Daily Respiratory Research Analysis

BACKGROUND: A post-marketing, parallel-controlled clinical trial (REST trial) was conducted to evaluate the safety and efficacy of cipepofol versus propofol for the induction of anesthesia/sedation in Chinese elderly patients undergoing gastroscopy. METHODS: All enrolled patients aged ≥65 years were assigned randomly in a 1:1 ratio to be administered intravenous cipepofol-0.3 mg/kg or propofol-1.5 mg/kg. The primary endpoint was incidence of respiratory-related adverse events (AEs) including respiratory depression (respiratory rate < 8 breaths/min lasting for >30 s), apnea (loss of thoracic movement for >15 s) and hypoxemia (SpO RESULTS: Among 890 randomized patients, 871 were finally included in the full analysis set (FAS), with 431 receiving cipepofol and 440 receiving propofol. Patients treated with cipepofol had a significantly lower incidence of respiratory-related AEs compared to propofol treatment (FAS: 22.3 % vs. 33.9 %, per-protocol set: 20.6 % vs. 34.5 %, all P < 0.001), regardless of sex. Multivariable analysis revealed that the risk of patients experiencing respiratory-related AEs was 1.82 times higher in the propofol group compared to cipepofol group (P < 0.001). The success rates of the gastroscopy procedure and gastroscope insertion were both 100 % in the two groups. Gastroscopy procedure-related durations were shorter in propofol group compared to cipepofol group (all P < 0.05). Patients treated with cipepofol exhibited a significantly lower rate of treatment-emergent AEs (TEAEs) (55.0 % vs. 67.7 %, P < 0.001), TEAEs of special interest (53.4 % vs. 65.2 %, P < 0.001) and injection pain (2.6 % vs. 28.4 %, P < 0.001). CONCLUSIONS: Cipepofol-0.3 mg/kg is a safe and effective intravenous anesthetic for Chinese elderly patients undergoing gastroscopy, especially complimented by lower incidences of respiratory-related AEs and injection pain. CLINICAL TRIALS REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2100052299, registered on October 24, 2021.

INTRODUCTION: Despite warnings from the US Food and Drug Administration about respiratory adverse events associated with gabapentinoids, direct evidence of their risk in patients with asthma is lacking. METHODS: Using a national administrative claims database, we prepared two active comparators-new user cohorts of patients with a history of neuropathic or chronic pain and asthma-initiating gabapentinoids and comparator drugs (tricyclic antidepressants (TCAs) or serotonin norepinephrine reuptake inhibitors (SNRIs)). Overlap propensity score weighting was used to control for potential confounders. The initial occurrence of asthma exacerbation requiring systemic corticosteroids (primary) or those requiring hospitalisation for asthma (secondary) was assessed using a weighted Cox proportional hazards model. FINDINGS: In the TCAs cohort (171 393 gabapentinoids users and 5916 TCAs users), gabapentinoids use was associated with a higher incidence of primary (59.4 vs 33.7 per 100 person-years; HR 1.46, 95% CI 1.34 to 1.60) and secondary outcomes (0.91 vs 0.42 per 100 person-years; 2.02, 1.11 to 3.68). In the SNRIs cohort (189 055 gabapentinoids users and 19 800 SNRIs users), using gabapentinoids was also associated with a higher incidence of primary outcome (63.5 vs 42.8 per 100 person-years; HR 1.24, 1.19 to 1.30). However, the difference in the secondary outcome did not reach statistical significance (0.93 vs 0.68 per 100 person-years; 1.24, 0.94 to 1.63). INTERPRETATION: Gabapentinoids were associated with an increased risk of asthma exacerbations compared with TCAs or SNRIs. Managing neuropathic or chronic pain in patients with asthma using gabapentinoids should be approached with caution.

Differentiated primary human respiratory epithelial cells grown at air-liquid interface have become a widely used cell culture model of the human conducting airways. These cultures contain secretory cells such as goblet and club cells, which produce and secrete mucus. Here, we characterize the composition of mucus harvested from airway cultures of nasal and bronchial origin. We find that despite inter-donor variability, the salt, sugar, lipid, and protein content and composition are very similar between nasal and bronchial mucus. However, subtle differences in the abundance of individual components in nasal versus bronchial mucus can influence its antimicrobial properties. The ability of mucus to neutralize influenza A virus varies with the anatomical origin of the airway cultures and correlates with the abundance of triglycerides and specific sialylated glycoproteins and glycolipids.IMPORTANCERespiratory mucus plays an important role during the transmission and infection process of microbes in the human respiratory tract. In the case of influenza A virus, the mucus stabilizes the virions in infectious respiratory particles and droplets but hampers virus particles before they reach the respiratory epithelium through its physicochemical properties and the presence of sialylated decoy receptors. However, it is thus far not well understood which components of mucus mediate protection and inhibition. Our study now provides a comprehensive analysis of bronchial and nasal mucus from primary human airway cultures that can be used as a resource for future experimental designs and interpretations.