American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Apr 2020
Impact of Sleep Deprivation on Respiratory Motor Output and Endurance: A Physiological Study.
Rationale: Sleep deprivation can alter endurance of skeletal muscles, but its impact on respiratory command is unknown. Objectives: We aimed to assess the effect of sleep deprivation on respiratory motor output and inspiratory endurance. Methods: Inspiratory endurance was investigated twice in random order, following a normal sleep night and a sleepless night. ⋯ Such decreases did not occur in the normal-sleep condition. Conclusions: One night of sleep deprivation reduces respiratory motor output by altering its cortical component with subsequent reduction of inspiratory endurance by half. These results suggest that altered sleep triggers severe brain dysfunctions that could precipitate respiratory failure.
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Am. J. Respir. Crit. Care Med. · Apr 2020
Randomized Controlled TrialLung Screen Uptake Trial (LSUT): Randomised Controlled Trial Testing Targeted Invitation Materials.
Rationale: Low uptake of low-dose computed tomography (LDCT) lung cancer screening, particularly by current smokers of a low socioeconomic position, compromises effectiveness and equity. Objectives: To compare the effect of a targeted, low-burden, and stepped invitation strategy versus control on uptake of hospital-based Lung Health Check appointments offering LDCT screening. Methods: In a two-arm, blinded, between-subjects, randomized controlled trial, 2,012 participants were selected from 16 primary care practices using these criteria: 1) aged 60 to 75 years, 2) recorded as a current smoker within the last 7 years, and 3) no prespecified exclusion criteria contraindicating LDCT screening. ⋯ Regardless of trial arm, uptake was considerably higher than previous clinical and real-world studies, particularly given that the samples were predominantly lower socioeconomic position smokers. Strategies common to both groups, including a Lung Health Check approach, could represent a minimum standard. Clinical trial registered with www.clinicaltrials.gov (NCT02558101) and registered prospectively with the International Standard Registered Clinical/Social Study (N21774741).
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Am. J. Respir. Crit. Care Med. · Apr 2020
TMEM16A Potentiation: A Novel Therapeutic Approach for the Treatment of Cystic Fibrosis.
Rationale: Enhancing non-CFTR (cystic fibrosis transmembrane conductance regulator)-mediated anion secretion is an attractive therapeutic approach for the treatment of cystic fibrosis (CF) and other mucoobstructive diseases. Objectives: To determine the effects of TMEM16A potentiation on epithelial fluid secretion and mucociliary clearance. Methods: The effects of a novel low-molecular-weight TMEM16A potentiator (ETX001) were evaluated in human cell and animal models of airway epithelial function and mucus transport. ⋯ In ovine models of mucus clearance (tracheal mucus velocity and mucociliary clearance), inhaled ETX001 was able to accelerate clearance both when CFTR function was reduced by administration of a pharmacological blocker and when CFTR was fully functional. Conclusions: Enhancing the activity of TMEM16A increases epithelial fluid secretion and enhances mucus clearance independent of CFTR function. TMEM16A potentiation is a novel approach for the treatment of patients with CF and non-CF mucoobstructive diseases.