American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Dec 2024
Meta AnalysisHypnotics on Obstructive Sleep Apnea Severity and Endotypes: A Systematic Review and Meta-Analysis.
Rationale: Low arousal threshold and poor muscle responsiveness are common determinants of obstructive sleep apnea (OSA). Hypnotics were hypothesized as an alternative OSA treatment via raising the arousal threshold and possibly genioglossus responsiveness. Objectives: To examine the effect of common hypnotics on arousal threshold, OSA severity, and genioglossus responsiveness. ⋯ However, people with very low arousal threshold or those who exhibited a 0-25% arousal threshold increase from placebo experienced the greatest, yet still modest, post-treatment AHI reductions (∼10%). Hypnotics did not affect genioglossus responsiveness (high QoE). Conclusions: Further research testing or clinical use of hypnotics as OSA alternative treatments should be discouraged, unless in the presence of comorbid insomnia or as part of combination therapy in individuals with very low arousal threshold.
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Am. J. Respir. Crit. Care Med. · Dec 2024
ReviewLentiviral Gene Therapy for Cystic Fibrosis: A Promising Approach and First-In-Human Trial.
Cystic fibrosis (CF) is a genetic disease caused by mutations in the CFTR (cystic fibrosis transmembrane conductance regulator) gene. Although CF is a multiorgan disease, the leading causes of morbidity and mortality are related to progressive lung disease. Current understanding of the effects of the broad spectrum of CFTR mutations on CFTR function has allowed for the development of CFTR modulator therapies. ⋯ A third-generation lentiviral vector pseudotyped with Sendai virus F and HN envelope proteins (rSIV. F/HN) has been developed for the treatment of CF. Promising preclinical results support the progression of this vector carrying a full-length CFTR transgene (BI 3720931) into a first-in-human clinical trial expected to begin in 2024.