Influenza significantly impacts global health, particularly vulnerable populations like the elderly and those with chronic conditions. This study evaluated the safety of GlaxoSmithKline (GSK)'s quadrivalent seasonal influenza vaccine (IIV4) during the 2023/24 influenza season in Belgium, Germany, and Spain, per the European Medicines Agency's enhanced safety surveillance guidelines. This prospective, multicenter, non-interventional study, conducted from October 2, 2023, to January 4, 2024, included adults from Belgium and both children and adults from Germany and Spain. Participants received GSK's IIV4 and completed an adverse drug reaction (ADR) questionnaire via an electronic patient-reported outcome portal. Adverse events (AEs) were categorized by severity and analyzed by age group and risk status. Overall, 997 participants received at least one dose of IIV4. Of these, 900 who received Dose 1 and all 14 who received Dose 2 completed the ADR questionnaire. Overall, 42.6% of participants reported AEs post-Dose 1, primarily injection site pain (33.2%), fatigue (14.1%), and headache (12.7%), and 28.6% reported AEs post-Dose 2, primarily injection site pain (21.4%). The AE profile was consistent across age groups and risk statuses, with no serious AEs reported. The study's findings align with those from the previous two influenza seasons (2021-2023), confirming the vaccine's stable safety profile. High compliance rates ( >90%) for ADR reporting and consistency with earlier studies further validate these results. No new or unexpected AEs were identified, supporting the vaccine's safe use in the indicated age groups. Thus, GSK's IIV4 has a favorable safety profile and is suitable for broad use across various demographics.

This work explored the mechanism of EGF affecting chronic obstructive pulmonary disease (COPD) development. The most significantly differentially expressed gene (DEG) and its downstream pathway was analyzed by Microarray analysis. By constructing COPD mouse and cell models, a series of in vivo and in vitro experiments were performed to verify whether EGF regulated COPD development by the ERBB2/DNMT3A/FAM8A1 signaling. As the most significantly DEG in COPD, EGF was associated with endoplasmic reticulum stress and exhibited the highest sensitivity as a biopredictive marker for COPD. ERBB2/DNMT3A/FAM8A1 signaling was the downstream pathway of EGF. In lung tissues of COPD mice, up-regulated EGF, ERBB2 and DNMT3A, but down-regulated FAM8A1 was found. EGF silencing improved pulmonary function and airway remodeling in COPD mice. AG-825 (ERBB2 inhibitor) relieved lung tissue damage and down-regulated GRP78, CHOP and Caspase-12 in lung tissues of COPD mice, but was counteracted by Eeyarestatin I (ERAD inhibitor). In COPD cell model, FAM8A1 up-regulation enhanced viability and proliferation; relieved apoptosis; and down-regulated GRP78, CHOP and Caspase-12. Eeyarestatin I abolished these influences of FAM8A1 on COPD cell model. DNMT3A knockdown increased FAM8A1 but decreased GRP78, CHOP and Caspase-12 in COPD cell model. FAM8A1 silencing or Eeyarestatin I treatment abrogated these influences of DNMT3A silencing. Similar to AG-825, EGF silencing enhanced viability; attenuated apoptosis; down-regulated DNMT3A; and up-regulated FAM8A1 in COPD cell model. EGF/ERBB2 represses endoplasmic reticulum-associated degradation to promote COPD development by reducing FAM8A1 via increasing DNMT3A. Blocking EGF/ERBB2 may help clinical treatment of COPD.

Allergic rhinitis (AR) is a common immune-mediated chronic inflammatory disease with a complex pathogenesis involving multiple responses of the immune system and epigenetic changes. In recent years, DNA methylation, a key epigenetic mechanism, has been shown to play an important role in the onset and development of AR. GuoMinKang (GMK) have been used in the treatment of AR through their multi-component properties. However, its specific epigenetic regulatory mechanisms have not been fully investigated. The aim of this study was to explore the epigenetic regulatory mechanisms of the traditional Chinese medicine compound GMK in the treatment of AR. By analysing DNA methylation and transcriptome data from AR patients, we identified differentially methylated regions (DMRs) and differentially expressed genes (DEGs) associated with AR. Through network pharmacology analysis, we screened the active components of GMK and their potential target genes, particularly those related to DNA methyltransferases (DNMTs). An AR mouse model was established to observe the behavioural and pathological changes of the nasal mucosa of mice after drug administration; the expression of IgE cytokines was detected by ELISA, and the expression of nasal mucosa genes was verified by qPCR. Total IgE (tIgE) levels were significantly reduced in AR patients after GMK treatment, suggesting a possible role in immunomodulation. Our analysis revealed that GMK was able to restore aberrant methylation patterns in AR patients by modulating specific DNA methylation regions. Through differential methylation analysis, we identified 10 genes whose methylation levels were significantly restored to normal after GMK treatment and which already showed significant differential expression in AR patients, particularly in immune regulation and epithelial cell function. These genes include LERP, NFIA, etc., suggesting that they may play a key role in the onset and development of AR. Further through target prediction and network pharmacological analyses, we confirmed that the active ingredients of GMK (e.g., quercetin, coumarin, and geranylgeranyl) may exert their epigenetic regulatory functions by targeting the protein activity of DNMTs. In vivo experiments showed that GMK reduced the number of nose scratching and sneezing in mice, glandular hyperplasia in the nasal mucosa was alleviated, with a reduction in the number and volume of glands, and serum tIgE levels were reduced. The increase in LERP expression in the AR model was reduced after treatment with GMK, and the change in NFIA expression was not significant. It suggests that GMK may regulate LERP activity through DNMTs to alleviate allergic symptoms. This study reveals the potential therapeutic mechanism of the traditional Chinese medicine compound GMK in regulating AR through epigenetic mechanisms. These findings provide a theoretical basis and molecular foundation for the clinical application of GMK in AR and open up new research directions.

This article explores the role of early noninvasive ventilation in improving the quality of life and survival rates in patients with amyotrophic lateral sclerosis (ALS). It discusses how the goals of ventilatory support may vary depending on whether hospitalization is elective or emergent. The article emphasizes the importance of protocol-based optimization of nocturnal noninvasive positive pressure ventilation, focusing on patient tolerance and neuromuscular considerations. Additionally, it highlights the different approaches required for nocturnal and daytime ventilatory support, underscoring the need for tailored management strategies in ALS care.

Obesity hypoventilation syndrome (OHS) is defined by a body mass index ≥30 kg/m², sleep-disordered breathing, daytime partial pressure of arterial carbon dioxide ≥45 mm Hg, and the exclusion of other disorders of chronic hypoventilation. Positive airway pressure therapy and weight loss have been shown to improve OHS outcomes and are the mainstay of management in patients with OHS. In this review article, we discuss management of ambulatory patients with OHS, as well as management during hospitalization.

Sleep disordered breathing (SDB), periodic limb movements of sleep, insomnia, sleep curtailment, and sleep architectural changes are associated with cardiac arrhythmias in community-based and clinical cohort studies. Findings appear to be strongest in magnitude and most consistent for SDB and atrial fibrillation (AF). The mechanisms most consistently identified in animal experimental models include autonomic nervous system fluctuations and intrathoracic pressure alterations, the latter resulting in direct mechanical effects on the thin-walled atria. Other studies point toward intermittent hypoxia. Nonrandomized interventional studies suggest that the treatment of SDB reduces AF recurrence after ablation or cardioversion.

Continuous positive airway pressure is the gold standard for treatment of obstructive sleep apnea. For certain conditions, such as central sleep apnea, hypoventilation, hypercapnic respiratory failure, and restrictive lung disease, noninvasive ventilation (NIV), which includes respiratory assist devices and home mechanical ventilators, may be indicated. This article will review the various positive airway pressure and NIV devices currently available as well as the modes, settings, indications, and contraindications of these devices in both the inpatient and outpatient settings. Additional device features, accessories, troubleshooting, and insurance guidelines will also be discussed.

Opioids are widely used in acute and chronic pain management, but have significant respiratory effects that pose risks, especially in hospital settings. Opioid-induced respiratory depression occurs with opioids suppress the body's respiratory rate and response to CO2, leading to life-threatening gas exchange impairment. Chronic use of opioids causes central sleep apnea with an irregular breathing pattern, and contributes to complexity in managing obstructive sleep apnea. Mitigating respiratory risks of opioids involves limiting doses, careful monitoring, and sometimes the use of respiratory support like non-invasive ventilation.

The role of noninvasive ventilation (NIV) in hypercapnic chronic obstructive pulmonary disease (COPD) respiratory failure and overlap syndrome have been confusing over the last several years. In addition, if able to understand the timing and indications for NIV use, the clinical practice approach is riddled with hurdles to obtain in the United States. NIV for acute respiratory failure secondary to COPD exacerbation and NIV to prevent extubation failure in this patient population are not discussed here. Evidence for NIV in acute hospitalization is clearly accepted; however, bridging NIV from inpatient to home in hypercapnic COPD patients is a topic of debate, and a challenge for providers who are not experts in this space. This article discusses the evidence, interventions, timing, and insurance guidelines to assist health care providers.

The integration of sleep medicine into hospital care is critical for addressing sleep-disordered breathing (SDB), a condition highly prevalent among hospitalized patients. Effective management of SDB is linked to improved patient outcomes, reduced recovery times, and decreased hospital readmission rates. Advancements in technology, such as wearable devices and noninvasive monitoring tools, have enhanced real-time assessment and management of SDB. Early detection and intervention through structured hospital sleep medicine programs have shown improvements in patient care and overall health care costs. The evolving field of hospital sleep medicine emphasizes the importance of addressing SDB to enhance patient well-being and health care efficiency.