Reduced lung function predicts mortality and is key to the diagnosis of chronic obstructive pulmonary disease (COPD). In a genome-wide association study in 400,102 individuals of European ancestry, we define 279 lung function signals, 139 of which are new. In combination, these variants strongly predict COPD in independent patient populations. Furthermore, the combined effect of these variants showed generalizability across smokers and never-smokers, and across ancestral groups. We highlight biological pathways, known and potential drug targets for COPD and, in phenome-wide association studies, autoimmune-related and other pleiotropic effects of lung function associated variants. This new genetic evidence has potential to improve future preventive and therapeutic strategies for COPD.

No abstract

Circulation Journal Official Journal of the Japanese Circulation Society http://www. j-circ.or.jp he number of patients with severe angina pectoris without indications for coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) is rapidly increasing worldwide and their prognosis still remains poor. 1,2 Thus, it is crucial to develop new therapeutic strategies for these patients. We have previously demonstrated that extracorporeal cardiac shock wave (SW) therapy with low-energy SW (≈10% of the energy density used for urolithiasis) ameliorates myocardial ischemia and dysfunction in a porcine model of chronic myocardial ischemia in vivo. 3, 4 We subsequently demonstrated in an open trial that our SW therapy effectively improved chest pain symptoms and exercise tolerance without any adverse effects in 9 patients with severe angina pectoris. 3,5 In the present study, to further confirm the effectiveness and safety of our SW therapy, we performed a double-blind placebo-controlled trial in patients with severe angina pectoris. MethodsWe enrolled 8 consecutive patients with severe angina pectoris who already had undergone CABG or PCI, but who no longer had further indications for these therapies even though they still suffered from stable effort angina under intensive medication (M/F, 5/3; age, 70±3 years) (Table).The patients were treated with one series of placebo and the SW therapy in a double-blind and cross-over manner with an interval of 3 months. One series of therapy comprised 3 sessions per week. Throughout the study, the patient and the doctor in charge were not informed of the type of therapy. We performed the SW therapy (200 shoots/spot at 0.09 mJ/mm 2 for 40-60 spots per session; Modulith SLC, Storz Medical, Kreuzlingen, Switzerland) as described previously. 3,5 As placebo, the patients underwent the procedure of SW therapy but without irradiation. The patients were followed-up for 3 months after completion of the therapy. We evaluated symptoms using the Canadian Cardiovascular Society (CCS) class score, the patient's requirement for nitroglycerin, 5 exercise tolerance in a 6-min walk, and a cardiopulmonary exercise test, and cardiac function assessed by MRI (Achieva 1.5 T, Philips, Eindhoven, Netherlands). The left ventricular ejection fraction (LVEF) was measured using contiguous short-axis slices obtained by cine MRI; end-diastolic and end-systolic endocardial traces were used to determine end-diastolic and end-systolic left ventricular (LV) volumes, respectively. We also evaluated the number of circulating progenitor cells in peripheral blood by FACS analysis 2 days before the 1 st session and 1 h after the 3 rd session in 7 of the 8 patients Background: Low-energy shock wave (SW) therapy has improved myocardial ischemia in both a porcine model and in patients with severe angina pectoris.

These results provide the first evidence that coronary spasm is associated with inflammation of coronary adventitia and PVAT, where F-FDG PET/CT could be useful for disease activity assessment. (Morphological and Functional Change of Coronary Perivascular Adipose Tissue in Vasospastic Angina [ADIPO-VSA Trial]; UMIN000016675).

No abstract