COVID-19-associated Aspergillus tracheobronchitis: the interplay between viral tropism, host defence, and fungal invasion.

Invasive pulmonary aspergillosis is emerging as a secondary infection in patients with COVID-19, which can present as alveolar disease, airway disease (ie, invasive Aspergillus tracheobronchitis), or both. Histopathology of invasive Aspergillus tracheobronchitis in patients with severe COVID-19 confirms tracheal ulcers with tissue invasion of Aspergillus hyphae but without angioinvasion, which differs from patients with severe influenza, where early angioinvasion is observed. We argue that aggregation of predisposing factors (eg, factors that are defined by the European Organisation for Research and Treatment of Cancer and Mycoses Study Group Education and Research Consortium or genetic polymorphisms), viral factors (eg, tropism and lytic effects), immune defence factors, and effects of concomitant therapies will determine whether and when the angioinvasion threshold is reached. Management of invasive Aspergillus tracheobronchitis should include reducing viral lytic effects, rebalancing immune dysregulation, and systemic and local antifungal therapy. Future study designs should involve approaches that aim to develop improved diagnostics for tissue invasion and airways involvement and identify the immune status of the patient to guide personalised immunotherapy.

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.

The alterations of tracheal microbiota and inflammation caused by different levels of ammonia exposure in broiler chickens.

Ammonia (NH3) is a known harmful gas and exists in haze, forming secondary organic aerosols. Exposure to ambient ammonia correlates with the respiratory tract infection, and microbiota in the upper respiratory tract is an emerging crucial player in the homeostatic regulation of respiratory tract infection, and microbiota perturbation is usually accompanied by the inflammatory reactions; however, the effects of different levels of ammonia exposure on tracheal microbiota and inflammation are unclear. A total of 288 22-day-old male Arbor Acres broilers were chosen and divided into 4 groups with 6 replicates of 12 chickens, and respectively exposed to ammonia at 0, 15, 25, and 35 ppm for 21-d trial period. Cytokines (interleukin (IL)-1ß, IL-6, and IL-10) in the trachea were measured at the 21 d of exposure to NH3. Tracheal microbiota at the 21 d was analyzed by the 16S rRNA gene analysis. The results showed that an increase in ammonia levels, even in 15 ppm, significantly decreased the alpha diversity and changed the bacterial community structure. Six genera (Faecalibacterium, Ruminococcus]_torques_group, unclassified_f__Lachnospiraceae, Ruminococcaceae_UCG-014, Streptococcus, Blautia) significantly increased, whereas Lactobacillus significantly decreased under different levels of ammonia exposure. We also observed positive associations of Faecalibacterium, Blautia, g__Ruminococcaceae_UCG-014, unclassified_f__Lachnospiraceae and Ruminococcus]_torques_group abundances with tracheal IL-1ß concentration. Moreover, an increase in ammonia levels, even in 15 ppm, caused respiratory tract inflammatory injury. The results indicated that 15 ppm ammonia exposure changed the composition of tracheal microbiota that caused the tracheal injury possibly through increasing the IL-1ß, which might make the broiler more sensitive to the changes of environment and pathogenic micro-organisms in the poultry house, and may be also a critical value that needs high alertness. Herein, the present experiment also suggested that the standard limit of ammonia concentration in adult poultry house is 15 ppm. This research provides an insight into the relationship between the upper respiratory tract microbiota and inflammation under ammonia exposure.

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.

Clinical characteristics and treatment outcome of Candida tracheobronchitis.

ABSTRACT: Although Candida species can cause invasive fungal diseases, such as disseminated infection and pneumonia, they rarely cause tracheobronchitis, which is often fatal.To identify the clinical characteristics of Candida tracheobronchitis, we retrospectively evaluated 8 patients who had pathologically proven Candida tracheobronchitis.Their median age was 64 (range: 51-70) years and 5 were females. Three patients had solid cancers and 5 had hematological malignancies. We classified tracheobronchitis into localized and diffuse types. Of the 8 patients, 5 had localized and 3 had diffuse tracheobronchitis. While all patients with diffuse tracheobronchitis had predisposing risk factors for invasive fungal disease, such as prolonged corticosteroid use, recent use of nucleoside analogues, or recent neutropenia (<500/m3), only 2 of the 5 with localized tracheobronchitis had predisposing risk factors. Four of the 5 patients with localized tracheobronchitis had loco-regional bronchial mucosal damage (e.g., radiation or photodynamic therapy). Although all 8 patients ultimately died, some improved with or without antifungal treatment. Two of the 5 patients (1 with localized and the other with diffuse tracheobronchitis) who received antifungal agents improved after treatment, and 1 patient with localized tracheobronchitis who did not receive antifungal treatment improved spontaneously. Two of the 3 patients with diffuse tracheobronchitis did not respond to antifungal treatment.Candida tracheobronchitis can present as both localized and diffuse types. While the former was influenced more by loco-regional mucosal damage, the latter was influenced more by the patient's immune status. The treatment outcomes were especially poor in patients with diffuse tracheobronchitis.

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.

Fulminant Tracheobronchial Aspergillosis in an Apparently Healthy Adult.

A 56-year-old healthy man who was a current smoker died from fulminant tracheobronchial aspergillosis despite a month of treatment with a combination of intravenous anti-fungal agents that had been started immediately after the diagnosis. This case report is important for understanding and managing fulminant Aspergillus infections in healthy subjects, although the pathogenesis and underlying pathways are still unknown.

Invasive Aspergillus tracheobronchitis in a patient with hairy cell leukemia and previous Plasmodium falciparum infection.

Invasive Aspergillus tracheobronchitis is a relatively rare form of invasive pulmonary aspergillosis characterized by invasion of the tracheobronchial tree by Aspergillus spp. Invasive pulmonary aspergillosis is predominantly detected in severely immunocompromised patients. Notably however, pulmonary and tracheobronchial cases of invasive aspergillosis have also been reported, particularly in the context of severe malaria caused by Plasmodium falciparum. Herein, we present a case of invasive Aspergillus tracheobronchitis in a patient with hairy cell leukemia and previous Plasmodium falciparum infection.

Traqueobronquitis obstructiva por Aspergillus fumigatus en un paciente inmunocompetente / Obstructive tracheobronchitis due to Aspergillus fumigatus in an immunocompetent patient

Antecedentes: La traqueobronquitis aspergilar (TBA) es una forma clínica infrecuente de aspergilosis pulmonar invasiva donde la afectación fúngica se limita al árbol traqueobronquial. Aunque las formas más graves, como la TBA pseudomembranosa y ulcerativa, son casi exclusivas de pacientes inmunocomprometidos, la forma obstructiva, más leve, puede cursar en pacientes sin déficit inmunitario. Caso clínico: Se presenta el caso de un varón de 32 años sin antecedentes de interés que es evaluado por presentar neumonía recidivante del lóbulo inferior derecho. En los estudios microbiológicos del esputo destacaba el crecimiento de Serratia marcescens y escaso crecimiento de Aspergillus fumigatus, que se interpretó como una contaminación de la muestra. La fibrobroncoscopia reveló al nivel B10 del lóbulo inferior derecho un tapón mucoso muy denso que no se pudo extraer; no hubo otros hallazgos macroscópicos de interés. Durante la hospitalización el paciente logró expectorar el tapón mucoso y presentó una importante broncorrea posterior; en los cultivos microbiológicos se observaron numerosas colonias de A. fumigatus. Se indicó tratamiento con voriconazol, lo que llevó a la resolución del cuadro, sin nuevas recidivas. Conclusiones: La TBA obstructiva se caracteriza por la producción excesiva de moco denso cargado de hifas que puede llegar a obstruir la luz de la vía aérea y generar neumonías postobstructivas recidivantes. Es importante considerar este diagnóstico en pacientes inmunocompetentes con infecciones respiratorias recurrentes que presentan aislamiento repetido de colonias de Aspergillus en el esputo, aunque sean en escasa cuantía

Background: Aspergillus tracheobronchitis (ATB) is an uncommon type of invasive pulmonary aspergillosis in which fungal involvement is limited to the tracheobronchial tree. While the more severe forms, such as pseudomembranous and ulcerative ATB, occur almost exclusively in immunocompromised patients, the milder obstructive form may occur in patients without immune deficiency. Case report: The case of a 32 year-old man with no previous history of illness, who was evaluated for recurrent right lower lobe pneumonia, is presented. Microbiological sputum studies revealed growth of Serratia marcescens, and a limited growth of Aspergillus fumigatus, the latter interpreted as a contaminant in the specimen. Bronchoscopy revealed a dense mucous plug at level B10 of the right lower lobe, which could not be removed; no other macroscopic findings of interest were observed. During his hospital admission, the patient expectorated the mucous plug and had a significant subsequent bronchorrhoea. A substantial number of colonies of A. fumigatus grown in the sputum cultures. The patient was given voriconazole, leading to a clinical resolution, with no recurrences. Conclusions: Obstructive ATB is characterised by the excessive production of thick, hyphae-laden mucus, which can obstruct the airway lumen and generate relapsing post-obstructive pneumonias. It is important to consider this diagnosis in immunocompetent patients with recurrent respiratory infections and who show repeated isolation of Aspergillus colonies in the sputum, even in small quantities

[Obstructive tracheobronchitis due to Aspergillus fumigatus in an immunocompetent patient]. / Traqueobronquitis obstructiva por Aspergillus fumigatus en un paciente inmunocompetente.

BACKGROUND: Aspergillus tracheobronchitis (ATB) is an uncommon type of invasive pulmonary aspergillosis in which fungal involvement is limited to the tracheobronchial tree. While the more severe forms, such as pseudomembranous and ulcerative ATB, occur almost exclusively in immunocompromised patients, the milder obstructive form may occur in patients without immune deficiency. CASE REPORT: The case of a 32 year-old man with no previous history of illness, who was evaluated for recurrent right lower lobe pneumonia, is presented. Microbiological sputum studies revealed growth of Serratia marcescens, and a limited growth of Aspergillus fumigatus, the latter interpreted as a contaminant in the specimen. Bronchoscopy revealed a dense mucous plug at level B10 of the right lower lobe, which could not be removed; no other macroscopic findings of interest were observed. During his hospital admission, the patient expectorated the mucous plug and had a significant subsequent bronchorrhoea. A substantial number of colonies of A. fumigatus grown in the sputum cultures. The patient was given voriconazole, leading to a clinical resolution, with no recurrences. CONCLUSIONS: Obstructive ATB is characterised by the excessive production of thick, hyphae-laden mucus, which can obstruct the airway lumen and generate relapsing post-obstructive pneumonias. It is important to consider this diagnosis in immunocompetent patients with recurrent respiratory infections and who show repeated isolation of Aspergillus colonies in the sputum, even in small quantities.

Pediatric Bacterial Tracheitis-A Variable Entity: Case Series with Literature Review.

OBJECTIVE: To review the presentation and treatment of children diagnosed with bacterial tracheitis at our institution and to review the available literature focusing on key presenting symptoms and clinical outcomes of children diagnosed with bacterial tracheitis. STUDY DESIGN: Case series with literature review. SETTING: Tertiary children's hospital and available literature. SUBJECTS AND METHODS: Case series of children with bacterial tracheitis retrospectively reviewed at a tertiary children's hospital. Those with a tracheostomy or those who developed bacterial tracheitis as a complication of prolonged intubation were excluded. RESULTS: Thirty-six children were identified (mean ± SD age, 6.7 ± 4.5 years). The most common presenting symptom was cough (85%), followed by stridor (77%) and voice changes/hoarseness (67%). A concurrent viral illness was found for 55%, and the most common bacteria cultured was methicillin-sensitive Staphylococcus aureus. Pediatric intensive care admission occurred for 69%, and 43% required intubation. No patient required tracheostomy. One patient (2.7%) died secondary to airway obstruction and subsequent respiratory arrest. Four patients had recurrence of bacterial tracheitis 4 to 12 months following their initial presentation. CONCLUSION: Bacterial tracheitis is an uncommon condition with an atypical presentation and variable clinical course but serious consequences if left unrecognized. Staphylococcus is the most common bacteria identified, and many patients will have a prodromal viral illness. Changes in patient epidemiology and presentation may have occurred over time.

The challenges of treating tracheobronchitis in a laryngectomee due to nontypeable Haemophilus influenzae: a case report.

BACKGROUND: Laryngectomees run the risk of developing severe respiratory tract infections especially during the winter and when they do not wear a stoma cover. A case of severe tracheobronchitis in a laryngectomee is presented that illustrates the risks and difficulties encountered in managing this infection in a neck breather. CASE PRESENTATION: A 76-year-old Caucasian man, a laryngectomee, presented with bacterial tracheobronchitis and conjunctivitis due to beta-lactamase-producing nontypeable Haemophilus influenzae. He was febrile (38.9 °C; 102.0 F), and had repeated episodes of hypertension. He was treated with levofloxacin 500 mg/day, ciprofloxacin eye drops, acetaminophen, and guaifenesin. Humidification of his trachea and the airway was sustained by insertions of saline into the stoma as well as breathing humidified air. The main challenge was to maintain the patency of his airway as the mucus was very dry and viscous and tended to stick to the walls of his trachea and the stoma. His condition improved within 7 days and he had a complete recovery. CONCLUSIONS: Maintaining the patency of the airway in laryngectomees who suffer from lower respiratory tract infection is of utmost importance as the mucus can be very dry and viscous and can stick to the walls of the trachea and the stoma.

Occlusive mycotic tracheobronchitis and systemic Alphaherpesvirus coinfection in a free-living striped dolphin Stenella coeruleoalba in Italy.

A juvenile female striped dolphin Stenella coeruleoalba live stranded on 4 March 2016 at Alassio, western Ligurian Sea coast, Italy. The dolphin died shortly after stranding, and a complete postmortem examination was performed. Necropsy revealed severe tracheal occlusion and unilateral bronchial stenosis with luminal accumulation of abundant green-yellow mucous-gelatinous material. Histological features suggestive of tracheobronchial aspergillosis were observed. Cultures of lung tissue and tracheo-bronchial exudate isolated Aspergillus fumigatus, identified by a Microseq D2 LSUrDNA fungal sequencing kit. A pan-Herpesvirus nested-PCR assay on frozen samples obtained from multiple organs was positive. Phylogenetic analysis on the partial DNA polymerase gene revealed that the striped dolphin isolate was closely related to known cetacean Alphaherpesvirus sequences from the same host species. Attempted virus isolation was unsuccessful. The tissue levels of different persistent organic pollutants and the toxicological stress, evaluated using a theoretical model, showed a severely impaired immune response. This study reports the first case of occlusive mycotic tracheobronchitis in a free-living cetacean and the first molecular identification of an Alphaherpesvirus in a free-ranging striped dolphin stranded on the coast of Italy.

Nodular tracheobronchitis in a patient with lymphoma: an unusual presentation of viridans streptococcal respiratory tract infection.

Bacterial tracheobronchitis without lung parenchymal involvement is extremely rare in adults, except in patients who are intubated or mechanically ventilated. We present a case of nodular tracheobronchitis caused by viridans streptococci in a non-ventilated lymphoma patient. To our knowledge, this is the first report of viridans streptococcal infection that has caused nodular tracheobronchitis.

Update on childhood and adult infectious tracheitis.

The trachea is a pivotal organ of the respiratory tract. Rather than a genuine anatomic border, it acts as a crossroad in all respiratory infectious processes. Even though not strictly limited to the trachea, infections such as laryngotracheitis and tracheobronchitis are frequently diagnosed in children, in particular during the winter season. Infectious tracheitis etiologies are diverse and the distinction between viral and bacterial origins, albeit difficult, remains relevant considering the substantial differences in terms of gravity and therapeutic management. This literature review summarizes the microbiological and clinical aspects of community-acquired and nosocomial tracheitis in adults and children, as well as the adequate diagnostic and therapeutic approaches. It also highlights the emergence of fungal tracheitis in immunocompromised patients, of ventilator-associated tracheitis in intensive care medicine, and beyond all that the potential short and long-term consequences of tracheitis.