"Frequent exacerbator" is a phenotype of poor prognosis in Japanese patients with chronic obstructive pulmonary disease.

BACKGROUND: The prognosis of Japanese patients with COPD who suffer repeated exacerbations is unclear, although Westerners with such episodes have a poor prognosis. MATERIALS AND METHODS: We conducted a 1-year prospective observational trial involving 90 Japanese patients with COPD: 58 nonexacerbators, 12 infrequent exacerbators, and 20 frequent exacerbators classified on the basis of exacerbation frequency (zero, one, and two or more exacerbations/year), respectively, during the previous year were observed prospectively for 1 year. The characteristics of frequent exacerbators, the frequency of exacerbation, and the period until the first event were then compared among the groups. RESULTS: A total of 78 patients completed the study. Frequent exacerbators had a significantly higher risk of frequent exacerbation in the following year than the case for nonexacerbators (odds ratio [95% confidence interval] 2.94 [1.21-7.17], P=0.0340), but not in comparison with infrequent exacerbators (1.51 [0.49-4.63], P>0.05). The mean annual frequency of exacerbations in the following year was significantly (P=0.0020) higher in the frequent exacerbators (1.4 exacerbations/year) than in the nonexacerbators (0.4), but not in the infrequent exacerbators (0.9, P>0.05). The mean period until the first exacerbation was significantly shorter in the frequent exacerbators than in the infrequent or nonexacerbators (P=0.0012). Independent risk factors for future frequent exacerbation included the presence of gastroesophageal reflux disease, more severe airflow obstruction, and use of inhaled corticosteroids. CONCLUSION: Our present results indicate that Japanese COPD patients suffering frequent exacerbation have a poor prognosis. The characteristics of Japanese and Western COPD patients suffering frequent exacerbation are similar.

Evaluation of the Modified Medical Research Council Dyspnea Scale for Predicting Hospitalization and Exacerbation in Japanese Patients with Chronic Obstructive Pulmonary Disease.

OBJECTIVE: The modified Medical Research Council (mMRC) scale is recommended for conducting assessments of dyspnea and disability and functions as an indicator of exacerbation. The aim of this study was to investigate whether the mMRC scale can be used to predict hospitalization and exacerbation in Japanese patients with chronic obstructive pulmonary disease (COPD). METHODS: In a previous 52-week prospective study, 123 patients with COPD were classified into five groups (grades 0 to 4) according to the mMRC scale and four groups (stages I to IV) according to the spirometric Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification. The frequency and period until the first event of hospitalization and exacerbation were compared among the groups. RESULTS: The population of patients who experienced hospitalization and exacerbation during the 52-week study period, with an mMRC scale grade of 4, 3, 2, 1 and 0 was 50.0 and 100, 55.6 and 88.9, 21.1 and 73.7, 2.6 and 48.7, and 4.0 and 22.0%, respectively. A multivariate analysis adjusted for the GOLD stage and age showed that the patients with an mMRC scale grade of ≥3 had higher frequencies of hospitalization and exacerbation than those with lower grades. Meanwhile, the patients with an mMRC scale grade of ≥2 showed a significantly earlier time until the first exacerbation, but not hospitalization, in comparison with those with grade 0. CONCLUSION: The present results indicate that, among Japanese patients with COPD, those with an mMRC scale grade of ≥3 have a significantly poorer prognosis and that the mMRC scale can be used to predict hospitalization and exacerbation.

Paired maximum inspiratory and expiratory plain chest radiographs for assessment of airflow limitation in chronic obstructive pulmonary disease.

BACKGROUND: The usefulness of paired maximum inspiratory and expiratory (I/E) plain chest radiography (pCR) for diagnosis of chronic obstructive pulmonary disease (COPD) is still unclear. OBJECTIVES: We examined whether measurement of the I/E ratio using paired I/E pCR could be used for detection of airflow limitation in patients with COPD. METHODS: Eighty patients with COPD (GOLD stage I=23, stage II=32, stage III=15, stage IV=10) and 34 control subjects were enrolled. The I/E ratios of frontal and lateral lung areas, and lung distance between the apex and base on pCR views were analyzed quantitatively. Pulmonary function parameters were measured at the same time. RESULTS: The I/E ratios for the frontal lung area (1.25±0.01), the lateral lung area (1.29±0.01), and the lung distance (1.18±0.01) were significantly (p<0.05) reduced in COPD patients compared with controls (1.31±0.02 and 1.38±0.02, and 1.22±0.01, respectively). The I/E ratios in frontal and lateral areas, and lung distance were significantly (p<0.05) reduced in severe (GOLD stage III) and very severe (GOLD stage IV) COPD as compared to control subjects, although the I/E ratios did not differ significantly between severe and very severe COPD. Moreover, the I/E ratios were significantly correlated with pulmonary function parameters. CONCLUSIONS: Measurement of I/E ratios on paired I/E pCR is simple and reproducible, and can detect airflow limitation in patients with severe and very severe COPD.

COPD assessment tests scores are associated with exacerbated chronic obstructive pulmonary disease in Japanese patients.

BACKGROUND: Guidelines recommend chronic obstructive pulmonary disease (COPD) assessment tests (CATs) for evaluation of symptoms and management risks. To investigate whether CAT can predict moderate or severe exacerbations in Japanese COPD patients, a single-blinded prospective study was performed. METHODS: A 123 Japanese COPD patients were classified into high-CAT (n=64) and low-CAT (n=59) groups. The frequencies and periods of moderate or severe exacerbation and hospitalization were compared between the two groups. Multivariate logistic regression analysis was performed to investigate whether CAT could predict exacerbations. A receiver operating characteristic (ROC) curve analysis was employed to find an appropriate CAT score for exacerbation. RESULTS: The high-CAT group was significantly older, had a lower body mass index, and had a lower airflow obstruction as compared to the low CAT group. The frequency of moderate or severe exacerbation (1.3±1.3 events per patient per year, p<0.0001) and hospitalizations (0.2±0.4, p=0.0202) in the high-CAT group was significantly higher than in the low-CAT group (0.4±0.7 and 0.0±0.1, respectively). Multivariate logistic regression analysis showed that both high CAT score and low airflow obstruction were independently predictive of frequent moderate or severe COPD exacerbation. ROC analysis showed that the best cut-off CAT score for moderate or severe COPD exacerbation was 8 points. CONCLUSION: Our present results indicate that COPD Japanese patients showing high CAT scores have a poor prognosis, and that the CAT score is able to predict exacerbation in Japanese COPD.

Effect of postactivation treatment with latrunculin A on in vitro and in vivo development of cloned embryos derived from kidney fibroblasts of an aged Clawn miniature boar.

The objective of this study was to examine the effect of postactivation treatment with latrunculin A (LatA), an actin polymerization inhibitor, on in vitro and in vivo development of somatic cell nuclear transfer (SCNT) embryos derived from kidney fibroblasts of an aged Clawn miniature boar (12 years old). After electric activation, SCNT embryos were treated with 0, 0.5 or 1 µM LatA and cultured in vitro. The rate of blastocyst formation was significantly higher (P<0.05) in SCNT embryos treated with 0.5 µM LatA (38%) than those in control (14%). When cloned embryos treated with 0.5 µM LatA were transferred into the oviducts of two recipient miniature gilts to assess their development in vivo, both recipients became pregnant; one maintained pregnancy to term, and a live piglet (weighing 220 g) was delivered by Caesarean section. The results of this study indicated that the postactivation treatment with LatA was effective in improving in vitro developmental capacity of SCNT miniature pig embryos derived from kidney fibroblasts of an aged animal and that miniature pig cloned embryos treated with LatA had the ability to develop to term.