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Journal of Veterinary Internal Medicine 2023Nonbronchoscopic bronchoalveolar lavage (nBAL) is routinely performed in calves, and airway cytology has great potential in airway disease diagnostics. A good reference...
BACKGROUND
Nonbronchoscopic bronchoalveolar lavage (nBAL) is routinely performed in calves, and airway cytology has great potential in airway disease diagnostics. A good reference framework for nBAL cytology is lacking.
OBJECTIVES
To distinguish different cytological profiles in nBAL from grouped housed calves using cluster analysis, and characterize these profiles on individual and herd levels.
ANIMALS
Three hundred thirty-eight group-housed calves from 60 herds (mainly dairy and beef ).
METHODS
Cross-sectional study. Differential counts of white blood cells were determined on nBAL fluid, followed by differentiation of cytological profiles by K-means-based cluster analysis. These profiles were characterized by reference values, decision tree analysis, and associations with clinical, ultrasonographic, bacteriological, and cytological features.
RESULTS
A normal (55.9%), a neutrophilic (41.1%), and an eosinophilic profile (3.0%) were identified. The normal profile was characterized by reference values of 2.3% to 47.4% neutrophils, 35.1% to 95.1% macrophages, 0.4 to 22.9% lymphocytes, and 0.0% to 0.9% eosinophils. The neutrophilic profile was characterized by ≥44.5% neutrophils, <1.6% eosinophils, and <11.5% lymphocytes. This profile was associated with the isolation of Pasteurella multocida, the presence of neutrophils with toxic granulation, and the presence of phagocytosed bacteria in neutrophils. The eosinophilic profile was characterized by eosinophils ≥1.6% (neutrophilia present) or ≥2.4% (neutrophilia absent), and associated with the presence of mast cells. On herd level, the neutrophilic and eosinophilic profiles were present in 85.0% and 15.0% of the herds, respectively.
CONCLUSIONS AND CLINICAL IMPORTANCE
This study provides a first step in the development of cytological guidelines, aiding the assessment of airway health and inflammation in calves through nBAL fluid cytology.
Topics: Animals; Cattle; Bronchoalveolar Lavage Fluid; Cross-Sectional Studies; Bronchoalveolar Lavage; Inflammation; Cluster Analysis; Dimercaprol; Cattle Diseases
PubMed: 37731196
DOI: 10.1111/jvim.16855 -
Physiological Reports Sep 2023The circadian rhythm system regulates lung function as well as local and systemic inflammations. The alteration of this rhythm might be induced by a change in the eating...
The circadian rhythm system regulates lung function as well as local and systemic inflammations. The alteration of this rhythm might be induced by a change in the eating rhythm. Peroxisome proliferator-activated receptor gamma (PPARG) is a key molecule involved in circadian rhythm regulation, lung functions, and metabolic processes. We described the effect of the PPARG agonist pioglitazone (PZ) on the diurnal mRNA expression profile of core circadian clock genes (Arntl, Clock, Nr1d1, Cry1, Cry2, Per1, and Per2) and metabolism- and inflammation-related genes (Nfe2l2, Pparg, Rela, and Cxcl5) in the male murine lung disrupted by reversed feeding (RF). In mice, RF disrupted the diurnal expression pattern of core clock genes. It decreased Nfe2l2 and Pparg and increased Rela and Cxcl5 expression in lung tissue. There were elevated levels of IL-6, TNF-alpha, total cells, macrophages, and lymphocyte counts in bronchoalveolar lavage (BAL) with a significant increase in vascular congestion and cellular infiltrates in male mouse lung tissue. Administration of PZ regained the diurnal clock gene expression, increased Nfe2l2 and Pparg expression, and reduced Rela, Cxcl5 expression and IL-6, TNF-alpha, and cellularity in BAL. PZ administration at 7 p.m. was more efficient than at 7 a.m.
Topics: Animals; Male; Mice; Dimercaprol; Inflammation; Interleukin-6; Lung; Pioglitazone; PPAR gamma; RNA, Messenger; Tumor Necrosis Factor-alpha
PubMed: 37704580
DOI: 10.14814/phy2.15823 -
Immunity, Inflammation and Disease Aug 2023A systemic and local inflammatory immune imbalance is thought to be the cause of traumatic tracheal stenosis (TS). However, with CD4 T lymphocytes being the predominant...
A systemic and local inflammatory immune imbalance is thought to be the cause of traumatic tracheal stenosis (TS). However, with CD4 T lymphocytes being the predominant immune cells in TS, the mechanism of action and recruitment has not been described. In our research, using flow cytometry, ELISA, immunofluorescence, and Transwell chamber assays, the expression, distribution, and potential chemotactic function of CD4 T cells in TS patients were examined before and after treatment. The results showed that the untreated group had significantly more CD4 T cells and their secreted TGF-β1 than the treated group. Additionally, the untreated group's CD4 T cells showed a significant rise in CCL22 and CCL1, as well as a larger proportion of CCR4 and CCR8. CD4 T cells and CD68 macrophages located in TS also expressed CCL1 and CCL22. In vitro, anti-CCL1 and anti-CCL22 can partially block the chemoattractant effect of TS bronchoalveolar lavage (BAL) on purified CD4 T cells. The findings of this study indicated that TS contained unbalanced CD4 immune cells that were actively recruited locally by CCR4/CCL22 and CCR8/CCL1. As a result, it is anticipated that CD4 immune rebalancing can serve as a novel treatment for TS.
Topics: Humans; Tracheal Stenosis; Biological Assay; CD4-Positive T-Lymphocytes; Dimercaprol; Enzyme-Linked Immunosorbent Assay
PubMed: 37647429
DOI: 10.1002/iid3.916 -
The Brazilian Journal of Infectious... 2023COVID-19-Associated Pulmonary Aspergillosis (CAPA) is a relatively common complication in patients with severe forms of the disease caused by the SARS-CoV-2 virus....
COVID-19-Associated Pulmonary Aspergillosis (CAPA) is a relatively common complication in patients with severe forms of the disease caused by the SARS-CoV-2 virus. Diagnosing and confirming CAPA is challenging. In this study, Aspergillus spp. isolation in respiratory specimens from patients with COVID-19 was evaluated for identifying cases of CAPA. In 2020‒2021, 17 Aspergillus spp. were isolated from 15 COVID-19 patients admitted to a university hospital in Brazil. Patient records were retrospectively reviewed to obtain clinical-epidemiological data and other markers of Aspergillus spp. infection and then compared with the ECMM/ISHAM criteria for defining CAPA. Probable CAPA was defined in 5/10 patients, who had Aspergillus spp. isolated from Bronchoalveolar Lavage (BAL) or a positive galactomannan blood test. Additionally, anti-Aspergillus antibodies were detected in two of these patients, during active or follow-up phases of CAPA. In another seven patients with Aspergillus spp. isolated from tracheobronchial aspirate or sputum, CAPA was presumed, mainly due to deterioration of clinical conditions and new lung imaging suggestive of fungal infection. Antifungal agents to control CAPA, particularly voriconazole, were used in 9/15 cases. In cases of probable CAPA and remaining patients, clinical conditions and comorbidities were similar, with lethality being high, at 60% and 71%, respectively. The number of CAPA cases defined by scientific criteria was lower than that assumed in the clinical context. This was largely due to the lack of BAL collection for fungal culture and the non-intensive use of other markers of invasive aspergillosis. The isolation of Aspergillus spp. in different respiratory specimens should alert clinicians to the diagnosis of CAPA.
Topics: Humans; Retrospective Studies; COVID-19; SARS-CoV-2; Aspergillosis; Aspergillus; Pulmonary Aspergillosis; Dimercaprol
PubMed: 37507102
DOI: 10.1016/j.bjid.2023.102793 -
The Journal of Infectious Diseases Jan 2024The impact of metagenomic next-generation sequencing (mNGS) on antimicrobial stewardship in patients with lower respiratory tract infections (LRTIs) is still unknown.
Impact of Metagenomic Next-Generation Sequencing of Bronchoalveolar Lavage Fluid on Antimicrobial Stewardship in Patients With Lower Respiratory Tract Infections: A Retrospective Cohort Study.
BACKGROUND
The impact of metagenomic next-generation sequencing (mNGS) on antimicrobial stewardship in patients with lower respiratory tract infections (LRTIs) is still unknown.
METHODS
This retrospective cohort study included patients who had LRTIs diagnosed and underwent bronchoalveolar lavage between September 2019 and December 2020. Patients who underwent both mNGS and conventional microbiologic tests were classified as the mNGS group, while those with conventional tests only were included as a control group. A 1:1 propensity score match for baseline variables was conducted, after which changes in antimicrobial stewardship between the 2 groups were assessed.
RESULTS
A total of 681 patients who had an initial diagnosis of LRTIs and underwent bronchoalveolar lavage were evaluated; 306 patients were finally included, with 153 in each group. mNGS was associated with lower rates of antibiotic escalation than in the control group (adjusted odds ratio, 0.466 [95% confidence interval, .237-.919]; P = .02), but there was no association with antibiotic de-escalation. Compared with the control group, more patients discontinued the use of antivirals in the mNGS group.
CONCLUSIONS
The use of mNGS was associated with lower rates of antibiotic escalation and may facilitate the cessation of antivirals, but not contribute to antibiotic de-escalation in patients with LRTIs.
Topics: Humans; Bronchoalveolar Lavage Fluid; Antimicrobial Stewardship; Retrospective Studies; High-Throughput Nucleotide Sequencing; Respiratory Tract Infections; Anti-Bacterial Agents; Dimercaprol; Metagenomics; Antiviral Agents; Sensitivity and Specificity
PubMed: 37506257
DOI: 10.1093/infdis/jiad296 -
The American Journal of Case Reports Jul 2023BACKGROUND ThinPrep Cytolyt is a methanol-based cell preservation solution frequently used to fix tissue samples immediately following endobronchial ultrasound-guided...
BACKGROUND ThinPrep Cytolyt is a methanol-based cell preservation solution frequently used to fix tissue samples immediately following endobronchial ultrasound-guided fine-needle aspiration. Currently, no published reports describe an iatrogenic exposure to Cytolyt. We report the only known case of an accidental intraoperative administration of a methanol solution, with corresponding plasma concentrations, and successful treatment with fomepizole. CASE REPORT A 70-year-old woman with a history of stage IIIA rectal adenocarcinoma was referred for evaluation of a newly identified lung mass. During the procedure, a bronchoalveolar lavage (BAL) of the right upper lobe was performed. After BAL, the proceduralist was informed that the syringe used to instill fluid for the BAL contained Cytolyt rather than saline. The Department of Medical Toxicology was contacted immediately, and the patient received a 15 mg/kg dose of fomepizole. The first plasma methanol level, before fomepizole administration, was elevated to 21 mg/dL. The methanol level was 13 mg/dL 3 h after fomepizole treatment and even lower thereafter; therefore, no additional fomepizole was required. The patient did not develop signs of systemic toxicity and was discharged on hospital day 3. CONCLUSIONS Following methanol exposures, patients can exhibit metabolic acidosis, with potential for blindness, hemodynamic instability, and possibly death if untreated. Fomepizole (4-methylpyrazole) inhibits alcohol dehydrogenase and is a mainstay of treatment. Preventing medical errors is key in ensuring optimal patient care and decreasing adverse events. Providers using CytoLyt and any similar products should be aware of this potential error and approach the possibility of methanol toxicity as they would other routes of methanol exposure.
Topics: Female; Humans; Aged; Fomepizole; Methanol; Antidotes; Pyrazoles; Dimercaprol; Iatrogenic Disease
PubMed: 37461205
DOI: 10.12659/AJCR.937247 -
Frontiers in Immunology 2023Low-dose radiation therapy (LDRT) can suppress intractable inflammation, such as that in rheumatoid arthritis, and is used for treating more than 10,000 rheumatoid...
Low-dose radiation therapy (LDRT) can suppress intractable inflammation, such as that in rheumatoid arthritis, and is used for treating more than 10,000 rheumatoid arthritis patients annually in Europe. Several recent clinical trials have reported that LDRT can effectively reduce the severity of coronavirus disease (COVID-19) and other cases of viral pneumonia. However, the therapeutic mechanism of LDRT remains unelucidated. Therefore, in the current study, we aimed to investigate the molecular mechanism underlying immunological alterations in influenza pneumonia after LDRT. Mice were irradiated to the whole lung 1 day post-infection. The changes in levels of inflammatory mediators (cytokines and chemokines) and immune cell populations in the bronchoalveolar lavage (BALF), lungs, and serum were examined. LDRT-treated mice displayed markedly increased survival rates and reduced lung edema and airway and vascular inflammation in the lung; however, the viral titers in the lungs were unaffected. Levels of primary inflammatory cytokines were reduced after LDRT, and transforming growth factor-β (TGF-β) levels increased significantly on day 1 following LDRT. Levels of chemokines increased from day 3 following LDRT. Additionally, M2 macrophage polarization or recruitment was increased following LDRT. We found that LDRT-induced TGF-β reduced the levels of cytokines and polarized M2 cells and blocked immune cell infiltration, including neutrophils, in BALF. LDRT-induced early TGF-β production was shown to be a key regulator involved in broad-spectrum anti-inflammatory activity in virus-infected lungs. Therefore, LDRT or TGF-β may be an alternative therapy for viral pneumonia.
Topics: Animals; Mice; COVID-19; Pneumonia, Viral; Inflammation; Cytokines; Arthritis, Rheumatoid; Dimercaprol; Transforming Growth Factors
PubMed: 37304302
DOI: 10.3389/fimmu.2023.1182927 -
Microbiome May 2023The advent of culture-independent, next-generation DNA sequencing has led to the discovery of distinct lung bacterial communities. Studies of lung microbiome taxonomy...
BACKGROUND
The advent of culture-independent, next-generation DNA sequencing has led to the discovery of distinct lung bacterial communities. Studies of lung microbiome taxonomy often reveal only subtle differences between health and disease, but host recognition and response may distinguish the members of similar bacterial communities in different populations. Magnetic-activated cell sorting has been applied to the gut microbiome to identify the numbers and types of bacteria eliciting a humoral response. We adapted this technique to examine the populations of immunoglobulin-bound bacteria in the lung.
METHODS
Sixty-four individuals underwent bronchoalveolar lavage (BAL). We separated immunoglobulin G-bound bacteria using magnetic-activated cell sorting and sequenced the 16S rRNA gene on the Illumina MiSeq platform. We compared microbial sequencing data in IgG-bound bacterial communities compared to raw BAL then examined the differences in individuals with and without HIV as a representative disease state.
RESULTS
Immunoglobulin G-bound bacteria were identified in all individuals. The community structure differed when compared to raw BAL, and there was a greater abundance of Pseudomonas and fewer oral bacteria in IgG-bound BAL. Examination of IgG-bound communities in individuals with HIV demonstrated the differences in Ig-bound bacteria by HIV status that were not seen in a comparison of raw BAL, and greater numbers of immunoglobulin-bound bacteria were associated with higher pulmonary cytokine levels.
CONCLUSIONS
We report a novel application of magnetic-activated cell sorting to identify immunoglobulin G-bound bacteria in the lung. This technique identified distinct bacterial communities which differed in composition from raw bronchoalveolar lavage, revealing the differences not detected by traditional analyses. Cytokine response was also associated with differential immunoglobulin binding of lung bacteria, suggesting the functional importance of these communities. Video Abstract.
Topics: Humans; RNA, Ribosomal, 16S; Microbiota; Immunoglobulin G; Cytokines; Dimercaprol; Magnetic Phenomena; HIV Infections
PubMed: 37226179
DOI: 10.1186/s40168-022-01434-5 -
Journal of Applied Microbiology Jun 2023To perform a prospective diagnostic study exploring the clinical utility of metagenomic next-generation sequencing (mNGS) in diagnosing community-acquired pneumonia...
Application of metagenomic next-generation sequencing in the diagnosis and resistome analysis of community-acquired pneumonia pathogens from bronchoalveolar lavage samples.
AIMS
To perform a prospective diagnostic study exploring the clinical utility of metagenomic next-generation sequencing (mNGS) in diagnosing community-acquired pneumonia (CAP), and revealing resistome differences in bronchoalveolar lavage fluid (BALF) from CAP patients with varying severity of admission base on Pneumonia Patient Outcomes Research Team (PORT) risk classes.
METHODS AND RESULTS
We compared the diagnostic performances of mNGS and conventional testing for the detection of pathogens in BALF from 59 CAP patients, and performed resistome differences analysis of metagenomic data from 59 BALF samples, namely, 25 from CAP patients with PORT score I (I group), 14 from CAP patients with PORT score II (II group), 12 from CAP patients with PORT score III (III group), and 8 from CAP patients with PORT score IV (IV group). The diagnostic sensitivities of mNGS and conventional testing for the detection of pathogens in BALF in patients with CAP were 96.6% (57/59) and 30.5% (18/59), respectively. There was a significant difference in the overall relative abundance of resistance genes between the four groups (P = 0.014). The results of principal coordinate analysis based on Bray-Curtis dissimilarities showed that there were significant differences in the composition of resistance genes among the I, II, III, and IV groups (P = 0.007). A large number of antibiotic resistance genes, such as those affiliated with multidrug, tetracycline, aminoglycoside, and fosfomycin resistance, were enriched in the IV group.
CONCLUSIONS
In conclusion, mNGS has a high diagnostic value in CAP. There were significant differences present in microbiota resistance to antibiotics in BALF from CAP patients in different PORT risk classes, which should attract enough attention.
Topics: Humans; Prospective Studies; Bronchoalveolar Lavage; Bronchoalveolar Lavage Fluid; High-Throughput Nucleotide Sequencing; Anti-Bacterial Agents; Dimercaprol; Metagenomics; Pneumonia; Sensitivity and Specificity
PubMed: 37188649
DOI: 10.1093/jambio/lxad102