Daily Respiratory Research Analysis

Acute lung injury (ALI) or its more severe form, acute respiratory distress syndrome (ARDS), represents a critical condition characterized by extensive inflammation within the airways. Necroptosis, a form of cell death, has been implicated in the pathogenesis of various inflammatory diseases. However, the precise characteristics and mechanisms of necroptosis in ARDS remain unclear. Thus, our study seeks to elucidate the specific alterations and regulatory factors associated with necroptosis in ARDS and to identify potential therapeutic targets for the disease. We discovered that necroptosis mediates the progression of ALI through the activation and formation of the RIPK1/RIPK3/MLKL complex. Moreover, we substantiated the involvement of both MYD88 and TRIF in the activation of the TLR4 signaling pathway in ALI. Furthermore, we have developed a lipid micelle-encapsulated drug targeting MLKL in alveolar type II epithelial cells and successfully applied it to treat ALI in mice. This targeted nanoparticle selectively inhibited necroptosis, thereby mitigating epithelial cell damage and reducing inflammatory injury. Our study delves into the specific mechanisms of necroptosis in ALI and proposes novel targeted therapeutic agents, presenting innovative strategies for the management of ARDS.

OBJECTIVES: To describe the post-marketing safety profile of respiratory syncytial virus prefusion F (RSVpreF) vaccine among pregnant individuals. DESIGN: This study analysed adverse event (AE) reports submitted to the U.S. Food and Drug Administration's Vaccine Adverse Event Reporting System (VAERS) database following RSVpreF immunisation from 1 September 2023 to 23 February 2024. SETTING: VAERS, as a national spontaneous vaccine safety surveillance system, provides insights into the safety profile of the RSVpreF vaccine in a real-world setting. PARTICIPANTS: Surveillance data included all AE reports submitted to VAERS in pregnant individuals following vaccination. EXPOSURE: Receipt of RSVpreF vaccine among pregnant individuals in the USA. PRIMARY AND SECONDARY OUTCOME MEASURES: Descriptive statistics were used to assess all AE reports with RSVpreF, including frequency, gestational age at vaccination, time to AE onset, reported outcomes and proportion of serious reports. Data mining techniques were employed to identify disproportionate reporting of RSVpreF-event pairs. Reports of preterm births were clinically reviewed. RESULTS: VAERS received 77 reports pertaining to RSVpreF vaccination in pregnant individuals, with 42 (54.55%) classified as serious. The most frequently reported non-pregnancy-specific AEs were headache, injection site erythema and injection site pain. For pregnancy-specific AEs, preterm birth was the most frequently reported (12.8%), followed by AE terms such as preterm premature rupture of membranes and caesarean section (each at 3.3%), and cervical dilatation, haemorrhage during pregnancy and uterine contractions during pregnancy (each at 1.4%). Our disproportionality analysis indicated signals for various AEs, particularly preterm birth, indicating that reports of preterm birth in conjunction with RSVpreF vaccination were observed more frequently than statistically expected. Most of the reported preterm births were moderate to late, occurring between 32 and less than 37 weeks of gestation. The median time from immunisation to the onset of preterm birth was 3 days, with two-thirds of cases reported within a week of vaccination. CONCLUSIONS: The AEs reported to VAERS among pregnant individuals vaccinated with RSVpreF largely aligned with the safety profile observed in prelicensure studies; however, this analysis also highlights the previously observed safety signal for preterm birth. Active surveillance studies focusing on maternal and perinatal outcomes are needed to further evaluate this signal and guide future clinical recommendations.

BACKGROUND: Aspirin-exacerbated respiratory disease (AERD) is a chronic eosinophilic inflammatory disorder characterized by asthma, chronic rhinosinusitis with nasal polyps, and intolerance to cyclooxygenase-1 inhibitors. Intranasal aspirin challenge (IAC) is increasingly used for AERD diagnosis owing to its practicality and safety. However, the lack of standardized symptom score criteria and an optimal dosage complicates its diagnostic utility. OBJECTIVE: To establish symptom score criteria and determine the optimal cumulative dosage for IAC in diagnosing AERD. METHODS: A total of 116 patients with chronic rhinosinusitis with nasal polyps were enrolled, including 58 with AERD and 58 without it. Group A (n = 70, 35 AERD and 35 non-AERD) was used to establish the symptom score criteria, which were validated in group B (n = 46, 23 AERD and 23 non-AERD). Symptom severity was assessed using a visual analog scale (VAS), and diagnostic accuracy was evaluated using receiver operating characteristic curve analysis. The safety and optimal dosage of IAC were also investigated. RESULTS: The optimal cutoff value for the increase in total VAS (T-VAS) was 7.5 points, with a sensitivity of 80.0% and specificity of 97.1%. A maximal cumulative dosage of 70 mg achieved the highest diagnostic accuracy (91.3%) and sensitivity (87.0%). Nasal congestion and rhinorrhea were the most pronounced symptoms during IAC in patients with AERD. The IAC was generally well tolerated, and 4.3% of participants experienced acute worsening of asthma. CONCLUSION: This study identifies a T-VAS increase of 7.5 points and a maximal cumulative dosage of 70 mg as optimal for diagnosing AERD via IAC, providing a reliable, safe, and practical diagnostic approach.