Pilot multicenter study to determine the utility of point-of-care ultrasound to predict difficulty of tracheal intubation using videolaryngoscopy with the McGrath™ Mac videolaryngoscope.

Background: Clinical airway screening tests used to predict difficulties during airway management have low sensitivity and specificity. Point-of-care airway ultrasound has described measurements related to problems with difficult direct laryngoscopy. Nevertheless, the correlation between ultrasound parameters and videolaryngoscopy has not been published yet. The aim of this multicenter, prospective observational pilot study was to evaluate the applicability of clinical parameters and ultrasound measurements to find potential tracheal intubation difficulties when videolaryngoscopy is used. Methods: Preoperatively, six clinical airway assessments were performed: (1) modified Mallampati score, (2) thyromental distance, (3) sternomental distance, (4) interincisal distance, (5) upper lip bite test, and (6) neck circumference. Six ultrasound parameters were measured in awake patients: (1) distance from skin to hyoid bone, (2) distance from skin to epiglottis, (3) hyomental distance in neutral head position, (4) hyomental distance in head-extended position, (5) distance from skin to the deepest part of the palate, and (6) sagittal tongue area. And finally, there was one ultrasound measure obtained in anesthetized patients, the compressed sagittal tongue area during videolaryngoscopy. The difficulty for tracheal intubation using a McGrath™ Mac videolaryngoscope, the percentage of glottic opening, and Cormack-Lehane grade were also assessed. Results: In this cohort of 119 subjects, tongue dimensions, particularly the sagittal tongue area, showed a robust association with increased intubation difficulty using videolaryngoscopy. A multiparametric model combining the following three ultrasound variables in awake patients: (a) the distance from skin to epiglottis, (b) the distance from skin to the deepest part of the palate, and (c) the sagittal tongue area, yielded a sensitivity of 92.3%, specificity of 94.5%, positive predictive value of 82.8%, and negative predictive value of 97.8% (p < 0.001). Conclusion: Point-of-care airway ultrasound emerges as a more useful tool compared to traditional clinical scales to anticipate possible challenges during videolaryngoscopic intubation.

Design, manufacture, and control of a low-cost positive airway pressure device.

Current positive airway pressure devices cost NZ$800-$2500, posing a financial barrier for the estimated 1 billion individuals worldwide with sleep apnea and those researching respiratory diseases. Increasing diagnoses and research interest in the area necessitate a low-cost, easily accessible alternative. Thus, the mePAP, a high-quality, multipurpose, low-cost (∼NZ$250) positive airway pressure device, was designed and prototyped specifically for respiratory disease research, particularly for sleep apnea. The mePAP allows user customization and provides researchers with an affordable tool for testing positive airway pressure algorithms. Unlike typical commercial devices, the mePAP offers adaptability with open-source data collection and easily modifiable software for implementing and analysing different control and diagnostic algorithms. It features three control modes: constant; bilevel; and automatic; and provides pressures from 4 to 20 cmH2O, controlled via a phone app through Wi-Fi, with a mini-sensor added at the mask for increased accuracy. Validation tests showed the mePAP's performance is comparable to a gold-standard Fisher & Paykel device, with extremely similar output pressures. The mePAP's low cost enhances accessibility and equity, allowing researchers to test ventilation algorithms for sleep apnea and other respiratory conditions, with all data openly available for analysis. Its adaptability and multiple applications increase its usability and usefulness across various research and clinical settings.

Obstructive sleep apnea: Overlooked comorbidity in patients with diabetes.

In this review article, we explore the interplay between obstructive sleep apnea (OSA) and type 2 diabetes mellitus (T2DM), highlighting a significant yet often overlooked comorbidity. We delve into the pathophysiological links between OSA and diabetes, specifically how OSA exacerbates insulin resistance and disrupts glucose metabolism. The research examines the prevalence of OSA in diabetic patients and its role in worsening diabetes-related complications. Emphasizing the importance of comprehensive management, including weight control and positive airway pressure therapy, the study advocates integrated approaches to improve outcomes for patients with T2DM and OSA. This review underscores the necessity of recognizing and addressing OSA in diabetes care to ensure more effective treatment and better patient outcomes.

Successful management of carinal shift in aortic dissection: A case report of innovative airway management strategies.

The case underscores the necessity of adaptable airway management strategies in aortic dissection surgeries complicated by carinal shift. Successful lung isolation was achieved using a single-lumen endotracheal tube after failed attempts with traditional methods and bronchial blockers.

Camellia sinensis L. alleviates OVA-induced allergic asthma through NF-κB and MMP-9 pathways.

Allergic asthma, a type of chronic airway inflammation, is a global health concern because of its increasing incidence and recurrence rates. Camellia sinensis L. yields a variety type of teas, which are also used as medicinal plants in East Asia and are known to have antioxidant, anti-inflammatory, and immune-potentiating properties. Here, we examined the constituents of C. sinensis L. extract (CSE) and evaluated the protective effects of CSE on allergic asthma by elucidating the underlying mechanism. To induce allergic asthma, we injected the sensitization solution (mixture of ovalbumin (OVA) and aluminum hydroxide) into mice intraperitoneally on days 0 and 14. Then, the mice were exposed to 1% OVA by a nebulizer on days 21 to 23, while intragastric administration of CSE (30 and 100 mg/kg) was performed each day on days 18 to 23. We detected five compounds in CSE, including (-)-epigallocatechin, caffeine, (-)-epicatechin, (-)-epigallocatechin gallate, and (-)-epicatechin gallate. Treatment with CSE remarkably decreased the airway hyperresponsiveness, OVA-specific immunoglobulin E level, and inflammatory cell and cytokine levels of mice, with a decrease in inflammatory cell infiltration and mucus production in lung tissue. Treatment with CSE also decreased the phosphorylation of nuclear factor-κB (NF-κB) and the expression of matrix-metalloproteinase (MMP)-9 in asthmatic mice. Our results demonstrated that CSE reduced allergic airway inflammation caused by OVA through inhibition of phosphorylated NF-κB and MMP-9 expression.

An intubation technique using hyperangulated video laryngoscopy and a DuCanto suction catheter preloaded with a bougie: A case report with a video demonstration.

Video laryngoscopy outperforms direct laryngoscopy for successful orotracheal intubation in the emergency department. When performing video laryngoscopy, emergency physicians may use a standard geometry blade or a hyperangulated blade. Hyperangulated video laryngoscopy is easier when using a rigid hyperangulated stylet instead of a standard malleable stylet. The angulation of the hyperangulated blade makes it difficult to use an endotracheal tube (ETT) introducer ("bougie"). We describe a case report using a DuCanto suction catheter (SSCOR) with a preloaded bougie to perform orotracheal intubation during hyperangulated video laryngoscopy. An adult patient presented to the emergency department in status epilepticus and was intubated for airway protection. Hyperangulated video laryngoscopy was performed with a LoPro S4 (GlideScope) blade; a DuCanto suction catheter was used to deliver a bougie through the vocal cords. The bougie was advanced down the trachea, and the DuCanto suction catheter was removed. The bougie successfully delivered a size 8.0 ETT. Visualization of the larynx with hyperangulated video laryngoscopy is usually easy, but ETT delivery into the trachea can be challenging. Rigid hyperangulated stylets were created to facilitate ETT delivery, but these stylets are expensive and often not available. Traditional teaching says that a bougie cannot be used while intubating with a hyperangulated blade. This case report describes a method to deliver a bougie via a DuCanto suction catheter during hyperangulated video laryngoscopy. It allows for the use of a bougie with a hyperangulated blade and offers a technique to perform hyperangulated video laryngoscopy without a rigid stylet.

Universal C-MAC® videolaryngoscope use in adult patients: a single-centre experience.

Universal use of Storz C-MAC® videolaryngoscopes was implemented for adult tracheal intubations in the operating theatres, intensive care unit and emergency department at Royal United Hospitals Bath NHS Foundation Trust in 2017. We report data from 1099 intubations from March 2020 to March 2022, collected contemporaneously and anonymously using a smartphone app, representing an estimated 18% of intubations in operating theatres and 30% of intubations in other locations during this period. Intubation success was 100%. The first-pass success rate was 87.3% overall: 87% with a Macintosh videolaryngoscope, 92% with a hyperangulated videolaryngoscope and 81% for users with ≤ 20 previous uses. First-pass success without complications was 87% overall: 87% in operating theatres (836/962), 93% in the emergency department (38/41) and 83% in the intensive care unit (73/88). Complications occurred during 0.6% of intubations: 0/962 in operating theatres and 7/137 in non-theatre locations. The rate of complications was unaltered by blade type (Macintosh 5/994 vs. hyperangulated 2/105, p = 0.14); intubator experience with the device (≤ 20 previous clinical uses 2/260 vs. > 20 previous uses 5/832, p = 0.67) and use of airborne personal protective equipment (PPE 6/683 vs. no-PPE 1/410, p = 0.27). Complication rates increased outside theatres (theatres 0/963 vs. non-theatre 7/136, p < 0.001) and during rapid sequence induction (RSI 6/379 (1.6%) vs. non-RSI 1/720 (0.1%), p = 0.008).

Airway and Airway Obstruction Site Segmentation Study Using U-Net with Drug-Induced Sleep Endoscopy Images.

Obstructive sleep apnea is characterized by a decrease or cessation of breathing due to repetitive closure of the upper airway during sleep, leading to a decrease in blood oxygen saturation. In this study, employing a U-Net model, we utilized drug-induced sleep endoscopy images to segment the major causes of airway obstruction, including the epiglottis, oropharynx lateral walls, and tongue base. The evaluation metrics included sensitivity, specificity, accuracy, and Dice score, with airway sensitivity at 0.93 (± 0.06), specificity at 0.96 (± 0.01), accuracy at 0.95 (± 0.01), and Dice score at 0.84 (± 0.03), indicating overall high performance. The results indicate the potential for artificial intelligence (AI)-driven automatic interpretation of sleep disorder diagnosis, with implications for standardizing medical procedures and improving healthcare services. The study suggests that advancements in AI technology hold promise for enhancing diagnostic accuracy and treatment efficacy in sleep and respiratory disorders, fostering competitiveness in the medical AI market.

Obesity impairs ciliary function and mucociliary clearance in the murine airway epithelium.

Obesity is a risk factor for increased morbidity and mortality in viral respiratory infection. Mucociliary clearance (MCC) in the airway is the primary host defense against viral infections. However, the impact of obesity on MCC is unclear, prompting this study. Using murine tracheal tissue culture and in vitro influenza A virus (IAV) infection models, we analyzed cilia-driven flow and ciliary beat frequency (CBF) in the airway epithelium to evaluate MCC. Short-term IAV infection increased cilia-driven flow and CBF in control mice, but not in high-fat diet-induced obese mice. Basal cilia-driven flow and CBF were also lower in obese mice than in control mice. Mechanistically, the increase of extracellular adenosine triphosphate (ATP) release during IAV infection, which was observed in the control mice, was abolished in the obese mice, although the addition of ATP increased cilia-driven flow and CBF both in control and obese mice to a similar extent. Additionally, RNA sequencing and reverse transcription-polymerase chain reaction revealed the downregulation of several cilia-related genes, including Dnah1, Dnal1, Armc4, and Ttc12 (the dynein-related genes); Ulk4 (the polychaete differentiation gene); Cep164 (the ciliogenesis and intraflagellar transport gene); Rsph4a, Cfap206, and Ppil6 (the radial spoke structure and assembly gene); and Drc3(the nexin-dynein regulatory complex genes) in obese murine tracheal tissues compared to their control levels. In conclusion, our studies demonstrate that obesity attenuates MCC under basal conditions and during IAV infection by downregulating the expression of cilia-related genes and suppressing the release of extracellular ATP, thereby increasing the susceptibility and severity of IAV infection.

Causal inference analysis of the radiologic progression in the chronic obstructive pulmonary disease.

There is limited evidence regarding the causal inference of emphysema and functional small airway disease in the subsequent progression of chronic obstructive pulmonary disease (COPD). Patients consisting of two independent cohorts diagnosed with COPD and underwent two serial chest CT scans were included. Total percent emphysema (PRMEmph) and fSAD (PRMfSAD) was quantified via PRM. To investigate the progression of emphysema, we divided COPD patients with PRMEmph < 10% into low and high PRMfSADgroup, matched with similar baseline characteristics, and conducted nonparametric hypothesis tests based on randomization inference using Wilcoxon signed rank test and Huber's M statistics. In patients with baseline PRMEmph < 10%, there were 26 and 16 patients in the low PRMfSA group and 52 and 64 patients in the high PRMfSA in the derivation and validation cohorts, respectively. In the both low and high PRMfSAD groups, there were 0.11 and 1.43 percentage point increases (Huber's M statistic p = 0.016) and 0.58 and 2.09 percentage point increases (p = 0.038) in the proportion of emphysema in the derivation and validation cohorts, respectively. On the contrary, among patients with baseline PRMfSAD < 20%, there was no significant differences in the interval changes of PRMfSAD between the low and high PRMEmph groups in both cohorts. In COPD patients with low emphysema, group with baseline high PRMfSAD showed greater change of PRMEmph than those with low PRMfSAD in both the derivation and validation cohorts. Imaging-based longitudinal quantitative analysis may provide important evidence that small airway disease precedes emphysema in CT-based early COPD patients.

Early predictive values of clinical assessments for ARDS mortality: a machine-learning approach.

Acute respiratory distress syndrome (ARDS) is a devastating critical care syndrome with significant morbidity and mortality. The objective of this study was to evaluate the predictive values of dynamic clinical indices by developing machine-learning (ML) models for early and accurate clinical assessment of the disease prognosis of ARDS. We conducted a retrospective observational study by applying dynamic clinical data collected in the ARDSNet FACTT Trial (n = 1000) to ML-based algorithms for predicting mortality. In order to compare the significance of clinical features dynamically, we further applied the random forest (RF) model to nine selected clinical parameters acquired at baseline and day 3 independently. An RF model trained using clinical data collected at day 3 showed improved performance and prognostication efficacy (area under the curve [AUC]: 0.84, 95% CI: 0.78-0.89) compared to baseline with an AUC value of 0.72 (95% CI: 0.65-0.78). Mean airway pressure (MAP), bicarbonate, age, platelet count, albumin, heart rate, and glucose were the most significant clinical indicators associated with mortality at day 3. Thus, clinical features collected early (day 3) improved performance of integrative ML models with better prognostication for mortality. Among these, MAP represented the most important feature for ARDS patients' early risk stratification.

Improving oxygenation in a patient with respiratory failure due to morbid obesity by applying airway pressure release ventilation: a case report.

INTRODUCTION: Morbidly obese patients occasionally have respiratory problems owing to hypoventilation. Airway pressure release ventilation is one of the ventilation settings often used for respiratory management of acute respiratory distress syndrome. However, previous reports indicating that airway pressure release ventilation may become a therapeutic measure as ventilator management in morbid obesity with respiratory failure is limited. We report a case of markedly improved oxygenation in a morbidly obese patient after airway pressure release ventilation application. CASE REPORT: A 50s-year-old Asian man (body mass index 41 kg/m2) presented with breathing difficulties. The patient had respiratory failure with a PaO2/FIO2 ratio of approximately 100 and severe atelectasis in the left lung, and ventilator management was initiated. Although the patient was managed on a conventional ventilate mode, oxygenation did not improve. On day 11, we changed the ventilation setting to airway pressure release ventilation, which showed marked improvement in oxygenation with a PaO2/FIO2 ratio of approximately 300. We could reduce sedative medication and apply respiratory rehabilitation. The patient was weaned from the ventilator on day 29 and transferred to another hospital for further rehabilitation on day 31. CONCLUSION: Airway pressure release ventilation ventilator management in morbidly obese patients may contribute to improving oxygenation and become one of the direct therapeutic measures in the early stage of critical care.

Cardiopulmonary crisis caused by bronchial blocker malposition in a patient with aberrant tracheal anatomy: a case report.

BACKGROUND: Double-lumen tubes (DLTs) and bronchial blockers (BBs) can be used to establish one-lung ventilation (OLV) for thoracic surgery. BBs are a good alternative when DLTs are not suitable or patients have difficult airways. However, BBs are more prone to malposition, leading to adverse events. CASE PRESENTATION: We present a 68-year-old male patient who was scheduled for thoracoscopic left lower lobectomy. The patient was not expected to have airway malformation preoperatively. When the DLT could not be inserted into the bronchus after general anesthesia induction, we used a BB to perform OLV. During surgery, malposition of the BB resulted in the development of an "incomplete balloon valve", leading to a cardiopulmonary crisis. CONCLUSIONS: Previewing chest computed tomography scans to assess the airway anatomy before thoracic surgery is essential. Three-dimensional reconstruction of the airway can provide a more intuitive assessment of airway anatomy. During OLV with BBs, we should pay attention to balloon malposition to prevent cardiopulmonary crises.

Comparison of dental force applied during endotracheal intubation with hyper-angulated and macintosh-type video laryngoscopy blades used by emergency medicine trainees: A randomized cross-over manikin study.

OBJECTIVES: This study aimed to compare the effects of Macintosh-type and hyperangulated video laryngoscopy (VL) blades on dental force during endotracheal intubation (ETI) using Glidescope and McGrath VL devices. METHODS: In this randomized, crossover, manikin study conducted at a university emergency medicine (EM) program, 65 EM trainees included interns and residents performed 520 intubations using four different VL blades (GlideScope VL with Macintosh-type Mac T3 and hyperangular Lo Pro T3 blades and McGrath VL Macintosh-type MAC 4 and hyperangular McGrath X3 blades) in normal and difficult airway scenarios. The primary outcome of this study was the dental pressure (Newton) exerted during ETI. The secondary outcomes included c-spine motion (degree), intubation success (%), duration (seconds), successful glottic view (%), and intubator comfort (7-point Likert). RESULTS: Significant differences were observed in dental force (H(3) = 11.7, P = 0.008), c-spine motion (H(3) = 8.34, P = 0.039), duration (H(3) = 16.56, P = 0.001), and comfort (H(3) = 174.96, P < 0.001) across blade types. Glidescope LoPro T3 provided a significant lower dental force (adjusted P = 0.01), less c-spine motion (adjusted P = 0.031), and shorter intubation duration (adj P < 0.01) than the McGrath Mac 4. First attempt success and intubator comfort were significantly better with all Glidescope blades (z score of 3.7 and 4.7) than with McGrath blades (z score of-4.1 and-4.4). CONCLUSION: The Glidescope LoPro T3 blade demonstrated advantages in dental force, c-spine motion, and intubation duration compared with McGrath Mac 4. Overall, the Glidescope blades provided superior comfort and higher first attempt success rates.

Factors influencing the continuity of evidence-based practice in perioperative airway management for elderly patients with fractures: A qualitative study.

BACKGROUND: More and more evidence-based practices are emerging, but researchers mostly focus on short-term effects, resulting in evidence-based practices not being applied in the clinic in the long term. In this study, we took the evidence-based practice of perioperative airway management in elderly fracture patients as an example and adopted a descriptive phenomenological approach to understand the influencing factors of its sustainability to provide a reference basis for promoting the continuity of evidence-based practice in the clinic. AIM: To explore factors influencing the persistence of evidence-based practice in perioperative airway management in elderly patients with fractures. METHODS: This study was qualitative research. Nine nurses who implemented evidence-based practice in the orthopedic ward of a tertiary comprehensive hospital in Shanghai from September 2023 to October 2023 were selected using purposive sampling as research subjects. Semi-structured interviews were conducted with them, and the data were analyzed using the Colaizzi phenomenological analysis method based on the three dimensions and ten factors of the NHS sustainability model. RESULTS: Three main themes and ten subthemes were identified: Process aspects (benefits to patients, benefits to nurses, lack of follow-up, complex processes); staff aspects (insufficient human resources, inadequate training and education, lack of leadership support); and organizational environment aspects (inadequate infrastructure, poor patient compliance, poor doctor cooperation). CONCLUSION: Human resources, training and education, leadership support, infrastructure, and patient-physician collaboration are important factors influencing the sustainability of evidence-based practice for perioperative airway management in older patients with fractures.

A Randomised Control Study Comparing Ultrasonography with Standard Clinical Methods in Assessing Endotracheal Tube Tip Positioning.

Introduction: Airway ultrasound has been increasingly used in correct positioning of endotracheal tube. We hypothesize that a safe distance between endotracheal tube tip and carina can be achieved with the aid of ultrasound. Aim of the study: Our primary objective was to determine whether ultrasound guided visualisation of proximal end of endotracheal tube cuff is better when compared to conventional method in optimal positioning of tube tip. The secondary objective was to find the optimal endotracheal tube position at the level of incisors in adult Indian population. Materials and Methods: There were 25 patients each in the conventional group and the ultrasound group. Conventional method includes auscultation and end tidal capnography. In the ultrasound group the upper end of the endotracheal tube cuff was positioned with an intent to provide 4 cm distance from the tube tip to the carina. X ray was used in both groups for confirmation of tip position and comparison between the two groups. Further repositioning of the tube was done if indicated and the mean length of the tube at incisors was then measured. Results: After x ray confirmation, endotracheal tube repositioning was required in 24% of patients in the USG group and 40 % of patients in the conventional group. However, this result was not found to be statistically significant (p = 0.364). The endotracheal tube length at the level of teeth was 19.4 ± 1.35 cm among females and 20.95 ± 1.37 cm among males. Conclusions: Ultrasonography is a reliable method to determine ETT position in the trachea. There was no statistically significant difference when compared to the conventional method. The average length of ETT at the level of incisors was 19.5 cm for females and 21 cm for males.

Causal Effects of Asthma on Upper Airway Diseases and Allergic Diseases: A Two-Sample Mendelian Randomization.

INTRODUCTION: Asthma is associated with upper airway diseases and allergic diseases; however, the causal effects need to be investigated further. Thus, we performed this two-sample Mendelian randomization (MR) analysis to explore and measure the causal effects of asthma on allergic rhinitis (AR), vasomotor rhinitis (VMR), allergic conjunctivitis (AC), atopic dermatitis (AD), and allergic urticaria (AU). METHODS: The data for asthma, AR, VMR, AC, AD, and AU were obtained from large-scale genome-wide association studies summarized recently. We defined single-nucleotide polymorphisms satisfying the MR assumptions as instrumental variables. Inverse-variance weighted (IVW) approach under random-effects was applied as the dominant method for causal estimation. The weighted median approach, MR-Egger regression analysis, MR pleiotropy residual sum and outlier test, and leave-one-out sensitivity analysis were performed as sensitivity analysis. Horizontal pleiotropy was measured using MR-Egger regression analysis. Significant causal effects were attempted for replication and meta-analysis. RESULTS: We revealed that asthma had causal effects on AR (IVW, odds ratio [OR] = 1.93; 95% confidence interval [CI], 1.74-2.14; p < 0.001), VMR (IVW, OR = 1.40; 95% CI, 1.15-1.71; p < 0.001), AC (IVW, OR = 1.65; 95% CI, 1.49-1.82; p < 0.001), and AD (IVW, OR = 2.13; 95% CI, 1.82-2.49; p < 0.001). No causal effect of asthma on AU was observed. Sensitivity analysis further assured the robustness of these results. The evaluation of the replication stage and meta-analysis further confirmed the causal effect of asthma on AR (IVW OR = 1.81, 95% CI 1.62-2.02, p < 0.001), AC (IVW OR = 1.44, 95% CI 1.11-1.87, p < 0.001), and AD (IVW OR = 1.85, 95% CI 1.42-2.41, p < 0.001). CONCLUSIONS: We revealed and quantified the causal effects of asthma on AR, VMR, AC, and AD. These findings can provide powerful causal evidence of asthma on upper airway diseases and allergic diseases, suggesting that the treatment of asthma should be a preventive and therapeutic strategy for AR, VMR, AC, and AD.

Transcriptomic analysis of primary nasal epithelial cells reveals altered interferon signalling in preterm birth survivors at one year of age.

Introduction: Many survivors of preterm birth (<37 weeks gestation) have lifelong respiratory deficits, the drivers of which remain unknown. Influencers of pathophysiological outcomes are often detectable at the gene level and pinpointing these differences can help guide targeted research and interventions. This study provides the first transcriptomic analysis of primary nasal airway epithelial cells in survivors of preterm birth at approximately 1 year of age. Methods: Nasal airway epithelial brushings were collected, and primary cell cultures established from term (>37 weeks gestation) and very preterm participants (≤32 weeks gestation). Ex vivo RNA was collected from brushings with sufficient cell numbers and in vitro RNA was extracted from cultured cells, with bulk RNA sequencing performed on both the sample types. Differential gene expression was assessed using the limma-trend pipeline and pathway enrichment identified using Reactome and GO analysis. To corroborate gene expression data, cytokine concentrations were measured in cell culture supernatant. Results: Transcriptomic analysis to compare term and preterm cells revealed 2,321 genes differentially expressed in ex vivo samples and 865 genes differentially expressed in cultured basal cell samples. Over one third of differentially expressed genes were related to host immunity, with interferon signalling pathways dominating the pathway enrichment analysis and IRF1 identified as a hub gene. Corroboration of disrupted interferon release showed that concentrations of IFN-α2 were below measurable limits in term samples but elevated in preterm samples [19.4 (76.7) pg/ml/µg protein, p = 0.03]. IFN-γ production was significantly higher in preterm samples [3.3 (1.5) vs. 9.4 (17.7) pg/ml/µg protein; p = 0.01] as was IFN-ß [7.8 (2.5) vs. 13.6 (19.5) pg/ml/µg protein, p = 0.01]. Conclusion: Host immunity may be compromised in the preterm nasal airway epithelium in early life. Altered immune responses may lead to cycles of repeated infections, causing persistent inflammation and tissue damage which can have significant impacts on long-term respiratory function.

Blocking HXA3-mediated neutrophil elastase release during S. pneumoniae lung infection limits pulmonary epithelial barrier disruption and bacteremia.

Streptococcus pneumoniae (Sp), a leading cause of community-acquired pneumonia, can spread from the lung into the bloodstream to cause septicemia and meningitis, with a concomitant threefold increase in mortality. Limitations in vaccine efficacy and a rise in antimicrobial resistance have spurred searches for host-directed therapies that target pathogenic immune processes. Polymorphonuclear leukocytes (PMNs) are essential for infection control but can also promote tissue damage and pathogen spread. The major Sp virulence factor, pneumolysin, triggers acute inflammation by stimulating the 12-lipoxygenase (12-LOX) eicosanoid synthesis pathway in epithelial cells. This pathway is required for systemic spread in a mouse pneumonia model and produces a number of bioactive lipids, including hepoxilin A3 (HXA3), a hydroxy epoxide PMN chemoattractant that has been hypothesized to facilitate breach of mucosal barriers. To understand how 12-LOX-dependent inflammation promotes dissemination during Sp lung infection and dissemination, we utilized bronchial stem cell-derived air-liquid interface cultures that lack this enzyme to show that HXA3 methyl ester (HXA3-ME) is sufficient to promote basolateral-to-apical PMN transmigration, monolayer disruption, and concomitant Sp barrier breach. In contrast, PMN transmigration in response to the non-eicosanoid chemoattractant N-formyl-L-methionyl-L-leucyl-phenylalanine (fMLP) did not lead to epithelial disruption or bacterial translocation. Correspondingly, HXA3-ME but not fMLP increased the release of neutrophil elastase (NE) from Sp-infected PMNs. Pharmacologic blockade of NE secretion or activity diminished epithelial barrier disruption and bacteremia after pulmonary challenge of mice. Thus, HXA3 promotes barrier-disrupting PMN transmigration and NE release, pathological events that can be targeted to curtail systemic disease following pneumococcal pneumonia.IMPORTANCEStreptococcus pneumoniae (Sp), a leading cause of pneumonia, can spread from the lung into the bloodstream to cause systemic disease. Limitations in vaccine efficacy and a rise in antimicrobial resistance have spurred searches for host-directed therapies that limit pathologic host immune responses to Sp. Excessive polymorphonuclear leukocyte (PMN) infiltration into Sp-infected airways promotes systemic disease. Using stem cell-derived respiratory cultures that reflect bona fide lung epithelium, we identified eicosanoid hepoxilin A3 as a critical pulmonary PMN chemoattractant that is sufficient to drive PMN-mediated epithelial damage by inducing the release of neutrophil elastase. Inhibition of the release or activity of this protease in mice limited epithelial barrier disruption and bacterial dissemination, suggesting a new host-directed treatment for Sp lung infection.

Effect of positive airway pressure on obese patients undergoing surgery: a systematic review and meta-analysis.

This systematic review and meta-analysis (SRMA) evaluates the efficacy and safety of Positive Airway Pressure (PAP) therapy in perioperative care for obese surgical patients. We reviewed 24 studies, encompassing data up to March 23, 2023, analyzing the impacts of Continuous Positive Airway Pressure (CPAP) and Bilevel Positive Airway Pressure (BIPAP) on postoperative adverse outcomes, oxygenation, and pulmonary function. Our findings underscore the significant potential of PAP therapy in managing obese patients during the perioperative period, particularly those at substantial risk for postoperative respiratory complications. PAP therapy not only enhances oxygenation levels and lung function but also substantially reduces the incidence of atelectasis and shortens hospital stays, thereby affirming its vital role in improving perioperative outcomes for this patient population.