe exacerbations of BA.

Guillain-Barré syndrome in two patients with respiratory failure and a review of the Japanese literature

We described two patients with Guillain-Barré syndrome and respiratory failure with or without mechanical ventilation. Case 1 was a 44-year-old man who treated as pneumonia under mechanical ventilation for a month and transferred to our hospital with unsuccessful weaning trials because of phrenic nerve palsy. Case 2 was a 74-year-old man who presented with aspiration pneumonia because of bulbar palsy. The present two cases with review of the Japanese literature showed that antecedent infection with initial symptoms within the most recent 5 to 46 days is a clinical clue to the diagnosis even in patients with Guillain-Barré syndrome accompanied by respiratory failure.

A case of malignant peritoneal mesothelioma revealed with limitation of PET-CT in the diagnosis of thoracic metastasis

A 47-year-old man was referred to our hospital because of a 2-month history of dry cough, 2-kg weight loss, and a feeling of abdominal fullness. The PET-CT scan depicts the intense standard uptake values (SUVs) of the anterior and subphrenic lymphnodes, and intraperitoneal cavity, especially in the omentum, while, no uptake was found in the pleural cavity. Based on the pathological findings of the open lung biopsy specimens, he was diagnosed with malignant peritoneal mesothelioma of epithelioid type with thoracic metastasis. The present case demonstrated the some of the limitations of PET-CT in the diagnosis of malignant mesothelioma, which failed to detect pleural involvement despite aggressive invasion by this tumor.

A new diagnostic approach for bilious pleural effusion

BACKGROUND Bilious pleural effusion is an extremely rare condition associated with liver diseases, subphrenic or subhepatic abscess formation, biliary peritonitis, and invasive procedures (i.e., percutaneous biliary drainage or liver biopsy). The current diagnostic test is based on the measurement of the ratio of pleural total bilirubin to serum total bilirubin, which is greater than 1 in patients with bilious pleural effusion. Given the low incidence of bilious pleural effusion, the precise diagnostic yield of this ratio based test has not been evaluated. METHODS We retrospectively reviewed the medical records of our institution and searched the PubMed database for reports of bilious pleural effusion. RESULTS We identified a total of 12 cases of bilious pleural effusion (9 from 8 Pubmed reports and 3 from our institutional records). The factors causing this condition were broadly classified into three categories based on the pathophysiology: 1) liver diseases (echinococcosis, tuberculosis and amebiasis); 2) subhepatic/subphrenic abscess or biliary peritonitis, with or without biliary tract obstruction; and 3) iatrogenic disease after percutaneous biliary drainage and/or liver biopsy. The sensitivity of detection was 76.9% when the ratio of pleural total bilirubin to serum total bilirubin was greater than 1. The sensitivity increased to 100% when a combination test including pleural glycoholic acid was adopted. CONCLUSIONS This study demonstrates the high diagnostic yield for bilious pleural effusion using a combination of two test criteria; a ratio of pleural total bilirubin to serum total bilirubin greater than 1 and the presence of pleural glycoholic acid.