Comprehensive risk assessment for hospital-acquired pneumonia: sociodemographic, clinical, and hospital environmental factors associated with the incidence of hospital-acquired pneumonia

Background Social and hospital environmental factors that may be associated with hospital-acquired pneumonia (HAP) have not been evaluated. Comprehensive risk assessment for the incidence of HAP including sociodemographic, clinical, and hospital environmental factors was conducted using national health insurance claims data. Methods This is a population-based retrospective cohort study of adult patients who were hospitalized for more than 3 days from the Health Insurance Review and Assessment Service-National Inpatient Sample data between January 1, 2016 and December 31, 2018 in South Korea. Multivariable logistic regression analyses were conducted to identify the factors associated with the incidence of HAP. Results Among the 512,278 hospitalizations, we identified 25,369 (5.0%) HAP cases. In multivariable analysis, well-known risk factors associated with HAP such as older age (over 70 vs. 20–29; adjusted odds ratio [aOR], 3.66; 95% confidence interval [CI] 3.36–3.99), male sex (aOR, 1.35; 95% CI 1.32–1.39), pre-existing lung diseases (asthma [aOR, 1.73; 95% CI 1.66–1.80]; chronic obstructive pulmonary disease [aOR, 1.62; 95% CI 1.53–1.71]; chronic lower airway disease [aOR, 1.79; 95% CI 1.73–1.85]), tube feeding (aOR, 3.32; 95% CI 3.16–3.50), suctioning (aOR, 2.34; 95% CI 2.23–2.47), positioning (aOR, 1.63; 95% CI 1.55–1.72), use of mechanical ventilation (aOR, 2.31; 95% CI 2.15–2.47), and intensive care unit admission (aOR, 1.29; 95% CI 1.22–1.36) were associated with the incidence of HAP. In addition, poverty (aOR, 1.08; 95% CI 1.04–1.13), general hospitals (aOR, 1.54; 95% CI 1.39–1.70), higher bed-to-nurse ratio (Grade ≥ 5; aOR, 1.45; 95% CI 1.32–1.59), higher number of beds per hospital room (6 beds; aOR, 3.08; 95% CI 2.77–3.42), and ward with caregiver (aOR, 1.19; 95% CI 1.12–1.26) were related to the incidence of HAP. Conclusions The incidence of HAP was associated with various sociodemographic, clinical, and hospital environmental factors. Thus, taking a comprehensive approach to prevent and treat HAP is important.

Evaluating a Social Media Campaign for a Parent Educational Video on Bronchiolitis

Bronchiolitis, or lower airway swelling, is a common cause of pediatric hospital admissions. Parents have expressed wishes for more information regarding bronchiolitis but had difficulty finding reliable information, suggesting the need for more effective and easily accessible information resources. Knowledge translation (KT) tools like videos provide research-based information and may be conveniently disseminated to large audiences through social media. The purpose of this project was to evaluate the effectiveness of a social media campaign to promote a video on bronchiolitis. A social media campaign was conducted from 14 October to 30 November 2019. User interactions were recorded for the Facebook and Twitter accounts, website, and YouTube of Evidence in Child Health to Enhance Outcomes (ECHO), Alberta Research Centre for Health Evidence (ARCHE), and Translating Emergency Knowledge for Kids (TREKK). Baseline metrics were collected from 1 August to 30 September 2019 and post-campaign metrics were collected from 1 December 2019 to 31 March 2020. Mean monthly changes, standard deviations, and percent changes between periods were generated for the baseline, campaign, and post-campaign periods. Overall, there was a visible increase in user interactions throughout the campaign period. There was an overall downward trend in user interactions following the campaign. These findings suggest that social media may be a useful method of KT tool dissemination when consistently used. The downward trend post-campaign highlights the need for further research to investigate methods to maintain continuous interaction following a campaign.

Integrin/TGF-Beta1 inhibitor GLPG-0187 blocks SARS-CoV-2 Delta and Omicron pseudovirus infection of airway epithelial cells which could attenuate disease severity

As COVID-19 continues to pose major risk for vulnerable populations including the elderly, immunocompromised, patients with cancer, and those with contraindications to vaccination, novel treatment strategies are urgently needed. SARS-CoV-2 infects target cells via RGD-binding integrins either independently or as a co-receptor with surface receptor angiotensin-converting enzyme 2 (ACE2). We used pan-integrin inhibitor GLPG-0187 to demonstrate blockade of SARS-CoV-2 pseudovirus infection of target cells. Omicron pseudovirus infected normal human small airway epithelial (HSAE) cells significantly less than D614G or Delta variant pseudovirus, and GLPG-0187 effectively blocked SARS-CoV-2 pseudovirus infection in a dose-dependent manner across multiple viral variants. GLPG-0187 inhibited Omicron and Delta pseudovirus infection of HSAE cells more significantly than other variants. Pre-treatment of HSAE cells with MEK inhibitor (MEKi) VS-6766 enhanced inhibition of pseudovirus infection by GLPG-0187. Because integrins activate TGF-beta; signaling, we compared plasma levels of active and total TGF-beta; in COVID-19+ patients. Plasma TGF-beta1 levels correlated with age, race, and number of medications upon presentation with COVID-19, but not with sex. Total plasma TGF-beta1 levels correlated with activated TGF-beta1 levels. In our preclinical studies, Omicron infects lower airway lung cells less efficiently than other COVID-19 variants. Moreover, inhibition of integrin signaling prevents SARS-CoV-2 Delta and Omicron pseudovirus infectivity, and may mitigate COVID-19 severity through decreased TGF-beta1 activation. This therapeutic strategy may be further explored through clinical testing in vulnerable and unvaccinated populations.

Bacterial Signatures of Paediatric Respiratory Disease: An Individual Participant Data Meta-Analysis

Introduction: The airway microbiota has been linked to specific paediatric respiratory diseases, but studies are often small. It remains unclear whether particular bacteria are associated with a given disease, or if a more general, non-specific microbiota association with disease exists, as suggested for the gut. We investigated overarching patterns of bacterial association with acute and chronic paediatric respiratory disease in an individual participant data (IPD) meta-analysis of 16S rRNA gene sequences from published respiratory microbiota studies.Methods: We obtained raw microbiota data from public repositories or via communication with corresponding authors. Cross-sectional analyses of the paediatric (<18 years) microbiota in acute and chronic respiratory conditions, with >10 case subjects were included. Sequence data were processed using a uniform bioinformatics pipeline, removing a potentially substantial source of variation. Microbiota differences across diagnoses were assessed using alpha- and beta-diversity approaches, machine learning, and biomarker analyses.Results: We ultimately included 20 studies containing individual data from 2624 children. Disease was associated with lower bacterial diversity in nasal and lower airway samples and higher relative abundances of specific nasal taxa including Streptococcus and Haemophilus. Machine learning success in assigning samples to diagnostic groupings varied with anatomical site, with positive predictive value and sensitivity ranging from 43 to 100 and 8 to 99%, respectively.Conclusion: IPD meta-analysis of the respiratory microbiota across multiple diseases allowed identification of a non-specific disease association which cannot be recognised by studying a single disease. Whilst imperfect, machine learning offers promise as a potential additional tool to aid clinical diagnosis.

The Hexosamine Biosynthetic Pathway Links Innate Inflammation With Epithelial-Mesenchymal Plasticity in Airway Remodeling

Disruption of the lower airway epithelial barrier plays a major role in the initiation and progression of chronic lung disease. Here, repetitive environmental insults produced by viral and allergens triggers metabolic adaptations, epithelial-mesenchymal plasticity (EMP) and airway remodeling. Epithelial plasticity disrupts epithelial barrier function, stimulates release of fibroblastic growth factors, and remodels the extracellular matrix (ECM). This review will focus on recent work demonstrating how the hexosamine biosynthetic pathway (HBP) links innate inflammation to airway remodeling. The HBP is a core metabolic pathway of the unfolded protein response (UPR) responsible for protein N-glycosylation, relief of proteotoxic stress and secretion of ECM modifiers. We will overview findings that the IκB kinase (IKK)-NFκB pathway directly activates expression of the SNAI-ZEB1 mesenchymal transcription factor module through regulation of the Bromodomain Containing Protein 4 (BRD4) chromatin modifier. BRD4 mediates transcriptional elongation of SNAI1-ZEB as well as enhancing chromatin accessibility and transcription of fibroblast growth factors, ECM and matrix metalloproteinases (MMPs). In addition, recent exciting findings that IKK cross-talks with the UPR by controlling phosphorylation and nuclear translocation of the autoregulatory XBP1s transcription factor are presented. HBP is required for N glycosylation and secretion of ECM components that play an important signaling role in airway remodeling. This interplay between innate inflammation, metabolic reprogramming and lower airway plasticity expands a population of subepithelial myofibroblasts by secreting fibroblastic growth factors, producing changes in ECM tensile strength, and fibroblast stimulation by MMP binding. Through these actions on myofibroblasts, EMP in lower airway cells produces expansion of the lamina reticularis and promotes airway remodeling. In this manner, metabolic reprogramming by the HBP mediates environmental insult-induced inflammation with remodeling in chronic airway diseases.

Effects of Bedding Material on Equine Lower Airway Inflammation: A Comparison of Two Peat Beddings, Wood Pellet, and Straw Pellet

The effects of bedding material on air quality are important amongst horses worldwide. Respiratory diseases, especially equine asthma, are highly prevalent with air hygiene playing a major role on the pathophysiology of these diseases. The objective of our study was to investigate the effects of four bedding materials on the respiratory signs, tracheal mucus score, and tracheal wash (TW) and bronchoalveolar lavage fluid (BALF) cytology in healthy adult horses. The study design was a prospective controlled cross-over study, and the subjects were healthy adult riding school horses (n = 32) from a single stable. Wood pellet, straw pellet, and loosely stored peat (Peat 3) were compared to peat packed in plastic-covered bales (Peat 2). Lower airway endoscopy and sampling (TW and BALF) for cytological examination were performed after each 35-day bedding period. The tracheal mucus scores (P = 0.014) and respiratory rate (P = 0.026) were higher during the straw pellet period compared to the Peat 2 period. The respiratory rate was lower during the wood pellet period compared to the Peat 2 period (P = 0.004). The TW neutrophil percentage during the straw pellet period was higher compared to the Peat 2 period (P = 0.0003). The BALF neutrophil percentage was higher during the straw pellet period (P = 0.005) and during the Peat 3 period compared to the Peat 2 period (P = 0.04). We conclude that baled peat (Peat 2) caused lower neutrophil percentages in the airway samples compared to straw pellet and loosely stored peat (Peat 3). No difference was observed between Peat 2 and wood pellet. The information gained from this study may assist veterinarians and horse owners in selecting appropriate bedding materials, especially for horses with equine asthma.

Clinical Implications of Airway Anomalies and Stenosis in Patients with Heterotaxy Syndrome

In heterotaxy syndrome, bronchopulmonary situs usually reflects atrial situs, resulting in either right (RAI) or left atrial isomerism (LAI). This study determines airway anomalies and its implications in patients with heterotaxy. This retrospective study included 223 patients with heterotaxy syndrome who received an integrated cardiac computed tomography evaluation. Patient database from 1995 to 2020 was reviewed. The patients were examined by a congenital heart disease team comprising pediatric cardiologists, radiologists, pulmonologists, and cardiovascular surgeons. Among the 223 patients, 189 (84.8%, M/F=1.66) had RAI and 29 had LAI (13.0%, M/F=0.71). Five patients had indeterminate isomerism (2.2%, M/F=1.5). Discordant bronchopulmonary and atrial situs occurred in 4% patients, while discordant bronchopulmonary, atrial, and splenic situs occurred in 23.2% patients. Lower airway stenosis was observed in 61 patients (27.4%), including 27.5%, 20.7%, and 60% RAI, LAI, and indeterminate isomerism patients, respectively (p=0.189). One patient had an intrinsic long segment lower tracheal stenosis and received slide tracheoplasty. Initial cardiac operation was performed in 213 patients. Higher surgical mortality occurred in patients with RAI (19.5% vs. none for LAI and indeterminate isomerism, p=0.038). In patients with RAI, lower airway anomaly/stenosis increased the duration of ventilator usage (p=0.030) but did not affect surgical mortality. Total anomalous pulmonary venous return to systemic veins and pulmonary venous stenosis were major surgical risk factors. Bronchopulmonary isomerism shares a similar isomeric pattern to cardiac atrial appendage. Lower airway anomalies/stenosis was common in patients with heterotaxy, resulting in prolonged ventilator therapy in patients with RAI.

Mechanical ventilation affects the microecology of the rat respiratory tract

Background: The most common 'second strike' in mechanically ventilated patients is a pulmonary infection caused by the ease with which bacteria can invade and colonize the lungs due to mechanical ventilation. At the same time, metastasis of lower airway microbiota may have significant implications in the development of intubation mechanical ventilation lung inflammation. Thus, we establish a rat model of tracheal intubation with mechanical ventilation and explore the effects of mechanical ventilation on lung injury and microbiological changes in rats. Methods: Sprague-Dawley rats were randomized into control, Spontaneously Breathing (1, 3, 6 hours), Mechanical ventilation(1, 3, 6 hours) groups. Lung wet to dry weight ratio (W/D weight ratio) and Lung histopathological injury score were evaluated.16SrDNA sequencing was performed to explore respiratory flora changes. Results: Bacterial diversity was comparable between healthy and intubation mechanical ventilation rats, with time relation. Ordination analyses revealed that samples clustered more dispersing by tracheal intubation and mechanical ventilation. Finally, predicted metagenomes suggested a substantial increase in biofilm formation phenotype during early tracheal intubation and mechanical ventilation. Conclusion: Collectively, these results establish a link between the duration of mechanical ventilation and alterations to the respiratory tract microecology. In future studies, we hope to discover the effectiveness of new immunomodulatory or probiotic bacteria to prevent airway diseases associated with ventilator therapy.

Diagnostic Accuracy of Nasopharyngeal Swab Cultures in Children Less Than Five Years with Chronic Wet Cough

Background: It is necessary to find a non-invasive and accurate procedure to predict persistent bacterial bronchitis (PBB) causative organisms and guide antibiotic therapy. The study objective was to compare the diagnostic accuracy of nasopharyngeal swab cultures with bronchoalveolar lavage (BAL) cultures in children with PBB. Methods: Nasopharyngeal swab and BAL fluid specimens were collected and cultured for bacterial pathogens prospectively from less than five-year-old children undergoing flexible bronchoscopy for chronic wet cough. Results: Of the 59 children included in the study, 26 (44.1%) patients had a positive BAL bacterial culture with neutrophilic inflammation. Prevalence of positive cultures for any of the four common respiratory pathogens implicated in PBB (Moraxella catarrhalis, Streptococcus pneumoniae, Staphylococcus aureus, and Haemophilus influenzae) was significantly higher (p = 0.001) in NP swabs compared to BAL fluids (86.4% and 44.1% of PBB cases, respectively). NP swab cultures for any of the four main bacterial pathogens had 85% (95% CI: 65–96%) and 48% (95% CI: 31–66%) sensitivity and specificity of detecting PBB, respectively. Positive and negative predictive values were 56% (95% CI: 47–65%) and 80% (95% CI: 60–91%), respectively. In conclusion, in children less than 5 years of age with chronic wet cough (PBB-clinical), a negative NP swab result reduces the likelihood of lower airway infection; however, a positive NP swab does not accurately predict the presence of lower airway pathogens. Flexible bronchoscopy should be considered in those with recurrent PBB-clinical or with clinical pointers of central airway anomalies.