American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Dec 2022
Genome-Wide Association Study of Obstructive Sleep Apnea and Objective Sleep-Related Traits Identifies Novel Risk Loci in Han Chinese Individuals.
Rationale: Previous genetic studies of obstructive sleep apnea (OSA) have limitations in terms of precise case definition, integrated quantitative traits, and interpretation of genetic functions; thus, the heritability of OSA remains poorly explained. Objectives: To identify novel genetic variants associated with OSA and objective sleep-related traits and to explore their functional roles. Methods: A genome-wide association study was performed in 20,590 Han Chinese individuals (5,438 OSA and 15,152 control samples). ⋯ Rs3746804 was associated with elevated serum riboflavin concentrations, and the corresponding mutation in mice increased riboflavin concentrations, suggesting that this variant may facilitate riboflavin uptake and riboflavin-dependent physiological activity. Conclusions: We identified several novel genome-wide significant loci associated with OSA and objective sleep-related traits. Our findings provide insight into the genetic architecture of OSA and suggest that SLC52A3 might be a therapeutic target, whereas riboflavin might be a therapeutic agent.
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Am. J. Respir. Crit. Care Med. · Dec 2022
Saracatinib, a Selective Src Kinase Inhibitor, Blocks Fibrotic Responses in Preclinical Models of Pulmonary Fibrosis.
Rationale: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and often fatal disorder. Two U. S. ⋯ Transcriptomic analysis of whole-lung extracts from the two animal models of pulmonary fibrosis revealed that saracatinib reverted many fibrogenic pathways, including epithelial-mesenchymal transition, immune responses, and extracellular matrix organization. Amelioration of fibrosis and inflammatory cascades in human precision-cut lung slices confirmed the potential therapeutic efficacy of saracatinib in human lung fibrosis. Conclusions: These studies identify novel Src-dependent fibrogenic pathways and support the study of the therapeutic effectiveness of saracatinib in IPF treatment.
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Am. J. Respir. Crit. Care Med. · Dec 2022
Randomized Controlled Trial Multicenter StudyHigh-Flow Versus VenturiMask Oxygen Therapy to Prevent Re-Intubation in Hypoxemic Patients After Extubation: A Multicenter, Randomized Clinical Trial.
Rationale: When compared with VenturiMask after extubation, high-flow nasal oxygen provides physiological advantages. Objectives: To establish whether high-flow oxygen prevents endotracheal reintubation in hypoxemic patients after extubation, compared with VenturiMask. Methods: In this multicenter randomized trial, 494 patients exhibiting PaO2:FiO2 ratio ⩽ 300 mm Hg after extubation were randomly assigned to receive high-flow or VenturiMask oxygen, with the possibility to apply rescue noninvasive ventilation before reintubation. ⋯ Conclusions: Reintubation rate did not significantly differ between patients treated with VenturiMask or high-flow oxygen after extubation. High-flow oxygen yielded less frequent use of rescue noninvasive ventilation. Clinical trial registered with www.clinicaltrials.gov (NCT02107183).