Transcriptomics reveals shared immunosuppressive landscapes in ventilator-associated lower respiratory tract infections (VA-LRTI) patients.

BACKGROUND: Ventilator-associated pneumonia (VAP) represents a transitory status of immunoparalysis, and we hypothesized that ventilator-associated tracheobronchitis (VAT) could share also some degree of immune response to a respiratory infection. RESEARCH DESIGN AND METHODS: A prospective observational study in five medical ICUs to evaluate immunological alterations of patients with VA-LRTI. Immunological gene expression profiles in the blood using whole transcriptome microarrays in the first 24 hours following diagnosis. The area under the receiver operating characteristic curve (AUROC) was used to assess the accuracy of mRNA levels to differentiate VA-LRTI and lack of infection. A principal component analysis (PCA) was employed for analyzing the impact of each genetic expression footprint variable in explaining the variance of the cohort. RESULTS: There was overlapping between the three classes of patients encompassing gene expression levels of 8 genes (i.e. HLA, IL2RA, CD40LG, ICOS, CCR7, CD1C, CD3E). HLA-DRA was equally low among VAT and VAP patients characterizing immune depression, and significantly lower than the control group. CONCLUSIONS: Our findings suggest that VAP and VAT are not so different regarding gene expression levels suggesting a degree of immunosuppression. Our results indicate a state of immunoparalysis in respiratory infections in critically ill patients.

Improving management of ventilator associated tracheitis in a level IV NICU.

BACKGROUND: There are no published guidelines regarding the diagnosis and treatment of ventilator-associated tracheitis (VAT) in the neonatal intensive care unit (NICU). VAT is likely over-diagnosed and over-treated, increasing antibiotic burden and cost. LOCAL PROBLEM: Diagnosis and treatment of VAT were entirely NICU provider dependent. METHODS: Retrospective pre- and post-intervention chart reviews were performed. INTERVENTIONS: A VAT diagnosis and treatment algorithm was created for use in the care of intubated patients without tracheostomies. 3 plan-do-study-act (PDSA) cycles were used to implement change. RESULTS: Intubated patients treated for VAT with <25 PMNs on Gram stain decreased from 79% to 35% following the quality improvement (QI) initiative. Treatment of VAT with >7 days of antibiotic therapy decreased from 42% to 10%. CONCLUSION: Implementing a QI initiative to improve the diagnosis and treatment of VAT in the NICU decreased the percent of patients treated inappropriately for VAT.

Next-Generation Sequencing as an Auxiliary Tool in Pediatric Laryngeal Lymphoma Diagnosis.

Lymphomatous involvement of the larynx is a rare entity. We present a case of atypical laryngotracheitis as the initial manifestation of non-Hodgkin's lymphoma in a pediatric patient. The diagnosis was aided through the use of microbial cell-free DNA (mcfDNA) testing, which detected the presence of Epstein-Barr virus in the patient's plasma. This enabled the consideration of an Epstein-Barr virus-related lymphoproliferative process, leading to additional workup and the final diagnosis of lymphoma. To our knowledge, this is the first case of mcfDNA testing leading not simply to an infectious organism, but further to a new oncologic diagnosis. Plasma mcfDNA testing has the potential to inform clinical practice beyond classic infectious disease manifestations. In this article, we review both the possible future applications and the areas of further investigation that remain.

Ear, Nose, Throat: Beyond Pharyngitis: Retropharyngeal Abscess, Peritonsillar Abscess, Epiglottitis, Bacterial Tracheitis, and Postoperative Tonsillectomy.

Ear, nose, and throat (ENT) emergencies presenting with a chief complaint of pharyngitis can be due to infection, trauma, or postprocedure complications. The entities described in this article include retropharyngeal abscess, peritonsillar abscess, epiglottitis, bacterial tracheitis, and post-tonsillectomy bleeding. This article provides the emergency physician with the tools needed to decipher between the mundane and the critical, variations in presentation, and their emergent management. All of them require early recognition for any airway compromise or obstruction in order to avoid serious complications.

Demographic Characteristics of Children Diagnosed with Bacterial Tracheitis.

OBJECTIVES: Examine the presentation and clinical course of patients with bacterial tracheitis (BT). Identify if socioeconomic differences exist among children who present with BT. METHODS: This was a retrospective case series from a tertiary care pediatric medical center. The study group included patients less than 18 years old who were diagnosed with BT from January 2011 to March 2019. Patients with a tracheostomy and those who developed BT after prolonged hospitalization were excluded. Patient demographics were compared with the demographics of the counties surrounding the hospital. RESULTS: 33 patients with BT met inclusion criteria. The most common presenting symptoms were difficulty breathing, stridor, and sore throat (81.8% each), followed by cough (78.8%). Median length of stay was 3 days [interquartile range (IQR):2-4]. 19 patients (57.5%) were admitted to the intensive care unit. Intubation was required for 13 patients (39.4%), for a median length of 2 days [IQR:2-2]. Methicillin sensitive staphylococcus aureus was the most common bacterial etiology (33%). Mean presenting age was 8.58 years [95% confidence interval:7.3-9.9] and 14 patients were female (42.4%). 31 patients were white (93.9%), 1 was black (3%), and 1 was Hispanic (3%). BT patients were more likely to have private insurance compared to comparison (81.8% vs 63.4%, P < .001). CONCLUSION: Children who presented with BT were more likely to be privately insured than a comparison population.

Genotypic and Phenotypic Characterization of Staphylococcus aureus Isolates from the Respiratory Tract in Mechanically-Ventilated Patients.

Staphylococcus aureus is a commensal and frequent colonizer of the upper respiratory tract. When mechanical ventilation disrupts natural defenses, S. aureus is frequently isolated from the lower airways, but distinguishing between colonization and infection is difficult. The objectives of this study were (1) to investigate the bacterial genome sequence in consecutive isolates in order to identify changes related to the pathological adaptation to the lower respiratory tract and (2) to explore the relationship between specific phenotypic and genotypic features with the patient's study group, persistence of the clinical isolate and clinical outcome. A set of 94 clinical isolates were selected and corresponded to 34 patients that were classified as having pneumonia (10), tracheobronchitis (11) and bronchial colonization (13). Clinical strains were phenotypically characterized by conventional identification and susceptibility testing methods. Isolates underwent whole genome sequencing using Illumina HiSeq4000. Genotypic characterization was performed with an in-house pipeline (BacterialTyper). Genomic variation arising within-host was determined by comparing mapped sequences and de novo assemblies. Virulence factors important in staphylococcal colonization and infection were characterized using previously established functional assays. (1) Toxin production was assessed using a THP-1 cytotoxicity assay, which reports on the gross cytotoxicity of individual isolates. In addition, we investigated the expression of the major virulence factor, alpha-toxin (Hla) by Western blot. (2) Adhesion to the important extracellular matrix molecule, fibronectin, was determined using a standardized microtitre plate assay. Finally, invasion experiments using THP-1 and A539 cell lines and selected clinical strains were also performed. Repeated isolation of S. aureus from endotracheal aspirate usually reflects persistence of the same strain. Within-host variation is detectable in this setting, but it shows no evidence of pathological adaptation related to virulence, resistance or niche adaptations. Cytotoxicity was variable among isolates with 14 strains showing no cytotoxicity, with these latter presenting an unaltered Fn binding capacity. No changes on cytotoxicity were reported when comparing study groups. Fn binding capacity was reported for almost all strains, with the exception of two strains that presented the lowest values. Strains isolated from patients with pneumonia presented a lower capacity of adhesion in comparison to those isolated during tracheobronchitis (p = 0.002). Hla was detected in 71 strains (75.5%), with most of the producer strains in pneumonia and bronchial colonization group (p = 0.06). In our cohort, Hla expression (presence or absence) in sequential isolates was usually preserved (70%) although in seven cases the expression varied over time. No relationship was found between low cytotoxicity and intracellular persistence in invasion experiments. In our study population, persistent S. aureus isolation from airways in ventilated patients does not reflect pathological adaptation. There is an important diversity of sequence types. Cytotoxicity is variable among strains, but no association with study groups was found, whereas isolates from patients with pneumonia had lower adhesion capability. Favorable clinical outcome correlated with increased bacterial adhesion in vitro. Most of the strains isolated from the lower airways were Hla producers and no correlation with an adverse outcome was reported. The identification of microbial factors that contribute to virulence is relevant to optimize patient management during lower respiratory tract infections.

Usefulness of Sepsis-3 in diagnosing and predicting mortality of ventilator-associated lower respiratory tract infections.

BACKGROUND: Early distinguishing ventilator-associated tracheobronchitis (VAT) and ventilator-associated pneumonia (VAP) remains difficult in the daily practice. However, this question appears clinically relevant, as treatments of VAT and VAP currently differ. In this study, we assessed the accuracy of sepsis criteria according to the Sepsis-3 definition in the early distinction between VAT and VAP. METHODS: Retrospective single-center cohort, including all consecutive patients with a diagnosis of VAT (n = 70) or VAP (n = 136), during a 2-year period. Accuracy of sepsis criteria according to Sepsis-3, total SOFA and respiratory SOFA, calculated at time of microbiological sampling were assessed in differentiating VAT from VAP, and in predicting mortality on ICU discharge. RESULTS: Sensitivity and specificity of sepsis criteria were found respectively at 0.4 and 0.91 to distinguish VAT from VAP, and at 0.38 and 0.75 for the prediction of mortality in VA-LRTI. A total SOFA ≥ 6 and a respiratory SOFA ≥ 3 were identified as the best cut-offs for these criteria in differentiating VAT from VAP, with sensitivity and specificity respectively found at 0.63 and 0.69 for total SOFA, and at 0.49 and 0.7 for respiratory SOFA. Additionally, for prediction of mortality, a total SOFA ≥ 7 and a respiratory SOFA = 4 were identified as the best-cut-offs, respectively yielding sensitivity and specificity at 0.56 and 0.61 for total SOFA, and at 0.22 and 0.95 for respiratory SOFA. CONCLUSIONS: Sepsis criteria according to the Sepsis-3 definition show a high specificity but a low sensitivity for the diagnosis of VAP. Our results do not support the use of these criteria for the early diagnosis of VAP in patients with VA-LRTI.

A Curious Case of Croup: Laryngotracheitis Caused by COVID-19.

We describe a case of croup in a 14-month-old boy caused by severe acute respiratory syndrome coronavirus 2, the virus that causes coronavirus disease 2019. The patient presented with classic signs and symptoms consistent with croup. Workup was remarkable for a positive point-of-care test for severe acute respiratory syndrome coronavirus 2. This case represents recognition of a new clinical entity caused by coronavirus disease 2019.

Pseudomembranous Tracheobronchitis With Severe Tracheal Stenosis and Masked Bronchial Obstruction.

BACKGROUND: Pseudomembranous tracheobronchitis (PMTB) is a rare condition characterized by the formation of endobronchial pseudomembranes. PMTB overlaps with necrotizing tracheobronchitis or plastic bronchitis. The reported infectious etiology mainly includes invasive aspergillosis. PMTB can cause serious airway obstruction; however, urgent tracheotomy is rarely required. CASE REPORT: A 46-year-old woman was transferred to the emergency department (ED) with a 1-week history of progressive dyspnea and cough that was preceded by fever and sore throat. She was previously healthy except for a 20-year history of mild palmoplantar pustulosis. Stridor was evident. Nasolaryngoscopy performed in the ED revealed severe tracheal stenosis caused primarily by mucosal edema and secondarily by pseudomembranes. Initially, tracheitis was considered the sole cause of dyspnea. Although she underwent urgent tracheotomy to prevent asphyxia, her respiration deteriorated progressively. Bronchoscopy revealed massive pseudomembranes obstructing the bilateral bronchi, which led to the clinical diagnosis of PMTB. Subsequent toilet bronchoscopy markedly improved her ventilation. The causative pathogen was not identified despite extensive work-up, including molecular biological testing. Histopathologic examination of the pseudomembranes revealed fibrin with abundant neutrophils, which was consistent with PMTB. Associated conditions, including immunodeficiency, were not found. Her condition improved with antibiotics and repeated toilet bronchoscopy. WHY SHOULD AN EMERGENCY PHYSICIANS BE AWARE OF THIS?: PMTB is an important differential diagnosis of airway emergencies. PMTB can present with critical edematous tracheal stenosis and masked bronchial pseudomembranous obstruction. Emergency physicians should include PMTB in the differential diagnosis in adult patients with acute central airway obstruction because it requires prompt multimodal treatment.

Caracterización de las infecciones en niños portadores de cánula de traqueotomía: revisión sistemática de la literatura / Characterization of infections in children with Tracheostomy Tube: A Systematic Review of the Literature

Resumen Introducción: actualmente los profesionales de la salud se enfrentan al manejo de las vías aéreas artificiales en grupos pediátricos, esto requiere de cuidados delicados y mucha atención para detectar, establecer y manejar situaciones apremiantes; por esta razón, existe un mayor riesgo de aparición de infecciones bacterianas traqueopulmonares. El objetivo del estudio fue analizar la caracterización de las infecciones en pacientes pediátricos portadores de cánula de traqueotomía en las diferentes publicaciones científicas. Materiales y métodos: se realizó una revisión sistemática mediante la búsqueda de la literatura existente entre los años 2015-2020 en las bases de datos Elsevier, PubMed, Google Académico y SciELO, teniendo en cuenta los criterios de inclusión artículos en idioma inglés, español y población de edad entre los 0-15 años con infección de cánula de traqueotomía en los años 2015-2020. Resultados: de 258 artículos distribuidos en las bases de datos, se seleccionaron 21 artículos que cumplían con los criterios de inclusión. Conclusiones: a pesar de que en la actualidad existan criterios clínicos, factores de riesgo y pruebas de laboratorio asociados a infecciones de la cánula postraqueotomía en pacientes pediátricos, se requiere mayor investigación para definir las guías clínicas de manejo en la toma de decisiones médicas. Asimismo, se consideró como limitación importante la cantidad de literatura existente con respecto al tema.

Abstract Introduction: Currently, health professionals face the management of artificial airways in pediatric groups, this requires delicate care and a lot of attention to detect, establish and manage pressing situations, which is why there is a greater risk of tracheo-pulmonary bacterial infections. The objective was to analyze the characterization of infections in pediatric patients with tracheostomy tubes in the different scientific publications. Method: A systematic review of the literature was carried out between the years 2015-2020 in Elsevier, PubMed, Google Academic and SciELO databases, taking into account the inclusion criteria of the population aged 0-15 years in the years 2015-2020. The amount of existing literature on the subject was considered an important limitation. Results: From 258 articles distributed in the databases, 21 articles were selected that met the inclusion criteria. Conclusions: Although there are currently clinical criteria, risk factors and laboratory tests associated with infections of the post-tracheotomy tube in pediatric patients, further research is required to define clinical guidelines for management in medical decision-making.

Pediatric Emergency Medicine Simulation Curriculum: Bacterial Tracheitis.

Introduction: Pediatric bacterial tracheitis is a rare but life-threatening upper airway infection with mortality rates estimated as high as 20%, typically affecting children between 6 months and 12 years old. Given such high mortality rates, we felt it was important to train medical personnel to evaluate and manage this condition. Methods: This simulation-based curriculum was developed for health care professionals involving the evaluation and management of an 8-year-old male with symptoms of fever, stridor, worsening barking cough, and increased work of breathing. Critical actions included identifying stridor and airway respiratory distress; monitoring and supporting airway, breathing, and circulation; administering racemic epinephrine and dexamethasone; and identifying and treating bacterial tracheitis as the underlying cause. Scenario-specific debriefing tools were put together to elicit scenario feedback and aid in formative learning. Results: The scenario was conducted with six fellows and 12 residents and medical students. Per the survey data, the case was rated as highly relevant (median = 5) and highly realistic (median = 5) by participants on a 5-point Likert scale. Discussion: Pediatric bacterial tracheitis is a low frequency, but high-risk scenario that was amenable to simulation as an educational modality and was well-received by participants. The debriefing tools were implemented as a means of helping instructors customize the scenario for learners based on respective educational backgrounds and learning styles.

Appearance and management of COVID-19 laryngo-tracheitis: two case reports.

We present two cases of coronavirus disease 2019 (COVID-19)-related laryngotracheitis in good-prognosis, ventilated patients who had failed extubation. As the pandemic continues to unfold across the globe and better management of those with respiratory failure develops, this may be an increasingly common scenario. Close ENT-intensivist liaison, meticulous team preparation, early consideration of rigid endoscopy and prospective data collection and case sharing are recommended.

Significance of positive tracheal cultures in the 30 days following tracheostomy.

INTRODUCTION: Positive tracheal cultures obtained after tracheostomy are often considered organ/space surgical site infections by the National Surgical Quality Improvement Project. However, the definition of bacterial tracheitis after tracheostomy is not well described. OBJECTIVE: To determine the relationship of positive tracheal cultures in the 30 days following pediatric tracheostomy, antibiotic treatment of these cultures, and signs/symptoms of respiratory infection. METHODS: A retrospective chart review was performed on subjects who underwent tracheostomy from November 2012-September 2017 at a tertiary care pediatric center. The following data was studied: positive tracheal cultures, antibiotic treatment for positive cultures, and other signs/symptoms of infection including fever and elevated white blood cell count. Descriptive data analysis was performed, and relative risk and 95% confidence intervals were calculated. Multivariate logistic regression model was used to assess independent association when applicable. RESULTS: There were 173 subjects who met study criteria. Median age at tracheostomy was 4.6 months. Fifty-one percent (89/173) of subjects had at least one positive tracheal culture in the 30 days following tracheostomy. Of those subjects, 38% (34/89) had fever, 71% (32/45) had an elevated white blood cell count, 31% (22/72) had consolidation on chest imaging, 61% (54/89) had increased tracheal secretions, 70% (62/89) had increased ventilation requirements, and 60% (53/89) were treated with antibiotics for a diagnosis of tracheitis. There was no meaningful difference when comparing fever, increased white blood cell count, lung consolidation, increased tracheal secretions, or increased ventilation requirements in those with and without a positive tracheal culture or in those with and without antibiotic treatment for a positive culture. Multivariate logistic regression analysis showed that increased age at time of tracheostomy, more days on the ventilator after tracheostomy, and an increased number of positive cultures in the year after tracheostomy were related to having a positive tracheal culture within 30 days of tracheostomy. CONCLUSION: For post-operative pediatric tracheostomy subjects, there were no meaningful differences when comparing signs/symptoms of infection between those with and without a positive tracheal culture and between those with and without antibiotic treatment for a positive culture.

Acute pediatric tracheitis: Distinguishing the disease by tracheostomy status.

OBJECTIVES: Tracheitis is an upper airway infection that often presents in patients with tracheostomies and can potentially cause airway obstruction. This study aims to use a nationwide database to identify a large cohort of pediatric patients admitted with tracheitis to elucidate the management and resource utilization associated with the disease both with and without tracheostomies. METHODS: The Kids' Inpatient Database (KID) 2012 was used to identify 2394 weighted discharges with acute tracheitis, with or without obstruction, as the primary diagnosis. Data on prior tracheostomy status, demographics, hospital characteristics, management, and resource utilization were obtained. Two groups of interest, based on presence of prior tracheostomy, were studied. Linear regression was performed to determine independent predictors of total charges. RESULTS: The mean age was 5.52 years (SD: 5.54), mean length of stay (LOS) was 6.37 days (SD: 10.18), and mean total charges were $60,996.61 (SD: 107,798.41). Patients with prior tracheostomy had lower rates of endoscopy and endotracheal intubation than patients without (p < 0.0005). There was no significant difference in LOS (p = 0.076) or total charges (p = 0.210) between the groups based on prior tracheostomy status. CONCLUSION: Pediatric tracheitis should be differentiated on the basis of tracheostomy status. We propose that tracheitis diagnosis codes should be distinguished by the presence of tracheostomy as "open" and the absence of tracheostomy as "closed."

Analysis of the Clinical Features of Tracheobronchial Fungal Infections with Tumor-Like Lesions.

BACKGROUND: Tracheobronchial fungal infections (TBFI) cause life-threatening complications in immunocompromised hosts but are rarely reported. Misdiagnosis and delayed antifungal treatment are associated with the high mortality rate of patients with TBFI. OBJECTIVES: This study analyzed the bronchoscopic features of TBFI and their roles in the early diagnosis of TBFI. METHODS: The demographic, clinical, radiologic, and bronchoscopic data of 53 patients diagnosed with TBFI in our department during a 15-year period were retrospectively analyzed. RESULTS: Most of the TBFI patients were male, and mass was the most common radiologic abnormality. Obvious predilection in primary bronchus distributions was observed. 41.9% of the 43 Aspergillus tracheobronchitis (AT) patients, 70% of the 10 tracheobronchial mucormycosis (TM) patients, and 100% of the 3 endobronchial cryptococcosis patients had been misdiagnosed as having cancer on bronchoscopy because of the presence of tumor-like lesions. The most common features of AT were bronchial occlusion with a mass or mucosal necrosis, bronchial stenosis with mucosal hyperplasia, or uneven mucosa. The main descriptions of TM were bronchial stenosis or obstruction due to mucosal necrosis, uneven mucosa, or a mass. The endoscopic characteristics of endobronchial cryptococcosis included occlusion due to uneven mucosa or mass, or external compressive stricture. CONCLUSION: Immunocompromised patients and immunocompetent patients with underlying disease displaying tumor-like lesions on bronchoscopy should be differentially diagnosed with cancer. Bronchial biopsy is indispensable for the early diagnosis of TBFI.