Group III secreted phospholipase A2 -driven lysophospholipid pathway protects against allergic asthma.

Asthma is a chronic inflammatory disease of the airways characterized by recurrent episodes of airway obstruction, hyperresponsiveness, remodeling, and eosinophilia. Phospholipase A2 s (PLA2 s), which release fatty acids and lysophospholipids from membrane phospholipids, have been implicated in exacerbating asthma by generating pro-asthmatic lipid mediators, but an understanding of the association between individual PLA2 subtypes and asthma is still incomplete. Here, we show that group III-secreted PLA2 (sPLA2 -III) plays an ameliorating, rather than aggravating, role in asthma pathology. In both mouse and human lungs, sPLA2 -III was expressed in bronchial epithelial cells and decreased during the asthmatic response. In an ovalbumin (OVA)-induced asthma model, Pla2g3-/- mice exhibited enhanced airway hyperresponsiveness, eosinophilia, OVA-specific IgE production, and type 2 cytokine expression as compared to Pla2g3+/+ mice. Lipidomics analysis showed that the pulmonary levels of several lysophospholipids, including lysophosphatidylcholine, lysophosphatidylethanolamine, and lysophosphatidic acid (LPA), were decreased in OVA-challenged Pla2g3-/- mice relative to Pla2g3+/+ mice. LPA receptor 2 (LPA2 ) agonists suppressed thymic stromal lymphopoietin (TSLP) expression in bronchial epithelial cells and reversed airway hyperresponsiveness and eosinophilia in Pla2g3-/- mice, suggesting that sPLA2 -III negatively regulates allergen-induced asthma at least by producing LPA. Thus, the activation of the sPLA2 -III-LPA pathway may be a new therapeutic target for allergic asthma.

[A case of meningeal carcinomatosis of lung adenocarcinoma well controlled by re-treatment with gefitinib].

A 74-year-old-woman who had never smoked was diagnosed in 2004 with cT3N2M1, stage IV primary pulmonary adenocarcinoma. After seven courses of chemotherapy with carboplatin and paclitaxel, she was given gefitinib as second-line therapy and made satisfactory progress. However, gefitinib was discontinued after 3 years of treatment due to re-growth of the tumors. She was then given chemotherapy with docetaxel as a third-line therapy. Over the course of time, meningeal carcinomatosis occurred in conjunction with her previous disease. Upon re-treatment with gefitinib, her meningeal carcinomatosis showed some improvement despite the growing primary tumor, so her QOL was improved. She is now visiting a hospital as an outpatient. When analysis of the EGFR gene mutant was conducted, deletion mutation of E746-A750 in exon 19 was revealed in the 2004 pulmonary tissue, as well as the cytological examination of cerebrospinal fluid and pulmonary tissue after recurrence. No change has been observed. Once gefitinib proved effective, re-treatment with gefitinib was considered useful after its discontinuation.

[A possible case of drug-induced pneumonia due to L-carbocisteine].

A 70-year-old man presented with a deteriorating fever and productive cough after the administration of drugs including L-carbocisteine against the common cold. Since chest radiograph revealed pulmonary infiltrates in the right lower lung field, he was admitted to our hospital, then L-carbocisteine was continued and antibiotics started. However, his symptoms, laboratory findings, and hypoxia worsened. Pulmonary infiltrates on his chest radiograph increased and chest CT demonstrated pulmonary consolidation with traction bronchiectasis and ground glass opacity with thickened of interlobular septae in the right lung field. Analysis of bronchoalveolar lavage fluid showed elevated numbers of total cells, neutrophils and eosinophils, and the CD4/CD8 ratio was 5.65. Under a suspected diagnosis of drug-induced pneumonia, we halted L-carbocisteine administration stopped and began corticosteroid therapy. Subsequently his symptoms and findings markedly improved. The drug lymphocyte stimulation test for L-carbocisteine using peripheral blood lymphocytes showed positive results. On the basis of the clinical course, laboratory and radiographic findings, we considered this case to possibly be drug-induced pneumonia due to L-carbocisteine. To our knowledge, this is possibly the first case of L-carbocisteine-induced pneumonia to be reported.

[Bronchial asthma attack with lactic acidosis and hypokalemia in a case receiving high dose inhalation of procaterol hydrochloride].

We report a case of bronchial asthma attack with lactic acidosis and hypokalemia in a patient receiving high-dose inhalation of procaterol hydrochloride. A 28-year-old man was transferred to our hospital because of adynamia, nausea and dyspnea. He had used inhaled procaterol hydrochloride with a pressurized metered dose inhaler about 20 times before admission. On admission, there were no signs of shock state or hypoxemia and laboratory data showed hypokalemia, hyperglycemia and metabolic acidosis with elevated anion gap. Lactic acidosis was identified as the reason for the metabolic acidosis with elevated anion gap. Lactic acidosis improved after 12 hours. Lactic acidosis due to high dose inhalation of procaterol hydrochloride was suggested.