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.

Protection Efficacy of the Infectious Laryngotracheitis (ILT) Serva CEO Vaccine Strain in Broiler Chickens Under Different Vaccination Coverage Conditions.

Mass vaccination against infectious laryngotracheitis virus (ILTV) in drinking water can result in variable initial vaccine take. Partial initial vaccine coverage of 20% with an Australian ILT vaccine (A20) previously resulted in significant protection against virulent ILTV challenge. This follow-up study used the international Serva ILT vaccine strain in a factorial design testing four levels of vaccination coverage (0%, 10%, 20%, or 100% of chicks eye-drop vaccinated with the live vaccine at 7 days of age) and three levels of ILTV challenge (no challenge or challenge at 7 or 21 days postvaccination [DPV]). The increase in ILTV load in choanal cleft swabs detected by qPCR after challenge was significantly reduced by 20% and 100% but not by 10% vaccination coverage. Vaccination reduced weight gain in unchallenged birds. Daily weight gain of birds was not affected by ILTV challenge at 7 DPV in any group, but following challenge at 21 DPV, it was significantly reduced in unvaccinated and 10% vaccinated groups relative to 20% and 100% vaccinated groups. Vaccination of 20% of the chickens provided substantial but incomplete protection (protective index range 44%-70%) against the severity of clinical signs and mortality following challenge while 10% vaccination coverage provided limited or no protection. Clinical signs were more severe and appeared earlier following challenge at 21 DPV than at 7 DPV. Within the vaccination treatments, eye-drop-vaccinated birds were better protected than their in-contact cohorts. In conclusion, partial vaccination of 20%, but not 10% of chickens, induced substantial protection against subsequent challenge. However, the attendant risks of reduced protection against early challenge and the possible reversion to virulence of vaccine virus when transmitted to unvaccinated chickens make it essential that 100% initial vaccine take be the goal of mass vaccination programs.

Eficacia protectora de la cepa vacunal CEO Serva del virus de la laringotraqueítis infecciosa (ILT) en pollos de engorde bajo diferentes condiciones de cobertura vacunal. La vacunación masiva contra el virus de la laringotraqueítis infecciosa (ILTV) en el agua de bebida puede resultar en una cobertura vacunal inicial variable. La cobertura vacunal inicial parcial del 20 % con una vacuna ILT australiana (A20) previamente resultó en una protección significativa contra el desafío virulento con el virus de la laringotraqueítis. Este estudio de seguimiento utilizó la cepa de la vacuna vacunal internacional Serva ILT en un diseño factorial para probar cuatro niveles de cobertura de vacunación (0 %, 10 %, 20 % o 100 % de pollitos vacunados por gota ocular con la vacuna viva a los siete días de edad) y tres niveles de desafío con el virus de la laringotraqueítis (sin desafío o con desafío a los 7 o 21 días después de la vacunación [DPV]). El aumento en la carga viral en hisopos de la hendidura coanal detectados por qPCR después del desafío se redujo significativamente con cobertura de vacunación del 20% y 100%, pero no con el 10%. La vacunación redujo el aumento de peso en las aves no desafiadas. La ganancia diaria de peso de las aves no se vio afectada por el desafío con el virus de la laringotraqueítis a los siete días después de la vacunación en ningún grupo, pero después del desafío a los 21 días después de la vacunación, se redujo significativamente en los grupos no vacunados y con cobertura del 10% en comparación con los grupos con cobertura del 20% y 100%. La vacunación del 20 % de los pollos brindó una protección sustancial pero incompleta (con un rango de índice de protección del 44 % al 70 %) contra la severidad de los signos clínicos y la mortalidad después del desafío, mientras que la cobertura de vacunación del 10 % brindó protección limitada o nula. Los signos clínicos fueron más graves y aparecieron más temprano después del desafío a los 21 días después de la vacunación en comparación con el desafío a los siete días después de la vacunación. Dentro de los tratamientos de vacunación, las aves vacunadas con gota ocular estaban mejor protegidas que sus cohortes en contacto. En conclusión, la cobertura de vacunación parcial del 20%, pero no del 10% de los pollos, indujo una protección sustancial contra el desafío posterior. Sin embargo, los riesgos concomitantes de una protección reducida contra el desafío temprano y la posible reversión a la virulencia del virus vacunal cuando se transmite a pollos no vacunados hacen que sea esencial que la cobertura vacunal inicial del 100% sea el objetivo de los programas de vacunación masiva.

Pathogenesis of Bohle iridovirus infection in Krefft's freshwater turtle hatchlings (Emydura macquarii krefftii).

Ranaviruses have been detected in over 12 families of reptiles including many genera of turtles, tortoises, and terrapins, but the pathogenesis of these infections is still poorly understood. Krefft's river turtle hatchlings (N = 36; Emydura macquarii krefftii) were inoculated intramuscularly with Bohle iridovirus (BIV, Ranavirus, isolate) or saline, and euthanized at 9 timepoints (3 infected and 1 control per timepoint) over a 24-day period. Samples of lung, liver, kidney, and spleen were collected for quantitative polymerase chain reaction (PCR); internal organs, skin, and oral cavity samples were fixed for histopathological examination. The earliest lesions, at 8 days postinoculation (dpi), were lymphocytic inflammation of the skin and fibrinoid necrosis of regional vessels at the site of inoculation, and mild ulcerative necrosis with lymphocytic and heterophilic inflammation in the oral, nasal, and tongue mucosae. Fibrinonecrotic foci with heterophilic inflammation were detected in spleen and gonads at 16 dpi. Multifocal hepatic necrosis, heterophilic inflammation, and occasional basophilic intracytoplasmic inclusion bodies were observed at 20 dpi, along with ulcerative lymphocytic and heterophilic tracheitis and bronchitis. Tracheitis, bronchitis, and rare bone marrow necrosis were present at 24 dpi. Of the viscera tested for ranaviral DNA by PCR, the liver and spleen had the highest viral loads throughout infection, and thus appeared to be major targets of viral replication. Testing of whole blood by qPCR was the most-effective ante-mortem method for detecting ranaviral infection compared with oral swabs. This study represents the first time-dependent pathogenesis study of a ranaviral infection in turtles.

Late relapse of ulcerative colitis presenting as tracheobronchitis: a case report.

BACKGROUND: Lung involvement in inflammatory bowel diseases usually follows colitis. However, the time to lung involvement onset varies depending on the case, and pulmonary lesions are usually not parallel to exacerbations of the colitis. CASE PRESENTATION: A 67-year-old Asian woman with a 38-year history of ulcerative colitis presented to our hospital with a complaint of prolonged dry cough for 2 months. The colitis had remained quiescent for > 35 years with low-dose salazosulfapyridine treatment. Chest computed tomography indicated circumferential thickening of the tracheal wall, while bronchoscopy examination revealed widespread erythematous edema and diffuse narrowing of the bronchial lumen. Biopsy of the bronchial mucosa showed submucosal lymphocytic infiltration. She was diagnosed with ulcerative-colitis-related tracheobronchitis and successfully treated with corticosteroids. CONCLUSIONS: Tracheobronchitis, in our case, occurred despite the longest remission period previously reported. Careful follow-up is necessary for the early recognition and treatment of pulmonary disease in patients with ulcerative colitis, regardless of the disease duration and long-term remission of colitis.

Evaluation of barometric whole-body plethysmography for therapy monitoring in cats with feline lower airway disease.

OBJECTIVES: Feline lower airway disease (FLAD) is a common respiratory condition in cats. Traditionally, response to therapy is monitored only by evaluation of clinical signs and radiographic examination of the lungs. Barometric whole-body plethysmography (BWBP) is considered a non-invasive, well-tolerated form of measuring airway reactivity in cats. The aim of the study was to assess pulmonary function testing by BWBP for non-invasive evaluation of response to therapy in cats with FLAD and to investigate whether BWBP parameters correlate with clinical severity. MATERIAL AND METHODS: The prospective study included 25 client-owned cats, diagnosed with FLAD on the basis of their medical history, clinical signs, radiographic findings, and bronchoalveolar lavage fluid (BALF) examination. At three time points (day 0, 14, and 60), a standardised owner questionnaire, a clinical examination and BWBP measurements were carried out. Results of the questionnaire and the clinical examination were evaluated using a clinical 12-point score. Individual therapy was administered to all patients after diagnosis, based on the severity of disease and compliance of the cat. RESULTS: The total clinical score significantly improved over the entire study period (p<0.001). Significant improvement was detected for the frequency of coughing (p = 0.009), respiratory distress (p = 0.001), lung auscultation findings (p = 0.002), and general condition and appetite (p = 0.045). The BWBP parameter Penh, an indicator of bronchoconstriction, improved significantly under initial therapy between day 0 and 14 (p = 0.009). A significant correlation between Penh and the severity of auscultation findings was seen on day 0 (r = 0.40; p = 0.013). CONCLUSION: The study supports the role of Penh as a non-invasive parameter for monitoring initial treatment response in cats with FLAD. Further studies are needed to address whether other BWBP parameters might be suitable for non-invasive therapy monitoring of FLAD. Clinical evaluation is always essential in cats with FLAD to evaluate treatment response.

Necrotizing Tracheitis Complicated by Tracheal Wall Perforation.

Necrotizing tracheitis is a rare condition, mainly seen in immunocompromised patients, that may lead to pseudomembrane formation, airway obstruction and in severe cases, tracheal perforation. We present a case of a 32-year-old male with poorly controlled diabetes who presented with productive cough, dysphagia, and respiratory distress. Bronchoscopy revealed extensive tracheal necrosis along a 4-5 cm segment of cartilaginous trachea and was complicated by tracheal perforation with false passage into the anterior mediastinum. Once the airway was re-established, a multidisciplinary team discussed options for definitive airway management, including tracheal reconstruction, pulmonary stent, or tracheostomy. Ultimately, a distal XLT tracheostomy was placed. Microbiology specimens of the tracheal tissue were positive for Actinomyces. The patient was started on long-term antibiotics and diabetes management. At three-month follow-up, the trachea was patent with near complete mucosalization of the previously necrotic segment. An area of proximal tracheal stenosis was successfully managed with a customized tracheal T-tube. In conclusion, this is a case of necrotizing tracheitis complicated by tracheal perforation. Successful treatment required a multidisciplinary team for airway management as well as medical treatment of immunocompromising risk factors and antimicrobial therapy. This enabled timely healing of the trachea and a durable airway.

Generalized and fatal felid alphaherpesvirus-1 natural infection with liver involvement in a feline leukaemia virus-positive adult cat: a case report.

Generalized and fatal felid alphaherpesvirus-1 (FeHV-1) natural infection with liver involvement is rarely reported in cats, and the occurrence of herpesvirus viraemia with internal organ histologic lesions in adult cats is unknown. A 1.5-year-old cat, female, mixed breed, positive for feline leukaemia virus (FeLV) presented in a veterinary teaching hospital with sneezing, nasal discharge, anorexia, and diarrhoea after two weeks, evolving to inspiratory dyspnoea. Complete blood count and serum biochemistry analysis showed marked leukopenia and thrombocytopenia. After clinical worsening and lack of treatment response, the cat was euthanized. Pathological findings included hepatic necrosis, fibrinonecrotic tracheitis, and bronchointerstitial pneumonia. Marked amounts of coccobacillary bacteria were observed covering the necrotic tracheal and bronchial mucosa, at the cytoplasm of alveolar macrophages, and free in alveoli lumen, mimicking a primary bacterial tracheitis and pneumonia. Both lung and tracheal bacteria exhibited marked immunolabeling in anti-Escherichia coli immunohistochemistry. In addition, rare epithelial cells of bronchi contained round, eosinophilic, intranuclear viral inclusion bodies (4-7 µm) that marginate the chromatin, characteristic of FeHV-1 infection. Strong multifocal anti-FeHV-1 immunolabeling was observed in necrotic epithelial cells of the liver, trachea, and lungs. Generalized herpesvirus infection with the occurrence of acute hepatic necrosis and severe respiratory illness is a potential differential diagnosis in FeLV-positive cats with respiratory signs. The immunodepression in these cats probably favours a FeHV-1 viraemia in addition to the development of opportunistic bacterial infections, such as Escherichia coli, and it is associated with a poor outcome.

Radiation-induced pseudomembranous tracheobronchitis: A report of two cases.

Radiation therapy can cause radiation pneumonitis, organizing pneumonia, and lung fibrosis. Radiation-induced pseudomembranous bronchitis is a rare condition. Here, we describe a rare case each of pseudomembranous tracheobronchitis and pseudomembrane with total bronchial obstruction which developed after thoracic radiotherapy. A 50-year-old man presented paroxysmal severe cough 1 month after concurrent chemoradiotherapy for small-cell lung cancer. Bronchoscopy revealed a whitish membrane in the trachea and bronchus, which were the fields of radiation. Another 60-year-old man complained of dyspnea 7 months after radiation therapy for metastatic lymph node adenocarcinoma. Bronchoscopy demonstrated a membrane with total obstruction of right lower lobar bronchus, which was the area of radiation. The pathological findings of histological examination in both cases demonstrated radiation-induced pseudomembranous tracheobronchitis. Patients in both cases responded well to steroids and the pseudomembrane disappeared. If patients who have received thoracic radiation therapy complain of persistent cough, bronchoscopy may be helpful.

Tracheitis Diagnosed With 68 Ga-PSMA PET/CT in a Patient With COVID-19.

ABSTRACT: A 57-year-old man with newly diagnosed with prostate cancer was admitted to our department for 68 Ga-prostate-specific membrane antigen PET/CT imaging. The patient, who was asymptomatic at the time of imaging, had increased diffuse 68 Ga-prostate-specific membrane antigen uptake in the trachea on PET/CT. No ground-glass density suggestive of pneumonia in both lungs was observed. The patient, whose symptoms developed 2 days after PET/CT imaging, was diagnosed with coronavirus disease 2019 by real-time polymerase chain reaction.

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.