American journal of respiratory and critical care medicine
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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.
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Am. J. Respir. Crit. Care Med. · Apr 2020
Comparative StudyThe Quality of End-of-Life Care Among Intensive Care Unit Versus Ward Decedents.
Rationale: Admissions to ICUs are common during terminal hospitalizations, but little is known about how ICU care affects the end-of-life experience for patients dying in hospitals and their families. Objectives: We measured the association between ICU care during terminal hospitalization and family ratings of end-of-life care for patients who died in 106 Veterans Affairs hospitals from 2010 to 2016. Methods: Patients were divided into four categories: no-ICU care, ICU-only care, mixed care (died outside ICU), and mixed care (died in ICU). ⋯ Among patients with mixed care, increasing ICU time was associated with higher ratings on these same measures (all P < 0.001 for comparisons of those spending >75% time in ICU vs. ≤25% time). Conclusions: Among hospital decedents, ICU care was associated with higher family ratings of quality of end-of-life care than ward care. Reducing ICU use among hospital decedents may not improve end-of-life quality, and efforts to understand how ICU care improves end-of-life quality could help provide better care outside ICUs.