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Background and objectivesCardiovascular disease (CVD) and chronic obstructive pulmonary disease (COPD) commonly coexist and share common risk factors. The prevalence of COPD in outpatients with a smoking history and CVD in Japan is unknown. The aim of this study was to determine the proportion of Japanese patients with a smoking history being treated for CVD who have concurrent airflow limitation compatible with COPD. A secondary objective was to test whether the usage of lung function tests performed in the clinic influenced the diagnosis rate of COPD in the patients identified with airflow limitation.MethodsIn a multicenter observational prospective study conducted at 17 centers across Japan, the prevalence of airflow limitation compatible with COPD (defined as forced expiratory volume (FEV)1/FEV6 <0.73, by handheld spirometry) was investigated in cardiac outpatients ≥40 years old with a smoking history who routinely visited the clinic for their CVD. Each patient completed the COPD Assessment Test prior to spirometry testing.ResultsData were available for 995 patients with a mean age of 66.6±10.0 years, of whom 95.5% were male. The prevalence of airflow limitation compatible with COPD was 27.0% (n=269), and 87.7% of those patients (n=236) did not have a prior diagnosis of COPD. The prevalence of previously diagnosed airflow limitation was higher in sites with higher usage of lung function testing (14.0%, 15.2% respectively) compared against sites where it is performed seldom (11.1%), but was still low.ConclusionThe prevalence of airflow limitation in this study indicates that a quarter of outpatients with CVD have COPD, almost all of whom are undiagnosed. This suggests that it is important to look routinely for COPD in CVD outpatients.

Background:Recent advances in fibrosis biology have identified transforming growth factor (TGF)-β type I receptor-mediated activation of Smads as playing a central part in the development of fibrosis. However, to date, there have been few studies that examined the localisation and distribution of receptor-activated Smads protein (R-Smads: Smad2 and 3) during the fibrosis progression.Aims:To histopathologically assess the time-course change of the localisation and distribution of the Smads protein in pulmonary fibrosis.Methods:Pulmonary fibrosis was induced by intranasal injection of bleomycin (0.3 U/mouse). Lungs were isolated 2, 5, 7, 9 and 14 days after bleomycin treatment. Histological changes in the lungs were evaluated by haematoxylin-eosin stain or Masson’s trichrome stain, and scored. TGF-β1, Smad3 and phosphorylated Smad2 localisations in lung tissues were determined by immunohistochemistry.Results:The bleomycin treatment led to considerable pulmonary fibrotic changes accompanied by marked increase in TGF-β1 expression in infiltrating macrophages. With the progression in fibrosis (day 7–14), marked increases in Smad3-positive and pSmad2-positive cells were observed. There were intense Smad3-positive and pSmad2-positive signals localised to the nuclei of the infiltrating macrophages and to type II epithelial cells, and less intense signals in fibroblasts and hyperplastic alveolar/bronchiolar epithelial cells.Conclusions:The time-course data of TGF-β1 and R-Smads indicate that progressive enhancement of TGF-β1 signalling via R-Smad is activated in the process of fibrosis progression.

ABSTRACT:The in vivo conversion ratio of N 1 -methylnicotinamide (NMN) to N 1 -methyl-2-pyridone-5-carboxamide (2-PY) and N 1 -methyl-4-pyridone-3-carboxamide (4-PY) as a parameter for the estimation of aldehyde oxidase level in rats was examined. NMN and its pyridones (2-PY and 4-PY) are usually detected in the urine of rats. When we measured the ratio of the amount of pyridones to the total amount of NMN and pyridones (RP value) in the urine of rats, marked intraspecies variations were observed. The variation in RP value among strains was closely related to the differences of liver aldehyde oxidase activity measured with NMN as a substrate. RP values after administration of NMN to different strains of rats confirmed the existence of strain differences of aldehyde oxidase activity in vivo. We demonstrated that measurements of NMN and its pyridones usually excreted in the urine can be used to predict the in vivo level of aldehyde oxidase.Aldehyde oxidase (EC 1.2.3.1), a cytosolic enzyme, contains FAD, molybdenum, and iron-sulfur centers, and is closely related to xanthine oxidase (Beedham, 1987). The two enzymes have a very close evolutionary relationship, based on the recent cloning of the genes, and they show a high degree of amino acid sequence homology (Calzi et al., 1995;Wright et al., 1999;Terao et al., 2000). They have been suggested to be relevant to the pathophysiology of a number of clinical disorders (Berger et al., 1995;Wright et al., 1995;Moriwaki et al., 1997). Aldehyde oxidase commonly exists in vertebrates. The enzyme in liver of various species catalyzes the oxidation of a number of aldehydes and nitrogenous heterocyclic xenobiotics, such as methotrexate and cyclophosphamide (Beedham, 1987), and also catalyzes the metabolism of physiological compounds such as retinaldehyde and monoamine neurotransmitters (Huang and Ichikawa, 1994). Moreover, the enzyme in the presence of its electron donor can mediate the reduction of a variety of compounds, such as sulfoxides, N-oxides, nitrosamines, hydroxamic acids, azo dyes, oximes, epoxides, aromatic nitro compounds, and 1,2-benzisoxazole derivatives (Sugihara et al., 1996). Recently, aldehyde oxidase homologs, which may exhibit different metabolic roles, were identified in mice (Garattini et al., 2003;Kurosaki et al., 2004;Vila et al., 2004). Marked interspecies variation of the enzyme activity in oxidative and reductive reactions was reported (Sugihara et al., 1996;Schofield et al., 2000). We found a significant variation of liver aldehyde oxidase activity in 12 strains of rats in an assay using benzaldehyde or methotrexate as a substrate (Sugihara et al., 1995;Kitamura et al., 1999). Variations of benzaldehyde oxidase in white people and Japanese have also been reported (Rodrigues, 1994;Sugihara et al., 1997). However, no report is available on the prediction of aldehyde oxidase levels in vivo. N 1 -Methylnicotinamide (NMN), which is formed from nicotinamide by nicotinamide methyltransferase, is widely distributed in animals, like nicotinamide (Yan et al...

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