American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Sep 2024
Ivacaftor for Chronic Obstructive Pulmonary Disease - Results from a Phase 2, Randomized Controlled Trial.
Patients with chronic obstructive pulmonary disease (COPD) exhibit acquired cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction. CFTR modulators may improve outcomes in patients with COPD, although recent data regarding magnitude of benefit have been inconclusive and effects on mucociliary clearance are unknown. We conducted a phase 2, randomized, double blind placebo control trial to determine safety and tolerability, and explore the potential mechanism of ivacaftor for the treatment of COPD. ⋯ gov, ID: NCT03085485.
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Am. J. Respir. Crit. Care Med. · Sep 2024
Randomized Controlled TrialImpact of High Dose Early Mobilization on Outcomes for Patients with Diabetes: A Secondary Analysis of the TEAM Trial.
Rationale: Patients with diabetes represent almost 20% of all ICU admissions and might respond differently to high-dose early active mobilization. Objectives: To assess whether diabetes modified the relationship between the dose of early mobilization on clinical outcomes in the TEAM trial. Methods: All TEAM trial patients were included. ⋯ In patients receiving high-dose early mobilization, the number of days alive and out of the hospital at Day 180 was 73.0 (0.0-144.5) in patients with diabetes and 146.5 (95.8-163.0) in patients without diabetes (P value for interaction = 0.108). However, in patients with diabetes, high-dose early mobilization increased the odds of mortality at 180 days (adjusted odds ratio, 3.47; 95% confidence interval, 1.67-7.61; P value for interaction = 0.001). Conclusions: In this secondary analysis of the TEAM trial, in patients with diabetes, a high-dose early mobilization strategy did not significantly decrease the number of days alive and out of the hospital at Day 180, but it increased 180-day mortality.
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Am. J. Respir. Crit. Care Med. · Sep 2024
ReviewAerosolized Antibiotic Therapy in Mechanically Ventilated Patients.
Delivering antibiotics directly to the respiratory tract through inhalation to address lung infections has garnered clinical and scientific interest for decades, given the potential favorable pharmacokinetic profile of this administration route. Among critically ill patients, the burden of healthcare-associated pulmonary infections particularly drove continued interest in delivering inhaled antibiotics to intubated patients. We present a concise overview of the existing rationale and evidence and provide guidance for implementing inhaled antibiotics among ventilated critically ill patients, emphasizing insights from recent literature.
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Am. J. Respir. Crit. Care Med. · Sep 2024
Pulmonary Ionocytes Regulate Airway Surface Liquid pH in Primary Human Bronchial Epithelial Cells.
Rationale: Pulmonary ionocytes are a newly discovered airway epithelial cell type proposed to be a major contributor to cystic fibrosis (CF) lung disease based on observations they express the cystic fibrosis transmembrane conductance regulator (CFTR) anion channel at a higher level than any other cell type in the airway epithelia. Moreover, genetically manipulated experimental models that lack ionocytes develop NaCl transport abnormalities and airway surface liquid (ASL) dehydration consistent with CF. However, no direct evidence indicates ionocytes engage in NaCl transport or contribute to ASL formation, questioning the relevance of ionocytes to CF lung disease. ⋯ Conclusions: We conclude that ionocytes do not contribute to ASL formation but regulate ASL pH. Club cells secrete the bulk of airway fluid. In CF, abnormal ionocyte and club cell function results in acidic and dehydrated ASL, causing reduced antimicrobial properties and mucociliary clearance.