Direct hemoperfusion with polymyxin B-immobilized fiber for the treatment of the acute exacerbation of idiopathic pulmonary fibrosis in patients requiring invasive mechanical ventilation.

The prognosis of acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) in individuals undergoing invasive mechanical ventilation is known to be poor. We describe the cases of three men, who were former smokers and required mechanical ventilation, whose AE-IPF was treated with direct hemoperfusion with polymyxin B-immobilized fiber column (PMX-DHP). In all cases, we successfully weaned the patients from mechanical ventilation. Two of the patients survived for more than 180 days after development of AE-IPF. PMX-DHP may improve the prognosis of severe respiratory failure in patients with AE-IPF.

[A case of pulmonary pleomorphic carcinoma treated with S-1 following radiotherapy].

Pleomorphic carcinoma is a rare malignancy of the lung. Here we present a 68-year-old man who was admitted to our hospital for examination of an abnormal radiogram of the chest. The radiogram revealed a large mass in the right lung field. A chest computed tomographic (CT) scan demonstrated a nonsegmentalmass like consolidation. Percutaneous CT-guided fine-needle needle biopsy from the lung was performed, and the specimen demonstrated pulmonary pleomorphic carcinoma. The patient was initially treated with two courses of cisplatin (CDDP) and docetaxel (DOC), and still showed progressive disease (PD). Therefore, we administered S-1 following radiotherapy. The chest CT revealed partial response after 4 months. We experienced a pulmonary pleomorphic carcinoma which showed a response to salvage chemotherapy with S-1.

Clara cell secretory protein and phospholipase A2 activity modulate acute ventilator-induced lung injury in mice.

Lung vascular permeability is acutely increased by high-pressure and high-volume ventilation. To determine the roles of mechanically activated cytosolic PLA2 (cPLA2)and Clara cell secretory protein (CCSP), a modulator of cPLA2 activity, we compared lung injury with and without a PLA2 inhibitor in wild-type mice and CCSP-null mice (CCSP-/-) ventilated with high and low peak inflation pressures (PIP) for 2- or 4-h periods. After ventilation with high PIP, we observed significant increases in the bronchoalveolar lavage albumin concentrations, lung wet-to-dry weight ratios, and lung myeloperoxidase in both genotypes compared with unventilated controls and low-PIP ventilated mice. All injury variables except myeloperoxidase were significantly greater in the CCSP-/- mice relative to wild-type mice. Inhibition of cPLA2 in wild-type and CCSP-/- mice ventilated at high PIP for 4 h significantly reduced bronchoalveolar lavage albumin and total protein and lung wet-to-dry weight ratios compared with vehicle-treated mice of the same genotype. Membrane phospho-cPLA2 and cPLA2 activities were significantly elevated in lung homogenates of high-PIP ventilated mice of both genotypes but were significantly higher in the CCSP-/- mice relative to the wild-type mice. Inhibition of cPLA2 significantly attenuated both the phospho-cPLA2 increase and increased cPLA2 activity due to high-PIP ventilation. We propose that mechanical activation of the cPLA2 pathway contributes to acute high PIP-induced lung injury and that CCSP may reduce this injury through inhibition of the cPLA2 pathway and reduction of proinflammatory products produced by this pathway.

Time and pressure dependence of transvascular Clara cell protein, albumin, and IgG transport during ventilator-induced lung injury in mice.

We compared the transport of three proteins with different hydrodynamic radii with ultrastructural changes in lungs of intact mice ventilated at peak inflation pressures (PIP) of 15, 35, 45, and 55 cmH(2)O for 2 h and PIP of 55 cmH(2)O for 0.5 and 1 h. After 2 h of ventilation, significant increases were observed in plasma Clara cell secretory protein (1.9 nm radius) at 35 cmH(2)O PIP and in bronchoalveolar lavage fluid albumin (3.6 nm radius) at 45 cmH(2)O PIP and IgG (5.6 nm radius) at 55 cmH(2)O PIP. Increased concentrations of all three proteins and lung wet-to-dry weight ratios were significantly correlated with PIP and ventilation time. Clara cell secretory protein and albumin increased significantly after 0.5 h of 55 cmH(2)O PIP, but IgG increased only after 2 h. Separation of endothelium or epithelium to form blebs was apparent only in small vessels (15-30 microm diameter) at 45 cmH(2)O PIP and after 0.5 h at 55 cmH(2)O PIP but became extensive after 2 h of ventilation at 55 cmH(2)O PIP. Junctional gaps between cells were rarely observed. Ultrastructural lung injury and protein clearances across the air-blood barrier were related to ventilation time and PIP levels. Protein clearances increased in relation to molecular size, consistent with increasing dimensions and frequency of transmembrane aqueous pathways.