Steps expressed relative to body fat mass predicts body composition and cardiometabolic risk in adults eating ad libitum.

BACKGROUND: Excess body fatness is a consequence of a chronic energy surplus (energy intake is greater than energy expenditure). Given the serious health consequences of excess body fatness, factors that influence energy balance and body composition are increasingly important to understand. METHODS: A total of 34 adults between the ages of 19-40 years made a laboratory visit in which height, weight, body composition, and cardiometabolic risk (CMR) factors were quantified. Participants wore accelerometers for 21-28 days, then returned to the laboratory for a second body composition assessment. Changes in weight and body composition were used to quantify energy balance, and data derived from accelerometers provided markers of physical activity (PA) and sedentariness. RESULTS: Of the markers of PA that we measured, daily step counts expressed relative to fat mass was most strongly and consistently associated with body fatness and CMR status. CONCLUSIONS: Step counts expressed relative to fat mass were strongly associated with body composition and CMR in adults eating ad libitum. Longitudinal interventional studies are necessary to determine the efficacy of step count prescriptions expressed relative to existing and target body fatness and CMR levels for improving weight management and metabolic outcomes.

Efficacy and Safety of the CFTR Potentiator Icenticaftor (QBW251) in COPD: Results from a Phase 2 Randomized Trial.

Rationale: Excess mucus plays a key role in COPD pathogenesis. Cigarette smoke-induced cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction may contribute to disease pathogenesis by depleting airway surface liquid and reducing mucociliary transport; these defects can be corrected in vitro by potentiating CFTR. Objective: To assess the efficacy of the CFTR potentiator icenticaftor in improving airflow obstruction in COPD patients with symptoms of chronic bronchitis. Methods: In this double-blind, placebo-controlled study, COPD patients were randomized (2:1) to either icenticaftor 300 mg or placebo b.i.d. This non-confirmatory proof of concept study was powered for lung clearance index (LCI) and pre-bronchodilator FEV1, with an estimated sample size of 90 patients. The primary endpoint was change from baseline in LCI for icenticaftor versus placebo at Day 29; key secondary endpoints included change from baseline in pre- and post-bronchodilator FEV1 on Day 29. Key exploratory endpoints included change from baseline in sweat chloride, plasma fibrinogen levels, and sputum colonization. Results: Ninety-two patients were randomized (icenticaftor, n=64; placebo, n=28). At Day 29, icenticaftor showed no improvement in change in LCI (treatment difference: 0.28 [19% probability of being better than placebo]), an improvement in pre-bronchodilator FEV1 (mean: 50 mL [84% probability]) and an improvement in post-bronchodilator FEV1 (mean: 63 mL [91% probability]) over placebo. Improvements in sweat chloride, fibrinogen and sputum bacterial colonization were also observed. Icenticaftor was safe and well tolerated. Conclusion: The CFTR potentiator icenticaftor increased FEV1 versus placebo after 28 days and was associated with improvements in systemic inflammation and sputum bacterial colonization in COPD patients; no improvements in LCI with icenticaftor were observed.