Objective To determine the efficacy of a 23-valent pneumococcal polysaccharide vaccine in people at high risk of pneumococcal pneumonia.Design Prospective, randomised, placebo controlled double blind study.Setting Nursing homes in Japan.Participants 1006 nursing home residents.Interventions Participants were randomly allocated to either 23-valent pneumococcal polysaccharide vaccine (n=502) or placebo (n=504).Main outcome measures The primary end points were the incidence of all cause pneumonia and pneumococcal pneumonia. Secondary end points were deaths from pneumococcal pneumonia, all cause pneumonia, and other causes.Results Pneumonia occurred in 63 (12.5%) participants in the vaccine group and 104 (20.6%) in the placebo group. Pneumococcal pneumonia was diagnosed in 14 (2.8%) participants in the vaccine group and 37 (7.3%) in the placebo group (P<0.001). All cause pneumonia and pneumococcal pneumonia were significantly more frequent in the placebo group than in the vaccine group: incidence per 1000 person years 55 v 91 (P<0.0006) and 12 v 32 (P<0.001), respectively. Death from pneumococcal pneumonia was significantly higher in the placebo group than in the vaccine group (35.1% (13/37) v 0% (0/14), P<0.01). The death rate from all cause pneumonia (vaccine group 20.6% (13/63) v placebo group 25.0% (26/104), P=0.5) and from other causes (vaccine group 17.7% (89/502) v placebo group (80/504) 15.9%, P=0.4) did not differ between the two study groups.Conclusion The 23-valent pneumococcal polysaccharide vaccine prevented pneumococcal pneumonia and reduced mortality from pneumococcal pneumonia in nursing home residents.Trial registration Japan Medical Association Center for Clinical Trials JMA-IIA00024.

The mechanism of airway remodeling in asthmatic patients is poorly understood. Thrombin is a multifunctional protease that, in addition to its critical role in thrombotic processes, has also been described as inducing cellular and molecular events relevant to tissue remodeling. The present investigation was undertaken to evaluate the activity of thrombin in the sputum of asthmatic patients and its potential role in airway remodeling. The study population comprised 8 healthy subjects and 14 stable patients with bronchial asthma. The concentrations of thrombin, thrombin-antithrombin complex (TAT), and tissue factor were measured in the sputum of all subjects. The concentrations of thrombin (p = 0. 007), TAT (p = 0.01), and tissue factor (p = 0.02) in sputum were significantly higher in asthmatic patients than in healthy controls. The proliferative effects that sputum from asthmatic patients (p = 0. 01) and thrombin (p = 0.03) have on cultured human smooth muscle cells was inhibited significantly in the presence of recombinant hirudin, a specific thrombin inhibitor. Significant statistical correlation was observed between the degree of bronchial responsiveness and the sputum concentrations of thrombin (r = -0.8; p = 0.02) and TAT (r = -0.9; p = 0.01). The results of this study showed that increased thrombin generation occurs in the airway of patients with asthma and that it may play a role in the pathogenesis of airway remodeling. Further studies should be carried out to assess whether these findings are also observed in other airway diseases.

Japan Medical Association Center for Clinical Trials, JMA-IIA00054.

There are no prospective comparison of the etiology and clinical outcome between hospital-acquired pneumonia (HAP) and nursing home-acquired pneumonia (NHAP) in non-intubated elderly. This study prospectively evaluated the etiology of HAP and NHAP in non-intubated elderly. A prospective cohort study was carried out in a rural region of Japan where the population over 65 years of age represents 30% of the population. A total of 108 patients were enrolled. There were 33 patients with HAP and 75 with NHAP. Etiologic diagnosis was established in 78.8% of HAP and in 72% of NHAP patients. The most frequent pathogens were Chlamydophila pneumoniae followed by Streptococcus pneumoniae, Staphylococcus aureus and Influenza virus. The frequency of Streptococcus pneumoniae and Influenza virus was significantly higher, whereas the frequency of Staphylococcus aureus and Enterobacteriaceae was significantly lower in NHAP compared to HAP. Performance and nutritional status were significantly worse in patients with HAP than in those with NHAP. Hospital mortality was significantly lower in patients with NHAP compared to those with HAP. This study demonstrated that C. pneumoniae, Streptococcus pneumoniae, Staphylococcus aureus and Influenza virus are frequent causative agents of pneumonia in non-intubated elderly and that the responsible pathogens and clinical outcome differ between NHAP and HAP.

Abstractprotein components of the extracellular matrix, activate latent enzymes such as type IV colBackground -The peripheral blood concentrations of several proteases of the clot-lagenase, and dissolve tumour associated fibrin clots. 2 Circulating markers of the fibrinolysis ting system have been shown to predict survival in patients with malignancy. A system are raised in patients with lung cancer and they have been shown to correlate with study was undertaken to investigate the independent value of the plasma levels of tumour burden, clinical progression, and the response to chemotherapy. 3 The aim of this the D-dimer degradation product of fibrin before treatment for predicting prognosis study was to investigate the independent value of the pretreated plasma levels of -dimer fibrin in patients with lung cancer. Methods -The study comprised 70 patients degradation products for predicting prognosis in patients with lung cancer. with lung cancer (49 non-small cell lung cancer and 21 small cell lung cancer). Plasma levels of D-dimer were measured using an enzyme immunoassay kit. Multi-Methods variate statistical analysis was carried Seventy consecutive patients with lung cancer, out using the Cox's proportional hazards of median age 65 years (range 20-83), admitted model.to the Mie University Hospital from July 1990 Results -The median value of the plasma to December 1991 took part in the study. There level of D-dimer differentiated two groups were 49 cases with non-small cell lung cancer of patients with different outcomes: a (non-SCLC) and 21 with small cell lung cancer group with a D-dimer level of <150 ng/ml (SCLC). Clinical staging was performed ac-(low DD group) and those with D-dimer cording to the new international staging system. levels of [150 ng/ml (high DD group). Patients underwent curative surgery (n=20) Survival time was significantly better in or combination chemotherapy followed by patients in the low DD group than in those radiotherapy (n=50). Venous blood samples in the high DD group in all patients (haz-were taken 1-5 days (median two days) before ard ratio for high DD group=4.7; 95% starting any treatment and stored at −80°C confidence interval (CI) 1.8 to 11.7). The until needed. Plasma levels of -dimer were plasma levels of D-dimer predicted sur-determined using an enzyme immunoassay kit vival independently from the clinical stage (Dimertest, Agen, Mountain View, California, of disease, histological type, performance USA). -dimer levels were also measured in status, and tumour size (hazard ratio= blood samples from age matched healthy vo-3.9; 95% CI 1.6 to 9.2).lunteers (n=40) and from patients with benign Conclusions -These results suggest that pulmonary disease (n=25). There was a history plasma levels of D-dimer might be useful of smoking in 50 patients with lung cancer, in for predicting the clinical outcome in 15 with benign disease, and in 10 healthy patients with lung cancer. However, fur-subjects. The intra-assay and inter-assay prether prospective studies are needed in a cisio...

Japan Medical Association Center for Clinical Trials JMA-IIA00146.

X-linked immunodeficiency with hyper-IgM (HIGM1), characterized by failure of immunoglobulin isotype switching, is caused by mutations of the CD40 ligand (CD40L), which is normally expressed on activated CD4(+) T cells. As constitutive expression of CD40L induces lymphomas, we corrected the mutation while preserving the natural regulation of CD40L using pre-mRNA trans-splicing. Bone marrow from mice lacking CD40L was modified with a lentivirus trans-splicer encoding the normal CD40L exons 2-5 and was administered to syngenic CD40L-knockout mice. Recipient mice had corrected CD40L mRNA, antigen-specific IgG1 responses to keyhole limpet hemocyanin immunization, regulated CD4(+) T-cell CD40L expression after CD3 stimulation in primary and secondary transplanted mice, attenuation of Pneumocystis carinii pneumonia, and no evidence of lymphoproliferative disease over 1 year. Thus, HIGM1 can be corrected by CD40L trans-splicing, leading to functional correction of the genetic defect without the adverse consequences of unregulated expression of the CD40L gene.

The results from this study provide further evidence for the role of circulating fibrocytes in fibrotic lung diseases.