Emphysema severity is independently associated with a rapid annual decline in FEV1 in COPD. Sustainers and Rapid decliners warrant specific attention in clinical practice.

ung cancer is the most common fatal malignancy, because most of the tumors are discovered at advanced stages, and the incidence of this type of cancer is increasing worldwide. Platinum-based chemotherapy and irradiation have low effectiveness due to frequent recurrence and metastasis of the neoplasm; the overall 5-year survival rate after diagnosis remains at only 10-15%. 1) To improve the poor prognosis of this type of tumor, studies of new therapeutic strategies including immunotherapy are in progress.Although the specific functions of tumor infiltrating lymphocytes (TILs) are poorly understood, TILs are found in a variety of solid cancer tissues and have been considered to be manifestations of host immune reactions against cancer cells.2-4) It has been shown in animal models that infiltration of tumors by tumor-reactive T lymphocytes is required for efficient tumor regression.5, 6) Therefore, local cytokine effects and modulation of host cells are essential for adoptive immunotherapy rather than systemic effects. In humans, the majority of TILs consists of T cells and expresses significantly high amounts of various activation antigens, suggesting an activation of the host defense mechanism.7-9) Moreover, a multitude of tumor-specific cytotoxic T lymphocytes (CTLs) has been isolated from TILs. 10,11)

Retrospective analysis has shown that activating mutations in exons 18 -21 of the epidermal growth factor receptor (EGFR) gene are a predictor of response to gefitinib. We conducted a phase II trial to evaluate the efficacy and safety of gefitinib as first-line therapy for advanced non-small cell lung cancer (NSCLC) with EGFR mutations. Patients with stage IIIB or IV chemotherapy-naïve NSCLC with EGFR mutation were treated with 250 mg gefitinib daily. For mutational analysis, DNA was extracted from paraffin-embedded tissues and EGFR mutations were analysed by direct sequence of PCR products. Twenty (24%) of the 82 patients analysed had EGFR mutations (deletions in or near E746-A750, n ¼ 16; L858R, n ¼ 4). Sixteen patients were enrolled and treated with gefitinib. Twelve patients had objective response and response rate was 75% (95% CI, 48 -93%). After a median follow-up of 12.7 months (range, 3.1 -16.8 months), 10 patients demonstrated disease progression, with median progression-free survival of 8.9 months (95% CI, 6.7 -11.1 months). The median overall survival time has not yet been reached. Most of the toxicities were mild. This study showed that gefitinib is very active and well tolerated as first-line therapy for advanced NSCLC with EGFR mutations.

Endothelial glycocalyx coats healthy vascular endothelium and plays an important role in vascular homeostasis. Although cerebral capillaries are categorized as continuous, as are those in the heart and lung, they likely have specific features related to their function in the blood brain barrier. To test that idea, brains, hearts and lungs from C57BL6 mice were processed with lanthanum-containing alkaline fixative, which preserves the structure of glycocalyx, and examined using scanning and transmission electron microscopy. We found that endothelial glycocalyx is present over the entire luminal surface of cerebral capillaries. The percent area physically covered by glycocalyx within the lumen of cerebral capillaries was 40.1 ± 4.5%, which is significantly more than in cardiac and pulmonary capillaries (15.1 ± 3.7% and 3.7 ± 0.3%, respectively). Upon lipopolysaccharide-induced vascular injury, the endothelial glycocalyx was reduced within cerebral capillaries, but substantial amounts remained. By contrast, cardiac and pulmonary capillaries became nearly devoid of glycocalyx. These findings suggest the denser structure of glycocalyx in the brain is associated with endothelial protection and may be an important component of the blood brain barrier.

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