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Yuki Abe, Masaru Suzuki, Hirokazu Kimura, Kaoruko Shimizu, Hironi Makita, Masaharu Nishimura, Satoshi Konno Department of Respiratory Medicine, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Kita-ku, Sapporo 060-8638, JapanCorrespondence: Masaru SuzukiDepartment of Respiratory Medicine, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Kita 15, Nishi 7, Kita-ku, Sapporo 060-8638, JapanTel +81-11-706-5911Fax +81-11-706-7899Email suzumasa@med.hokudai.ac.jpPurpose: Fractional exhaled nitric oxide (FENO) reflects eosinophilic inflammation of the airways. However, the significance of longitudinal assessment of FENO, including its variability, in the clinical course of severe asthma remains unclear. The aim of this study is to examine the association between long-term changes in FENO and the development of exacerbations in severe asthma.Patients and Methods: Among the severe asthma patients enrolled in the Hokkaido Severe Asthma Cohort Study, 100 patients with severe asthma who completed a 3-year follow-up in which FENO was measured annually were included. According to the FENO level at baseline, 1 year, and 2 years, the patients were classified into three groups: the sustained high group (≥ 50 ppb at all three visits), the sustained low group (< 25 ppb at all three visits), and the intermediate group (other). Subjects in the intermediate group were further classified into two groups based on the median value of the coefficient of variation (CV) of FENO during the 3 years (high CV and low CV intermediate groups).Results: The sustained high group experienced shorter exacerbation-free survival and more frequent exacerbations than the sustained low group (median number of exacerbation events, 3 vs 0, p = 0.01). In the intermediate group, the high CV group experienced shorter exacerbation-free survival than the low CV group, and the CV of FENO was an independent contributing factor to the development of exacerba

Right ventricular function critically affects the prognosis of patients with pulmonary arterial hypertension. We aimed to analyze the prognostic value of right ventricular indices calculated using magnetic resonance imaging and right heart catheterization metrics in pulmonary arterial hypertension. We retrospectively collected data from 57 Japanese patients with pulmonary arterial hypertension and 18 controls and calculated six indices of right ventricular function: two indices of contractility (end-systolic elastance calculated with right ventricular maximum pressure and with magnetic resonance imaging metrics); two indices of right ventricular-pulmonary arterial coupling (end-systolic elastance/arterial elastance calculated with the pressure method (end-systolic elastance/arterial elastance (P)) and with the volume method (end-systolic elastance/arterial elastance (V)); and two indices of right ventricular diastolic function (stiffness (beta) and end-diastolic elastance). We compared the indices between controls and patients with pulmonary arterial hypertension and examined their prognostic role. In patients with pulmonary arterial hypertension, end-systolic elastance (right ventricular maximum pressure) was higher (pulmonary arterial hypertension 0.94 (median) vs control 0.42 (mmHg/mL),p < 0.001), end-systolic elastance/arterial elastance (V) was lower (pulmonary arterial hypertension 0.72 vs control 1.69,p < 0.001), and beta and end-diastolic elastance were significantly higher than those in the controls. According to the log-rank test, end-systolic elastance/arterial elastance (P) and end-diastolic elastance were significantly associated with the composite event rate. According to the multivariate Cox regression analysis, decreased end-systolic elastance/arterial elastance (P) was associated with a higher composite event rate (hazard ratio 11.510, 95% confidence interval: 1.954-67.808). In conclusion, an increased right ventricular contractility, diastolic dysf

Background Fractal dimension (D) characterises the size distribution of low attenuation clusters on CT and assesses the spatial heterogeneity of emphysema that per cent low attenuation volume (%LAV) cannot detect. This study tested the hypothesis that %LAV and D have different roles in predicting decline in FEV1, exacerbation and mortality in patients with COPD. Methods Chest inspiratory CT scans in the baseline and longitudinal follow-up records for FEV1, exacerbation and mortality prospectively collected over 10 years in the Hokkaido COPD Cohort Study were examined (n=96). The associations between CT measures and long-term outcomes were replicated in the Kyoto University cohort (n=130). Results In the Hokkaido COPD cohort, higher %LAV, but not D, was associated with a greater decline in FEV1 and 10-year mortality, whereas lower D, but not %LAV, was associated with shorter time to first exacerbation. Multivariable analysis for the Kyoto University cohort confirmed that lower D at baseline was independently associated with shorter time to first exacerbation and that higher LAV% was independently associated with increased mortality after adjusting for age, height, weight, FEV1 and smoking status. Conclusion These well-established cohorts clarify the different prognostic roles of %LAV and D, whereby lower D is associated with a higher risk of exacerbation and higher %LAV is associated with a rapid decline in lung function and long-term mortality. Combination of %LAV and fractal D may identify COPD subgroups at high risk of a poor clinical outcome more sensitively.

Purpose: Fractional exhaled nitric oxide (FENO) reflects eosinophilic inflammation of the airways. However, the significance of longitudinal assessment of FENO, including its variability, in the clinical course of severe asthma remains unclear. The aim of this study is to examine the association between long-term changes in FENO and the development of exacerbations in severe asthma. Patients and Methods: Among the severe asthma patients enrolled in the Hokkaido Severe Asthma Cohort Study, 100 patients with severe asthma who completed a 3-year follow-up in which FENO was measured annually were included. According to the FENO level at baseline, 1 year, and 2 years, the patients were classified into three groups: the sustained high group (>= 50 ppb at all three visits), the sustained low group (<25 ppb at all three visits), and the intermediate group (other). Subjects in the intermediate group were further classified into two groups based on the median value of the coefficient of variation (CV) of FENO during the 3 years (high CV and low CV intermediate groups). Results: The sustained high group experienced shorter exacerbation-free survival and more frequent exacerbations than the sustained low group (median number of exacerbation events, 3 vs 0, p = 0.01). In the intermediate group, the high CV group experienced shorter exacerbation-free survival than the low CV group, and the CV of FENO was an independent contributing factor to the development of exacerbations. Conclusion: Persistence of FENO above 50 ppb over the years as well as the presence of large variations in FENO levels was associated with the development of exacerbations in patients with severe asthma.

Hironi Makita,1,2,* Masaru Suzuki,1,* Satoshi Konno,1 Kaoruko Shimizu,1 Yasuyuki Nasuhara,1 Katsura Nagai,1,3 Yasushi Akiyama,3 Satoshi Fuke,4 Hiroshi Saito,5 Takeshi Igarashi,5 Kimihiro Takeyabu,6 Masaharu Nishimura1,2 1Department of Respiratory Medicine, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan; 2Hokkaido Medical Research Institute for Respiratory Diseases, Sapporo, Japan; 3Center for Respiratory Diseases, JCHO Hokkaido Hospital, Sapporo, Japan; 4Department of Internal Medicine, KKR Sapporo Medical Center, Sapporo, Japan; 5Department of Internal Medicine, Hokkaido Chuo Rosai Hospital, Iwamizawa, Japan; 6Department of Respiratory Medicine, Otaru Kyokai Hospital, Otaru, Japan*These authors contributed equally to this workCorrespondence: Masaharu NishimuraDepartment of Respiratory Medicine, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, JapanTel +81 11 706 5911Fax +81 11 706 7899Email ma-nishi@med.hokudai.ac.jpPurpose: Causes of death may be unique and different in Japanese patients with COPD because they are generally older, thinner, experience fewer exacerbations, and live longer than those in other countries. We investigated the detailed mortality profile in the Hokkaido COPD cohort study, which completed a 10-year follow-up with a very low dropout rate.Patients and Methods: We prospectively examined the 10-year natural history in 279 Japanese patients with COPD (GOLD 1, 26%; GOLD 2, 45%; GOLD 3, 24%; and GOLD 4, 5%). The majority of patients were male, and the average age at baseline was 69 years old. About 95% of all patients had accurate mortality data. The risk factors for mortality were also analyzed.Results: During the 10 years, 112 patients (40%) died. Their median survival time was 6.1 years (interquartile range: 4.7– 7.9 years), and age at death was 79 ± 6 years old (mean ± SD). Respiratory diseases, including pneumonia, were the leading cau