Plasminogen activation to plasmin protects from lung fibrosis, but the mechanism underlying this antifibrotic effect remains unclear. We found that mice lacking plasminogen activation inhibitor-1 (PAI-1), which are protected from bleomycin-induced pulmonary fibrosis, exhibit lung overproduction of the antifibrotic lipid mediator prostaglandin E 2 (PGE 2 ). Plasminogen activation upregulated PGE 2 synthesis in alveolar epithelial cells, lung fibroblasts, and lung fibrocytes from saline-and bleomycin-treated mice, as well as in normal fetal and adult primary human lung fibroblasts. This response was exaggerated in cells from Pai1 -/-mice. Although enhanced PGE 2 formation required the generation of plasmin, it was independent of proteinase-activated receptor 1 (PAR-1) and instead reflected proteolytic activation and release of HGF with subsequent induction of COX-2. That the HGF/COX-2/PGE 2 axis mediates in vivo protection from fibrosis in Pai1 -/-mice was demonstrated by experiments showing that a selective inhibitor of the HGF receptor c-Met increased lung collagen to WT levels while reducing COX-2 protein and PGE 2 levels. Of clinical interest, fibroblasts from patients with idiopathic pulmonary fibrosis were found to be defective in their ability to induce COX-2 and, therefore, unable to upregulate PGE 2 synthesis in response to plasmin or HGF. These studies demonstrate crosstalk between plasminogen activation and PGE 2 generation in the lung and provide a mechanism for the well-known antifibrotic actions of the fibrinolytic pathway.

Context: Spinal cord injury commonly results in neuromuscular weakness that impacts respiratory function. This would be expected to be associated with an increased likelihood of sleep-disordered breathing. Results: Given the current literature limitations, sleep disordered breathing as currently defined is high in patients with spinal cord injury, approaching 60% in motor complete persons with tetraplegia. Central apnea is more common in patients with tetraplegia than in patients with paraplegia. Conclusion: Early formal sleep study in patients with acute complete tetraplegia is recommended. In patients with incomplete tetraplegia and with paraplegia, the incidence of sleep-disordered breathing is significantly higher than the general population. With the lack of correlation between symptoms and SDB, formal study would be reasonable. There is insufficient evidence in the literature on the impact of treatment on morbidity, mortality and quality of life outcomes.

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; on behalf of the RENEW Study Group * BACKGROUND: The Lung Volume Reduction Coil Treatment in Patients With Emphysema (RENEW) trial reported improvements in quality of life, pulmonary function, and exercise performance following endobronchial coil treatment. OBJECTIVES: The purpose of this post hoc analysis was to identify baseline predictors, including quantitative CT measures, that identify patients most likely to significantly benefit from endobronchial coil therapy. METHODS: Quantitative CT analysis by an independent radiology laboratory and a qualitative evaluation by five blinded experts of the baseline thoracic CT imaging were performed. Univariate and multivariate logistic regression analyses were performed to elucidate characteristics associated with clinical response. RESULTS: In total, 125 patients underwent coil treatment and had evaluable 12-month followup results. Of these, 78 patients received treatment of lobes with the highest emphysematous destruction determined by quantitative CT analysis (quantitative visual match [QVM]þ), and 47 received treatment in at least one lobe that was not the most destroyed (QVM-). From the 78 patients with QVMþ treatment, a subgroup of 50 patients (64%) was identified with baseline residual volume > 200% predicted, emphysema score > 20% low attenuation area, and absence of airway disease. In this subgroup, greater lobar residual volume reduction in the treated lobes was achieved, which was associated with significant mean AE SE improvement in FEV 1 (15.2 AE 3.1%), St. George's Respiratory Questionnaire (-12 AE 2 points), and residual volume (-0.57 AE 0.13 L). DISCUSSION: This post hoc analysis found that both significant hyperinflation (residual volume $ 200% predicted) and CT analysis are critical for patient selection and treatment planning for endobronchial coil therapy. Quantitative CT analysis is important to identify optimal lobar treatment and to exclude patients with insufficient emphysema (< 20% low attenuation area), whereas visual assessment identifies patients with signs of airway disease associated with worse outcomes.

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