View references (28)Background Programmed death 1 (PD-1) programmed death-ligand 1 (PD-L1) inhibitors show significant clinical activity in non-small cell lung carcinoma (NSCLC). However, they are often associated with potentially fatal immune-mediated pneumonitis. Preliminary reports of trials suggest a difference in the rate of pneumonitis with PD-1 and PD-L1 inhibitors. We sought to determine the overall incidence of pneumonitis and differences according to type of inhibitors and prior chemotherapy use. Methods MEDLINE, Embase, and Scopus databases were searched up to November 2016. Rates of pneumonitis of any grade and grade ≥ 3 from all clinical trials investigating nivolumab, pembrolizumab, atezolizumab, durvalumab, and avelumab as single agents in NSCLC were collected. The incidence of pneumonitis across trials was calculated using DerSimonian-Laird random effects models. We compared incidences between PD-1 and PD-L1 inhibitors and between treatment naive and previously treated patients. Results Nineteen trials (12 with PD-1 inhibitors [n = 3,232] and 7 with PD-L1 inhibitors [n = 1,806]) were identified. PD-1 inhibitors were found to have statistically significant higher incidence of any grade pneumonitis compared with PD-L1 inhibitors (3.6%; 95% CI, 2.4%-4.9% vs 1.3%; 95% CI, 0.8%-1.9%, respectively; P =.001). PD-1 inhibitors were also associated with higher incidence of grade 3 or 4 pneumonitis (1.1%; 95% CI, 0.6%-1.7% vs 0.4%; 95% CI, 0%-0.8%; P =.02). Treatment naive patients had higher incidence of grade 1 through 4 pneumonitis compared with previously treated patients (4.3%; 95% CI, 2.4%-6.3% vs

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Background-Prior studies have reported an inverse association between physical activity (PA) and risk of heart failure (HF). However, a comprehensive assessment of the quantitative dose-response association between PA and HF risk has not been reported previously. Methods and Results-Prospective cohort studies with participants >18 years of age that reported association of baseline PA levels and incident HF were included. Categorical dose-response relationships between PA and HF risk were assessed with random-effects models. Generalized least-squares regression models were used to assess the quantitative relationship between PA (metabolic equivalent [

P ulmonary hypertension is a chronic cardiopulmonary disorder characterized by progressive increasing pulmonary vascular resistance, leading to right ventricular heart failure. 1 Prevalence of pulmonary hypertension is estimated to be 10 to 15 cases per million with a mortality rate of 15% per year. 2 Over the past 2 decades, targeted pharmacological therapies have been effective in reducing disease progression and improving the survival rate among patients with pulmonary hypertension.3,4 However, most patients remain symptomatic with significant exercise intolerance and reduced quality of life despite being on optimal medical therapy. 5,6 Thus, there is an unmet need for adjunctive therapeutic strategies to improve exercise tolerance and quality of life among these patients. Clinical Perspective on p 1043Exercise intolerance in patients with pulmonary hypertension is associated with a reduced maximal oxygen uptake and early onset of anaerobic threshold, similar to patients with severe heart failure. 7 The decrease in pulmonary vasculature distensibility associated with pulmonary hypertension leads to marked increases in pulmonary arterial mean pressure during exercise. This results in reduced pulmonary blood flow and low cardiac output insufficient to meet the metabolic demands of exercise. [7][8][9] Furthermore, pulmonary hypertension patients have significant skeletal muscle abnormalities leading to impaired peripheral oxygen utilization. These central and peripheral abnormalities contribute significantly to the exercise intolerance and functional limitation in patients with pulmonary hypertension. 10,11 Exercise training has been shown to improve cardiorespiratory fitness, functional status, and clinical outcomes in patients with cardiopulmonary conditions, such as heart failure and chronic obstructive pulmonary disease (COPD). 12,13 Considering the overlap in the pathophysiological derangements Original Article© 2015 American Heart Association, Inc.Circ Heart Fail is available at http://circheartfailure.ahajournals.org DOI: 10.1161/CIRCHEARTFAILURE.115.002130Background-Exercise training has been shown to improve cardiorespiratory fitness, physical capacity, and quality of life in patients with cardiopulmonary conditions, such as heart failure and chronic obstructive pulmonary disease. However, its role in management of pulmonary hypertension is not well defined. In this study, we aim to evaluate the efficacy and safety of exercise training in patients with pulmonary hypertension. Methods and Results-We included all prospective intervention studies that evaluated the efficacy and safety of exercise training in patients with pulmonary hypertension. Primary outcome of this meta-analysis was a change in 6-minute walk distance. We also assessed the effect of exercise on peak oxygen uptake, resting pulmonary arterial systolic pressure, peak exercise heart rate, and quality of life. A total of 469 exercise-training participants enrolled in 16 separate training studies were included. In the pooled ana...